ascorbic-acid and Neoplasms

Vitamin C, a small organic molecule, is widely found in fruits and vegetables and is an essential nutrient in the human body. Vitamin C is closely associated with some human diseases such as cancer. Many studies have shown that high doses of vitamin C have anti-tumor ability and can target tumor cells in multiple targets. This review will describe vitamin C absorption and its function in cancer treatment. We will review the cellular signaling pathways associated with vitamin C against tumors depending on the different anti-cancer mechanisms. Based on this, we will further describe some applications of the use of vitamin C for cancer treatment in preclinical and clinical trials and the possible adverse events that can occur. Finally, this review also assesses the prospective advantages of vitamin C in oncology treatment and clinical applications.

Topics: Ascorbic Acid; Humans; Neoplasms; Prospective Studies; Signal Transduction; Vitamins

Indoloquinoline (IQ) is an important class of naturally occurring antimalarial alkaloids, mainly represented by cryptolepine, isocryptolepine, and neocryptolepine. The IQ structural framework consists of four isomeric ring systems differing via the linkage of indole with quinoline as [3,2-b], [3,2-c], [2,3-c], and [2,3-b]. Structurally, IQs are planar and thus they bind strongly to the DNA which largely contributes to their biological properties. The structural rigidity and associated nonspecific cellular toxicity is a key shortcoming of the IQ structural framework for preclinical development. Thus, the lead optimization efforts were aimed at improving the therapeutic window and ADME properties of IQs. The structural modifications mainly involved attaching the basic aminoalkyl chains that positively modulates the vital physicochemical and topological parameters, thereby improves biological activity. Our analysis has found that the aminoalkylation consistently improved the selectivity index and provided acceptable in-vivo antimalarial/anticancer activity. Herein, we critically review the role of aminoalkylation in deciphering the antimalarial and cytotoxic activity of IQs.

Topics: Alkaloids; Antimalarials; Antineoplastic Agents; Cell Proliferation; Indoles; Malaria; Molecular Structure; Neoplasms; Quinolines

Vitamin C also known as L-ascorbic acid is a nutrient naturally occurring in many fruits and vegetables and widely known for its potent antioxidant activity. Several studies have highlighted the importance of using high dose vitamin C as an adjuvant anti-cancer therapy. Interestingly, it has been shown that vitamin C is able to modulate the anti-cancer immune response and to help to overcome the resistance to immune checkpoints blockade (ICB) drugs such as cytotoxic T-lymphocyte antigen 4 (CLTA-4) and programmed cell death ligand 1 (PD-L1/PD-1) inhibitors. Indeed, it was reported that vitamin C regulates several mechanisms developed by cancer cells to escape T cells immune response and resist ICB. Understanding the role of vitamin C in the anti-tumor immune response will pave the way to the development of novel combination therapies that would enhance the response of cancer patients to ICB immunotherapy. In this review, we discuss the effect of vitamin C on the immune system and its potential role in empowering cancer immunotherapy through its pro-oxidant potential, its ability to modulate epigenetic factors and its capacity to regulate the expression of different cytokines involved in the immune response.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Cell Line, Tumor; Cell Survival; Cytokines; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Epigenesis, Genetic; Humans; Immune Checkpoint Inhibitors; Neoplasms; Oxidative Stress; T-Lymphocytes; Tumor Microenvironment

Since the first reports describing the anti-cancer properties of vitamin C published several decades ago, its actual effectiveness in fighting cancer has been under investigation and widely discussed. Some scientific reports indicate that vitamin C in high concentrations can contribute to effective and selective destruction of cancer cells. Furthermore, preclinical and clinical studies have shown that relatively high doses of vitamin C administered intravenously in 'pharmacological concentrations' may not only be well-tolerated, but significantly improve patients' quality of life. This seems to be particularly important, especially for terminal cancer patients. However, the relatively high frequency of vitamin C use by cancer patients means that the potential clinical benefits may not be obvious. For this reason, in this review article, we focus on the articles published mainly in the last two decades, describing possible beneficial effects of vitamin C in preventing and treating selected malignant neoplasms in women, including breast, cervical, endometrial, and ovarian cancer. According to the reviewed studies, vitamin C use may contribute to an improvement of the overall quality of life of patients, among others, by reducing chemotherapy-related side effects. Nevertheless, new clinical trials are needed to collect stronger evidence of the role of this nutrient in supportive cancer treatment.

Topics: Ascorbic Acid; Female; Humans; Neoplasms; Quality of Life; Vitamins

Vitamin C (ascorbic acid, AA) is a weak sugar acid structurally related to glucose. All known physiological and biochemical functions of AA are due to its action as an electron donor. Ascorbate readily undergoes pH-dependent autoxidation creating hydrogen peroxide (H

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Humans; Hydrogen Peroxide; Mice; Neoplasms; Vitamins

Cancer is a disease of high mortality, and its prevalence has increased steadily in the last few years. However, during the last decade, the development of modern chemotherapy schemes, new radiotherapy techniques, targeted therapies and immunotherapy has brought new hope in the treatment of these diseases. Unfortunately, cancer therapies are also associated with frequent and, sometimes, severe adverse events. Ascorbate (ascorbic acid or vitamin C) is a potent water-soluble antioxidant that is produced in most mammals but is not synthesised endogenously in humans, which lack enzymes for its synthesis. Ascorbate has antioxidant effects that correspond closely to the dose administered. Interestingly, this natural antioxidant induces oxidative stress when given intravenously at a high dose, a paradoxical effect due to its interactions with iron. Importantly, this deleterious property of ascorbate can result in increased cell death. Although, historically, ascorbate has been reported to exhibit anti-tumour properties, this effect has been questioned due to the lack of available mechanistic detail. Recently, new evidence has emerged implicating ferroptosis in several types of oxidative stress-mediated cell death, such as those associated with ischemia-reperfusion. This effect could be positively modulated by the interaction of iron and high ascorbate dosing, particularly in cell systems having a high mitotic index. In addition, it has been reported that ascorbate may behave as an adjuvant of favourable anti-tumour effects in cancer therapies such as radiotherapy, radio-chemotherapy, chemotherapy, immunotherapy, or even in monotherapy, as it facilitates tumour cell death through the generation of reactive oxygen species and ferroptosis. In this review, we provide evidence supporting the view that ascorbate should be revisited to develop novel, safe strategies in the treatment of cancer to achieve their application in human medicine.

Topics: Animals; Antioxidants; Ascorbic Acid; Humans; Iron; Mammals; Neoplasms; Oxidative Stress; Reactive Oxygen Species

Pharmacological ascorbate (i.e., intravenous infusions of vitamin C reaching ~ 20 mM in plasma) is under active investigation as an adjuvant to standard of care anti-cancer treatments due to its dual redox roles as an antioxidant in normal tissues and as a prooxidant in malignant tissues. Immune checkpoint inhibitors (ICIs) are highly promising therapies for many cancer patients but face several challenges including low response rates, primary or acquired resistance, and toxicity. Ascorbate modulates both innate and adaptive immune functions and plays a key role in maintaining the balance between pro and anti-inflammatory states. Furthermore, the success of pharmacological ascorbate as a radiosensitizer and a chemosensitizer in pre-clinical studies and early phase clinical trials suggests that it may also enhance the efficacy and expand the benefits of ICIs.

Topics: Antineoplastic Agents; Ascorbic Acid; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms

Association between vitamins C (VC)/ E (VE) and cancer survival is inconsistent. This systematic review is aimed to summarize trials for effects of VC/VE on cancer survival.. Relevant English trials were retrieved from PubMed, Cochrane Library, Embase, Web of Science, Scopus databases, and Clinicaltrials.gov through 21/June/2022. Inclusion criteria were all trials which assessed sole/combinations intake of VC/VE on survival rate, mortality, or remission of any cancer. Exclusion criteria were observational and animal studies.. We reached 30 trials conducted on 38,936 patients with various cancers. Due to severe methodological heterogeneity, meta-analysis was impossible. High dose VC + chemotherapy or radiation was safe with an overall survival (OS) 182 days - 21.5 months. Sole oral or intravenous high dose VC was safe with non-significant change in OS (2.9-8.2 months). VE plus chemotherapy was safe, resulted in stabling diseases for 5 years in 70- 86.7% of patients and OS 109 months. It was found 60% and 16% non-significant reductions in adjusted hazard ratio (HR) deaths or recurrence by 200 mg/d tocotrienol + tamoxifen in breast cancer, respectively. Sole intake of 200-3200 mg/d tocotrienol before resectable pancreatic cancer was safe and significantly increased cancer cells' apoptosis. Combination VC and VE was non-significantly reduced 7% in rate of neoplastic gastric polyp.. Although our study is supported improvement of survival and progression rates of cancers by VC/VE, more high quality trials with large sample sizes are required to confirm.. CRD42020152795.

Topics: Antineoplastic Agents; Ascorbic Acid; Neoplasms; Tamoxifen; Tocotrienols; Vitamins

The turn-on mutations of the

Topics: Arsenic Trioxide; Ascorbic Acid; Cell Line, Tumor; Humans; Neoplasms; Oxidation-Reduction; Oxidative Stress; Proto-Oncogene Proteins p21(ras); Reactive Oxygen Species; Vitamins

Interest in the use of pharmacological ascorbate as a treatment for cancer has increased considerably since it was introduced by Cameron and Pauling in the 1970s. Recently, pharmacological ascorbate has been used in preclinical and early-phase clinical trials as a selective radiation sensitizer in cancer. The results of these studies are promising. This review summarizes data on pharmacological ascorbate (1) as a safe and efficacious adjuvant to cancer therapy; (2) as a selective radiosensitizer of cancer via a mechanism involving hydrogen peroxide; and (3) as a radioprotector in normal tissues. Additionally, we present new data demonstrating the ability of pharmacological ascorbate to enhance radiation-induced DNA damage in glioblastoma cells, facilitating cancer cell death. We propose that pharmacological ascorbate may be a general radiosensitizer in cancer therapy and simultaneously a radioprotector of normal tissue.

Topics: Animals; Antioxidants; Ascorbic Acid; Humans; Hydrogen Peroxide; Neoplasms; Oxidants; Oxidative Stress; Radiation Tolerance; Radiation-Sensitizing Agents; Reactive Oxygen Species

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and boosting immune response. Moreover, high-dose IVC is powerful as an adjuvant treatment for cancer, acting synergistically with many standard (chemo-) therapies, as well as a method for mitigating the toxic side-effects of chemotherapy. Despite the rationale and ample evidence, strong clinical data and phase III studies are lacking. Therefore, there is a need for more extensive awareness of the use of this highly promising, non-toxic cancer treatment in the clinical setting. In this review, we provide an elaborate overview of pre-clinical and clinical studies using high-dose IVC as anti-cancer agent, as well as a detailed evaluation of the main known molecular mechanisms involved. A special focus is put on global molecular profiling studies in this respect. In addition, an outlook on future implications of high-dose vitamin C in cancer treatment is presented and recommendations for further research are discussed.

Topics: Administration, Intravenous; Ascorbic Acid; Humans; Neoplasms

The Western-style diet, which is common in developed countries and spreading into developing countries, is unbalanced in many respects. For instance, micronutrients (vitamins A, B complex, C, D, E, and K plus iron, zinc, selenium, and iodine) are generally depleted in Western food (causing what is known as 'hidden hunger'), whereas some others (such as phosphorus) are added beyond the daily allowance. This imbalance in micronutrients can induce cellular damage that can increase the risk of cancer. Interestingly, there is a large body of evidence suggesting a strong correlation between vitamin intake as well as vitamin blood concentrations with the occurrence of certain types of cancer. The direction of association between the concentration of a given vitamin and cancer risk is tumor specific. The present review summarized the literature regarding vitamins and cancer risk to assess whether these could be used as diagnostic or prognostic markers, thus confirming their potential as biomarkers. Despite many studies that highlight the importance of monitoring vitamin blood or tissue concentrations in cancer patients and demonstrate the link between vitamin intake and cancer risk, there is still an urgent need for more data to assess the effectiveness of vitamins as biomarkers in the context of cancer. Therefore, this review aims to provide a solid basis to support further studies on this promising topic.

Topics: Ascorbic Acid; Biomarkers, Tumor; Diet, Western; Female; Humans; Male; Micronutrients; Neoplasms; Risk Factors; Vitamin A; Vitamin B Complex; Vitamin E; Vitamin K; Vitamins

Vitamin C (VitC), in addition to its role as a general antioxidant, has long been considered to possess direct anti-cancer activity at high doses. VitC acts through oxidant and epigenetic mechanisms, which at high doses can exert direct killing of tumor cells

Topics: Animals; Ascorbic Acid; Dietary Supplements; Humans; Immunotherapy; Killer Cells, Natural; Neoplasms; T-Lymphocytes; Vitamins

To study post-diagnosis dietary supplement use in relation to total mortality, cancer mortality and recurrence among cancer survivors. PubMed and Cochrane Library were searched until April 2019 for observational studies (OS) and randomized clinical trials (RCT). Pooled risk ratios (RR) were calculated using random-effects models. Compared to no supplementation, calcium supplementation was associated with lower total (RR = 0.88, 95% confidence interval (CI): 0.77-1.00, I

Topics: Ascorbic Acid; Dietary Supplements; Humans; Neoplasms; Odds Ratio; Vitamins

Topics: Apoptosis; Ascorbic Acid; Autophagy; Cell Death; DNA Breaks, Double-Stranded; Ferroptosis; Humans; Necroptosis; Neoplasms; Oxidative Stress; Poly (ADP-Ribose) Polymerase-1; Reactive Oxygen Species

Vitamin C (ascorbate) is an essential dietary requirement, with fundamental redox, anti-oxidant functions at physiologic concentrations. Vitamin C is a cofactor for Fe

Topics: Antineoplastic Agents; Ascorbic Acid; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Proteins; Neoplasms

Chemotherapy and radiotherapy are the most frequent treatment for patients suffering from malignant progression of cancer. Even though new treatments are now being implemented, administration of these chemotherapeutic agents remains as the first line option in many tumor types. However, the secondary effects of these compounds represent one of the main reasons cancer patients lose life quality during disease progression. Recent data suggests that Ocoxin, a plant extract and natural compound based nutritional complement rich in antioxidants and anti-inflammatory mediators exerts a positive effect in patients receiving chemotherapy and radiotherapy. This mixture attenuates the chemotherapy and radiotherapy-related side effects such as radiation-induced skin burns and mucositis, chemotherapy-related diarrhea, hepatic toxicity and blood-infection. Moreover, it has been proven to be effective as anticancer agent in different tumor models both

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Chemoradiotherapy; Clinical Trials as Topic; Drug Resistance, Neoplasm; Drug Synergism; Drug-Related Side Effects and Adverse Reactions; Folic Acid; Humans; Neoplasms; Pantothenic Acid; Plant Extracts; Radiation Injuries; Radiation Tolerance; Treatment Outcome; Vitamin B 12; Vitamin B 6; Zinc Sulfate

There is a rapidly growing body of literature supporting the notion that differential oxidative metabolism in cancer versus normal cells represents a metabolic frailty that can be exploited to open a therapeutic window into cancer therapy. These cancer cell-specific metabolic frailties may be amenable to manipulation with non-toxic small molecule redox active compounds traditionally thought to be antioxidants. In this review we describe the potential mechanisms and clinical applicability in cancer therapy of four small molecule redox active agents: melatonin, vitamin E, selenium, and vitamin C. Each has shown the potential to have pro-oxidant effects in cancer cells while retaining antioxidant activity in normal cells. This dichotomy can be exploited to improve responses to radiation and chemotherapy by opening a therapeutic window based on a testable biochemical rationale amenable to confirmation with biomarker studies during clinical trials. Thus, the unique pro-oxidant/antioxidant properties of melatonin, vitamin E, selenium, and vitamin C have the potential to act as effective adjuvants to traditional cancer therapies, thereby improving cancer patient outcomes.

Topics: Antioxidants; Ascorbic Acid; Humans; Neoplasms; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Vitamin E

Cancer cells increase their metabolic activity by enhancing glucose uptake through overexpression of hexose transporters (Gluts). Gluts also have the capacity to transport other molecules besides glucose, including fructose, mannose, and dehydroascorbic acid (DHA), the oxidized form of vitamin C. The majority of research studies in this field have focused on the role of glucose transport and metabolism in cancer, leaving a substantial gap in our knowledge of the contribution of other hexoses and DHA in cancer biology. Here, we summarize the most recent advances in understanding the role that the multifunctional transport capacity of Gluts plays in biological and clinical aspects of cancer, and how these characteristics can be exploited in the search for novel diagnostic and therapeutic strategies.

Topics: Ascorbic Acid; Biological Transport; Dehydroascorbic Acid; Glucose; Hexoses; Humans; Monosaccharide Transport Proteins; Neoplasms

Topics: Antioxidants; Ascorbic Acid; Dehydroascorbic Acid; Glucose Transport Proteins, Facilitative; Humans; Mitochondria; Neoplasms; Sodium-Coupled Vitamin C Transporters

High-dose intravenously administered vitamin C (IVC) is widely used in cancer patients by complementary and alternative medicine practitioners. The most frequent indications for IVC therapy result from the belief in its effectiveness as a potent anti-cancer agent which additionally enhances chemosensitivity of cancer cells and reduces chemotherapy-related toxicities and fatigue intensity. In this narrative review, we decided to deal with this issue, trying to answer the question whether there is any scientific evidence supporting the rationale for application of high-dose IVC therapy in advanced-stage cancer patients. Although results obtained from preclinical studies demonstrated that millimolar ascorbate plasma concentrations achievable only after IVC administration were cytotoxic to fast-growing malignant cells and inhibited tumor growth as well as prolonged the survival of laboratory animals, such positive effects were not found in human studies with advanced-stage cancer patients. We also have not found the rationale for the use of IVC to increase the effectiveness of chemotherapy and to reduce the chemotherapy-induced toxicity in the above mentioned group. Nevertheless, in palliative care, high-dose IVC might be considered as a therapy improving the quality of life and reducing cancer-related symptoms, such as fatigue and bone pain. However, because of the absence of placebo-controlled randomized trials on IVC efficacy in advanced-stage cancer patients, the placebo effect cannot be excluded.

Topics: Administration, Intravenous; Animals; Antineoplastic Agents; Ascorbic Acid; Cancer Pain; Fatigue; Humans; Neoplasms; Palliative Care; Treatment Outcome

The role of vitamin C in the treatment of cancer has been subject to controversy for decades. Within the past 10 years, mechanistic insight into the importance of vitamin C in epigenetic regulation has provided a new rationale for its potential anti-cancer effects. At physiological concentrations, vitamin C is a potent antioxidant and thereby co-factor for a range of enzymes including the Fe(II)- and α-ketoglutarate-dependent dioxygenases that represent some of the most important epigenetic regulators; the ten-eleven translocation (TET) methylcytosine dioxygenases and the Jumonji-C domain-containing histone demethylases. Epigenetic deregulation is a hallmark of many cancers and reduced activity of these enzymes or somatic loss-of-function mutations in the genes encoding them, are observed in many cancer types. The present review outlines the growing literature on the role of vitamin C in epigenetic therapy of cancer. In the vast majority of in vitro, animal and clinical studies included in this review, vitamin C showed ability across cancer types to increase the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine catalyzed by the TET enzymes - the first step in DNA demethylation. Most consistently, vitamin C in combination with the class of epigenetic drugs, DNA methyltransferase inhibitors, has demonstrated efficacy in the treatment of hematological malignancies in both preclinical and the limited number of available clinical studies. Yet, the pertinent question of what is the optimal dose of vitamin C in cancer studies remains to be answered. High-quality randomized placebo-controlled trials are needed to determine whether supplementation with vitamin C may benefit subgroups of patients with (pre-)cancer.

Topics: Animals; Antioxidants; Ascorbic Acid; Dioxygenases; DNA Methylation; Epigenesis, Genetic; Humans; Neoplasms; Vitamins

Vitamin C, also called ascorbic acid, is a water-soluble antioxidant and free radical scavenger. It is required in the body for numerous metabolic functions and is involved in the development of proteins and connective tissue.. In April 2020, a systematic search was carried out on five electronic databases (Medline, Embase, Cochrane, Cinahl, PsycINFO) to find studies on the use, efficacy and safety of a complementary therapy with vitamin C in oncological patients.. Out of the initial 23,195 search results, 21 studies with 1961 patients were included in this review. Five of the included studies (n = 417) were randomized controlled trials (RCTs). The remaining 16 studies belonged to a lower class of evidence. The patients who were treated with vitamin C suffered from various malignant diseases, some in an advanced and palliative stage. Vitamin C was applied intravenously or orally. It was either the only treatment or was combined with chemo- or radiotherapy. Endpoints included the development of the disease-related symptoms, quality of life, mortality, progression-free survival and safety of vitamin C. The studies were of moderate quality and showed either no effect of vitamin C or a positive trend, although this has rarely been statistically proven in group comparisons. No or only slight side effects with both oral and intravenous administration of vitamin C were reported.. Oral intake of vitamin C does not appear to have any effect in patients with malignancies. Data are heterogeneous for intravenous administration. There are no RCTs with statistical group comparisons.

Topics: Administration, Oral; Antioxidants; Ascorbic Acid; Humans; Injections, Intravenous; Neoplasms; Prognosis

Cancer, a fatal disease, is also one of the main causes of death worldwide. Despite various developments to prevent and treat cancer, the side effects of anticancer drugs remain a major concern. Ascorbic acid is an essential vitamin required by our bodies for normal physiological function and also has antioxidant and anticancer activity. Although the body cannot synthesize ascorbic acid, it is abundant in nature through foods and other natural sources and also exists as a nutritional food supplement. In anticancer drug development, ascorbic acid has played an important role by inhibiting the development of cancer through various mechanisms, including scavenging reactive oxygen species (ROS), selectively producing ROS and encouraging their cytotoxicity against tumour cells, preventing glucose metabolism, serving as an epigenetic regulator, and regulating the expression of HIF in tumour cells. Several ascorbic acid analogues have been produced to date for their anticancer and antioxidant activity. The current review summarizes the mechanisms behind ascorbic acid's antitumor activity, presents a compilation of its derivatives and their biological activity as anticancer agents, and discusses delivery systems such as liposomes, nanoparticles against cancer, and patents on ascorbic acid as anticancer agents.

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; Biotransformation; Dietary Supplements; Drug Carriers; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Glucose Transporter Type 1; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Liposomes; Nanoparticles; Neoplasms; p300-CBP Transcription Factors; Patents as Topic; Reactive Oxygen Species; Signal Transduction

Cancer metastasis to distant organs is initiated by tumor cells that disseminate from primary heterogeneous tumors. The subsequent growth and survival of tumor metastases depend on different metabolic changes, which constitute one of the enigmatic properties of tumor cells. Aerobic glycolysis, 'the Warburg effect', contributes to tumor energy supply, by oxidizing glucose in a faster manner compared to oxidative phosphorylation, leading to an increased lactate production by lactate dehydrogenase A (LDH-A), which in turn affects the immune response. Surrounding stromal cells contribute to feedback mechanisms further prompting the acquisition of pro-invasive metabolic features. Hence, therapeutic strategies targeting the glycolytic pathway are intensively investigated, with a special interest on their anti-metastatic properties. Various small molecules, such as LDH-A inhibitors, have shown pre-clinical activity against different cancer types, and blocking LDH-A could also help in designing future complimentary therapies. Modulation of specific targets in cells with an altered glycolytic metabolism should indeed result in a milder and distinct toxicity profile, compared to conventional cytotoxic therapy, while a combination treatment with vitamin C leading to increasing reactive oxygen species levels, should further inhibit cancer cell survival and invasion. In this review we describe the impact of metabolic reprogramming in cancer metastasis, the contribution of lactate in this aberrant process and its effect on oncogenic processes. Furthermore, we discuss experimental compounds that target glycolytic metabolism, such as LDH-A inhibitors, and their potential to improve current and experimental therapeutics against metastatic tumors.

Topics: Antineoplastic Agents; Ascorbic Acid; Energy Metabolism; Glucose; Glycolysis; Humans; L-Lactate Dehydrogenase; Metabolic Networks and Pathways; Mitochondria; Molecular Targeted Therapy; Neoplasms; Oxidative Phosphorylation; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Stromal Cells; Tumor Microenvironment

Our graphical review expands the analysis of cancer vulnerabilities for high dose vitamin C, based on several facts, illustrating the cytotoxic potential of the ascorbate free radical (AFR) via impairment of mitochondrial respiration and the mechanisms of its elimination in mammals by the membrane-bound NADH:cytochrome b5 oxidoreductase 3 (Cyb5R3). We propose that vitamin C can function in "protective mode" or "destructive mode" affecting cellular homeostasis, depending on the intracellular "steady-state" concentration of AFR and differential expression/activity of Cyb5R3 in cancerous and normal cells. Thus, a specific anti-cancer effect can be achieved at high doses of vitamin C therapy. The review is intended for a wide audience of readers - from students to specialists in the field.

Topics: Ascorbic Acid; Biomarkers, Tumor; Chemotherapy, Adjuvant; Cytochrome-B(5) Reductase; Free Radicals; Homeostasis; Humans; Neoplasms

Cancer remains one of the most feared and dreaded diseases in this era of modern medicine, claiming the lives of many, and affecting the quality of life of several others around the globe despite major advances in the diagnosis, treatment, palliative care and the immense resources invested into cancer research. While research in cancer has largely focused on the neoplasm/tumor and the cancerous cells that make up the tumor, more recently, the existence, proliferation, differentiation, migration and invasion of cancer stem cells (CSCs) and the role that CSCs play in tumor initiation, progression, metastasis, drug resistance and relapse/recurrence of the disease has gained widespread interest in cancer research. Although the conventional therapeutic approaches such as surgery, chemotherapy and radiation therapy are effective cancer treatments, very often these treatment modalities fail to target the CSCs, which then later become the source of disease recurrence. A majority of the anti-cancer agents target rapidly dividing cancer cells and normal cells and hence, have side effects that are not expected. Targeting CSCs remains a challenge due to their deviant nature with a low proliferation rate and increased drug resistance mechanism. Ascorbic acid/Vitamin C (Vit.C), a potent antioxidant, is a cofactor for several biosynthetic and gene regulatory enzymes and a vital contributor to immune defense of the body, and was found to be deficient in patients with advanced stages of cancer. Vit.C has gained importance in the treatment of cancer due to its ability to modulate the redox status of the cell and influence epigenetic modifications and significant roles in HIF1α signaling. Studies have reported that intravenous administration of Vit.C at pharmacological doses selectively kills tumor cells and targets CSCs when administered along with chemotherapeutic drugs. In the current article, we provide an in-depth review of how Vit.C plays an important role in targeting CSCs and its possible use as an adjuvant, neoadjuvant or co-treatment in the treatment of cancers.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Cell Differentiation; Cell Transformation, Neoplastic; Combined Modality Therapy; Drug Resistance, Neoplasm; Humans; Neoplasms; Neoplastic Stem Cells; Signal Transduction

Anti-angiogenesis effect of ascorbic acid (AA) is still controversial. However, most of the scientific evidence suggests that AA has anti-angiogenesis effects on a number of test systems, including laboratory animals, human beings, and their derived cell lines. The information provided in this paper suggests that AA may be a hopeful angiostatic agent for the treatment of cancer.

Topics: Angiogenesis Inhibitors; Animals; Ascorbic Acid; Humans; Neoplasms; Neovascularization, Pathologic

Vitamin C as a cancer therapy has a controversial history. Much of the controversy arises from the lack of predictive biomarkers for stratification of patients, as well as a clear understanding of the mechanism of action and its multiple targets underlying the anticancer effect. Our review expands the analysis of cancer vulnerabilities for high-dose vitamin C, based on several facts, illustrating the cytotoxic potential of the ascorbyl free radical (AFR) via impairment of mitochondrial respiration and the mechanisms of its elimination in mammals by the membrane-bound NADH:cytochrome b5 oxidoreductase 3 (Cyb5R3). This enzyme catalyzes rapid conversion of AFR to ascorbate, as well as reduction of other redox-active compounds, using NADH as an electron donor. We propose that vitamin C can function in "protective mode" or "destructive mode" affecting cellular homeostasis, depending on the intracellular "steady-state" concentration of AFR and differential expression/activity of Cyb5R3 in cancerous and normal cells. Thus, a specific anticancer effect can be achieved at high doses of vitamin C therapy. The review is intended for a wide audience of readers-from students to specialists in the field.

Topics: Animals; Ascorbic Acid; Cell Respiration; Free Radicals; Humans; Mitochondria; Neoplasms; Oxidation-Reduction

Vitamin C has been known for decades. It is common in everyday use as an element of the diet, supplementation, and a preservative. For years, research has been conducted to precisely determine the mechanism of action of ascorbate in the cell. Available results indicate its multi-directional cellular effects. Vitamin C, which belongs to antioxidants scavenging free radicals, also has a 'second face'-as a pro-oxidative factor. However, whether is the latter nature a defect harmful to the cell, or whether a virtue that is a source of benefit? In this review, we discuss the effects of vitamin C treatment in cancer prevention and the role of ascorbate in maintaining redox balance in the central nervous system (CNS). Finally, we discuss the effect of vitamin C supplementation on biomarkers of oxidative DNA damage and review the evidence that vitamin C has radioprotective properties.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Biomarkers; Central Nervous System; DNA Damage; Free Radicals; Humans; Neoplasms; Oxidants; Oxidation-Reduction; Oxidative Stress; Radiation-Protective Agents

Treatment options for effective treatment of cancer with minimum off-target effects and maximum clinical outcomes have remained overarching goals in the clinical oncology. Vitamin C has remained in the shadows of controversy since the past few decades; burgeoning evidence has started to shed light on wide-ranging anticancer effects exerted by Vitamin C to induce apoptosis in drug-resistant cancer cells, inhibit uncontrolled proliferation of the cancer cells and metastatic spread. Landmark achievements in molecular oncology have ushered in a new era, and researchers have focused on the identification of oncogenic pathways regulated by Vitamin C in different cancers. However, there are visible knowledge gaps in our understanding related to the ability of Vitamin C to modulate a myriad of transduction cascades. There are scattered pieces of scientific evidence about promising potential of Vitamin C to regulate JAK-STAT, TGF/SMAD, TRAIL and microRNAs in different cancers. However, published data is insufficient and needs to be investigated comprehensively to enable basic and clinical researchers to reap full benefits and promote result-oriented transition of Vitamin C into various phases of clinical trials. In this review, we will emphasize on available evidence related to the regulation of oncogenic cell signaling pathways by Vitamin C in different cancers. We will also highlight the conceptual gaps, which need detailed and cutting-edge research.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Humans; Neoplasm Proteins; Neoplasms; Signal Transduction

Vitamin C serves as a cofactor for Fe(II) and 2-oxoglutarate-dependent dioxygenases including TET family enzymes, which catalyze the oxidation of 5-methylcytosine into 5-hydroxymethylcytosine and further oxidize methylcytosines. Loss-of-function mutations in epigenetic regulators such as TET genes are prevalent in hematopoietic malignancies. Vitamin C deficiency is frequently observed in cancer patients. In this review, we discuss the role of vitamin C and TET proteins in cancer, with a focus on hematopoietic malignancies, T regulatory cells, and other immune system cells.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Dioxygenases; Humans; Immunity; Ketoglutaric Acids; Leukopoiesis; Neoplasms; T-Lymphocytes, Regulatory

Vitamin C is an electron donor and is involved in a variety of biochemical reactions in stem cell and cancer stem cell, as well as collagen synthesis and the regulation of hypoxia-inducible factor synthesis, which two affect extracellular matrix remodelling and hence cancer metastasis. Specific doses of vitamin C can stop cancer cell glycolysis and block nitroso synthesis, indicating the potential of vitamin C in cancer treatment. Recent studies preliminary revealed Vitamin C enhance the cancer's immune response to anti PD-L1 therapy through multiple indirect approaches. Herein we reviewed the recent function of vitamin C for further research in sequential aspects of cancer stem cell, extracellular matrix remodeling, cancer metastasis and cancer immunotherapy.

Topics: Animals; Antioxidants; Ascorbic Acid; B7-H1 Antigen; Extracellular Matrix; Humans; Immunotherapy; Neoplasms; Neoplastic Stem Cells

Ocoxin Oral Solution (OOS) is a nutritional supplement whose formulation includes several plant extracts and natural products with demonstrated antitumoral properties. This review summarizes the antitumoral action of the different constituents of OOS. The action of this formulation on different preclinical models as well as clinical trials is reviewed, paying special attention to the mechanism of action and quality of life improvement properties of this nutritional supplement. Molecularly, its mode of action includes a double edge role on tumor biology, that involves a slowdown in cell proliferation accompanied by cell death induction. Given the safety and good tolerability of OOS, and its potentiation of the antitumoral effect of other standard of care drugs, OOS may be used in the oncology clinic in combination with conventional therapies.

Topics: Amino Acids; Animals; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Cinnamomum zeylanicum; Dietary Supplements; Disease Models, Animal; Drug Evaluation, Preclinical; Folic Acid; Glucosamine; Glycyrrhiza; Humans; Neoplasms; Pantothenic Acid; Plant Extracts; Sucrose; Tea; Vitamin B 12; Vitamin B 6; Zinc Sulfate

Fe(II)/2-oxoglutarate (2OG)-dependent oxygenases are a conserved enzyme class that catalyse diverse oxidative reactions across nature. In humans, these enzymes hydroxylate a broad range of biological substrates including DNA, RNA, proteins and some metabolic intermediates. Correspondingly, members of the 2OG-dependent oxygenase superfamily have been linked to fundamental biological processes, and found dysregulated in numerous human diseases. Such findings have stimulated efforts to understand both the biochemical activities and cellular functions of these enzymes, as many have been poorly studied. In this review, we focus on human 2OG-dependent oxygenases catalysing the hydroxylation of protein and polynucleotide substrates. We discuss their modulation by changes in the cellular microenvironment, particularly with respect to oxygen, iron, 2OG and the effects of oncometabolites. We also describe emerging evidence that these enzymes are responsive to cellular stresses including hypoxia and DNA damage. Moreover, we examine how dysregulation of 2OG-dependent oxygenases is associated with human disease, and the apparent paradoxical role for some of these enzymes during cancer development. Finally, we discuss some of the challenges associated with assigning biochemical activities and cellular functions to 2OG-dependent oxygenases.

Topics: Ascorbic Acid; Biological Phenomena; Catalysis; DNA; DNA Damage; Gene Expression Regulation; Humans; Hydroxylation; Hypoxia; Ketoglutaric Acids; Mixed Function Oxygenases; Models, Molecular; Neoplasms; Oxidation-Reduction; Oxygen; Oxygenases; Protein Processing, Post-Translational; RNA

Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe

Topics: Ascorbic Acid; Basic Helix-Loop-Helix Transcription Factors; Brain Neoplasms; Breast Neoplasms; Carcinogenesis; Dehydroascorbic Acid; Dioxygenases; DNA Methylation; DNA-Binding Proteins; Epigenesis, Genetic; Female; Glioma; Glucose Transport Proteins, Facilitative; Hematologic Neoplasms; Homeostasis; Humans; Hypoxia-Inducible Factor 1; Ketoglutaric Acids; Male; Melanoma; Mixed Function Oxygenases; Neoplasms; Oxidation-Reduction; Polymorphism, Genetic; Prostatic Neoplasms; Proto-Oncogene Proteins; Sodium-Coupled Vitamin C Transporters; Vitamins

Vitamin C is an antioxidant that may scavenge reactive oxygen species preventing DNA damage and other effects important in cancer transformation. Dietary vitamin C from natural sources is taken with other compounds affecting its bioavailability and biological effects. High pharmacological doses of vitamin C may induce prooxidant effects, detrimental for cancer cells. An oxidized form of vitamin C, dehydroascorbate, is transported through glucose transporters, and cancer cells switch from oxidative phosphorylation to glycolysis in energy production so an excess of vitamin C may limit glucose transport and ATP production resulting in energetic crisis and cell death. Vitamin C may change the metabolomic and epigenetic profiles of cancer cells, and activation of ten-eleven translocation (TET) proteins and downregulation of pluripotency factors by the vitamin may eradicate cancer stem cells. Metastasis, the main reason of cancer-related deaths, requires breakage of anatomical barriers containing collagen, whose synthesis is promoted by vitamin C. Vitamin C induces degradation of hypoxia-inducible factor, HIF-1, essential for the survival of tumor cells in hypoxic conditions. Dietary vitamin C may stimulate the immune system through activation of NK and T cells and monocytes. Pharmacological doses of vitamin C may inhibit cancer transformation in several pathways, but further studies are needed to address both mechanistic and clinical aspects of this effect.

Topics: Animals; Antioxidants; Ascorbic Acid; Carcinogenesis; Chemokine CCL1; Dietary Supplements; Gene Expression Regulation, Neoplastic; Glucose; Glycolysis; Humans; Immunologic Surveillance; Killer Cells, Natural; Neoplasms; Oxidants

RAS protein family members (KRAS4A, KRAS4B, HRAS and NRAS) function as GDP-GTP-regulated on-off switches, which regulate cytoplasmic-nuclear signaling networks ruling diverse normal cellular processes. Constitutive activating mutations in RAS genes are found in up to 30% of human cancers, and remarkably, the oncogenic Ras mutations and mutations in other components of Ras/MAPK signaling pathways seem to be mutually exclusive in most tumors, pointing out that deregulation of Ras-dependent signaling is an essential requirement for tumorigenesis. Up to 30% of solid tumors are known to have a mutated (abnormal) KRAS gene. Unfortunately, patients harboring mutated KRAS CRC are unlikely to benefit from anti-EGFR therapy. Moreover, it remains unclear that patients with KRAS wild-type CRC will definitely respond to such therapies. Although some clinically designed-strategies to modulate KRAS aberrant activation have been designed, all attempts to target KRAS have failed in the clinical assays and K-RAS has been assumed to be invulnerable to chemotherapeutic attack. Recently, different encouraging publications reported that ascorbate may have a selective antitumoral effect on KRAS mutant cancer cells. In this review we aim to describe the prevalence and importance of KRAS mutation in cancer and associated problems for the clinical handling of patients harboring these tumors. We highlight the role of mutated KRAS in boosting and keeping the tumor associated aberrant cell metabolism stating that further in-depth studies on the molecular mechanism of ascorbate to bypass mutated KRAS-related metabolic alterations may constitute a new pathway to design novel molecules in order handle tumor resistance to anti EGFR-therapies.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Biomarkers, Tumor; Cell Transformation, Neoplastic; Drug Discovery; Energy Metabolism; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Mutation; Neoplasms; ras Proteins; Signal Transduction

Chemoradiation has remained the standard of care treatment for many of the most aggressive cancers. However, despite effective toxicity to cancer cells, current chemoradiation regimens are limited in efficacy due to significant normal cell toxicity. Thus, efforts have been made to identify agents demonstrating selective toxicity, whereby treatments simultaneously sensitize cancer cells to protect normal cells from chemoradiation. Pharmacological ascorbate (intravenous infusions of vitamin C resulting in plasma ascorbate concentrations ≥20 mM; P-AscH

Topics: Antioxidants; Ascorbic Acid; Chemoradiotherapy; Humans; Hydrogen Peroxide; Neoplasms; Oxidative Stress; Radiation-Sensitizing Agents

Ascorbic acid (vitamin C) has been gaining attention as a potential treatment for human malignancies. Various experimental studies have shown the ability of pharmacological doses of vitamin C alone or in combinations with clinically used drugs to exert beneficial effects in various models of human cancers. Cytotoxicity of high doses of vitamin C in cancer cells appears to be related to excessive reactive oxygen species generation and the resulting suppression of the energy production via glycolysis. A hallmark of cancer cells is a strongly upregulated aerobic glycolysis, which elevates its relative importance as a source of ATP (Adenosine 5'-triphosphate). Aerobic glycolysis is maintained by a highly increased uptake of glucose, which is made possible by the upregulated expression of its transporters, such as GLUT-1, GLUT-3, and GLUT-4. These proteins can also transport the oxidized form of vitamin C, dehydroascorbate, permitting its preferential uptake by cancer cells with the subsequent depletion of critical cellular reducers as a result of ascorbate formation. Ascorbate also has a potential to affect other aspects of cancer cell metabolism due to its ability to promote reduction of iron(III) to iron(II) in numerous cellular metalloenzymes. Among iron-dependent dioxygenases, important targets for stimulation by vitamin C in cancer include prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and histone and DNA demethylases. Altered metabolism of cancer cells by vitamin C can be beneficial by itself and promote activity of specific drugs.

Topics: Animals; Ascorbic Acid; Combined Modality Therapy; Drug Synergism; Humans; Hypoxia; Neoplasms; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Treatment Outcome

For a long time, the effect of vitamin C on cancer cells has been a controversial concept. From Linus Pauling's studies in 1976, it was proposed that ascorbic acid (AA) could selectively kill tumor cells. However, further research suggested that vitamin C has no effect on tumor survival. In the last decade, new and emerging functions for vitamin C have been discovered using the reduced form, AA, and the oxidized form, dehydroascorbic acid (DHA), independently. In this review, we summarized the latest findings related to the effects of DHA on the survival and metabolism of tumor cells. At the same time, we put special emphasis on the bystander effect and the recycling capacity of vitamin C in various cellular models, and how these concepts can affect the experimentation with vitamin C and its therapeutic application in the treatment against cancer.

Topics: Ascorbic Acid; Biological Transport; Dehydroascorbic Acid; Humans; Neoplasms; Oxidation-Reduction

Over the past century, the notion that vitamin C can be used to treat cancer has generated much controversy. However, new knowledge regarding the pharmacokinetic properties of vitamin C and recent high-profile preclinical studies have revived interest in the utilization of high-dose vitamin C for cancer treatment. Studies have shown that pharmacological vitamin C targets many of the mechanisms that cancer cells utilize for their survival and growth. In this Opinion article, we discuss how vitamin C can target three vulnerabilities many cancer cells share: redox imbalance, epigenetic reprogramming and oxygen-sensing regulation. Although the mechanisms and predictive biomarkers that we discuss need to be validated in well-controlled clinical trials, these new discoveries regarding the anticancer properties of vitamin C are promising to help identify patient populations that may benefit the most from high-dose vitamin C therapy, developing effective combination strategies and improving the overall design of future vitamin C clinical trials for various types of cancer.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Epigenesis, Genetic; Humans; Neoplasms; Oxidation-Reduction

Many cancer patients on intensive chemotherapy lack vitamin C. Vitamin C stimulates the production and activation of immune cells, so perhaps supplementation could be used to improve the immunity in those patients. This review assesses the effectiveness and safety of vitamin C administration in cancer. The PubMed and EMBASE databases were searched and all study designs except for phase I studies, and case reports were included in this review. A total of 19 trials were included. In only 4 trials randomization was used to determine if patients received vitamin C or a placebo. The result of this review does not prove that there is a clinically relevant positive effect of vitamin C supplementation in cancer patients in general on the overall survival, clinical status, quality of life (QOL) and performance status (PS), since the quality of the studies published is low. Interventions and patient groups are very diverse, hence an effect in some patient groups is possible. There seems to be a better effect with intravenous than oral administration. Nevertheless, treatment with vitamin C is safe with minimal side effects. Thereby, we think it is safe to examine the effects of vitamin C on specific groups of patients in a randomized controlled setting.

Topics: Ascorbic Acid; Dietary Supplements; Drug Administration Routes; Humans; Neoplasms

Although vitamin C is essentially a nontoxic vitamin; however, it is important to be aware regarding the safety of high doses before the wide clinical use.. Minor side effects of vitamin C have been reported, many being reported in earlier studies. High doses of vitamin C (up to 1.5 g/kg three times a week as intravenously) were safe in cancer patients with normal renal function and perfect glucose-6-phosphate dehydrogenase activity. As the dose and duration of administration of vitamin C in sepsis are lower and shorter than those used in cancer patients, it seems that it is relatively safe for this population. In ongoing trials, safety of high doses of vitamin C is considered.. Data regarding the safety of high doses of vitamin C are scant. Until more data become available, caution should be applied in the use of high doses of vitamin C in patients with hemochromatosis, glucose-6-phosphate dehydrogenase deficiency, renal dysfunction, kidney stone, oxaluria, and pediatrics.

Topics: Ascorbic Acid; Clinical Trials as Topic; Humans; Neoplasms; Sepsis

Regarding cancer as a genetic multi-factorial disease, a number of aspects need to be investigated and analyzed in terms of cancer's predisposition, development and prognosis. One of these multi-dimensional factors, which has gained increased attention in the oncological field due to its unelucidated role in risk assessment for cancer, is diet. Moreover, as studies advance, a clearer connection between diet and the molecular alteration of patients is becoming identifiable and quantifiable, thereby replacing the old general view associating specific phenotypical changes with the differential intake of nutrients. Respectively, there are two major fields concentrated on the interrelation between genome and diet: nutrigenetics and nutrigenomics. Nutrigenetics studies the effects of nutrition at the gene level, whereas nutrigenomics studies the effect of nutrients on genome and transcriptome patterns. By precisely evaluating the interaction between the genomic profile of patients and their nutrient intake, it is possible to envision a concept of personalized medicine encompassing nutrition and health care. The list of nutrients that could have an inhibitory effect on cancer development is quite extensive, with evidence in the scientific literature. The administration of these nutrients showed significant results in vitro and in vivo regarding cancer inhibition, although more studies regarding administration in effective doses in actual patients need to be done.

Topics: Ascorbic Acid; Fatty Acids, Unsaturated; Folic Acid; Humans; Micronutrients; Neoplasms; Nutrigenomics; Prebiotics; Probiotics; Risk Assessment; Selenium; Vitamin A; Vitamin D

Vitamin C (Vit C or Ascorbate) is essential for many fundamental biochemical processes. Vit C is an essential nutrient with redox functions at normal physiologic concentrations. The main physiologic function of this vitamin is related to its capacity to act as a co-factor for a large family of enzymes, collectively known as Fe and 2-oxoglutarate-dependent dioxygenases. It also modulates epigenetic gene expression through the control of TET enzymes activity. Vit C also has several biological properties allowing to restore the deregulated epigenetic response observed in many tumors. High-dose Vit C has been investigated as a treatment for cancer patients since the 1969. Pharmacologic ascorbate acts as a pro-drug for hydrogen peroxide formation (H

Topics: Animals; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Cell Proliferation; DNA Methylation; DNA Modification Methylases; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Histone Demethylases; Humans; Neoplasms

Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed in patients with cancer. Genes encoding epigenetic regulators are often mutated in cancer, underscoring their central roles in carcinogenesis. In hematological cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), drugs that reverse epigenetic aberrations are now the standard of care. Recent in vitro studies suggest that vitamin C at physiological concentrations, combined with hypomethylating agents may act synergistically to cause DNA demethylation through active and passive mechanisms, respectively. Additionally, several recent studies have renewed interest in the use of pharmacological doses of vitamin C injected intravenously to selectively kill tumor cells. This review will focus on the potential of vitamin C to optimize the outcome of epigenetic therapy in cancer patients and alternatively to act as a therapeutic at high doses.

Topics: Animals; Antioxidants; Ascorbic Acid; DNA Methylation; Epigenesis, Genetic; Epigenomics; Gene Expression Regulation, Neoplastic; Humans; Neoplasms

This review is directed to the redox-modulating properties and anticancer effect of vitamin K. The concept is focused on two aspects: (i) redox-cycle of vitamin K and its effect on the calcium homeostasis, "oncogenic" and "onco-suppressive" reactive oxygen species and the specific induction of oxidative stress in cancer; (ii) vitamin K plus C as a powerful redox-system, which forms a bypass between mitochondrial complexes II and III and thus prevents mitochondrial dysfunction, restores oxidative phosphorylation and aerobic glycolysis, modulates the redox-state of endogenous redox-pairs, eliminates the hypoxic environment of cancer cells and induces cell death. The analyzed data suggest that vitamin C&K can sensitize cancer cells to conventional chemotherapy, which allows achievement of a lower effective dose of the drug and minimizing the harmful side-effects. The review is intended for a wide audience of readers - from students to specialists in the field.

Topics: Ascorbic Acid; Humans; Mitochondria; Neoplasms; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Vitamin K

This article reviews intravenous vitamin C (IV C) in cancer care and offers a rational approach to enable medical oncologists and integrative practitioners to safely provide IV C combined with oral vitamin C to patients. The use of IV C is a safe supportive intervention to decrease inflammation in the patient and to improve symptoms related to antioxidant deficiency, disease processes, and side effects of standard cancer treatments. A proposed rationale, together with relevant clinical safety considerations for the application of IV C in oncologic supportive care, is provided.

Topics: Administration, Intravenous; Administration, Oral; Antioxidants; Ascorbic Acid; Humans; Neoplasms; Oxidative Stress; Quality of Life; Vitamin D Deficiency

Topics: Animals; Antioxidants; Ascorbic Acid; Cellular Reprogramming; Epigenesis, Genetic; Humans; Neoplasms; Stem Cells

The consumption of vitamins C and D for prevention and treatment of cancer is still an uncertain recommendation due to their controversial roles in cancer. The epidemiological studies document that vitamins C and D possess potential antineoplastic property. In addition, accumulating experimental studies strongly support their anticancer efficacy both in vitro and in vivo, although the mechanisms of action are not completely clear. Vitamin C at pharmacological concentration has cancer-selective cytotoxicity in several cancer cell lines. Moreover, the cognition of vitamin D has become "hormone D", which modulates a variety of molecular targets and signaling pathways, contributing to the inhibition of cancer. Furthermore, limited small-scale clinical trials favor their roles as the adjuncts of standard cancer therapies. On the other hand, opposite opinions also exist, and high-quality evidence are still lacking to ascertain the roles of vitamins C and D in cancer. In general, in light of the potential and promising anticancer values of vitamins C and D, it is essential to gain insight into their roles in cancer based on current epidemiological, experimental and clinical studies.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Dietary Supplements; Epigenesis, Genetic; Humans; Incidence; Mice; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Signal Transduction; Vitamin D

Radiotherapy is a mainstay of cancer treatment since decades. Ionizing radiation (IR) is used for destruction of cancer cells and shrinkage of tumors. However, the increase of radioresistance in cancer cells and radiation toxicity to normal tissues are severe concerns. The exposure to radiation generates intracellular reactive oxygen species (ROS), which leads to DNA damage by lipid peroxidation, removal of thiol groups from cellular and membrane proteins, strand breaks and base alterations.. Plants have to deal with radiation-induced damage (UV-light of sun, other natural radiation sources). Therefore, it is worth speculating that radioprotective mechanisms have evolved during evolution of life. We hypothesize that natural products from plants may also protect from radiation damage caused as adverse side effects of cancer radiotherapy.. The basis of this systematic review, we searched the relevant literature in the PubMed database.. Flavonoids, such as genistein, epigallocatechin-3-gallate, epicatechin, apigenin and silibinin mainly act as antioxidant, free radical scavenging and anti-inflammatory compounds, thus, providing cytoprotection in addition to downregulation of several pro-inflammatory cytokines. Comparable effects have been found in phenylpropanoids, especially caffeic acid phenylethylester, curcumin, thymol and zingerone. Besides, resveratrol and quercetin are the most important cytoprotective polyphenols. Their radioprotective effects are mediated by a wide range of mechanisms mainly leading to direct or indirect reduction of cellular stress. Ascorbic acid is broadly used as antioxidant, but it has also shown activity in reducing cellular damage after irradiation mainly due to its antioxidant capabilities. The metal ion chelator, gallic acid, represents another natural product attenuating cellular damage caused by radiation.. Some secondary metabolites from plants reveal radioprotective features against cellular damage caused by irradiation. These results warrant further analysis to develop phytochemicals as radioprotectors for clinical use.

Topics: Antioxidants; Ascorbic Acid; Curcumin; DNA Damage; Flavonoids; Humans; Lipid Peroxidation; Neoplasms; Phytochemicals; Plants; Polyphenols; Radiation Injuries; Radiation-Protective Agents; Radiotherapy; Reactive Oxygen Species; Resveratrol; Stilbenes

Vitamin C (ascorbic acid, ascorbate), despite controversy, has re-emerged as a promising anti-cancer agent. Recent knowledge of intravenous ascorbate pharmacokinetics and discovery of unexpected mechanisms of ascorbate action have spawned many investigations. Two mechanisms of anti-cancer activity with ascorbate have gained prominence: hydrogen peroxide-induced oxidative stress and DNA demethylation mediated by ten-eleven translocation enzyme activation. Here, we highlight salient aspects of the evolution of ascorbate in cancer treatment, provide insights into the pharmacokinetics of ascorbate, describe mechanisms of its anti-cancer activity in relation to the pharmacokinetics, outline promising preclinical and clinical evidence, and recommend future directions.

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; DNA Demethylation; Humans; Hydrogen Peroxide; Mixed Function Oxygenases; Neoplasms; Oxidative Stress; Proto-Oncogene Proteins

Vitamin C (ascorbate) is maintained at high levels in most immune cells and can affect many aspects of the immune response. Intracellular levels generally respond to variations in plasma ascorbate availability, and a combination of inadequate intake and increased turnover during severe stress can result in low plasma ascorbate status. Intracellular ascorbate supports essential functions and, in particular, acts as an enzyme cofactor for Fe- or Cu-containing oxygenases. Newly discovered enzymes in this family regulate cell metabolism and epigenetics, and dysregulation of their activity can affect cell phenotype, growth and survival pathways, and stem cell phenotype. This brief overview details some of the recent advances in our understanding of how ascorbate availability can affect the hydroxylases controlling the hypoxic response and the DNA and histone demethylases. These processes play important roles in the regulation of the immune system, altering cell survival pathways, metabolism and functions.

Topics: Animals; Ascorbic Acid; Cell Hypoxia; Copper; Dendritic Cells; Epigenesis, Genetic; Histone Demethylases; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immune System; Inflammation; Iron; Killer Cells, Natural; Macrophages; Mice; Monocytes; Neoplasms; Neutrophils; Phenotype; Signal Transduction; Stem Cells; T-Lymphocytes

High dietary intake or blood concentrations (as biomarkers of dietary intake) of vitamin C, carotenoids, and vitamin E have been associated with reduced risk of cardiovascular disease, cancer, and mortality, but these associations have not been systematically assessed.. We conducted a systematic review and meta-analysis of prospective studies of dietary intake and blood concentrations of vitamin C, carotenoids, and vitamin E in relation to these outcomes.. We searched PubMed and Embase up to 14 February 2018. Summary RRs and 95% CIs were calculated with the use of random-effects models.. Sixty-nine prospective studies (99 publications) were included. The summary RR per 100-mg/d increment of dietary vitamin C intake was 0.88 (95% CI: 0.79, 0.98, I2 = 65%, n = 11) for coronary heart disease, 0.92 (95% CI: 0.87, 0.98, I2 = 68%, n = 12) for stroke, 0.89 (95% CI: 0.85, 0.94, I2 = 27%, n = 10) for cardiovascular disease, 0.93 (95% CI: 0.87, 0.99, I2 = 46%, n = 8) for total cancer, and 0.89 (95% CI: 0.85, 0.94, I2 = 80%, n = 14) for all-cause mortality. Corresponding RRs per 50-μmol/L increase in blood concentrations of vitamin C were 0.74 (95% CI: 0.65, 0.83, I2 = 0%, n = 4), 0.70 (95% CI: 0.61, 0.81, I2 = 0%, n = 4), 0.76 (95% CI: 0.65, 0.87, I2 = 56%, n = 6), 0.74 (95% CI: 0.66, 0.82, I2 = 0%, n = 5), and 0.72 (95% CI: 0.66, 0.79, I2 = 0%, n = 8). Dietary intake and/or blood concentrations of carotenoids (total, β-carotene, α-carotene, β-cryptoxanthin, lycopene) and α-tocopherol, but not dietary vitamin E, were similarly inversely associated with coronary heart disease, stroke, cardiovascular disease, cancer, and/or all-cause mortality.. Higher dietary intake and/or blood concentrations of vitamin C, carotenoids, and α-tocopherol (as markers of fruit and vegetable intake) were associated with reduced risk of cardiovascular disease, total cancer, and all-cause mortality. These results support recommendations to increase fruit and vegetable intake, but not antioxidant supplement use, for chronic disease prevention.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Carotenoids; Cause of Death; Diet; Feeding Behavior; Humans; Neoplasms; Nutritional Status; Vitamin E

For the last two decades, classical phenothiazines have attracted attention of researchers, as the hitherto investigations have revealed many significant biological activities within this class of compounds, other than originally discovered neuroleptic ones. Important, new pharmaceutical results on phenothiazines, as 10-substituted dibenzothiazines, were recently highlighted in several reviews. Azaphenothiazines are structurally modified phenothiazines by substitution of one or both benzene rings in the phenothiazine ring system with the azine rings, such as: pyridine, pyridazine, pyrimidine, pyrazine, 1,2,4-triazine, quinoline, quinoxaline, benzoxazine and benzothiazine. They form over 50 different heterocyclic systems, of tri-, tetra-, penta- and hexacyclic structures, and contain from one to even four azine nitrogen atoms. This review summarizes the methodical knowledge on azaphenothiazines, referring to their nomenclature, synthesis, structure analysis and above all significant varied biological activities, examined in vitro and in vivo. It describes, in addition, current trends in the synthesis of azaphenothiazines. The influence of the azaphenothiazine ring system, the nature of the substituents, predominantly at the thiazine nitrogen atom, as well as at the azine nitrogen atom and carbon atom, on the biological activities, were also discussed.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Antiprotozoal Agents; Antipsychotic Agents; Bacteria; Fungi; Humans; Leishmania; Molecular Structure; Neoplasms; Phenothiazines

Epidemiological data indicate a constant worldwide increase in cancer mortality, although the age of onset is increasing. Recent accumulation of genomic data on human cancer via next-generation sequencing confirmed that cancer is a disease of genome alteration. In many cancers, the Nrf2 transcription system is activated via mutations either in Nrf2 or Keap1 ubiquitin ligase, leading to persistent activation of the genes with antioxidative functions. Furthermore, deep sequencing of passenger mutations is clarifying responsible cancer causative agent(s) in each case, including aging, APOBEC activation, smoking and UV. Therefore, it is most likely that oxidative stress is the principal initiating factor in carcinogenesis, with the involvement of two essential molecules for life, iron and oxygen. There is evidence based on epidemiological and animal studies that excess iron is a major risk for carcinogenesis, suggesting the importance of ferroptosis-resistance. Microscopic visualization of catalytic Fe(II) has recently become available. Although catalytic Fe(II) is largely present in lysosomes, proliferating cells harbor catalytic Fe(II) also in the cytosol and mitochondria. Oxidative stress catalyzed by Fe(II) is counteracted by thiol systems at different functional levels. Nitric oxide, carbon monoxide and hydrogen (per)sulfide modulate these reactions. Mitochondria generate not only energy but also heme/iron sulfur cluster cofactors and remain mostly dysfunctional in cancer cells, leading to Warburg effects. Cancer cells are under persistent oxidative stress with a delicate balance between catalytic iron and thiols, thereby escaping ferroptosis. Thus, high-dose L-ascorbate and non-thermal plasma as well as glucose/glutamine deprivation may provide additional benefits as cancer therapies over preexisting therapeutics.

Topics: Animals; Ascorbic Acid; Cell Death; Humans; Iron; Neoplasms; Oxidation-Reduction; Oxidative Stress; Signal Transduction; Sulfhydryl Compounds

Vitamin C (L-ascorbic acid) is a micronutrient best known for its anti-scurvy activity in humans. Vitamin C is involved in many biological processes involving enzymatic reactions that are catalyzed by members of dioxygenases which use Fe(II) and 2-oxoglutarate as a co-substrate.The article reviews recent data that suggest the involvement of ascorbate in dioxygenases catalyzed chromatin and DNA modifications which thereby contribute to epigenetic regulation. Concerning chromatin modification, the dioxygenases are involved in distinct demethylation reactions with varying specificity for the position of the lysine on the target histone. TET hydroxylases catalyse the oxidation of methyl groups in the 5 position of cytosine in DNA yielding 5-hydroxymethylcytosine, while further iterative oxidation reactions results in the formation of 5-formylcytosine and 5-carboxylcytosine. A few previous studies demonstrated that ascorbate may enhance generation of 5-hydroxymethylcytosine in cultured cells, probably acting as a cofactor of TETs during hydroxylation of 5-methylcytosine. Physiological concentrations of ascorbate in human serum (10-100 μM) may guarantee stable level of 5-hydroxymethylcytosine, a modification necessary for epigenetic function of the cell. 5-Hydroxymethylcytosine level is substantially decreased in almost all investigated cancers, what may be linked with cancer development. Therefore, it is possible that supplementation with ascorbate could contribute to better management of individual cancer patient. This issue is also discussed in our paper.

Topics: Ascorbic Acid; Enzymes; Epigenesis, Genetic; Humans; Neoplasms

Vitamins E and C are well known small molecules that have been used to maintain health for decades. Recent studies of the cellular and molecular pathways leading to immunomodulation by these molecules have been of interest, as have their anti-oxidant properties and signal transduction pathways for curing or improving infectious diseases and cancer. Areas covered: Herein, the authors provide a definition and the structural classification of vitamins E and C and how these molecules influence cellular function. The studies include in vitro, ex vivo and in vivo studies in animal models as well as clinical trials. The authors give particular focus to the scientifically factual and putative roles of these molecules in innate and adaptive immunomodulation and prevention or cure of diseases. Expert opinion: The antioxidant properties of vitamins E and C are well studied. However, whether there is a link between their antioxidant and immunomodulation properties is unclear. In addition, there is a strong, albeit putative, prevailing notion that vitamin C can prevent or cure infectious diseases or cancer. Presently, while there is proven evidence that vitamin E possesses immunomodulatory properties that may play a positive role in disease outcomes, this evidence is less available for vitamin C.

Topics: Animals; Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Humans; Neoplasms; Signal Transduction; Vitamin E

Cancers have been the leading cause of death worldwide and poor diet and physical inactivity are major risk factors in cancer-related deaths. Micronutrients such as vitamins and minerals appear to have preventive properties against cancer. One important mechanism by which dietary changes can exert preventive effects on cancer is via the modulation of micronutrient concentrations in target tissues. Many of these micronutrients are available in the form of dietary supplements, and the intake of these supplements is prevalent in various parts of the world. However, in most cases, it is not known which micronutrient (or combination of micronutrients) is best when it comes to lowering the risk of cancer. The present review illustrates the effect of vitamin D and ascorbic acid intake on preventing cancer.

Topics: Ascorbic Acid; Diet; Dietary Supplements; Humans; Micronutrients; Neoplasms; Vitamin D; Vitamins

Recent advances have uncovered a previously unknown function of vitamin C in epigenetic regulation. Vitamin C exists predominantly as an ascorbate anion under physiological pH conditions. Ascorbate was discovered as a cofactor for methylcytosine dioxygenases that are responsible for DNA demethylation, and also as a likely cofactor for some JmjC domain-containing histone demethylases that catalyze histone demethylation. Variation in ascorbate bioavailability thus can influence the demethylation of both DNA and histone, further leading to different phenotypic presentations. Ascorbate deficiency can be presented systematically, spatially and temporally in different tissues at the different stages of development and aging. Here, we review how ascorbate deficiency could potentially be involved in embryonic and postnatal development, and plays a role in various diseases such as neurodegeneration and cancer through epigenetic dysregulation.

Topics: Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Dioxygenases; DNA Methylation; Embryonic Development; Epigenesis, Genetic; F-Box Proteins; Histones; Humans; Jumonji Domain-Containing Histone Demethylases; Neoplasms; Neurodegenerative Diseases; Scurvy

Vitamin C has been suggested as beneficial in preventing and curing the common cold, decreasing the incidence of preterm delivery and preeclampsia, decreasing risk of cancer and cardiovascular disease, and improving the quality of life by inhibiting blindness and dementia. In this article, we review the hypothesized mechanisms of these purported health benefits and the evidence behind such claims.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Common Cold; Dementia; Female; Humans; Neoplasms; Obstetric Labor, Premature; Pre-Eclampsia; Pregnancy; Vision Disorders; Vitamins

Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB) demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP)-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract) with vitamin C, amino acids and other micronutrients (EPQ) demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM) also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion, angiogenesis, and cell growth as well as induction of apoptosis. The presence of vitamin C, amino acids and other micronutrients could enhance inhibitory effect of epigallocatechin gallate (EGCG) on secretion of MMPs. In addition, enrichment of NM with quercetin (EPQ mix) enhanced anticancer activity of NM in vivo. In conclusion, polyphenols, especially in combination with other polyphenols or micronutrients, have been shown to be effective against multiple targets in cancer development and progression, and s

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Biological Availability; Catechin; Cell Line, Tumor; Cell Proliferation; Curcumin; Disease Models, Animal; Humans; Micronutrients; Neoplasms; Plant Extracts; Polyphenols; Quercetin; Resveratrol; Stilbenes; Tea

This review is aimed at the systematic mapping of ascorbic acid in the prevention and/or treatment of cancer in clinical and non-clinical studies from 2011 to 2015, in order to understand dose-response variations as well as its mechanisms of action as an antioxidant and antitumor agent. Seventy-eight articles were retrieved from the PubMed/Bireme database, of which only 30 included ascorbic acid in the prevention and/or treatment of cancer. However, there are controversies regarding doses and a lack of clinical studies featuring its mechanism of action more clearly. Other studies are needed to understand dose-response variations, as well as its targeting mechanisms of action, both as an antioxidant and antitumor agent, to assist treatment and prevention of cancer, aiming at better quality of life for both patients and the general population.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Dose-Response Relationship, Drug; Humans; Neoplasms; Reproducibility of Results; Treatment Outcome

The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Humans; Lipogenesis; Neoplasms; Oxidative Stress; Pentose Phosphate Pathway; Phosphogluconate Dehydrogenase; Protein Serine-Threonine Kinases; Ribulosephosphates; Signal Transduction

Many cancer patients receive supplemental ascorbate (vitamin C) in the belief that it synergizes the anticancer effects of chemotherapy and reduces its toxicity.. A systematic review was performed to evaluate the antitumor effects and toxicity of ascorbate treatment. Medline (1946 to March 2014), EMBASE (1947 to March 2014), and the Cochrane central register (1993 to March 2014) were searched for randomized and observational studies.. Of 696 identified records, 61 full-text articles were screened and 34 were included. In total, 5 randomized controlled trials (RCTs) (n = 322), 12 phase I/II trials (n = 287), 6 observational studies (n = 7,599), and 11 case reports (n = 267) were identified. Because of study heterogeneity, no meta-analyses were performed. No RCTs reported any statistically significant improvements in overall or progression-free survival or reduced toxicity with ascorbate relative to control arm. Evidence for ascorbate's antitumor effects was limited to case reports and observational and uncontrolled studies.. There is no high-quality evidence to suggest that ascorbate supplementation in cancer patients either enhances the antitumor effects of chemotherapy or reduces its toxicity. Given the high financial and time costs to patients of this treatment, high-quality placebo-controlled trials are needed.

Topics: Ascorbic Acid; Dietary Supplements; Disease-Free Survival; Humans; Neoplasms; Randomized Controlled Trials as Topic

Effectiveness and low-toxicity to normal tissues are ideal properties for a cancer treatment, and one that numerous research programs are aiming for. Vitamin C has long been used in the field of Complementary and Alternative Medicine as a cancer treatment, with profound safety and anecdotal efficacy. Recent studies revealed the scientific basis for this use, and indicated that vitamin C, at supra-nutritional doses, holds considerable promise as an effective and low-toxic therapeutic strategy to treat cancer. Reviewed here are the early controversies surrounding vitamin C and cancer treatment, the breakthrough discoveries that led to the current advancement, and recent clinical studies, as well as research into its mechanisms of action.

Topics: Animals; Ascorbic Acid; Humans; Neoplasms

Radiation-induced skin damage is one of the most common complications of radiotherapy. In order to combat these side effects, patients often turn to alternative therapies, which often include antioxidants. Antioxidants such as those in the polyphenol chemical class, xanthine derivatives, tocepherol, sucralfate, and ascorbate have been studied for their use in either preventing or treating radiotherapy-induced skin damage. Apart from their known role as free radical scavengers, some of these antioxidants appear to alter cytokine release affecting cutaneous and systemic changes. We review the role of antioxidants in treating and preventing radiation-induced skin damage as well as the possible complications of using such therapy.

Topics: Antioxidants; Ascorbic Acid; Free Radical Scavengers; Humans; Neoplasms; Pentoxifylline; Polyphenols; Radiodermatitis; Radiotherapy; Sucralfate

In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well-designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high-dose oral vitamin C. Marked differences are now recognized in the pharmacokinetics of vitamin C with oral and IV administration, opening the issue of therapeutic efficacy to question. In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant but may have pro-oxidant activity at high concentrations. The mechanism of its pro-oxidant action is not fully understood, and both intra- and extracellular mechanisms that generate hydrogen peroxide have been proposed. It remains to be proven whether vitamin C-induced reactive oxygen species occur in vivo and, if so, whether this will translate to a clinical benefit. Current clinical evidence for a therapeutic effect of high-dose IV vitamin C is ambiguous, being based on case series. The interpretation and validation of these studies is hindered by limited correlation of plasma vitamin C concentrations with response. The methodology exists to determine if there is a role for high-dose IV vitamin C in the treatment of cancer, but the limited understanding of its pharmacodynamic properties makes this challenging. Currently, the use of high-dose IV vitamin C cannot be recommended outside of a clinical trial.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Humans; Infusions, Intravenous; Neoplasms; Vitamins

Intravenous vitamin C (IVC) is a contentious adjunctive cancer therapy, widely used in naturopathic and integrative oncology settings. We conducted a systematic review of human interventional and observational studies assessing IVC for use in cancer patients.. We searched MEDLINE, EMBASE, The Cochrane Library, CINAHL, and AMED from inception to April 2013 for human studies examining the safety, effectiveness, or pharmacokinetics of IVC use in cancer patients.. Of 897 records, a total of 39 reports of 37 studies were included: 2 randomized controlled trials (RCTs), 15 uncontrolled trials, 6 observational studies, and 14 case reports. IVC dosing ranged from 1 g to more than 200 g ascorbic acid per infusion, typically administered 2 to 3 times weekly. IVC does not appear to increase toxicity or interfere with antitumor effects of gemcitabine/erlotinib therapy or paclitaxel and carboplatin. Based on 1 RCT and data from uncontrolled human trials, IVC may improve time to relapse and possibly enhance reductions in tumor mass and improve survival in combination with chemotherapy. IVC may improve quality of life, physical function, and toxicities associated with chemotherapy, including fatigue, nausea, insomnia, constipation, and depression. Case reports document several instances of tumor regression and long-term disease-free survival associated with use of IVC.. There is limited high-quality clinical evidence on the safety and effectiveness of IVC. The existing evidence is preliminary and cannot be considered conclusive but is suggestive of a good safety profile and potentially important antitumor activity; however, more rigorous evidence is needed to conclusively demonstrate these effects. IVC may improve the quality of life and symptom severity of patients with cancer, and several cases of cancer remission have been reported. Well-designed, controlled studies of IVC therapy are needed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Humans; Infusions, Intravenous; Neoplasms; Quality of Life; Survival Rate

The article presents the results of studies on potential risks associated with the abuse of vitamin supplements which until recently had been considered not only highly effica- cious, but also completely safe. Particular consideration is given to vitamins A, E, D and C. The necessity to control the intake of vitamin supplements and even to strictly super- vise the supply to high risk patients is highlighted.

Topics: Ascorbic Acid; Drug Overdose; Humans; Neoplasms; Risk Factors; Substance-Related Disorders; Vitamin A; Vitamin D; Vitamin E; Vitamins

Ewan Cameron reported that ascorbate, given orally and intravenously at doses of up to 10 g/day, was effective in the treatment of cancer. Double-blind placebo-controlled clinical trials showed no survival advantage when the same doses of ascorbate were given orally, leading the medical and scientific communities to dismiss the use of ascorbate as a potential cancer treatment. However, the route of administration results in major differences in ascorbate bioavailability. Tissue and plasma concentrations are tightly controlled in response to oral administration, but this can be bypassed by intravenous administration. These data provide a plausible scientific rationale for the absence of a response to orally administered ascorbate in the Mayo clinic trials and indicate the need to reassess ascorbate as a cancer therapeutic.. High dose ascorbate is selectively cytotoxic to cancer cell lines through the generation of extracellular hydrogen peroxide (H2O2). Murine xenograft models confirm a growth inhibitory effect of pharmacological concentrations. The safety of intravenous ascorbate has been verified in encouraging pilot clinical studies.. Neither the selective toxicity of pharmacologic ascorbate against cancer cells nor the mechanism of H2O2-mediated cytotoxicity is fully understood. Despite promising preclinical data, the question of clinical efficacy remains.. A full delineation of mechanism is of interest because it may indicate susceptible cancer types. Effects of pharmacologic ascorbate used in combination with standard treatments need to be defined. Most importantly, the clinical efficacy of ascorbate needs to be reassessed using proper dosing, route of administration, and controls.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Ascorbic Acid; Biological Availability; Cell Death; Drug Interactions; Drug Screening Assays, Antitumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Reactive Oxygen Species; Signal Transduction

Many patients receiving cancer treatment use micronutrient supplements, with the intention to complement their cancer treatment, or help them cope with the therapy- and disease-associated side-effects. Up to 90% of the cancer patients are adding antioxidants without the knowledge of the treating physician. There are many concerns that antioxidants might decrease the effectiveness of chemotherapy, but increasing evidence suggests a benefit when antioxidants and other micronutrients, such as selenium, L-carnitine and vitamin D are added to conventional cytotoxic therapies. It is imperative that physicians discuss the use ofantioxidant and other micronutrient supplements with their cancer patients and educate them about potentially negative, but also potentially beneficial effects.

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; Carnitine; Humans; Micronutrients; Neoplasms; Nutritional Status; Selenium; Vitamin D; Vitamins

The effect of high doses of vitamin C for the treatment of cancer has been controversial. Our previous studies, and studies by others, have reported that vitamin C at concentrations of 0.25-1.0 mM induced a dose- and time-dependent inhibition of proliferation in acute myeloid leukemia (AML) cell lines and in leukemic cells from peripheral blood specimens obtained from patients with AML. Treatment of cells with high doses of vitamin C resulted in an immediate increase in intracellular total glutathione content and glutathione-S transferase activity that was accompanied by the uptake of cysteine. These results suggest a new role for high concentrations of vitamin C in modulation of intracellular sulfur containing compounds, such as glutathione and cysteine. This review, discussing biochemical pharmacologic studies, including pharmacogenomic and pharmacoproteomic studies, presents the different pharmacological effects of vitamin C currently under investigation.

Topics: Animals; Ascorbic Acid; Cell Line, Tumor; Cell Survival; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione; Humans; Neoplasms; Pharmacogenetics; Proteomics

Vitamin C is a water soluble vitamin which is mainly fresh fruits and vegetables foodborne. Vitamin C deficiency is most often due to a lack of daily amount. Scurvy is characterized by the occurrence of fatigue, myalgia, arthralgia, purpura, bleeding disorders, and later by dental manifestations. Biological signs are nonspecific: anemia, hypocholesterolemia, hypoalbuminemia. Clinical suspicion is confirmed by the decrease in ascorbic acid level (< 2 mg/L). It must be interpreted in light of the acute phase reactants. The treatment is the administration of 1 g of vitamin C per day for 15 days. Vitamin C depletion (ascorbic acid: 2 to 5 mg/L) could induce long-term complications. The recommended dietary allowance of vitamin C protect from these risks.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Disease Progression; Humans; Neoplasms; Prevalence; Scurvy

Experimental evidence indicates a strong connection between oxidative damage, cancer, and aging. Epidemiological observations suggest that a diet rich in fruits and vegetables is associated with lower incidence of some cancers and longer life expectancy; since fruits and vegetables contain natural antioxidants, a considerable effort has been dedicated to understanding their effects in experimental studies and in human trials.. A: Effects of antioxidant-containing food and supplements on oxidation damage in humans. Intervention trials employing a variety of biomarkers have shown either a slight decrease in oxidation damage or no effect. B: Effects of selected antioxidants on mortality and cancer incidence. β-carotene and α-tocopherol, alone or in combination, increase cardiovascular and all-cause mortality or have no effect. In some studies, β-carotene and retinyl palmitate significantly increase the progression of lung cancer and aggressive prostate cancer. Protection against cardiovascular mortality or no effect of vitamin E has been reported, with an increase of all-cause mortality at dosages greater than 150 IU/day. Selenium showed beneficial effects on gastrointestinal cancer and reduced the risk of lung cancer in populations with lower selenium status. For multivitamin and mineral supplementation, no significant reduction of mortality or cancer incidence was observed, but some reports indicate a possible preventive effect in cervical cancer.. The majority of supplementation studies indicate no variation of general mortality and of cancer incidence or a detrimental effect on both. Antioxidant supplements so far tested seem to offer no improvement over a well-balanced diet, possibly because of the choice of the substances tested or of an excessive dosage. However, new natural or synthetic compounds effective in vitro and in experimental studies might still be worth investigating in human trials.

Topics: Aging; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Dietary Supplements; Diterpenes; Heart Diseases; Humans; Incidence; Life Expectancy; Neoplasms; Randomized Controlled Trials as Topic; Retinyl Esters; Selenium; Trace Elements; Vitamin A; Vitamin E; Vitamins

Since the discovery of vitamin C, the number of its known biological functions is continually expanding. Both the names ascorbic acid and vitamin C reflect its antiscorbutic properties due to its role in the synthesis of collagen in connective tissues. Ascorbate acts as an electron-donor keeping iron in the ferrous state thereby maintaining the full activity of collagen hydroxylases; parallel reactions with a variety of dioxygenases affect the expression of a wide array of genes, for example via the HIF system, as well as via the epigenetic landscape of cells and tissues. In fact, all known physiological and biochemical functions of ascorbate are due to its action as an electron donor. The ability to donate one or two electrons makes AscH(-) an excellent reducing agent and antioxidant. Ascorbate readily undergoes pH-dependent autoxidation producing hydrogen peroxide (H(2)O(2)). In the presence of catalytic metals this oxidation is accelerated. In this review, we show that the chemical and biochemical nature of ascorbate contribute to its antioxidant as well as its prooxidant properties. Recent pharmacokinetic data indicate that intravenous (i.v.) administration of ascorbate bypasses the tight control of the gut producing highly elevated plasma levels; ascorbate at very high levels can act as prodrug to deliver a significant flux of H(2)O(2) to tumors. This new knowledge has rekindled interest and spurred new research into the clinical potential of pharmacological ascorbate. Knowledge and understanding of the mechanisms of action of pharmacological ascorbate bring a rationale to its use to treat disease especially the use of i.v. delivery of pharmacological ascorbate as an adjuvant in the treatment of cancer.

Topics: Animals; Antioxidants; Ascorbic Acid; Histones; Humans; Hydrogen Peroxide; Neoplasms

Glucosinolates (thioglucoside-N-hydroxysulphates) constitute a homogeneous class of naturally occurring thiosaccharidic compounds mainly found in the botanical order Brassicales. They can be hydrolyzed by myrosinase to produce D-glucose and various other degradation products like isothiocyanates (ITCs)-depending on the aglycon part. The exact function of glucosinolates (GLSs) in the plant is unclear, however their potent odour and taste suggests a role in herbivore and microbial defense. They are known for their fungicidal, bacteriocidal, nematocidal and allelopathic properties and have recently attracted intense research interest because of their cancer chemo-protective attributes. Iso-thiocyanates, one of the hydrolyzed products, show best anti-carcinogenic activity.

Topics: Apoptosis; Ascorbic Acid; Brassicaceae; Diet; Fruit; Glucosinolates; Glycoside Hydrolases; Humans; Indoles; Neoplasms; Oxidative Stress; Signal Transduction; Vegetables

Chemoprevention, which is referred to as the use of nontoxic natural or synthetic chemicals to intervene in multistage carcinogenesis has since decades attracted a considerable interest in plant-derived chemical constituents often termed as "phytochemicals" or sometimes as "Nutraceuticals" in case they are derived from dietary sources. A comprehensive search of the literature show that such an interest in natural product pharmacology has surged in the last 25 years and particularly risen at exponential rates since the last one decade. Phytochemicals such as curcumin (from spice turmeric), resveratrol (from red wine) and genistein (from soy) share the major efforts as indicated by overwhelming publications, despite skepticism concerning their bioavailability. Ascorbic acid (AA), the popular anti-oxidant in fruits and vegetables, has even a longer historical perspective than these dietary agents as for more than 35 years; there had been lingering questions about the efficacy of AA in cancer therapy. The footprints of AA from "scurvy" to "cancer" though complex seems to carry potential provided the puzzle could be set right. The use of AA in cancer treatment has been debated extensively as evident from the literature but surprisingly the complementing early phase bench work on the mechanistic studies for anticancer action was rather retarded. Proposed mechanisms of action for AA in the prevention and treatment of cancer includes antioxidant as well as pro-oxidant properties, stimulation of the immune system, altering carcinogen metabolism, enhancement of collagen synthesis necessary for tumor encapsulation and interference with cancer cell signaling. The observation that the intravenous administration of AA enhances its bioavailability to the extent of deriving pharmacological benefits against cancer has in recent years partially supported the clinical plausibility (efficacy) of AA towards realizing its translational advantage. Here, we provide an overview of AA with regard to its potential in the management of cancer disease.

Topics: Animals; Antineoplastic Agents, Phytogenic; Ascorbic Acid; Chemoprevention; Fruit; Humans; Neoplasms; Translational Research, Biomedical; Treatment Outcome; Vegetables

Biological immunomodulators are routinely evaluated as a natural source of molecules with profound effects on the immune system. They belong to a group of physiologically active compounds, collectively termed biological response modifiers. Most of the studies were focused on immune system stimulation. Recently, they have become the focus of studies seeking molecules that are able to overcome negative effects of various immunotoxins. This paper concentrates on the effects of a glucan/resveratrol/vitamin C combination on immunosuppressive effects of mercury and perfluorinated hydrocarbons. Effects described in this review have strong clinical potential, as environmental contaminants have adverse effects on all aspects of the immune system and represent a serious threat to the health of both humans and animals.

Topics: Animals; Ascorbic Acid; Drug Combinations; Environmental Pollutants; Glucans; Humans; Immune System; Immunity, Cellular; Immunity, Humoral; Neoplasms; Protective Agents; Resveratrol; Stilbenes; Thimerosal

Cancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxygen species (ROS) can indeed play an important role in the initiation and progression of cancer, and advanced stage tumors frequently exhibit high basal levels of ROS that stimulate cell proliferation and promote genetic instability. In addition, an inverse correlation between histological grade and antioxidant enzyme activities is frequently observed in human tumors, further supporting the existence of a redox dysregulation in cancer cells. This biochemical property can be exploited by using redox-modulating compounds, which represent an interesting approach to induce cancer cell death. Thus, we have developed a new strategy based on the use of pharmacologic concentrations of ascorbate and redox-active quinones. Ascorbate-driven quinone redox cycling leads to ROS formation and provoke an oxidative stress that preferentially kill cancer cells and spare healthy tissues. Cancer cell death occurs through necrosis and the underlying mechanism implies an energetic impairment (ATP depletion) that is likely due to glycolysis inhibition. Additional mechanisms that participate to cell death include calcium equilibrium impairment and oxidative cleavage of protein chaperone Hsp90. Given the low systemic toxicity of ascorbate and the impairment of crucial survival pathways when associated with redox-active quinones, these combinations could represent an original approach that could be combined to standard cancer therapy.

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; Humans; Neoplasms; Oxidative Stress; Quinones

Vitamins are essential nutrients for human metabolism, playing an important role as coenzymes or enzymes in many vital processes for the normal functioning of the body. In recent years, it has become apparent that vitamins are crucial in health and human disease, due to several studies that studied this relationship. Currently, it is known that vitamins can have an important role in the prevention and treatment of cancer, but until now no conclusive results were obtained. In this review, we will present the work and more relevant conclusions obtained in recent years of investigation about the relationship between vitamins and cancer, namely vitamin A, vitamin B complex, vitamin C, vitamin D, vitamin E, and vitamin K.

Topics: Ascorbic Acid; Chemoprevention; Dietary Supplements; Humans; Neoplasms; Randomized Controlled Trials as Topic; Vitamin A; Vitamin B Complex; Vitamin D; Vitamin E; Vitamin K; Vitamins

The mechanistic properties of two dietary antioxidants that are required by humans, vitamins C and E, are discussed relative to their biological effects. Vitamin C (ascorbic acid) is an essential cofactor for α-ketoglutarate-dependent dioxygenases. Examples are prolyl hydroxylases, which play a role in the biosynthesis of collagen and in down-regulation of hypoxia-inducible factor (HIF)-1, a transcription factor that regulates many genes responsible for tumor growth, energy metabolism, and neutrophil function and apoptosis. Vitamin C-dependent inhibition of the HIF pathway may provide alternative or additional approaches for controlling tumor progression, infections, and inflammation. Vitamin E (α-tocopherol) functions as an essential lipid-soluble antioxidant, scavenging hydroperoxyl radicals in a lipid milieu. Human symptoms of vitamin E deficiency suggest that its antioxidant properties play a major role in protecting erythrocyte membranes and nervous tissues. As an antioxidant, vitamin C provides protection against oxidative stress-induced cellular damage by scavenging of reactive oxygen species, by vitamin E-dependent neutralization of lipid hydroperoxyl radicals, and by protecting proteins from alkylation by electrophilic lipid peroxidation products. These bioactivities bear relevance to inflammatory disorders. Vitamin C also plays a role in the function of endothelial nitric oxide synthase (eNOS) by recycling the eNOS cofactor, tetrahydrobiopterin, which is relevant to arterial elasticity and blood pressure regulation. Evidence from plants supports a role for vitamin C in the formation of covalent adducts with electrophilic secondary metabolites. Mechanism-based effects of vitamin C and E supplementation on biomarkers and on clinical outcomes from randomized, placebo-controlled trials are emphasized in this review.

Topics: Animals; Antioxidants; Ascorbic Acid; Cytoprotection; Energy Metabolism; Free Radicals; Humans; Hypoxia-Inducible Factor 1; Inflammation; Neoplasms; Randomized Controlled Trials as Topic; Vitamin E

Chemopreventive effects of broccoli, a highly valued vegetable, have been known for a long time. Several studies have demonstrated that broccoli might be beneficial by reducing the risk for the development of certain forms of cancer. These effects are generally attributed to glucosinolate-derived degradation products like isothiocyanates and indoles which are formed by the hydrolytic action of plant myrosinase and/or glucosidases deriving from the human microbial flora. However, recent in vitro and experimental animal studies indicate that broccoli, its extracts and the glucosinolate-derived degradation products might also have undesirable effects, especially genotoxic activities. However, the relevance of the genotoxic activities to human health is not known yet. This paper gives an overview on genotoxic, anti-genotoxic/chemopreventive, nutritive and antinutritive properties of broccoli, its ingredients and their degradation products. A qualitative comparison of the benefit and risk of broccoli consumption benefit-risk assessment shows that the benefit from intake in modest quantities and in processed form outweighs potential risks. For other preparations (fortified broccoli-based dietary supplements, diets with extraordinary high daily intake, consumption as a raw vegetable) further studies both for potential risks and beneficial effects are needed in order to assess the benefit and risk in the future.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Brassica; DNA Damage; Glucosinolates; Glycoside Hydrolases; Humans; Indoles; Isothiocyanates; Models, Animal; Neoplasms; Plant Extracts; Risk Assessment; Sulfoxides; Thiocyanates; Vegetables

A concentration-function approach to vitamin C (ascorbate) has yielded new physiology and pharmacology discoveries. To determine the range of vitamin C concentrations possible in humans, pharmacokinetics studies were conducted. They showed that when vitamin C is ingested by mouth, plasma and tissue concentrations are tightly controlled by at least 3 mechanisms in healthy humans: absorption, tissue accumulation, and renal reabsorption. A 4th mechanism, rate of utilization, may be important in disease. With ingested amounts found in foods, vitamin C plasma concentrations do not exceed 100 μmol/L. Even with supplementation approaching maximally tolerated doses, ascorbate plasma concentrations are always <250 μmol/L and frequently <150 μmol/L. By contrast, when ascorbate is i.v. injected, tight control is bypassed until excess ascorbate is eliminated by glomerular filtration and renal excretion. With i.v. infusion, pharmacologic ascorbate concentrations of 25-30 mmol/L are safely achieved. Pharmacologic ascorbate can act as a pro-drug for hydrogen peroxide (H(2)O(2)) formation, which can lead to extracellular fluid at concentrations as high as 200 μmol/L. Pharmacologic ascorbate can elicit cytotoxicity toward cancer cells and slow the growth of tumors in experimental murine models. The effects of pharmacologic ascorbate should be further studied in diseases, such as cancer and infections, which may respond to generation of reactive oxygen species via H(2)O(2).

Topics: Absorption; Animals; Ascorbic Acid; Female; Humans; Hydrogen Peroxide; Male; Mice; Mice, Knockout; Neoplasms; Vitamins

The mechanisms allowing the cellular transport of ascorbic acid represent a primary aspect for the understanding of the roles played by this vitamin in pathophysiology. Considerable research effort has been spent in the field, on several animal models and different cell types. Several mechanisms have been described to date, mediating the movements of different redox forms of ascorbic acid across cell membranes. Vitamin C can enter cells both in its reduced and oxidized form, ascorbic acid (AA) and dehydroascorbate (DHA), utilizing respectively sodium-dependent transporters (SVCT) or glucose transporters (GLUT). Modulation of SVCT expression and function has been described by cytokines, steroids and post-translational protein modification. Cellular uptake of DHA is followed by its intracellular reduction to AA by several enzymatic and non-enzymatic systems. Efflux of vitamin C has been also described in a number of cell types and different pathophysiological functions were proposed for this phenomenon, in dependence of the cell model studied. Cellular efflux of AA is mediated through volume-sensitive (VSOAC) and Ca(2+)-dependent anion channels, gap-junction hemichannels, exocytosis of secretory vesicles and possibly through homo- and hetero-exchange systems at the plasma membrane level. Altogether, available data suggest that cellular efflux of ascorbic acid - besides its uptake - should be taken into account when evaluating the cellular homeostasis and functions of this important vitamin.

Topics: Animals; Ascorbic Acid; Biological Transport, Active; Cell Membrane; Dehydroascorbic Acid; Glucose Transport Proteins, Facilitative; Humans; Ion Channels; Models, Biological; Neoplasms; Organic Anion Transporters, Sodium-Dependent; Oxidation-Reduction; Symporters

Catalytic therapy is a cancer treatment modality based on the generation of reactive oxygen species (ROS) through administration of ascorbate/medicinal herbal extracts and copper. It is known that antioxidants such as ascorbate also exhibit prooxidant activity in the presence of transition metals such as copper. Based on our work and that in the literature, in this review we propose a mechanism for the cytotoxic action of ascorbate against cancer cells. It involves redox cycling of exogenous/endogenous copper ions and the consequent generation of ROS leading to oxidative DNA breakage. Using human peripheral lymphocytes and the Comet assay, we have shown that ascorbic acid is able to cause oxidative breakage in cellular DNA. Such DNA degradation is inhibited by neocuproine (a Cu(I) sequestering agent) and scavengers of ROS indicating that the cellular DNA breakage involves the generation of Cu(I) and formation of ROS. Similar results are also obtained with plant polyphenol antioxidants that are important constituents of medicinal herbal extracts. Copper is an essential component of chromatin and can take part in redox reactions. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and ascorbate/plant polyphenols to generate ROS. In this review we cite evidence to indicate that in catalytic therapy cytotoxic action against cancer cells involves redox cycling of exogenous/endogenous copper ions.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Ascorbic Acid; Copper; DNA Breaks; DNA Cleavage; Flavonoids; Humans; Lymphocytes; Neoplasms; Oxidation-Reduction; Reactive Oxygen Species

In 1976 an article co-authored by Linus Pauling described that 100 terminal cancer patients treated with intravenous vitamin C, followed by oral maintenance, lived four times longer than a control group of 1,000 patients who did not receive vitamin C. The study was strongly criticized because the control group was very different from the group treated with vitamin C. The latter were declared terminally ill much sooner than the control group thus resulting in an artificially longer survival for the vitamin C group. Three double blind placebo controlled randomized trials performed at Mayo Clinic using oral vitamin C for cancer patients were negative. In a phase I-II trial performed by Riordan et al, none of 24 cancer patients treated with i.v. vitamin C responded. At this point we don't have information as to which is the actual plasma level of vitamin C that can produce tumor shrinkage. We don't have consistent information either regarding what is the clinical dose necessary to yield therapeutic plasma levels. In view of this lack of data after trials which have included at least 1,591 patients over 33 years, we have to conclude that we still do not know whether Vitamin C has any clinically significant antitumor activity. Nor do we know which histological types of cancers, if any, are susceptible to this agent. Finally, we don't know what the recommended dose of Vitamin C is, if there is indeed such a dose, that can produce an anti-tumor response.

Topics: Ascorbic Acid; Humans; Neoplasms; Time Factors; Vitamins

Vitamin C (ascorbic acid, ascorbate) has a controversial history in cancer treatment. Emerging evidence indicates that ascorbate in cancer treatment deserves re-examination. As research results concerning ascorbate pharmacokinetics and its mechanisms of action against tumor cells have been published, and as evidence from case studies has continued to mount that ascorbate therapy could be effective if the right protocols were used, interest among physicians and scientists has increased. In this review, high-dose vitamin C therapy in cancer treatment is re-evaluated.

Topics: Antioxidants; Ascorbic Acid; Humans; Neoplasms

The antioxidant perhaps most widely used in complementary oncology is vitamin C, particularly by intravenous injection. In light of the recent clinical pharmacokinetic findings, the in vitro evidence of anti-tumour mechanisms and some well-documented cases of advanced cancers the role of high-dose intravenous vitamin C therapy in cancer treatment should be reassessed. High dose intravenous vitamin C therapy may have benefits in patients with advanced cancers, and cancers with poor prognosis and limited therapeutic options, but further clinical studies regarding the safety and efficacy of this therapy are necessary, especially in Germany.

Topics: Antioxidants; Ascorbic Acid; Humans; Infusions, Intravenous; Neoplasms

The role of plant antioxidants as factors of civilization diseases prevention was described. The free-radical theory as a mechanism of action of antioxidants was mentioned. The main substances e.g. polyphenols including flavonoids, ascorbic acid, carotenoids and tocoferols were presented. Resveratrol of wine, as an example of possible health beneficial agent was stressed. On the other handsome doubts of beneficial effects of antioxidants e.g. beta-carotene, as supplement of diet, were mentioned. It is possible, that supplementation with flavonoids might create some health risk. But there was highlighted, that vegetables as a source of natural antioxidants are beneficial for health.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Chronic Disease; Dietary Supplements; Flavonoids; Health Promotion; Humans; Neoplasms; Phenols; Phytotherapy; Plant Extracts; Polyphenols; Resveratrol; Stilbenes

The properties of arsenic trioxide (arsenic) have been known for centuries. This compound has been used, among others, in the industrial production of paints and glass and also for the conservation of leather and wood. Although arsenic trioxide is highly toxic, this compound was shown to have a therapeutic potential as early as the fifteenth century. The period between the seventeenth and nineteenth centuries resulted in the development of new arsenic-based drugs which were applied for the treatment of skin diseases and acute promyelocytic leukemia. The mechanism of action of arsenic trioxide is mainly related to the induction of apoptosis (programmed cell death) in cancer cells. In particular it involves effects on the activities of JNK kinases, NF-kB transcription factor, glutathione, caspases, as well as pro- and anti-apoptotic proteins. Experiments investigating the effect of arsenic trioxide on cell lines such as glioma and prostate, breast, stomach, liver, and ovarian cancer are in progress. There are also clinical trials underway aimed at the use of arsenic trioxide with ascorbic acid, retinoid acid, and growth factors in combined therapy.

Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Ascorbic Acid; Caspases; Drug Therapy, Combination; Glutathione; Humans; Intercellular Signaling Peptides and Proteins; MAP Kinase Kinase 4; Neoplasms; NF-kappa B; Oxides; Tretinoin

In 2008, we celebrate the 80th anniversary of the discovery of vitamin C. Since then, we know that vitamin C possesses few pharmacological actions although it is still perceived by the public as a "miracle-pill" capable to heal a variety of illnesses. Cancer is one of the most common diseases for which a beneficial role of vitamin C has been claimed. Thus, its dietary use has been proposed in cancer prevention for several years. Apart from this nutritional aspect, an extensive and often confusing literature exists about the use of vitamin C in cancer that has considerably discredited its use. Nevertheless, recent pharmacokinetic data suggest that pharmacologic concentrations of vitamin C can be achieved by intravenous injections. Since these concentrations exhibit anticancer activities in vitro, this raises the controversial question of the re-evaluation of vitamin C in cancer treatment. Therefore, the purpose of this commentary is to make a critical review of our current knowledge of vitamin C, focusing on the rationale that could support its use in cancer therapy.

Topics: Ascorbic Acid; Drug Interactions; Humans; Neoplasms; Oxidative Stress

Despite the progress achieved in chemo- and radiotherapy, cancer is still a leading life-threatening pathology. In that sense, there is a need for novel therapeutic strategies based on our current knowledge of cancer biology. Among the phenotypical features of cancer cells, two of them are of particular interest: their nearly universal glycolytic phenotype and their sensitivity towards an oxidative stress, both resulting from the combination of high anabolic needs and hypoxic growth conditions. By using menadione (vitamin K3) and ascorbate (vitamin C), we took advantage of these features to develop an original approach that consists in the exposure of cancer cells to an oxidant insult. When used in combination, these compounds exhibit a synergistic action and are devoid of major toxicity in vivo. Thus, this review is dedicated to the analysis of the molecular pathways by which this promising combination exerts its antitumoural effect.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Ascorbic Acid; Humans; Neoplasms; Oxidants; Oxidative Stress; Vitamin K 3

Three discoveries together point the way to a potential treatment for cancer. In 1982, Poydock and colleagues found that dehydroascorbic acid has the remarkable ability to eliminate the aggressive mouse tumours, L1210, P388, Krebs sarcoma, and Ehrlich carcinoma. In 1993, Jakubowski found that cancer cells (but not normal cells) contain measurable quantities of homocysteine thiolactone. Recently, the author found that dehydroascorbic acid reacts with homocysteine thiolactone converting it to the toxic compound, 3-mercaptopropionaldehyde. Taken together, these findings suggest that rapidly-dividing tumour cells make unusually large amounts of homocysteine thiolactone and that administered dehydroascorbic acid enters the cells and converts the thiolactone to mercaptopropionaldehyde which kills the cancer cells. The effectiveness of dehydroascorbic acid might be further increased by combining it with methionine and/or methotrexate to increase the homocysteine concentration in cancer cells.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Dehydroascorbic Acid; Homocysteine; Humans; Methionine; Mice; Neoplasms

Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. Some have argued that antioxidants scavenge the reactive oxygen species integral to the activity of certain chemotherapy drugs, thereby diminishing treatment efficacy. Others suggest antioxidants may mitigate toxicity and thus allow for uninterrupted treatment schedules and a reduced need for lowering chemotherapy doses. The objective of this study is to systematically review the literature in order to compile results from randomized trials that evaluate concurrent use of antioxidants with chemotherapy.. MEDLINE, Cochrane, CinAhl, AMED, AltHealthWatch and EMBASE databases were searched. Only randomized, controlled clinical trials that reported survival and/or tumor response were included in the final tally. The literature searches were performed in duplicate following a standardized protocol. No meta-analysis was performed due to heterogeneity of tumor types and treatment protocols used in trials that met the inclusion criteria.. Of 845 articles considered, 19 trials met the inclusion criteria. Antioxidants evaluated were: glutathione (7), melatonin (4), vitamin A (2), an antioxidant mixture (2), vitamin C (1), N-acetylcysteine (1), vitamin E (1) and ellagic acid (1). Subjects of most studies had advanced or relapsed disease.. None of the trials reported evidence of significant decreases in efficacy from antioxidant supplementation during chemotherapy. Many of the studies indicated that antioxidant supplementation resulted in either increased survival times, increased tumor responses, or both, as well as fewer toxicities than controls; however, lack of adequate statistical power was a consistent limitation. Large, well-designed studies of antioxidant supplementation concurrent with chemotherapy are warranted.

Topics: Antioxidants; Ascorbic Acid; Glutathione; Humans; Melatonin; Neoplasms; Randomized Controlled Trials as Topic; Vitamin A; Vitamin E

Free radicals can affect the genetic material of cells, causing its gradual impairment and mutation. An accumulation of mutations in certain genes might lead to neoplasmic transformations of the cells and to cancer development. The deteriorative effects of free radicals are counteracted by the antioxidant vitamins A, C, and E that quench free radical reactions. Fruits and vegetables are excellent sources of antioxidant vitamins. The following article attempts a short review of the current knowledge about the influence of vitamins A, C, and E on oxidative damage to DNA, the activity of some transcription factors, and the expressions of certain genes. The aim of this review is to answer the question whether a diet rich in vitamins can protect against cancer.

Topics: Animals; Antioxidants; Ascorbic Acid; Carotenoids; Cell Transformation, Neoplastic; DNA Damage; DNA Repair; Fruit; Humans; Mice; Neoplasms; Oxidation-Reduction; Rabbits; Reactive Oxygen Species; Vegetables; Vitamin A; Vitamin E; Vitamins

Vitamin C is required for collagen synthesis and biosynthesis of certain hormones and recommended dietary intake levels are largely based these requirements. However, to function effectively as an antioxidant (or a pro-oxidant), relatively high levels of this vitamin must be maintained in the body. The instability of vitamin C combined with its relatively poor intestinal absorption and ready excretion from the body reduce physiological availability of this vitamin. This inability to maintain high serum levels of vitamin C may have serious health implications and is particularly relevant in the onset and progression of degenerative disease, such as cancer and cardiovascular disease (CVD), which have a strong contributing oxidative damage factor. In this review, we examine recent studies on the regulation of transport mechanisms for vitamin C, related clinical ramifications, and potential implications in high-dose vitamin C therapy. We also evaluate recent clinical and scientific evidence on the effects of this vitamin on cancer and CVD, with focus on the key mechanisms of action that may contribute to the therapeutic potential of this vitamin in these diseases. Several animal models that could be utilized to address unresolved questions regarding the feasibility of vitamin C therapy are also discussed.

Topics: Ascorbic Acid; Biological Transport; Cardiovascular Diseases; Humans; Neoplasms

Redox regulation has been shown to be an important component of malignant cell survival. Tipping the cellular redox balance through pharmacologic regulation in favor of increasing intracellular reactive oxygen species (ROS) and/or depleting protective reducing metabolites (such as glutathione and nicotinamide adenine dinucleotide phosphate) may lead to oxidative stress and resultant induction of apoptosis for the treatment of cancer. We review the biology and importance of ROS with regard to malignant and normal cells. Moreover, we discuss pre-clinical and clinical data regarding novel therapeutic agents that modulate the cellular redox system including buthionine sulfoximine, ascorbic acid, arsenic trioxide, imexon, and motexafin gadolinium as single-agents and in combination. Continued research is needed to better understand the mechanisms and specific apoptotic pathways involved in ROS-induced cell death, as well as, to determine the most rationale and effective combination of redox-active agents.

Topics: Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Arsenic Trioxide; Arsenicals; Ascorbic Acid; Buthionine Sulfoximine; Cell Death; Dose-Response Relationship, Drug; Glutathione; Hexanones; Humans; Metalloporphyrins; Models, Biological; Models, Chemical; Neoplasms; Oxidation-Reduction; Oxidative Stress; Oxides; Reactive Oxygen Species

The promising theoretical possibilities of antioxidant prevention and protection against vascular diseases and neoplasms could not have been realized as yet. The author searches into the causes of this failure by analyzing data of recent literature. Previous preventive trials as well as newly discovered pharmacological and molecular biological effects of antioxidants are reviewed. Results of meta-analyses on prevention trials of vascular disease by vitamin-E and those of gastrointestinal cancers are also included. The lately recognized properties of antioxidants are surveyed with special regard to their capability of modulating apoptosis, inducing gene expressions and their transformation into pro-oxidants. The harmful consequence of high doses of a single antioxidant is emphasized. The retinoids, vitamins D and K possess both pro-apoptotic and antiproliferative activity, while N-acetylcysteine exerts mainly anti-apoptotic effects. Since the effects of the eight vitamin E homologues are different in many respects, alpha-tocopherol can not be regarded as vitamin E of full value. Antioxidant supply from natural sources does not seem to be sufficient for an adequate preventive effect. The author recommends such a combination in which physiological amounts of vitamins C, D, K and B-complex, N-acetylcysteine, vitamin E of natural origin might be complemented by allopurinol, co-enzyme Q-10 and alpha-lipoic acid. A diet rich in flavonoids and carotenoids is essential. Application of appropriate laboratory methods is of great value in the individualization, monitoring and control of antioxidant treatment.

Topics: Acetylcysteine; Allopurinol; Antioxidants; Apoptosis; Ascorbic Acid; Cardiovascular Diseases; Clinical Trials as Topic; Coenzymes; Flavonoids; Humans; Meta-Analysis as Topic; Neoplasms; Selenium; Ubiquinone; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

To evaluate the evidence of the supplements vitamin C and vitamin E for treatment and prevention of cancer.. Systematic review of trials and meta-analysis. DATA SOURCES AND MAIN RESULTS: Thirty-eight studies showed scant evidence that vitamin C or vitamin E beneficially affects survival. In the ATBC Cancer Prevention Study Group, no statistically significant effect of treatment was seen for any cancer individually, and our pooled relative risk (regardless of tumor type) for alpha-tocopherol alone was 0.91 (95% confidence interval [CI]: 0.74, 1.12). All cause mortality was not significant. In the Linxian General Population Trial, the relative risks for cancer death for vitamin C (combined with molybdenum) was 1.06 (95% CI: 0.92, 1.21) and for vitamin E (combined with beta-carotene and selenium) was 0.87 (95% CI: 0.76, 1.00). We identified only 3 studies that reported statistically significant beneficial results: vitamin C (in combination with BCG) was found to be beneficial in a single trial of bladder cancer and vitamin E (in combination with omega-3 fatty acid) increased survival in patients with advanced cancer. In the ATBC trial, in analyses of 6 individual cancers, the prevention of prostate cancer in subjects treated with alpha-tocopherol was statistically significant (RR=0.64, 95% CI: 0.44, 0.94).. The systematic review of the literature does not support the hypothesis that the use of supplements of vitamin C or vitamin E in the doses tested helps prevent and/or treat cancer in the populations tested. There were isolated findings of benefit, which require confirmation.

Topics: Antioxidants; Ascorbic Acid; Humans; Neoplasms; Risk; Survival Analysis; Treatment Outcome; Vitamin E

For more than 50 years, the Food and Nutrition Board of the National Academy of Sciences has been reviewing nutrition research and defining nutrient requirements for healthy people, referred to as the Recommended Dietary Allowances (RDA). As new nutrition research is published, the importance of vitamins as vital nutrients is underscored, and new physiologic roles and applications to human health are examined and considered with regard to updating the RDA. Each year a substantial amount of new research is published on vitamins. This review examines recent research published on the importance of vitamin C with regard to general health.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Asthma; Cardiovascular Diseases; Diabetes Mellitus; Exercise; Humans; Hypersensitivity; Neoplasms

This is a review of the most relevant articles on the vitamin C-based therapy with emphasis to high per os and parenteral doses that might be effective on calories utilization, energy production, mythocondrial red-ox function, gene expression and metabolism. Ascorbic acid treatment in tumor bearing patients is a puzzling issue whose rationale is based on low vitamin plasma concentration and cancer uptake and sequestration; furthermore high parenteral dosages should be required to achieve a putative oxidative damage on tumor DNA, by this antioxidant molecule; thus bioavailability and metabolism as well as clinical effectiveness are reviewed on the basis of the evidence based medicine: specific evidence of vitamin C efficacy is quite limited, but areas like diabetic vascular complications and sideropenia might benefit of the treatment; high parenteral doses might be useful, perspectively also in relapsing urinary tract infection, after conventional treatment failure, due to the high output of ascorbic acid and potential saturation of the target tissues.

Topics: Ascorbic Acid; Humans; Neoplasms; Vitamins

The effect of ascorbic acid on cancer has been a subject of great controversy. This is a follow-up review of the 1979 article by Cameron, Pauling, and Leibovitz published in Cancer Research. In this updated version, the authors address general aspects of ascorbic acid and cancer that have been presented before, while reviewing, analyzing, and updating new existing literature on the subject. In addition, they present and discuss their own mechanistic hypothesis on the effect of ascorbic acid on the cancer cell. The objective of this review is to provide an updated scientific basis for the use of ascorbic acid, especially intravenously as adjuvant treatment in pharmacological nutritional oncology.

Topics: Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Humans; Infusions, Intravenous; Neoplasms; Pain; Palliative Care

Cells in multicellular organisms are exposed to both endogenous oxidative stresses generated metabolically and to oxidative stresses that originate from neighboring cells and from other tissues. To protect themselves from oxidative stress, cells are equipped with reducing buffer systems (glutathione/GSH and thioredoxin/thioredoxin reductase) and have developed several enzymatic mechanisms against oxidants that include catalase, superoxide dismutase, and glutathione peroxidase. Other major extrinsic defenses (from the diet) include ascorbic acid, beta-carotene and other carotenoids, and selenium. Recent evidence indicates that in addition to their antioxidant function, several of these redox species and systems are involved in regulation of biological processes, including cellular signaling, transcription factor activity, and apoptosis in normal and cancer cells. The survival and overall well-being of the cell is dependent upon the balance between the activity and the intracellular levels of these antioxidants as well as their interaction with various regulatory factors, including Ref-1, nuclear factor-kappaB, and activating protein-1.

Topics: Antioxidants; Ascorbic Acid; Carotenoids; Diet; Glutathione; Homeostasis; Humans; Mitochondria; Neoplasms; Nutritional Physiological Phenomena; Oxidation-Reduction; Oxidative Stress; Selenium; Signal Transduction; Tumor Cells, Cultured

The reactive oxygen species (ROS) can damage the nucleic acids. The oxidative modification of the DNA constitutes the fundamental molecular event in carcinogenesis and that is why the interest in the study of the involvement of ROS in that process. On the other hand, oxidative DNA damage-induced mutagenesis is widely hypothesized to be a frequent event in the normal human cell. The enormous evidence suggests an important role of ROS in the expansion and progression of tumor clones, being considered a relevant class of carcinogens. In addition, the use of immunohistochemical techniques has showed that the various types of cancer examined to date manifest an imbalance in their antioxidant mechanisms to respect the primary cell. In the near future new insights in cancer therapies, based on modulation of cellular redox status, may lead the way to additional tools against carcinogenesis from ROS.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Carotenoids; Disease Progression; DNA Damage; Free Radicals; Humans; Immunohistochemistry; Micronutrients; Models, Biological; Mutagenesis; Neoplasms; Oxidation-Reduction; Oxygen; Selenium; Vitamin A; Vitamin E

Vitamin C in humans must be ingested for survival. Vitamin C is an electron donor, and this property accounts for all its known functions. As an electron donor, vitamin C is a potent water-soluble antioxidant in humans. Antioxidant effects of vitamin C have been demonstrated in many experiments in vitro. Human diseases such as atherosclerosis and cancer might occur in part from oxidant damage to tissues. Oxidation of lipids, proteins and DNA results in specific oxidation products that can be measured in the laboratory. While these biomarkers of oxidation have been measured in humans, such assays have not yet been validated or standardized, and the relationship of oxidant markers to human disease conditions is not clear. Epidemiological studies show that diets high in fruits and vegetables are associated with lower risk of cardiovascular disease, stroke and cancer, and with increased longevity. Whether these protective effects are directly attributable to vitamin C is not known. Intervention studies with vitamin C have shown no change in markers of oxidation or clinical benefit. Dose concentration studies of vitamin C in healthy people showed a sigmoidal relationship between oral dose and plasma and tissue vitamin C concentrations. Hence, optimal dosing is critical to intervention studies using vitamin C. Ideally, future studies of antioxidant actions of vitamin C should target selected patient groups. These groups should be known to have increased oxidative damage as assessed by a reliable biomarker or should have high morbidity and mortality due to diseases thought to be caused or exacerbated by oxidant damage.

Topics: Animals; Antioxidants; Ascorbic Acid; Biological Availability; Cardiovascular Diseases; DNA; DNA Damage; Dose-Response Relationship, Drug; Fruit; Humans; Lipid Peroxidation; Neoplasms; Oxidation-Reduction; Proteins; Vegetables

Deficiency of alkaline and acid DNase is a hallmark in all non-necrotic cancer cells in animals and humans. These enzymes are reactivated at early stages of cancer cell death by vitamin C (acid DNase) and vitamin K(3) (alkaline DNase). Moreover, the coadministration of these vitamins (in a ratio of 100:1, for C and K(3), respectively) produced selective cancer cell death. Detailed morphological studies indicated that cell death is produced mainly by autoschizis, a new type of cancer cell death. Several mechanisms are involved in such a cell death induced by CK(3), they included: formation of H(2)O(2) during vitamins redox cycling, oxidative stress, DNA fragmentation, no caspase-3 activation, and cell membrane injury with progressive loss of organelle-free cytoplasm. Changes in the phosphorylation level of some critical proteins leading to inactivation of NF-kappaB appear as main intracellular signal transduction pathways. The increase knowledge in the mechanisms underlying cancer cells death by CK(3) may ameliorate the techniques of their in vivo administration. The aim is to prepare the introduction of the association of vitamins C and K(3) into human clinics as a new, non-toxic adjuvant cancer therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Cell Death; Chemotherapy, Adjuvant; DNA; Drug Synergism; Enzyme Inhibitors; Humans; Neoplasms; NF-kappa B; Oxidative Stress; Phosphorylation; Protein Serine-Threonine Kinases; Signal Transduction; Tumor Cells, Cultured; Vanadates; Vitamin K 3

Several studies have reported that even a moderate daily dose of supplementary vitamin C (200 mg) induces the formation of genotoxins from lipid hydroperoxides, thereby resulting in DNA damage and initiation of carcinogenesis. However, other reports questioned the experimental designs used and suggested that the chemopreventive effects of vitamin C may be linked to the inhibition of tumor promotion as well as to the blocking of tumor initiation. In this article, we discuss issues of contention and some controversies related to the potential chemopreventive effects of vitamin C in carcinogenesis.

Topics: Anti-Inflammatory Agents; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; Dietary Supplements; DNA Damage; Fruit; Humans; Neoplasms; Oxidation-Reduction; United States; Vegetables

Ascorbic acid is the single-nutrient supplement most commonly used by cancer patients, although in most cases this takes place without the physician's knowledge or supervision. A comprehensive review of the literature is presented on the impact of ascorbic acid on cancer survival. Findings from 6 uncontrolled studies suggest that ascorbic acid may increase survival, whereas 2 controlled trials have yielded null results. The relative strengths and limitations of these studies are discussed. A turning point occurred with the release of the 2 controlled (null) studies, which influenced many physicians to turn away from nutrition in the care of cancer patients. Controversy about these trials still persists, however, in the alternative cancer community.

Topics: Antioxidants; Ascorbic Acid; Complementary Therapies; Controlled Clinical Trials as Topic; Dietary Supplements; Female; Humans; Male; Neoplasms; Risk Assessment; Sensitivity and Specificity; Survival Analysis

Topics: Animals; Antioxidants; Ascorbic Acid; Chemoprevention; Clinical Trials as Topic; Dietary Supplements; Humans; Neoplasms; Sensitivity and Specificity

Topics: Antioxidants; Ascorbic Acid; Coenzymes; Humans; Neoplasms; Ubiquinone; Vitamin E

FREE RADICALS AND THE THEORY OF AGING: Severe oxidative stress progressively leads to cell dysfunction and ultimately cell death. Oxidative stress is defined as an imbalance between pro-oxidants and/or free radicals on the one hand, and anti-oxidizing systems on the other. The oxygen required for living may indirectly be responsible for negative effects; these deleterious effects are due to the production of free radicals, which are toxic for the cells (superoxide anions, hydroxyl radicals, peroxyl radicals, hydrogen peroxide, hydroperoxides and peroxinitrite anions). Free radical attacks are responsible for cell damage and the targeted cells are represented by the cell membranes, which are particularly rich in unsaturated fatty acids, sensitive to oxidation reactions; DNA is also the target of severe attacks by these reactive oxygen species (ROS).. These are represented by the enzymes and free radical captors. The latter are readily oxidizable composites. The free radical captor or neutralization systems of these ROS use a collection of mechanisms, vitamins (E and C), enzymes [superoxide dismutase (SOD), glutathion peroxidase (GPx) and others], and glutathion reductase (GSH), capable of neutralizing peroxinitrite. The efficacy of this system is dependent on the genome for the enzymatic defence systems, and on nutrition for the vitamins. Some strategies aimed at reducing oxidative stress-related alterations have been performed in animals. However, only a few can be used and are efficient in humans, such as avoidance of unfavourable environmental conditions (radiation, dietary carcinogens, smoking...) and antioxidant dietary supplementation.. Epidemiological data suggest that antioxidants may have a beneficial effect on many age-related diseases: atherosclerosis, cancer, some neurodegenerative and ocular diseases. However, the widespread use of supplements is hampered by several factors: the lack of prospective and controlled studies; insufficient knowledge on the pro-oxidant, oxidant and ant-oxidant properties of the various supplements; growing evidence that free radicals are not only by-products, but also play an important role in cell signal transduction, apoptosis and infection control.. Although current data indicate that antioxidants cannot prolong maximal life span, the beneficial impact of antioxidants on various age-related degenerative diseases may forecast an improvement in life span and enhance quality of life. The current lack of sufficient data does not permit the systematic recommendation of anti-oxidants. Nevertheless, antioxidant-rich diets with fruit and vegetables should be recommended.

Topics: Aging; Alzheimer Disease; Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Carotenoids; Cataract; Chronic Disease; Disease Models, Animal; Evidence-Based Medicine; Free Radicals; Humans; Lutein; Macular Degeneration; Neoplasms; Oxidative Stress; Parkinson Disease; Reactive Oxygen Species; Vitamin E

The decision of stressed cells to die or to survive is made by integrating signals at different levels through multiple check points. However, initiation and continued progression toward cell death by apoptosis in cancer cells may be blocked by mutation of the tumor suppressor p53 or overexpression of members of the bcl-2 family of proteins. The existence of such mechanisms indicates that cancer cells lose the controls regulating their cell cycle. Therefore, the activation of their programmed cell death appears as a major therapeutic target. Oxidative stress can stimulate growth, trigger apoptosis, or cause necrosis depending upon the dose and the exposure time of the oxidizing agent. A large body of evidence supports the idea that oxidative stress induced by redox cycling of vitamins C and K(3) in association surpasses cancer cellular defense systems and results in cell death. The molecular mechanisms underlying such a process are, however, still unknown. Indeed, several types of cell death may be produced, namely autoschizis, apoptosis and necrosis. Combined vitamin C and K(3) administration in vitro and in vivo produced tumor growth inhibition and increased the life-span of tumor-bearing mice. CK(3)-treatment selectively potentiated tumor chemotherapy, produced sensitization of tumors resistant to some drugs, potentiated cancer radiotherapy and caused inhibition of the development of cancer metastases without inducing toxicity in the host. We propose the association of vitamins C and K(3) as an adjuvant cancer therapy which may be introduced into human cancer therapy without any change in the classical anticancer protocols, and without any supplementary risk for patients.

Topics: Animals; Antioxidants; Ascorbic Acid; Cell Death; Chemotherapy, Adjuvant; Drug Synergism; Mice; Neoplasms; Oxidative Stress; Tumor Cells, Cultured; Vitamin K 3

The effect of vitamin C in cancer has been a subject of great controversy; mainly because of the inconsistent results obtained by oral intakes of ascorbate when used as an anticancer agent. We believe the intravenous application of ascorbate will provide more consistent results in cancer patients since Vitamin C blood levels attained are substantially higher in a range proven cytotoxic to malignant cells. In this article we will present and discuss our proposed mechanism on the chemotherapeutic activity exhibited by ascorbate.

Topics: Antioxidants; Ascorbic Acid; Humans; Injections, Intravenous; Neoplasms; Orthomolecular Therapy

Vitamin C (VC) and vitamin K(3) (VK(3)) administered in a VC:VK(3) ratio of 100:1 exhibit synergistic antitumor activity and preferentially kill tumor cells by autoschizis, a novel type of necrosis characterized by exaggerated membrane damage and progressive loss of organelle-free cytoplasm through a series of self-excisions. During this process, the nucleus becomes smaller, cell size decreases one-half to one-third of its original size, and most organelles surround an intact nucleus in a narrow rim of cytoplasm. While the mitochondria are condensed, tumor cell death does not result from ATP depletion. However, vitamin treatment induces a G(1)/S block, diminishes DNA synthesis, increases H(2)O(2) production, and decreases cellular thiol levels. These effects can be prevented by the addition of catalase to scavenge the H(2)O(2). There is a concurrent 8- to 10-fold increase in intracellular Ca(2+) levels. Electrophoretic analysis of DNA reveals degradation due to the caspase-3-independent reactivation of deoxyribonuclease I and II (DNase I, DNase II). Redox cycling of the vitamins is believed to increase oxidative stress until it surpasses the reducing ability of cellular thiols and induces Ca(2+) release, which triggers activation of Ca(2+)-dependent DNase and leads to degradation of DNA. Recent experiments indicate that oral VC:VK(3) increases the life-span of tumor-bearing nude mice and significantly reduces the growth rate of solid tumors without any significant toxicity by reactivating DNase I and II and inducing autoschizis. This report discusses the mechanisms of action employed by these vitamins to induce tumor-specific death by autoschizis.

Topics: Animals; Antioxidants; Ascorbic Acid; Cell Death; Humans; Necrosis; Neoplasms; Oxidative Stress; Vitamin K

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; Biomarkers; DNA Damage; Humans; Lipid Metabolism; Lipid Peroxidation; Neoplasms; Nutritional Requirements; Oxidation-Reduction; Oxidative Stress; Proteins; Reactive Oxygen Species; Smoking; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Carotenoids; Chronic Disease; Coronary Disease; Cross-Cultural Comparison; Epidemiologic Methods; Humans; Neoplasms; Observation; Risk Factors; Vitamin E

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Cell Transformation, Neoplastic; Diet; Free Radicals; Guinea Pigs; Humans; Incidence; Lung Neoplasms; Melanoma; Mice; Mice, Hairless; Models, Chemical; Neoplasms; Neoplasms, Radiation-Induced; Oxygen; Partial Pressure; Prospective Studies; Reactive Oxygen Species; Retrospective Studies; Selenium; Singlet Oxygen; Skin Neoplasms; Smoking; Structure-Activity Relationship; Ultraviolet Rays; Vegetables; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Biological Availability; Humans; Intestinal Absorption; Neoplasms; Nutritional Requirements; Research Design; Scurvy

Antioxidants are components of diet that are involved in DNA and cell maintenance and repair. Dietary antioxidants include carotenoids, vitamin C, vitamin E, and selenium. Across a variety of cancers, the observational studies have inconsistent results with respect to the relationship shown of specific dietary intake or serum levels of antioxidants and risk of certain cancers. The results of the micronutrient supplement trials clearly do not support a reductionist approach to promoting regression of precancerous lesions or prevention of new cancer, except in a few cancers and specific populations. The ability of the antioxidant micronutrients to influence the risk for tissue injury and for cancer, mediated by their antioxidant activities, remains hypothetical.

Topics: Animals; Antioxidants; Ascorbic Acid; Carotenoids; Humans; Neoplasms; Selenium; Vitamin E

There is growing interest concerning the role of vitamin C in physiological conditions. In this paper L-ascorbic acid is discussed in detail including its chemical activity and biological properties. The primary goal of this review is to present the chemical characteristics of this substance and to discuss its relation to various biological functions of vitamin C, mainly as an antioxidant barrier.

Topics: Antioxidants; Ascorbic Acid; Humans; Neoplasms; Spectrophotometry

Oxidation is a biochemical process of loss of electrons associated with another of reception called reduction. This process is capital for life, because it takes part in the production of cellular energy. Oxidative stress appears when oxidation is excessive. This reality is complex in all biological levels, and cannot be measured or defined by a single parameter. A great number of diseases have been related to oxidative stress and generation of free radicals. For this reason, antioxidant therapies and diets (such as mediterranean diet) rich or enriched with antioxidants seem to prevent or at least to attenuate the organic deterioration originated by an excessive oxidative stress.

Topics: Acute Kidney Injury; Aged; Aging; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cataract; Diabetes Mellitus; Diet; Humans; Hypertension; Liver Diseases; Neoplasms; Oxidation-Reduction; Oxidative Stress; Primary Prevention; Risk Factors; Selenium; Vitamin E

Malignancies have a distinguished role among leading causes of death around the world. As a result of more effective preventive efforts of cardiovascular diseases malignancies will reach the top of death statistics in the near future. The increased incidence of malignant tumors may be attributed to smoking, in temperate alcohol abuse, as well as inappropriate nutrition. Inappropriate nutrition is thought to be responsible for the development of about 30-50% of malignancies. In the present review the authors analyze the uniform theory of carcinogenesis and the possible mechanisms by which certain nutritive factors may interfere with the complex process of carcinogenesis. The mechanism of "oxidative stress" is detailed, in particular the impact of prooxidants (also referred to as free radicals) on tumor development and the central role of lipid peroxidation. In addition to alimentary free radicals the relevance of alcohol abuse in carcinogenesis is also studied. Against the undesirable free radical reactions a complex natural antioxidant (free radical scavenger) system exists, that is responsible for anticarcinogenesis. The authors introduce the dietary antioxidants, their known effects of mechanisms, and their possible role in chemoprevention and therapy of malignancies, based on several experimental and epidemiological data.

Topics: Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; Carcinogens; Flavonoids; Humans; Neoplasms; Nutritional Physiological Phenomena; Oxidants; Selenium; Superoxide Dismutase; Vitamin A; Vitamin E

Randomized controlled trials are generally regarded as the standard of study designs to determine potential causality. The inclusion of a placebo group in these trials, when appropriate, is generally needed to access the efficacy of a drug or dietary supplement. The recent increasing use of dietary supplements and herbal medications by patients makes it imperative to reevaluate the past findings of clinical studies. Several large-scale trials of dietary supplements have been tested in various populations to determine their effect on cancer prevention. Other trials have focused on patients already diagnosed with cancer. In the latter case, it is difficult to involve a placebo because of the serious nature of the disease. Nevertheless, much has been gleaned from these trials directly and indirectly. Overall, when analyzing primary endpoints in these trials, the results have been discouraging and even support the nonuse of certain supplements because of potential adverse effects. Other secondary endpoints in these same trials have revealed some potential encouraging and discouraging data. Individuals who currently qualify for the potential use of dietary supplements for cancer may be restricted to those who have a deficiency in a certain compound despite adequate dietary sources or lifestyle changes. Those individuals with a smoking history or other unhealthy lifestyle seem to have the most to gain or lose from taking certain dietary supplements for cancer. The time seems more than ripe to evaluate past adequate trials with supplements, such as beta-carotene, N-acetyl-cysteine, selenium, shark cartilage, vitamin C, vitamin E, and others. Again, these studies have been disappointing, but they provide insight for the clinician and patient of what to potentially expect when using these supplements for cancer. In addition, indirect trials for other conditions (cardiovascular) may provide future insight into possible results for future cancer prevention trials.

Topics: Acetylcysteine; Amygdalin; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Disease Progression; Humans; Neoplasms; Randomized Controlled Trials as Topic; Selenium; Tissue Extracts; Vitamin A; Vitamin E

To assess the balance of benefits and risks of supplementation with beta-carotene, vitamin E, vitamin C, and multivitamins on cancer, cardiovascular (CVD), and eye diseases.. Physicians' Health Study II (PHS II) is a randomized, double-blind, placebo-controlled trial enrolling 15,000 willing and eligible physicians aged 55 years and older. PHS II will utilize a 2 x 2 x 2 x 2 factorial design to test alternate day beta-carotene, alternate day vitamin E, daily vitamin C, and a daily multivitamin, in the prevention of total and prostate cancer, CVD, and the age-related eye diseases, cataract and macular degeneration. PRIOR RESULTS: The final results of the recently completed Physicians' Health Study I (PHS I), a randomized, double-blind, placebo-controlled trial in 22,071 healthy US male physicians, indicated that beta-carotene supplementation (50 mg on alternate days) had no significant benefit or harm on cancer or CVD during more than 12 years of treatment and follow-up. In regards to cancer, there were possible benefits on total and prostate cancer in those with low baseline levels assigned to beta-carotene, a finding compatible with the Chinese Cancer Prevention Study for combined treatment with beta-carotene, vitamin E, and selenium in a poorly nourished population. Further, with respect to CVD, there were apparent benefits of beta-carotene supplementation on subsequent vascular events among a small subgroup of 333 men with prior angina or revascularization. The currently available data from randomized trials of primary prevention are sparse and inconsistent for vitamin E and non-existent for vitamin C and multivitamins. For eye diseases, namely cataract and age-related macular degeneration, there are no completed large-scale randomized trials of antioxidant vitamins.. PHS II is unique in several respects. PHS II is the only primary prevention trial in apparently healthy men testing the balance of benefits and risks of vitamin E on cancer and CVD. In addition, PHS II is the only primary prevention trial in apparently healthy men to test the balance of benefits and risks of vitamin C, multivitamins, as well as any single antioxidant vitamin, alone and in combination, on cancer, CVD, and eye diseases. Finally, PHS II is the only trial testing a priori the hypotheses that beta-carotene and vitamin E may reduce the risks of prostate cancer. Thus, PHS II will add unique as well as importantly relevant and complementary information to the totality of evidence from other completed and ongoing large-scale randomized trials on the balance of benefits and risks of beta-carotene, vitamin E, vitamin C, and multivitamins alone and in combination on prevention of cancer, CVD and eye diseases.

Topics: Aged; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cataract; Double-Blind Method; Female; Follow-Up Studies; Humans; Macular Degeneration; Male; Middle Aged; Neoplasms; Sample Size; Vitamin E

Topics: Animals; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Clinical Trials as Topic; Diet; Free Radicals; Humans; Lipid Peroxidation; Neoplasms; Vitamin E

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

Topics: Animals; Antioxidants; Antiviral Agents; Ascorbic Acid; Blood Platelets; Coronary Disease; Cytoprotection; Enzyme Inhibitors; Flavonoids; Heart Diseases; Humans; Immune System; Inflammation; Lymphocytes; Mast Cells; Neoplasms; Xenobiotics

The current recommended dietary allowance (RDA) for vitamin C for adult nonsmoking men and women is 60 mg/d, which is based on a mean requirement of 46 mg/d to prevent the deficiency disease scurvy. However, recent scientific evidence indicates that an increased intake of vitamin C is associated with a reduced risk of chronic diseases such as cancer, cardiovascular disease, and cataract, probably through antioxidant mechanisms. It is likely that the amount of vitamin C required to prevent scurvy is not sufficient to optimally protect against these diseases. Because the RDA is defined as "the average daily dietary intake level that is sufficient to meet the nutrient requirement of nearly all healthy individuals in a group," it is appropriate to reevaluate the RDA for vitamin C. Therefore, we reviewed the biochemical, clinical, and epidemiologic evidence to date for a role of vitamin C in chronic disease prevention. The totality of the reviewed data suggests that an intake of 90-100 mg vitamin C/d is required for optimum reduction of chronic disease risk in nonsmoking men and women. This amount is about twice the amount on which the current RDA for vitamin C is based, suggesting a new RDA of 120 mg vitamin C/d.

Topics: Adult; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Cataract; Clinical Trials as Topic; Female; Humans; Lipid Peroxidation; Male; Neoplasms; Nutrition Policy; Scurvy

Interest in the role of vitamin E in disease prevention has encouraged the search for reliable indices of vitamin E status. Most studies in human subjects make use of static markers, usually alpha-tocopherol concentrations in plasma or serum. Plasma or serum alpha-tocopherol concentrations of < 11.6, 11.6-16.2, and > 16.2 mumol/l are normally regarded as indicating deficient, low and acceptable vitamin E status respectively, although more recently it has been suggested that the optimal plasma alpha-tocopherol concentration for protection against cardiovascular disease and cancer is > 30 mumol/l at common plasma lipid concentrations in combination with plasma vitamin C concentrations of > 50 mumol/l and > 0.4 mumol beta-carotene/l. Assessment of vitamin E status has also been based on alpha-tocopherol concentrations in erythrocytes, lymphocytes, platelets, lipoproteins, adipose tissue, buccal mucosal cells and LDL, and on alpha-tocopherol: gamma-tocopherol in serum or plasma. Erythrocyte susceptibility to haemolysis or lipid oxidation, breath hydrocarbon exhalation, oxidative resistance of LDL, and alpha-tocopheryl quinone concentrations in cerebrospinal fluid have been used as functional markers of vitamin E status. However, many of these tests tend to be non-specific and poorly standardized. The recognition that vitamin E has important roles in platelet, vascular and immune function in addition to its antioxidant properties may lead to the identification of more specific biomarkers of vitamin E status.

Topics: Ascorbic Acid; Biomarkers; Cardiovascular Diseases; Humans; Lipoproteins, LDL; Neoplasms; Nutritional Physiological Phenomena; Nutritional Status; Reference Values; Vitamin E

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Fruit; Heart Diseases; Humans; Neoplasms; Nutritional Requirements; Vegetables; Vitamin E; Vitamins

Topics: Animals; Ascorbic Acid; DNA; DNA Damage; DNA Repair; Folic Acid; Folic Acid Deficiency; Humans; Neoplasms; Niacin; Vitamin B 12 Deficiency; Vitamins

Antioxidants are crucial components of fruit/vegetable rich diets preventing cardiovascular disease (CVD) and cancer: plasma vitamins C, E, carotenoids from diet correlate prevalence of CVD and cancer inversely, low levels predict an increased risk of individuals which is potentiated by combined inadequacy (e.g., vitamins C + E, C + carotene, A + carotene); self-prescribed rectification of vitamins C and E at adequacy of other micronutrients reduce forthcoming CVD, of vitamins A, C, E, carotene and conutrients also cancer; randomized exclusive supplementation of beta-carotene +/- vitamin A or E lack benefits except prostate cancer reduction by vitamin E, and overall cancer reduction by selenium; randomized intervention with synchronous rectification of vitamins A + C + E + B + minerals reduces CVD and counteracts precancerous lesions; high vitamin E supplements reveal potentials in secondary CVD prevention. Plasma values desirable for primary prevention: > or = 30 mumol/l lipid-standardized vitamin E (alpha-tocopherol/cholesterol > or = 5.0 mumol/mmol); > or = 50 mumol/l vitamin C aiming at vitamin C/vitamin E ratio > 1.3-1.5; > or = 0.4 mumol/l beta- (> or = 0.5 mumol/l alpha+ beta-) carotene.. In CVD vitamin E acts as first risk discriminator, vitamin C as second one; optimal health requires synchronously optimized vitamins C + E, A, carotenoids and vegetable conutrients.

Topics: Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Health Promotion; Humans; Micronutrients; Neoplasms; Nutritional Physiological Phenomena; Randomized Controlled Trials as Topic; Risk Factors; Vitamin E

Topics: Ascorbic Acid; Clinical Trials as Topic; Complementary Therapies; Humans; Neoplasms; Treatment Outcome; Vitamin A; Vitamin E

Proposed mechanisms of action for ascorbic acid (ascorbate, vitamin C) in the prevention and treatment of cancer include enhancement of the immune system, stimulation of collagen formation necessary for "walling off" tumors, inhibition of hyaluronidase which keeps the ground substance around the tumor intact and prevents metastasis, prevention of oncogenic viruses, correction of an ascorbate deficiency often seen in cancer patients, expedition of wound healing after cancer surgery, enhancement of the effect of certain chemotherapy drugs, reduction of the toxicity of other chemotherapeutic agents such as Adriamycin, prevention of free radical damage, and neutralization of carcinogenic substances. Scottish as well as Japanese studies have pointed to the potential benefit of high dose vitamin C for the treatment of "terminal" cancer. Mayo Clinic studies, however, have contradicted the Scottish and Japanese findings, resulting in accusations of methodological flaws from both sides. Numerous epidemiological studies have pointed to the importance of dietary and supplemental ascorbate in the prevention of various types of cancer including bladder, breast, cervical, colorectal, esophageal, lung, pancreatic, prostate, salivary gland, stomach, leukemia, and non-Hodgkin's lymphoma.

Topics: Ascorbic Acid; Humans; Neoplasms

The known literature data concerning the mechanisms of molecular action of vitamin E in biological membrane systems are reviewed. The role of vitamin E, possessing a broad range of biological activities, as a universal stabilizer of biological membranes in normal oxygen metabolism and peroxidation, and also in disorders of normal metabolism resulting in pathological alterations, has been discussed. The participation of vitamin E in redox reactions taking place in lipid media, its interaction with singlet oxygen, free fatty acids and enzyme systems are considered. Physiological effects of vitamin E and its ability to prevent numerous pathologies are also considered. Vitamin E was concluded to be a universal participant of antioxidant defence reactions in biological membranes, since it acts at all stages of membrane oxidative damage.

Topics: Aging; Antioxidants; Ascorbic Acid; Fatty Acids, Unsaturated; Free Radicals; Glutathione; Heart Diseases; Humans; Kidney Diseases; Lipid Peroxidation; Liver Diseases; Membranes; Neoplasms; Vitamin E

The prospect that high intake of certain vitamins may confer protection against cancer has drawn substantial attention during the last decades. This paper gives a concise update of the role of a number of promising vitamins in prevention of cancer. Vitamin A and its analogues have an important role in cellular processes related to carcinogenesis. However, blood vitamin A levels are under strict control and a high intake of preformed vitamin A does not seem to be relevant for cancer prevention. The antioxidant vitamins C and E and beta-carotene may also have other biological activities than free radical trapping that relate to their cancer preventive properties. Mechanisms include immune stimulation, inhibition of nitrosamine formation, enhancement of cell communication and an influence on metabolic activation of carcinogens. Epidemiological data for the antioxidant vitamins are promising, but cannot rule out that another factor or combination of factors in fruits and vegetables might be responsible for a protective effect. The B vitamin folic acid is one of these potential factors that is currently thought to have an influence on DNA methylation and thus on proto-oncogene expression. Folic acid seems to be promising and deserves further study. Vitamin D might be relevant in colon cancer development due to its close links with calcium metabolism that might influence cell proliferation. Overall, results are promising, but the first human intervention trials on (antioxidant) vitamins and human cancer have yielded somewhat disappointing results. At this moment the data seem insufficient to make recommendations for vitamin supplementation to prevent cancer. The results are certainly in line with the advice that a diet rich in fruits and vegetables will help reduce cancer risk.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Female; Folic Acid; Humans; Male; Neoplasms; Proto-Oncogene Mas; Selenium; Vitamin A; Vitamin E; Vitamins

Topics: Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Diet; Health Status; Humans; Neoplasms

Understanding carcinogenesis is critical for development of rational approaches to cancer prevention. This paper uses N-nitrosamine carcinogenesis as an example. N-Nitrosamines are a large group of potent carcinogens. Approximately 300 different N-nitrosamines are carcinogenic. At least 30 animal species are responsive to their effects. There is little doubt that humans exposed to sufficient amounts of N-nitrosamines would also be susceptible to their carcinogenic effects. Human exposure to preformed N-nitrosamines occurs through the diet, in certain occupational settings, and through the use of tobacco products, cosmetics, pharmaceutical products, and agricultural chemicals. Diminishing human exposure to these carcinogens is one approach to prevention of cancer, and this has been accomplished in many instances, although exposure to N-nitrosamines in tobacco products is still unacceptably high. Human exposure to N-nitrosamines also occurs by nitrosation of amines in the body, via their acid or bacterial catalyzed reaction with nitrite, or by reaction with products of nitric oxide generated during inflammation or infection. A second approach toward prevention of N-nitrosamine carcinogenesis is inhibition of this endogenous N-nitrosamine formation. Substantial reductions have been achieved with ascorbic acid and other nitrite scavengers. N-Nitrosamines undergo a simple cytochrome P450-mediated metabolic activation step, which is critical for their carcinogenicity. The third approach involves the use of chemopreventive agents that block this step, or other steps in the carcinogenic process. A large number of potent chemopreventive agents against nitrosamine carcinogenesis have been identified. Chemoprevention of lung cancer induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is discussed as an example of this approach.

Topics: Animals; Anticarcinogenic Agents; Ascorbic Acid; Biotransformation; Carcinogens; Chemoprevention; Environmental Exposure; Humans; Inactivation, Metabolic; Neoplasms; Nicotiana; Nitrosamines; Plants, Toxic

Circulating free iron is lethal. Humans have two circulating iron binding proteins to soak up free iron to prevent it from generating toxic quantities of free radicals. These proteins are transferrin, a high-affinity, low-capacity protein (2 atoms of iron per molecule of transferrin) for which there are receptors on the surface of every iron-requiring cell; and ferritin, a lower-affinity, high-capacity protein (maximum of 4500 atoms of iron per molecule of ferritin) for which there are receptors only on the surface of iron-storage cells such as RE (reticulo-endothelial) cells. Iron is trapped inside the ferritin protein shell as harmless Fe3. When there is a high serum level of reduced ascorbic acid, it drives through the pores of the ferritin protein shell to the inside surface, where it converts the Fe3 to catalytic Fe2, which then leaks out of the pores of the ferritin protein shell and generates billions of free radicals. In normal individuals, per milliliter of serum, there are approximately 300,000 molecules of transferrin per molecule of ferritin. Ferritin protein is an acute phase reactant that sharply rises in the presence of inflammation of any kind, whereas transferrin is a reverse acute phase reactant that falls in the presence of inflammation of any kind.

Topics: Ascorbic Acid; Ferritins; Free Radicals; Heart Diseases; Humans; Iron; Neoplasms

The development of a beneficial or a detrimental cellular response by a nutrient will depend on the nutrient's antioxidant or prooxidant characteristics, which in turn are a product of the cellular oxygen environment. Nutrients such as carotenoids, tocopherols or ascorbate derivatives will demonstrate an antioxidant or prooxidant characteristic depending on the redox potential of the individual molecule and the inorganic chemistry of the cell. Nutrients acting as chemopreventives, inhibit the continual growth of transformed clones of cells through their prooxidant activity. In contrast, when an antioxidant activity occurs in transformed cells an enhanced growth may result. In addition, when an inappropriate prooxidant activity develops in normal cells, the reactive oxygen metabolites generated could damage the DNA and cellular membranes. The cellular response is usually a loss of normal regulatory function and activity, depressing cellular integrity. Therefore, the labile redox character of each nutrient must be considered in terms of the extracellular and intracellular microoxygen environment. To predict if a specific nutrient will have a beneficial or detrimental effect on a particular tissue or cell, it is important to identify markers that will characterize the biologic activities of each nutrient and elucidate a possible mechanism of action for that nutrient. In various tissues chemopreventive agents derived from nutrients have been shown in laboratory animal studies and in some human intervention trials to inhibit the growth and development of premalignant or malignant lesions. Examples of these tissues include oral tissues, esophagus, gastric cardia and lung tissues. Recently, some clinical studies demonstrated no reduction in the incidence of premalignant change, but, to the contrary, statistical evidence indicated an increase in cancer development. In general, the results of clinical intervention trials remains equivocal. The use of chemopreventive agents without considering their pharmacologic, oxygen-responsive characteristics will produce unwanted iatrogenic side effects or further cloud evidence of these nutrients' biologic activities.

Topics: Antioxidants; Ascorbic Acid; Carotenoids; Humans; Neoplasms; Oxidants; Retinoids; Vitamin E

Increased production of reactive oxygen species is a feature of most, if not all, human disease, including cardiovascular disease and cancer. Dietary antioxidants may be especially important in protecting against human diseases associated with free radical damage to cellular DNA, lipids, and proteins. Ascorbic acid is an effective water-soluble antioxidant, and epidemiologic studies suggest that increased ascorbate nutriture is associated with reduced risk of some degenerative diseases, especially cancer and eye cataracts. Population studies have also shown that high vitamin E intakes are associated with decreased risk of coronary heart disease, possibly as a result of inhibition of atherogenic forms of oxidized low-density lipoprotein. Recent data suggest that beta-carotene provides protection against lipid peroxidation in humans, as well as provitamin A activity. Yet, present data are not sufficient to quantitate micronutrient requirements needed to protect against oxidative damage. The antioxidant roles of many food constituents, such as polyphenols, have not been clarified. Most antioxidants can act as prooxidants under certain conditions, and more research is needed to determine the occurrence and importance of this in vivo. The few controlled intervention trials carried out so far have shown mixed results as to the potential of antioxidant supplements for reducing the incidence of chronic diseases. Definitive recommendations on antioxidant intakes for disease prevention must await evidence from controlled studies and intervention trials, some currently in progress. Overall, the present data suggest that protection against oxidative damage and related disease is best served by the variety of antioxidant substances found in fruit and vegetables.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Carotenoids; Exercise; Homocysteine; Humans; Lipid Peroxidation; Neoplasms; Oxidative Stress; Reactive Oxygen Species; Vitamin E

The recent scientific literature indicates that beyond merely protecting against scurvy vitamin C contributes to many aspects of human health. The main areas of research reviewed include: 1. Vitamin C requirements of smokers. The data indicate that the vitamin C requirement of smokers is higher by at least 60 mg per day (up to 140 mg per day) than that of nonsmokers. 2. Important functions of the body, such as immune response, pulmonary function, and iron absorption are related to vitamin C intakes. Daily vitamin C intake of at least 150-200 mg per day enhance these functions. 3. Vitamin C may play critical roles in the prevention of CHD, cancer and cataract. Based on the available data, vitamin C intakes of at least 80-120 mg per day are associated with lowering the risk of these chronic diseases. 4. The literature documents that these and much higher intake levels of vitamin C are safe.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Cataract; Diet; Health Status; Humans; Neoplasms; Nutrition Policy; Nutritional Requirements

Advances in diagnosis and treatment of cancer, as well as increased understanding of the mechanisms of the disease, have provided and will certainly continue to provide enormous benefit to affected individuals. At the same time, interventions that may prevent common cancers from developing in healthy people could, at least in theory, afford even greater benefits to society as a whole. The hypothesis that antioxidant vitamins might reduce cancer risk is based on a large body of both basic and human epidemiologic research. A large number of case-control and cohort studies provide remarkably consistent data suggesting that consumption of foods rich in antioxidant vitamins reduce risks of developing epithelial cancers. These data raise the question of a possible role of antioxidants, such as vitamins C and E, and beta carotene, in the primary prevention of cancer as well ar cardiovascular disease but do not provide a definitive answer. Despite the lack of clear benefit, there has been a rapid increase in the consumption of supplements of these micronutrients. Limited randomized trial data on the role of supplemental antioxidants are available. A number of randomized trials are currently underway designed to test the hypothesis that antioxidants prevent chronic diseases and to evaluate the long term safety of the widespread practice of supplementation. Well designed and well conducted large-scale randomized trials are necessary to provide a definitive positive or negative result on which public policy can be based, or a null result that is truly informative and that can then safely permit the rechanneling of already limited resources to other areas of research.

Topics: Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Humans; Neoplasms; Randomized Controlled Trials as Topic; Vitamin E

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Breast Neoplasms; Case-Control Studies; Cohort Studies; Colonic Neoplasms; Diet; Dietary Fats; Ethanol; Female; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Rectal Neoplasms; Risk Factors; Smoking; Stomach Neoplasms; Vegetables; Vitamin E

Topics: Ascorbic Acid; Chronic Disease; Diet; Disease; Epidemiologic Methods; Female; Fruit; Humans; Male; Neoplasms; Preventive Medicine; Risk Factors; Vegetables

Topics: Animals; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Cell Division; Cell Survival; Cell Transformation, Neoplastic; Cricetinae; Humans; Neoplasm Proteins; Neoplasms; Tumor Cells, Cultured

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Eye Diseases; Health Promotion; Humans; Neoplasms; Preventive Medicine; Vitamin E

Evidence from intervention trials with vitamins E and C and beta-carotene are reviewed as well as evidence from trials that have used intermediate endpoints with a special emphasis on biomarkers of cancer of the colorectum. The methodologic issues that require resolution before a second generation of clinical trials are launched to assess the efficacy of these antioxidants in the prevention of cancer are identified. Specific concerns regarding the validation of pathologic biomarkers of cancer and biochemical markers of mechanism of action for the antioxidants are discussed. Cellular proliferation indexes in the colon are used as an example of pathologic biomarkers for cancer and the measurement of plasma and tissue malondialdehyde concentrations is used as an example of problems with the development of biochemical markers of oxidative stress that can be used in prevention trials. The use of DNA oxidation products as promising biomarkers is also discussed.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers, Tumor; Carotenoids; Clinical Trials as Topic; Humans; Neoplasms; Oxidative Stress; Vitamin E

This paper presents a review of the significant body of literature liking dietary iron overload, not only to heart disease, but also to cancer, diabetes, osteoporosis, arthritis, and possibly other disorders. Following an analysis of our understanding of the mechanistic role iron plays in oxidative damage, an interpretation of the fact that plasma concentrations of several antioxidants are decreased in the presence of disease is offered. Evaluation of (1) age-related dietary trends over time and (2) factors involved in iron absorption leads to the hypothesis that the combination of citric acid and ascorbic acid (a synergistic pair of strong enhancers) is instrumental in causing a deleterious increase in iron load in aging populations. Iron overload may be the most important common etiologic factor in the development of the diseases mentioned; therefore, the synergistic combination of citric and ascorbic acids may play a major role in our worsening disease statistics. Evidence to support this hypothesis and possible experiments to test it are included. This combination needs further study, particularly because the iron overload produced may be correctable.

Topics: Aging; Ascorbic Acid; Citrates; Citric Acid; Diet; Disease; Free Radicals; Heart Diseases; Humans; Intestinal Absorption; Iron; Neoplasms

Epidemiological studies strongly suggest that high intakes of foods rich in beta carotene, as well as those rich in vitamin E or vitamin C, reduce the risk of some but not all cancers and cardiovascular disease. It is difficult to determine whether these antioxidant nutrients per se are the sole protective agents or whether other factors associated with foods containing them contribute to the foods' protective effects. With respect to vitamin E, a number of studies where dietary and supplementary vitamin E were clearly differentiated, a reduced risk of certain cancers or cardiovascular disease from supplemental vitamin E but not from dietary vitamin E was demonstrated. This provides strong presumptive evidence that high intakes of vitamin E per se provide a health benefit. Only a few intervention studies with specific nutrients are available and results are inconsistent.

Topics: Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Carotenoids; Humans; Neoplasms; Risk Factors; Selenium; Vitamin E

A comprehensive review of the literature indicates that populations with long-term consumption of higher than RDA levels of vitamin C (> or = 60 mg/day) from foods and/or supplements have reduced risks of cancer at several sites, cardiovascular disease, and cataracts. The safety of higher than RDA intakes of vitamin C is confirmed in eight placebo-controlled, double-blind studies and six non-placebo clinical trials in which up to 10,000 mg of vitamin C was consumed daily for up to 3 years. There are no clinical data which suggest that vitamin C's enhancement of non-heme iron absorption in individuals with low iron status could be a critical factor in the possible increased risk of heterozygous hemochromatosis-related cardiovascular disease. In fact, the cumulative data do not confirm that iron status is related to risk of cardiovascular disease. Moreover, higher than RDA intakes of vitamin C have been associated with several indices of lowered cardiovascular disease risk including increases in HDL, and decreases in LDL oxidation, blood pressure and cardiovascular mortality.

Topics: Ascorbic Acid; Cardiovascular Diseases; Cataract; Female; Humans; Iron; Iron Deficiencies; Male; Neoplasms

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coronary Disease; Fruit; Humans; Incidence; Neoplasms; Vegetables; Vitamin E

To assess whether antioxidants may reduce the risk of cancer, we reviewed the epidemiologic literature from 1985 through 1993. We assessed the separate relationships of three antioxidants (carotenoids, vitamin C, and vitamin E) with six sites of cancer (lung, upper aerodigestive tract, uterine cervix, colon, breast, prostate). This review was limited to dietary intake or serum nutrient studies that met a predefined set of methodologic standards. We judged the evidence in support of causal relationships based upon consistency of results across studies, strength of association, and evidence of a dose-response relationship. The data concerning carotenoids and lung cancer risk were most consistent (protection found in 4 of 8 diet studies and 5 of 6 serum studies), with strong associations that tended to follow a dose-response pattern. For lung cancer, there was weaker evidence of protection from vitamin C (2 of 6 diet studies) and vitamin E (3 of 4 serum studies). For upper aerodigestive tract cancers (oral cavity, pharynx, or larynx), there was evidence of a protective effect of carotenoids (3 of 4 diet studies) and vitamin C (4 of 5 diet studies). For cancer of the uterine cervix, we found suggestive evidence of protection from vitamin C (4 of 5 diet studies) and perhaps carotenoids (2 of 5 diet studies). For cancers of the colon, breast, and prostate, the current data do not support a protective effect of antioxidants. More definite conclusions about the benefits of antioxidants in cancer prevention will be derived from on-going intervention trials.

Topics: Antioxidants; Ascorbic Acid; Bias; Carotenoids; Dose-Response Relationship, Drug; Female; Humans; Male; Neoplasms; Nutrition Surveys; Population Surveillance; Research Design; Risk Factors; Vitamin E

It is established beyond doubt that free radicals in tissues and cells can damage DNA, proteins, carbohydrates and lipids. These potentially deleterious reactions are at least partly controlled by antioxidants capable of scavenging free radicals. It is widely believed that a proper balance between free radicals and antioxidants is essential for the health of an organism. A vast body of observational epidemiological studies has suggested that high intake of dietary or supplemental antioxidants protects against ischaemic heart disease, various types of cancer and several other diseases. Final proof for the beneficial effects of antioxidants can, however, be obtained from controlled studies. Conflicting results of the first three major clinical trials force us to postpone conclusions of the usefulness of antioxidant supplements in disease prevention until the other on-going trials have been published.

Topics: Animals; Antioxidants; Ascorbic Acid; Carotenoids; Food, Fortified; Free Radicals; Humans; Neoplasms; Vitamin E

Ascorbate, an essential nutrient in humans, primates, and guinea pig, is involved in many cellular functions. Ascorbate also modulates cell growth and differentiation. Ascorbate can reduce or stimulate the growth of tumor cells, depending on the cell type. The inhibitory effect is not specific for the biological active isomer L-ascorbate, and isoascorbate and D-ascorbate are more effective in reducing cell growth than L-ascorbate. These results indicate that ascorbate has a cytotoxic effect by killing cells directly, rather a cytostatic one. However, only L-ascorbate is able to stimulate cell growth, but the mechanism of this stimulation is still unknown. L-Ascorbate stimulates the in vitro differentiation of several mesenchyme-derived cell types by altering the expression of multiple genes as the cell progresses through specific differentiation programs. Stimulation of collagen matrix at gene transcription, mRNA stabilization, hydroxylation, and secretion is a key role for L-ascorbate. L-Ascorbate also prevents cell transformation by stabilization of the differentiated state and cooperates with other agents to induce differentiation in a leukemia cell line.

Topics: Animals; Ascorbic Acid; Calcitriol; Cartilage; Cell Differentiation; Cell Division; Growth Inhibitors; Guinea Pigs; Humans; Leukemia, Promyelocytic, Acute; Mesoderm; Mice; Neoplasms; Nutritional Requirements; Oxidative Stress; Species Specificity; Tumor Cells, Cultured

Reactive oxygen species (ROS) such as the superoxide (O2.-) and the hydroxyl radical (OH.) are aggressive chemical compounds that can induce tissue injury, e.g. by peroxidation of polyunsaturated fatty acids in cell membranes or directly by DNA damage. Many pathological conditions are in part caused by ROS. There are various biological defense systems directed towards radicals: specific enzymes, e.g. superoxide dismutase or glutathione peroxidase; nonessential antioxidants, e.g. the plasma proteins and uric acid; and the essential antioxidants, e.g. vitamin C, vitamin E and carotenoids. This review focuses on various clinical conditions where ROS are of major pathogenetic significance: ageing, cancer, stroke, hematologic disorders, adult respiratory distress syndrome (ARDS) and organ preservation in transplantation medicine. Moreover, the complementary system of the vitamins C and E in defense against ROS is shortly discussed and the need for further studies about the effects of antioxidant treatment, such as interventional studies, proposed. The chronic exposure of the organism to ROS is an important factor for tissue injury in the process of ageing. Lipofuscin is a typical product of lipid peroxidation and inversely correlates with longevity of an organism. The ingestion of higher doses of antioxidative vitamins was recently shown to be protective for the development of cataracts, a degenerative disorder of the eye. The impairment of the immune system in elderly people might be prevented by a higher intake of multivitamin supplements. Whether supplementation with antioxidative vitamins can extend the life span in humans, as was shown in experimental animals, remains unanswered.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Antioxidants; Ascorbic Acid; Carotenoids; Cerebrovascular Disorders; Free Radicals; Hematologic Diseases; Humans; Neoplasms; Reactive Oxygen Species; Respiratory Distress Syndrome; Vitamin E

Iron is a double-edged sword. In moderate quantities and leashed to protein, it is an essential element in all cell metabolism and growth, but it is toxic when unleashed. Because of its ability to switch back and forth between ferrous and ferric oxidation states, iron is both a strong biological oxidant and reductant. The human diet contains a multitude of natural chemicals which are carcinogens and anticarcinogens, many of which act by generating oxygen radicals, which initiate degenerative processes related to cancer, heart disease and aging (the "oxygen radical hypothesis of aging"). Among these many dietary chemicals are many redox agents, including vitamin C and beta carotene. Free radical damage is produced primarily by the hydroxyl radical (.OH). Most of the .OH generated in vivo comes from iron-dependent reduction of H2O2. Supporting too much iron as a free radical-generating culprit in the risk of cancer, NHANES I data indicated that high body iron stores, manifested by increased transferrin saturation, are associated with an increased cancer risk. Other data shows an increased heart attack risk.

Topics: Animals; Anticarcinogenic Agents; Apoferritins; Ascorbic Acid; Carcinogens; Deferoxamine; Diet; Ferritins; Free Radicals; Heart Diseases; Hemin; Humans; Iron; Neoplasms; Oxidation-Reduction; Superoxides

Ascorbic acid (ASC) consumption is negatively correlated with the incidence of certain cancers. This is a review and update of the theory, which has recently been neglected, that this negative correlation is due to ASC inhibition of in vivo nitrosation. The review covers the older literature on ASC inhibition of carcinogenesis by nitrite administered with amines or amides and more recent studies on ASC inhibition of nitrosation by bacteria, nitrogen oxides, and activated macrophages; the role of oxygen in ASC inhibition of gastric nitrosation; ASC inhibition of N-nitrosoproline formation in subjects from areas with high incidences of certain cancers; dose and temporal relationships between ASC and in vivo nitrosation in humans; the role of substances other than ASC in the inhibition of nitrosation by vegetables and fruits; and the active secretion of ASC into the human stomach.

Topics: Animals; Ascorbic Acid; Biotransformation; Diet; Fruit; Incidence; Neoplasms; Nitroso Compounds; Stomach Neoplasms; Vegetables

Topics: Animals; Ascorbic Acid; Glutathione; Humans; Mitochondria; Models, Biological; Neoplasms; Oxidation-Reduction; Tumor Cells, Cultured

A Round Table Discussion was held at the Fourth International Conference on Anticarcinogenesis and Radiation Protection. Scientists from government and academia were brought together to discuss the evidence for the preventive effect of foods, specific nutrients and drugs against cancer, and the most appropriate methods of initiating nutritional cancer prevention activities to improve the health of the public. The panel reviewed the epidemiological evidence of the role of diet and specific micronutrients for the prevention of cancer, the doses of specific micronutrients required for preventive effects and their safety, the evidence for aspirin as a chemopreventive agent, the issue of foods versus specific micronutrients in the prevention of cancer, food safety, and approaches to prevention such as food fortification or dietary supplements. The remarks of the panel members are summarized.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Ascorbic Acid; Aspirin; Colonic Neoplasms; Diet; Food; Food, Fortified; Humans; Neoplasms; Nutritional Physiological Phenomena; Vitamin E

Vitamins A (retinol, retinoids), beta-carotene (provitamin A), E (alpha-tocopherol), and C (ascorbic acid) are used in experimental, clinical and epidemiological studies for cancer chemoprevention and treatment. The cellular and metabolic effects are depending on the dose used, duration of exposure, and cancer cell type. Despite recent advances, the anticarcinogenic mechanisms remain as yet unknown. Studies regarding the role of vitamins A, beta-carotene, E and C in cancer cell biology and metabolism are of critical importance for their use in cancer treatment. Autoradiographic, ultrastructural and cell surface studies demonstrated that vitamins A, E and C are strong regulator factors of cancer cell differentiation, cell regression, membrane biogenesis, DNA, RNA, protein, and collagen synthesis, as well as transformation of precancer cells into cancer cells. These vitamins exert cytotoxic and cytostatic effects, and may reverse the cancer cell to the normal phenotype. Interrelation of vitamins A, E and C with oncogenes and growth factors play an important role in cancer cell biology. The data presented in this review can provide new insights for the understanding of anticarcinogenic mechanisms, and a rationale for the use of vitamins A, E and C in cancer chemo-prevention and treatment.

Topics: Animals; Anticarcinogenic Agents; Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; Humans; Neoplasms; Vitamin A; Vitamin E

There is an enormous amount of literature on vitamin C intake and health in animals, cell cultures, and humans. Beyond its function in collagen formation, ascorbic acid is known to increase absorption of inorganic iron, to have essential roles in the metabolism of folic acid and of some amino acids and hormones, and to act as an antioxidant. In recent years, research has increasingly focused on this latter function, stimulated by suggestions that "oxidative stress" may be a causal factor in the etiology of such diverse and important disorders of aging as cancer, cardiovascular disease, and cataract formation. The present evidence is strong enough to have convinced nutritionists that daily vitamin C intake should be many times higher than the amount needed to protect against scurvy, and this is reflected in the present Recommended Dietary Allowances. Suggestions that the recommended levels should be higher still are largely based on extrapolations from results of animal and tissue culture studies. How much ascorbic acid is necessary to achieve in humans the effects seen in animal studies is not clear. In general, the limited human studies have not been persuasive. The data are incomplete, and many of the studies have serious flaws. There are no toxicity studies of the type done for new compounds being considered for approval as therapy for major disease conditions. Intervention studies will be difficult, but are essential, and methods for tissue saturation measurement must be defined before new recommendations for the public are designed.

Topics: Animals; Ascorbic Acid; Female; Guinea Pigs; Humans; Male; Mice; Middle Aged; Neoplasms; Nutritional Requirements; Rabbits; Rats; Tumor Cells, Cultured

Humans are exposed through ingestion or inhalation to preformed N-nitroso compounds (NOC) in the environment and through the endogenous nitrosation of amino precursors in the body. Activated macrophages and bacterial strains isolated from human infections can enzymatically produce nitrosating agents and NOC from precursors at neutral pH. As a consequence, endogenous nitrosation may occur at various sites of the body, such as the oral cavity, stomach, urinary bladder, and at other sites of infection or inflammation. Numerous substances to which humans are exposed have been identified and shown to inhibit formation of NOC. Such inhibitors include vitamins C and E, certain phenolic compounds, and complex mixtures such as fruit and vegetable juices or other plant extracts. Nitrosation inhibitors normally destroy the nitrosating agents and, thus, act as competitors for the amino compound that serves as substrate for the nitrosating species. Independently, epidemiological studies have already established that fresh fruits and vegetables that are sources of vitamin C, other vitamins, and polyphenols have a protective effect against cancers at various sites and in particular gastric cancer. This article briefly reviews (a) the chemistry of NOC formation and inhibition; (b) the studies in experimental animals that showed that inhibition of endogenous NOC synthesis leads to a reduction of toxic, mutagenic, and carcinogenic effects; (c) recent studies in humans where the degree of inhibition of endogenous NOC synthesis was directly quantified; and (d) the possible contribution of nitrosation inhibitors to human cancer prevention.

Topics: Animals; Antimutagenic Agents; Ascorbic Acid; Cholangiocarcinoma; Esophageal Neoplasms; Humans; Incidence; Infant, Newborn; Macrophage Activation; Macrophages; Neoplasms; Nitroso Compounds; Opisthorchiasis; Phenols; Risk Factors; Stomach Neoplasms; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Carotenoids; Free Radicals; Fruit; Humans; Neoplasms; Nutritional Physiological Phenomena; Reactive Oxygen Species; Vegetables; Vitamin A; Vitamin E

Topics: Animals; Ascorbic Acid; Biological Factors; Cells; Glutathione; Humans; Neoplasms; Oxidation-Reduction

Increasing evidence is accumulating that a synergistic role of the so-called antioxidant vitamins (C, E, beta-carotene) may have a dominant role in the prevention of cancer, cardiovascular diseases and cataract formation. Controversy still exists regarding the optimum intake of vitamin C. This is partly due to lack of accurate and easily accessible health-relevant end-points, and lack of knowledge of the role of vitamin C in biochemical functions. Today, it is clearly recognized and broadly accepted that optimal health is a consequence of dietary optimization. Attainment of optimal health rather than prevention of deficiency symptoms is the goal. There can be little doubt that in this respect the requirements for vitamin C are greater than the amount required for the mere prevention of overt or classical scurvy. The recommendation of varying levels of requirement could overcome the controversy. The following is therefore proposed: The lowest level is that value which prevents deficiency symptoms. The second level is valid for healthy populations (< 200 mg/d). This level would take into account needs which differ according to age, sex, physical activity, physiological status (e.g. pregnancy or lactation) and environmental factors such as smoking, pollution and alcohol intake. Finally, a third level should be determined for the prevention of the above-mentioned non-communicable diseases. These diseases are an important cause of disability, resulting in costs of billions of dollars annually in medical costs. Many of the above-mentioned diseases can be prevented by supplementation with vitamin C. Medical costs could thereby also be dramatically reduced.

Topics: Ascorbic Acid; Cardiovascular Diseases; Common Cold; Humans; Neoplasms; Nutritional Requirements; Reference Standards

Topics: Anticarcinogenic Agents; Ascorbic Acid; Female; Humans; Male; Neoplasms; Nutritional Status; Risk Factors

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; Carotenoids; Diet; Humans; Neoplasms; Vitamin E

Topics: 2-Acetylaminofluorene; Animals; Ascorbic Acid; Carcinogens; Cell Division; DNA Replication; Humans; Models, Biological; Mutation; Neoplasms; Neoplastic Stem Cells; Saccharin

Approximately 90 epidemiologic studies have examined the role of vitamin C or vitamin-C-rich foods in cancer prevention, and the vast majority have found statistically significant protective effects. Evidence is strong for cancers of the esophagus, oral cavity, stomach, and pancreas. There is also substantial evidence of a protective effect in cancers of the cervix, rectum, and breast. Even in lung cancer, for which carotenoids show a consistent protective effect, there is recent evidence of a role for vitamin C. Vitamin C is an important antioxidant and free radical scavenger in plasma and acts to regenerate active vitamin E in lipid membranes. Although several different factors in fruits and vegetables probably act jointly, the epidemiologic and biochemical evidence indicate an important role for vitamin C.

Topics: Ascorbic Acid; Epidemiologic Methods; Female; Gastrointestinal Neoplasms; Humans; Lung Neoplasms; Neoplasms; Stomach Neoplasms; Urogenital Neoplasms; Uterine Neoplasms

Epidemiologic evidence of a protective effect of vitamin C for non-hormone-dependent cancers is strong. Of the 46 such studies in which a dietary vitamin C index was calculated, 33 found statistically significant protection, with high intake conferring approximately a twofold protective effect compared with low intake. Of 29 additional studies that assessed fruit intake, 21 found significant protection. For cancers of the esophagus, larynx, oral cavity, and pancreas, evidence for a protective effect of vitamin C or some component in fruit is strong and consistent. For cancers of the stomach, rectum, breast, and cervix there is also strong evidence. Several recent lung cancer studies found significant protective effects of vitamin C or of foods that are better sources of vitamin C than of beta-carotene. It is likely that ascorbic acid, carotenoids, and other factors in fruits and vegetables act jointly. Increased consumption of fruits and vegetables in general should be encouraged.

Topics: Ascorbic Acid; Case-Control Studies; Humans; Neoplasms; Neoplasms, Hormone-Dependent; Prospective Studies; Risk Factors

Epidemiological studies have shown that diets rich in one or more antioxidant nutrients may reduce the risk of cancers of the lung, uterine cervix, mouth, and gastrointestinal tract. Study of premalignant lesions offers a comparatively expedient approach to identifying and evaluating the efficacy of the cancer chemopreventive components of foods. Some recent findings suggest roles for beta-carotene and/or vitamin C in reversing or reducing the risk of cervical dysplasia and oral leukoplakia. There are some indications that vitamin C and beta-carotene may reduce the risk of atrophic gastritis and gastric cancer. Additional epidemiological and molecular biology studies and clinical intervention trials using premalignant lesions as the marker of specific cancer risks should become an important component of future research in the area of cancer chemoprevention.

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; Diet; Female; Humans; Neoplasms; Precancerous Conditions; Vitamin E

Antioxidant micronutrients are one of the body's primary defenses against free radicals and reactive oxygen molecules. Carotenoids, vitamin C, and vitamin E trap these molecules, and selenium is an essential component of an antioxidant enzyme. There is considerable support from animal studies for a protective effect of antioxidant micronutrients on cancer. However, the role of these micronutrients in cancer prevention in humans is less clear. Diet studies suggest protective effects of fruits and vegetables on risk of cancer at several sites. Inverse associations between dietary carotenoids and serum beta-carotene and lung cancer have been observed repeatedly. Vitamin C has also been consistently inversely associated with risk of oral and esophageal cancer in diet studies and with stomach cancer in both diet and plasma studies. It remains unknown, however, whether carotenoids and vitamin C or some other component of fruits and vegetables, the primary sources of these micronutrients, prevent cancer in humans. Selenium has been inversely correlated with cancers at numerous sites in ecologic studies, but observational studies do not provide strong support for a protective effect of selenium on cancer at any site. There also is not strong support for a protective effect of vitamin E on cancer in humans. Results of studies on the association of antioxidant micronutrients with cancer at many sites are inconsistent. This could be due to lack of a true protective effect or could be related to methodologic problems in assessing dietary intake in epidemiologic studies.

Topics: Animals; Antioxidants; Ascorbic Acid; Carotenoids; Humans; Neoplasms; Rats; Selenium; Vitamin E

Topics: Adult; Ascorbic Acid; Behavior Therapy; Child; Chronic Disease; Common Cold; Developmental Disabilities; Humans; Minerals; Neoplasms; Orthomolecular Therapy; Risk Factors

Topics: Adolescent; Ascorbic Acid; beta Carotene; Carotenoids; Connective Tissue; Humans; Neoplasms; Oxidation-Reduction; Phagocytes; Smoking; Vitamin E

Topics: Animals; Ascorbic Acid; Calcium; Humans; Lipid Metabolism; Neoplasms; Selenium; Trace Elements; Vitamin A; Vitamin D; Vitamin E; Vitamins; Zinc

The mass of experimental data on various possibilities of inhibiting the carcinogenic process is growing rapidly. However, the biological complexity of carcinogenesis and the intrinsic limitations of the animal models make it often very difficult to identify the real potentially effective agents among the hundreds currently being proposed. In fact, more than 600 potentially chemopreventive agents have been identified and approximately 30 of them are presently being tested in humans. The great heterogeneity of these compounds (they belong to over 20 different classes of chemicals) might be a positive feature as it indicates that a variety of approaches is possible and that the options for selecting effective compounds will be numerous. In recent years, what could be called 'clinical chemoprevention' (that is controlled studies to evaluate in human subjects the efficacy of potentially chemopreventive agents) has developed considerably: according to American estimates 4 chemopreventive agents were tested clinically in 1981, 10 in 1985 and 18 in 1988. The number of reported preclinical investigations was 10 in 1985 and 75 in 1988. This rapid expansion has obviously led to some confusion in terminology and in the evaluation of primary results; at present there is still a need for further investigations to better define clinical chemoprevention and to differentiate it from chemotherapy.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Hormones; Humans; Indoles; Neoplasms; Phenols; Protease Inhibitors; Retinoids; Selenium; Vitamin E

Topics: Animals; Ascorbic Acid; Feeding Behavior; Humans; Neoplasms; Nutritional Physiological Phenomena; Research; Selenium; Vitamin A; Vitamin E

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cocarcinogenesis; Humans; Neoplasms; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamin E Deficiency

Topics: Animals; Antioxidants; Ascorbic Acid; Combined Modality Therapy; Gastrointestinal Neoplasms; Humans; Neoplasms; Nitrosamines

This review focuses on specific effects of diet on cancer risk and the relevance of these dietary effects to the risk of cancer in the elderly. The authors address the impact of certain dietary factors on cancer risk by reviewing their roles in two distinct phases of carcinogenesis: "imitation" and "promotion."

Topics: Age Factors; Aged; Aged, 80 and over; Animals; Ascorbic Acid; Calcium, Dietary; Carcinogens; Colonic Neoplasms; Diet; Dietary Fats; Dietary Fiber; Female; Food Contamination; Humans; Male; Mice; Neoplasms; Nitrosamines; Nutritional Physiological Phenomena; Rectal Neoplasms

The potential for chemical intervention (chemoprevention) as a means of halting or delaying the process of carcinogenesis is assessed as a strategy for reducing the incidence of human cancer. The process of carcinogenesis is dissected into its constituent steps, thereby exposing sites for intervention. These sites are then critically discussed with regard to the existence of chemicals active at these sites using data gained from the laboratory and from epidemiological studies, intrinsic problems or advantages associated with intervention at specific sites in the carcinogenic process, and practical aspects of intervention in humans. The design and potential long-term positive and negative consequences of chemoprevention clinical trials are critically discussed, with the objective of exposing the major differences that exist between clinical trials in cancer chemoprevention and those in cancer chemotherapy. Results of completed prevention trials and details of ongoing trials are presented and discussed. Based on the laboratory, epidemiological, and clinical evidence presented, it is concluded that chemoprevention offers excellent prospects as a means of reducing cancer incidence. Among currently available agents, the retinoids possess the best combination of properties. However, much more research is needed to optimize drugs and protocols and to develop interim end points for assessing response. The authors finally caution that overambitious claims for the prospects for chemoprevention may lead to reduced emphasis on the need for changes in life-style (principally in smoking and diet) that are viewed as having the greatest potential for reducing cancer incidence.

Topics: Anti-Inflammatory Agents; Ascorbic Acid; Biotransformation; Carcinogens; Carotenoids; Cost-Benefit Analysis; Humans; Neoplasms; Nitrosamines; Protease Inhibitors; Research Design; Retinoids; Risk; Selenium; Sulfhydryl Compounds; Vitamin E

It has been estimated that 35% of all cancer incidence is related to diet. The potential appears great that high intakes of various nutrients can reduce the incidence of some types of cancer. Selenium and vitamins A, C, and E, discussed in this article, have many actions and interactions that are important in relationship to the study of nutrition and cancer. Even though only a few of the necessary human trials of efficacy have been conducted, epidemiological and animal data suggest that vitamins and/or minerals act as anticarcinogens, altering cancer incidence, differentiation, and growth. Thus, they may prove useful adjuncts to conventional therapies or in cancer prevention. However, the nutrients should not be viewed as cure-alls that work alone. Adequate intake ideally should be the result of increased dietary consumption rather than supplements because as yet unidentified components found in food may prove beneficial and protective. More research is needed prior to encouraging members of the general population to increase their intakes of various nutrients, even though there is now some evidence that those nutrients may help prevent some cancers.

Topics: Animals; Ascorbic Acid; Diet; Food Analysis; Humans; Neoplasms; Nutritional Requirements; Retinoids; Selenium; Vitamin A; Vitamin E

The data on the influence of antioxidant vitamins (E and C) on the growth of induced and transplantable tumours in animals and on the development of cancer process in man as well as on the course of chemo- and radiotherapy are analyzed; a degree of vitamin provision of the tumour-bearing organism is discussed. Special attention is paid to optimal doses of the above mentioned vitamins. The necessity of combined application of antioxidant vitamins in cancer therapy is established.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Transformation, Neoplastic; Dose-Response Relationship, Drug; Drug Evaluation; Drug Synergism; Humans; Lipid Metabolism; Lipid Peroxides; Mice; Neoplasms; Neoplasms, Experimental; Nitrosamines; Oxidation-Reduction; Oxidative Phosphorylation; Rabbits; Rats; Tissue Distribution; Vitamin E; Vitamin E Deficiency

Topics: Adult; Ascorbic Acid; Calcium; Clinical Trials as Topic; Drug Therapy; Education, Nursing, Continuing; Female; Folic Acid; Humans; Male; Neoplasms; Oncology Nursing; Research; Retinoids; Selenium; Tamoxifen; Vitamin A; Vitamin D; Vitamin E

Topics: Animals; Ascorbic Acid; Benzopyrene Hydroxylase; beta Carotene; Carcinogens; Carotenoids; Chemical Phenomena; Chemistry; Diet; Dietary Fiber; DNA; Food; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Hot Temperature; Humans; Inactivation, Metabolic; Neoplasms; Nitrosamines; Nitroso Compounds; Phenols; Phytosterols; Protease Inhibitors; Selenium; Vegetables; Vitamin A; Vitamin E

Evidence pertaining to the role of dietary factors in carcinogenesis comes from both epidemiological studies and laboratory experiments. In 1982, the Committee on Diet, Nutrition, and Cancer of the National Research Council conducted a comprehensive evaluation of this evidence. That assessment as well as recent epidemiological and laboratory investigations suggest that a high fat diet is associated with increased susceptibility to cancer of different sites, particularly the breast and colon, and to a lesser extent, the prostate. Current data permit no definitive conclusions about other dietary macroconstituents including cholesterol, total caloric intake, protein, carbohydrates and total dietary fiber. Specific components of fiber, however, may have a protective effect against colon cancer. In epidemiological studies, frequent consumption of certain fruits and vegetables, especially citrus fruits and carotene-rich and cruciferous vegetables, is associated with a lower incidence of cancers at various sites. The specific components responsible for these effects are not clearly identified, although the epidemiological evidence appears to be most consistent for a protective effect of carotene on lung cancer and less so for vitamins A and C and various cancer sites. The laboratory evidence is most consistent for vitamin A deficiency and enhanced tumorigenesis, and for the ability of various nonnutritive components in cruciferous vegetables to block in-vivo carcinogenesis. The data for minerals and carcinogenesis are extremely limited, although preliminary evidence from both epidemiological and laboratory studies suggests that selenium may protect against overall cancer risk. Frequent consumption of cured, pickled, or smoked foods, possibly because they may contain nitrosamines or polycyclic aromatic hydrocarbons, appears to increase the risk of esophageal or stomach cancer, however, the specific causative agents in these foods are not clearly identified. Excessive alcohol consumption among smokers appears to be associated with an elevated risk of cancers of the oral cavity, esophagus, larynx, and respiratory tract. The mechanisms of action of dietary factors on carcinogenesis are poorly understood. The NRC committee, and more recently, the National Cancer Institute and the American Cancer Society have proposed interim dietary guidelines to lower the risk of cancer. These guidelines are consistent with general dietary recommendations proposed by U.S. government

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Calcium; Carcinogens; Cholesterol; Colonic Neoplasms; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; Energy Intake; Environmental Pollutants; Ethanol; Food; Forecasting; Humans; Iron; Minerals; Mutagens; Neoplasms; Nutritional Physiological Phenomena; Research; Retinoids; Risk; Selenium; Vitamin D; Vitamin E; Vitamins; Zinc

Carcinogenicity tests showed that addition of the antioxidant BHA to the diet of F344 rats induced high incidences of papilloma and squamous cell carcinoma of the forestomach of both sexes. Male hamsters given BHA for 24 weeks also developed papilloma showing downward growth into the submucosa of the forestomach. These results indicate that BHA should be classified in the category of "sufficient evidence of carcinogenicity" as judged by IARC criteria. The 3-tert isomer of BHA seemed to be responsible for the carcinogenicity of crude BHA in the forestomach of rats. BHT was not found to be carcinogenic in rats or mice. In two-stage carcinogenesis in rats after appropriate initiation, BHA enhanced carcinogenesis in the forestomach and urinary bladder of rats, but inhibited carcinogenesis in the liver. BHT enhanced the induction of urinary bladder tumors and inhibited that of liver tumors, but had no effect on carcinogenesis in the forestomach. BHT could be a promoter of thyroid carcinogenesis. Sodium L-ascorbate enhanced forestomach and urinary bladder carcinogenesis. Ethoxyquin enhanced kidney and urinary bladder carcinogenesis, but inhibited liver carcinogenesis. Thus, these antioxidants modify two-stage chemical carcinogenesis in the forestomach, liver, kidney, urinary bladder, and thyroid, but show organ-specific differences in effects.

Topics: Animals; Anisoles; Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Cocarcinogenesis; Drug Synergism; Humans; Kidney Neoplasms; Liver Neoplasms; Methylnitrosourea; Neoplasms; Species Specificity; Stomach Neoplasms; Urinary Bladder Neoplasms

This monograph on the clinical chemistry of vitamin B12 reviews the literature on daily requirements, methods for measurement, the effects of drugs on vitamin B12 metabolism absorption, pregnancy, clinical conditions associated with vitamin B12 deficiency, errors of metabolism, and reactions to vitamin therapy. Although only very small quantities of vitamin B12 are required to satisfy the daily requirement, a sufficient supply is stored in the liver to meet normal requirements for at least a 3-year period. A number of drugs are known to affect the absorption of vitamin B12, including neomycin, potassium chloride, p-aminosalicylic acid, and colchicine. Significantly reduced serum concentrations of vitamin B12 have been noted in users of oral contraceptives (OCs), although concentrations still remain within the limits of normal. It appears that the vitamin B12 level in OC users reestablishes itself at a different and somewhat lower level. Vitamin B12 binding protein appears to remain unchanged. A vitamin B12 deficiency is unusual in pregnant women who consume a normal, varied diet. On the other hand, lactating women whose diets are low in animal protein and dairy products may have problems providing enough vitamin B12 to meet their own and their infant's needs; supplementary oral vitamins should be considered.

Topics: Absorption; Adult; Alcoholism; Anemia, Pernicious; Ascorbic Acid; Autoantibodies; Biguanides; Biological Transport; Chemical Phenomena; Chemistry; Chlorpromazine; Contraceptives, Oral; Diet; Female; Gastrectomy; Gastritis; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Middle Aged; Neoplasms; Nervous System Diseases; Nitrous Oxide; Nutritional Requirements; Pancreatic Diseases; Parasitic Diseases; Pregnancy; Pregnancy Complications; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Vitamins are a group of organic compounds occurring naturally in food and are necessary for good health. Lack of a vitamin may lead to a specific deficiency syndrome, which may be primary (due to inadequate diet) or secondary (due to malabsorption or to increased metabolic need), and it is rational to use high-dose vitamin supplementation in situations where these clinical conditions exist. However, pharmacological doses of vitamins are claimed to be of value in a wide variety of conditions which have no, or only a superficial, resemblance to the classic vitamin deficiency syndromes. The enormous literature on which these claims are based consists mainly of uncontrolled clinical trials or anecdotal reports. Only a few studies have made use of the techniques of randomisation and double-blinding. Evidence from such studies reveals a beneficial therapeutic effect of vitamin E in intermittent claudication and fibrocystic breast disease and of vitamin C in pressure sores, but the use of vitamin A in acne vulgaris, vitamin E in angina pectoris, hyperlipidaemia and enhancement of athletic capacity, of vitamin C in advanced cancer, and niacin in schizophrenia has been rejected. Evidence is conflicting or inconclusive as to the use of vitamin C in the common cold, asthma and enhancement of athletic capacity, of pantothenic acid in osteoarthritis, and folic acid (folacin) in neural tube defects. Most of the vitamins have been reported to cause adverse effects when ingested in excessive doses. It is therefore worthwhile to consider the risk-benefit ratio before embarking upon the use of high-dose vitamin supplementation for disorders were proof of efficacy is lacking.

Topics: Acne Vulgaris; Ascorbic Acid; Asthma; Cardiovascular Diseases; Common Cold; Fibrocystic Breast Disease; Humans; Neoplasms; Osteoporosis; Vitamin A; Vitamin B Complex; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Animals; Ascorbic Acid; Carotenoids; Diet; Epidemiologic Methods; Feeding Behavior; Humans; Neoplasms; Random Allocation; Research Design; Vitamin A; Vitamin E

Topics: Alcohol Drinking; Ascorbic Acid; Coffee; Diet; Dietary Fats; Humans; Neoplasms; Risk; Saccharin; Vegetables; Vitamin A

Skin carcinogenesis can be operationally and mechanistically divided into at least three stages; tumor initiation, stage I and stage II of promotion. Current information suggests that reactive intermediates of skin tumor initiators are mutagenic and bind convalently to DNA of epidermal stem cells (dark basal keratinocytes) leading to some irreversible alteration in the differentiation capacity of these cells. Inhibitors of skin tumor initiation by polycyclic aromatic hydrocarbons (PAH) decrease the level of the PAH diol-epoxide bound to specific DNA adducts. The tumor promoters have been shown to have many cellular and biochemical effects in the skin. Recent data suggests that free radicals may be important in skin tumor promotion. The first stage of promotion is partially irreversible and can be accomplished by a single treatment of a tumor promoter such as TPA or by non-promoting agents such as 4-0-methyl-TPA, calcium ionophore A23187, and hydrogen peroxide, as well as wounding. These agents increase the number of dark basal keratinocytes, which suggest that these cells are important in the first stage of promotion. Prostaglandin E2 was found to specifically enhance stage I of promotion whereas the protease inhibitor tosyl phenylalanine chloromethylketone (TPCK) specially inhibited stage I of promotion and the TPA-induced dark basal keratinocytes. The second stage of promotion is initially reversible but later becomes irreversible. The weak promoting agent mezerein is an effective stage II promoter. Polyamines and epidermal cell proliferation appear to be important events in stage II of promotion. Putrescine was found to specifically enhance stage II, whereas retinoic acid (RA), diflouromethylornithine (DFMO), and butylated hydroxyanisole (BHA) specially inhibited stage II of promotion and the mezerein-induced polyamine levels. Floucinolone acetonide (FA) was found to inhibit both stages but was more effective in counteracting stage I of promotion. Although, TPA can cause a decrease in the number of glucocorticoid receptors during promotion, FA can effectively prevent this loss. Recent data suggest that skin tumor promotion can be effectively inhibited by a combination of stage I and II inhibitors. Furthermore, skin carcinogenesis can be counteracted by a combination of low and nontoxic doses of BHA, TPCK, DFMO and vitamin E.

Topics: Animals; Ascorbic Acid; Carcinogens; Disease Models, Animal; Humans; Neoplasms; Phorbol Esters; Selenium; Skin Neoplasms; Vitamin E

Topics: Animals; Ascorbic Acid; Diet; Female; Humans; Immunity, Cellular; Male; Mice; Neoplasms; T-Lymphocytes; Vitamin A; Vitamin E

Optimum nutrition is the level of intake that should promote the highest level of health. Although excess caloric intake will lead to obesity, a deficit in nutrition may result in a tissue depletion of essential nutrients that can lead to biochemical changes and eventually to clinical signs and symptoms. Nutrition requirements may differ according to sex, age, activity, or physiological state and can be influenced by drugs, smoking, alcohol, and other factors. With ever-increasing sedentary life styles and less physically demanding jobs, the resulting reduced caloric requirements have made it more difficult to make nutritionally sound food choices. Nutrition is the single most important component of preventive health care. Diet has been associated with cancer, heart disease, diabetes, stroke and hypertension, arteriosclerosis, and cirrhosis of the liver. The ability of the human to respond to stresses, such as altitude, heat, trauma, surgery, and infection can be influenced by nutritional status. Nutritional status is reflected in a variety of metabolic processes that provide the basis for a number of methods for its assessment.

Topics: Alcoholism; Anemia, Hypochromic; Animals; Ascorbic Acid; Avitaminosis; Climate; Dietary Fats; Female; Folic Acid; Food Additives; Health; Humans; Immunocompetence; Lactation; Male; Neoplasms; Nutritional Physiological Phenomena; Nutritional Requirements; Obesity; Physical Exertion; Pregnancy; Protein-Energy Malnutrition; Pyridoxine; Riboflavin; Smoking; Stress, Physiological; Thiamine; Trace Elements; Vitamin A; Vitamins; Zinc

I have attempted to address in brief fashion the question as to whether we can recommend a dietary prevention of cancer. This same question was explored in hundreds of pages recently by the large number of advisors assembled by the National Academy of Sciences to assess the animal, cell culture, and human data with regard to diet and cancer (52). My brief assessment has resulted in recommendations to the scientific community not unlike those of the National Academy, but without their clear-cut recommendation against dietary fat. It is obvious that we need a great deal more research on the factors evaluated here, that is, fiber, ascorbic acid, retinoids, the cruciferae, nitrates, alcohol, coffee, saccharine, alpha-tocopherol, aflatoxins, selenium, and saturated and polyunsaturated fats. These factors need assessment not only as they might affect the incidence of any single cancer, but also in relationship to at least the incidence of the cancers that frequently occur in humans. The human epidemiologic inquires have barely begun. We have a few studies of cancer of the colon and of cancer of the lung, and only one or two studies of such important sites as cancer of the larynx, oropharynx, stomach, and breast. Not only have the studies of specific sites been lamentably too few, but only a small number of nutrients have been evaluated. To make matters worse, we have little notion as to the competing risk of different cancers and of other diseases associated with various nutrients. There may be factors that enhance the risk of some diseases at the same time they reduce the risk of others. It is not outside the realm of possibility that the relationship discovered to date with regard to serum cholesterol, heart disease, and cancer may continue to be replicated and may be found related to ingestion of dietary fats. If such should be the case, and the potential is there, we would need to weigh the risks associated with reducing dietary fats for cancer as well as for coronary disease. Questions will need to be answered. For example, what is the optimum level of serum cholesterol to lower the risk of heart disease and at the same time not to enhance the risk of cancer. The same may be said for the association of alcohol with the risk of coronary disease compared to the risk of cancer of the upper alimentary tract.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Alcohol Drinking; Animals; Ascorbic Acid; Coffee; Diet; Dietary Fats; Dietary Fiber; Food Additives; Food Preservatives; Humans; Neoplasms; Retinoids; Risk; United States; Vegetables

The evidence provided by epidemiologic studies and observations in human populations as well as the more controlled studies in animals point to some effects of vitamins C and E, and of selenium, on cancer. The nature of this relationship is not clear at present, but ongoing epidemiologic and experimental work should help to clarify these interrelationships.

Topics: Animals; Ascorbic Acid; Diet; Humans; Neoplasms; Neoplasms, Experimental; Risk; Selenium; Vitamin E

Topics: Animals; Ascorbic Acid; Carcinogens; Diet; Humans; Neoplasms; Neoplasms, Experimental; Nitrosamines

Topics: Anorexia; Ascorbic Acid; Cachexia; Drug-Related Side Effects and Adverse Reactions; Enteral Nutrition; Female; Humans; Lipid Metabolism; Male; Minerals; Neoplasms; Nutrition Disorders; Parenteral Nutrition; Pyridoxine; Serum Albumin; Taste Disorders; Thiamine; Vitamin A

The outcome of every cancer illness is determined to a significant extent by the inherent resistance of the individual patient to his or her disease. There is increasing recognition that resistance to cancer depends, to a certain extent, upon the availability of certain nutritional factors, of which ascorbic acid appears to be the most important. Ascorbic acid protects against the destructive effects of malignant invasiveness by stabilizing the ground substance and enhancing collagen encapsulation. It is also involved in the mechanisms of both cell-mediated and humoral immunity including the production of interferon, and other factors either known or thought to be involved collectively in host resistance to neoplasia. There is also some recent evidence suggesting that ascorbate exerts a selective cytotoxic effect against malignant cells. All these observations indicate that supplemental ascorbate should be of some therapeutic value in the treatment of cancer. Clinical trials conducted over the last decade are briefly reviewed, and the balance of evidence supports this contention. It is predicted that in the not-to-distant future, supplemental ascorbate will attain an established place in all comprehensive cancer treatment regimes.

Topics: Adenocarcinoma, Scirrhous; Animals; Anti-Infective Agents; Antiviral Agents; Ascorbic Acid; Cell Survival; Collagen; Complement System Proteins; Feedback; Humans; Immunity, Cellular; Immunoglobulins; Interferons; Neoplasms; Prostaglandins

Topics: Administration, Oral; Antineoplastic Agents; Ascorbic Acid; Dose-Response Relationship, Drug; Humans; Infusions, Parenteral; Neoplasms

Topics: Administration, Oral; Animals; Ascorbic Acid; Carcinogens; Drug Interactions; Gastric Mucosa; Humans; Mice; Mutagens; Neoplasms; Nitrites; Nitroso Compounds; Pharmaceutical Preparations; Rabbits; Rats

Topics: Animals; Animals, Laboratory; Ascorbic Acid; Breast Neoplasms; Carcinogens; Colonic Neoplasms; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Female; Humans; Male; Mammary Neoplasms, Experimental; Mice; Neoplasms; Neoplasms, Experimental; Rats; Selenium; Vitamin A

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Mice; Neoplasms; Neoplasms, Experimental

Ascorbic acid in physiological doses is essential for the normal functioning of the human body. Larger doses are required to treat a severe deficiency of vitamin C intake, as in the case of scurvy. Occasionally, massive doses may be required to treat a metabolic defect involving ascorbic acid. There has been some mention of megadose therapy with ascorbic acid for the prevention of colds, the improved healing of wounds and even the treatment of cancer, but no acceptable scientific data have been presented. In fact, in a few instances, such therapy has proved injurious.

Topics: Ascorbic Acid; Chediak-Higashi Syndrome; Common Cold; Female; Humans; Immunity; Infant; Male; Neoplasms; Scurvy; Wound Healing

Host resistance to neoplastic growth and invasiveness is recognized to be an important factor in determining the occurrence, the progress, and the eventual outcome of every cancer illness. The factors involved in host resistance are briefly reviewed, and the relationship between these factors and ascorbic acid metabolism is presented in detail. It is shown that many factors involved in host resistance to neoplasia are significantly dependent upon the availability of ascorbate.

Topics: Animals; Ascorbic Acid; Carcinogens; Collagen; Extracellular Space; History, 18th Century; History, 20th Century; Humans; Hyaluronoglucosaminidase; Immunity; Neoplasm Invasiveness; Neoplasms; Pituitary-Adrenal System; Scurvy

Topics: Ammonia; Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Colonic Neoplasms; Copper; Cricetinae; Dietary Fats; Dietary Fiber; Dietary Proteins; Energy Intake; Female; Humans; Iodine; Lipotropic Agents; Liver Neoplasms; Mammary Neoplasms, Experimental; Mice; Neoplasms; Neoplasms, Experimental; Nutritional Physiological Phenomena; Rats; Riboflavin; Selenium; Skin Neoplasms; Vitamin A; Vitamin B Complex; Zinc

As the second leading cause of death in the United States, cancer is a major public health problem today. Cancer incidence varies worldwide and tends to change with migration. These epidemiological observations have led to the concept that environmental factors may be important in carcinogenesis. Diet and nutrition are receiving increased attention and the National Cancer Institute, as mandated by the Nation Cancer Act Amendments of 1974, is playing a major leadership role in expanding research efforts in the areas of environmental carcinogenesis, and nutrition in relation to cancer. The subject of diet, nutrition, and cancer is complex. Different types of cancer are not necessarily affected by dietary components in the same manner. Although the development of certain neoplasms may be repressed by specific dietary deficiencies, other types, particularly those of the liver and upper gastrointestinal tract, are actually augmented or potentiated by such deficienceis. In extrapolating results from animal experiments to humans, caution must be exercised because of possible differences in species response to the same dietary stimulus and because spontaneous tumors may react differently from experimentally-induced tumors. Diet and nutrition are viewed more appropriately as modifiers, rather than initiators, of tumorigenesis. Caloric intake, type and amount of fat, protein, amino acids, vitamins, minerals, fiber, and other dietary constituents have been studied in regard to their influence on the development of neoplasms. Dietary components may have opposing effects on tumorigenesis, i.e., protective and predisposing, and the consequence to the host will depend on the balance between these opposing forces. Studies conducted to date indicate that the modifying effect of diet and nutrition may be exerted through specific effects on 1) intestinal bacteria and substrates for bacterial metabolism, 2) microsomal mixed-function oxidase system, 3) endocrine system, 4) immunological system, 5) availability of metabolites for cell proliferations, and 6) rate of carcinogen transfer and duration of exposure to the carcinogen. More research is needed to elucidate the interaction between diet and each of these factors and to test the validity of the mechanisms proposed to explain such interactions. These studies will lead not only to a better understanding of carcinogenesis itself but also to a new understanding of the influence of diet on human physiology and metabolism.

Topics: Animals; Ascorbic Acid; Bile Acids and Salts; Cholesterol; Diet; Dietary Fats; Digestive System; Energy Metabolism; Forecasting; Humans; Hypercholesterolemia; Intestines; Neoplasms; Nutrition Disorders; Nutritional Physiological Phenomena; Polysaccharides; Vitamin A; Vitamin A Deficiency; Vitamin B Complex; Vitamin B Deficiency

The relationship of vitamins to cancer is very complex. Three types of interactions are possible: the effect of vitamins on tumor growth, the effect of tumors on vitamin metabolism, and the effect of vitamins on chemical carcinogens and anti-tumor chemotherapeutic agents. The significance of vitamins with particular references to vitamins A,B-complex and C, in cancer has been reviewed.

Topics: Antineoplastic Agents; Ascorbic Acid; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Bronchial Neoplasms; Humans; Neoplasms; Nutritional Physiological Phenomena; Tryptophan; Vitamin A; Vitamin B Complex; Vitamin B Deficiency; Vitamins

Topics: Anti-Bacterial Agents; Antiviral Agents; Ascorbic Acid; Follow-Up Studies; Humans; Hyaluronoglucosaminidase; Immunity; Lymphocytes; Neoplasms; Steroids; Time Factors

Topics: Animals; Ascorbic Acid; Cell Division; Glycosaminoglycans; Hormones; Humans; Hyaluronoglucosaminidase; Neoplasms; Neoplasms, Experimental; Scurvy

Topics: Acid-Base Equilibrium; Acidosis; Alkalosis; Ascorbic Acid; Cell Division; Cell Membrane; Cystine; Cytosol; Electron Transport; Galactose; Glucose; Glutathione; Homeostasis; Humans; Hypoxia; Lactates; Lysosomes; Mitochondria; NAD; Neoplasms; Oxidation-Reduction; Oxygen Consumption; Proteins; Pyruvates; Sulfhydryl Compounds

Topics: Ascorbic Acid; Aspergillus; Biochemical Phenomena; Biochemistry; Carcinogens; Glycosides; Humans; Ketones; Lactones; Neoplasms; Neoplasms, Experimental; Penicillins; Research

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinoma 256, Walker; Guinea Pigs; Leukemia; Neoplasms; Neoplasms, Experimental; Rats; Research; Sarcoma; Sarcoma, Experimental; Sarcoma, Yoshida

High-dose intravenously (i.v) vitamin C in cancer patients is controversial. Numerous studies carried out on cancer cell lines and animal models demonstrated that millimolar vitamin C concentrations inhibit tumor cells viability, especially in association with chemotherapy. In cancer patients, high-dose i.v vitamin C in monotherapy does not show any anti-cancer activity. Clinical trials assessing high-dose i.v vitamin C concomitantly with chemotherapy do not conclude to reliable evidence for tumor control or overall survival benefit. Randomized double-blind trials are warranted.. La vitamine C administrée par voie intraveineuse (IV) chez les patients atteints de cancer est controversée. De nombreux travaux effectués sur des lignées cellulaires cancéreuses et des modèles animaux montrent que des concentrations plasmatiques pharmacologiques (≥ 15 mmol/l) de vitamine C sont capables de diminuer la viabilité des cellules cancéreuses. Chez les patients atteints de cancer, l’administration d’une haute dose IV de vitamine C seule ne montre pas de signe d’activité antitumorale. Elle a également été étudiée en association avec de la chimiothérapie, mais les essais cliniques réalisés ne permettent pas de conclure à un bénéfice pour les patients en termes de contrôle de la maladie oncologique ou de survie. Des études randomisées contre placebo et en double aveugle sont indispensables.

Topics: Administration, Intravenous; Animals; Antineoplastic Agents; Ascorbic Acid; Humans; Neoplasms; Vitamins

Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1-100 g.. A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. Healthy participants received IVC infusions of 1-100 g; oncology participants received IVC infusions of 25-100 g. Serial blood and complete urine samples were collected pre-infusion and for 24 h post-infusion. Pharmacokinetic parameters were computed using noncompartmental methods. Adverse events were monitored during the study.. In both cohorts, IVC exhibited first-order kinetics at doses up to 75 g. At 100 g, maximum concentration (C. IVC followed first-order pharmacokinetics up to 75 g and at up to 100 g had complete renal clearance in 24 h. IVC up to 100 g elicited no adverse effects or significant physiological/biochemical changes and appears to be safe. These data can be used to rectify existing misinformation and to guide future clinical trials.. ClinicalTrials.gov identifier number NCT01833351.

Topics: Administration, Intravenous; Area Under Curve; Ascorbic Acid; Healthy Volunteers; Humans; Infusions, Intravenous; Neoplasms

To investigate the antioxidant role in reversing cytogenetic changes caused by solvent exposure in paint industry.. A prospective controlled clinical trial was performed on 39 workers exposed to solvents and 39 workers not exposed to solvents by supplying a mixture of antioxidant vitamins (A, C, E and selenium) and the after effects of such regimen were analyzed. Environmental monitoring was carried out for air concentrations of different solvents at workplace. Exposed group was cytogenetically tested before and after giving the mixture of antioxidant vitamins for 1 month duration.. Frequency of chromosomal aberrations (CAs) and the mean of sister chromatid exchanges (SCEs) were statistically significantly higher among exposed workers than among controls. After the supplementation of antioxidants, there was a statistically significant decrease in the frequency of CAs, and 88% abnormal levels of SCEs were back to normal levels.. Antioxidant supplementation decreases the frequency of CAs and SCEs among exposed workers.

Topics: Air Pollutants, Occupational; Air Pollution, Indoor; Antioxidants; Ascorbic Acid; Chromosome Aberrations; Dietary Supplements; Directly Observed Therapy; Egypt; Environmental Monitoring; Humans; Ink; Male; Middle Aged; Mutagens; Neoplasms; Occupational Exposure; Paint; Selenium; Sister Chromatid Exchange; Solvents; Vitamin A; Vitamin E

Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials.. ClinicalTrials.gov NCT01050621.

Topics: Aged; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasms; Quality of Life; Tissue Distribution

Recent posttrial analysis of a completed randomized trial found an increased risk of prostate cancer among healthy men taking high-dose vitamin E supplements. Trials that examined the effect of vitamin C supplements on cancer risk are few.. We examined whether vitamin E or vitamin C supplementation affects the risk of cancer events during posttrial follow-up of the Physicians' Health Study II.. Beginning in 1997, a total of 14,641 US male physicians aged ≥50 y were randomly assigned to receive 400 IU of vitamin E every other day, 500 mg of vitamin C daily, or their respective placebos. The vitamin E and vitamin C treatment ended in 2007, and observational follow-up continued through June 2011.. This study included an additional 356 cases of incident prostate cancer and 771 total cancers that developed during a mean (maximum) of 2.8 (3.8) y of posttrial observation. During an overall mean of 10.3 (13.8) y, there were a total of 1373 incident prostate cancers and 2669 total cancers documented. In comparison with placebo, vitamin E supplementation had no effect on the incidence of prostate cancer (HR: 0.99; 95% CI: 0.89, 1.10) or total cancers (HR: 1.02; 95% CI: 0.95, 1.10). There was also no effect of vitamin C supplementation on total cancers (HR: 1.02; 95% CI: 0.94, 1.10) or incident prostate cancer (HR: 1.03; 95% CI: 0.93, 1.15). Neither vitamin E nor vitamin C supplementation had effects on other site-specific cancers overall. Stratification by known cancer risk factors, history of cancer, other randomized treatment, and follow-up time showed no significant interactions.. In this large-scale randomized trial in men, vitamin E and C supplementation had no immediate or long-term effects on the risk of total cancers, prostate cancer, or other site-specific cancers.

Topics: Aged; Antioxidants; Ascorbic Acid; Cohort Studies; Dietary Supplements; Double-Blind Method; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neoplasms; Physicians; Prostatic Neoplasms; Risk Factors; United States; Vitamin E

This phase I clinical trial evaluated the safety, tolerability, and pharmacokinetics of high-dose intravenous (i.v.) ascorbic acid as a monotherapy in patients with advanced solid tumors refractory to standard therapy.. Five cohorts of three patients received i.v. ascorbic acid administered at 1 g/min for 4 consecutive days/week for 4 weeks, starting at 30 g/m² in the first cohort. For subsequent cohorts, dose was increased by 20 g/m² until a maximum tolerated dose was found.. Ascorbic acid was eliminated by simple first-order kinetics. Half-life and clearance values were similar for all patients of all cohorts (2.0 ± 0.6 h, 21 ± 5 dL/h m², respectively). C(max) and AUC values increased proportionately with dose between 0 and 70 g/m², but appeared to reach maximal values at 70 g/m² (49 mM and 220 h mM, respectively). Doses of 70, 90, and 110 g/m² maintained levels at or above 10-20 mM for 5-6 h. All doses were well tolerated. No patient demonstrated an objective antitumor response.. Ascorbic acid administered i.v. at 1 g/min for 4 consecutive days/week for 4 weeks produced up to 49 mM ascorbic acid in patient's blood and was well tolerated. The recommended dose for future studies is 70-80 g/m².

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Antioxidants; Ascorbic Acid; Cohort Studies; Disease Progression; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Half-Life; Humans; Infusions, Intravenous; Male; Metabolic Clearance Rate; Middle Aged; Neoplasm Staging; Neoplasms; Quality of Life

Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.. To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.. The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.. Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.. Prostate and total cancer.. During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.. In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men.. clinicaltrials.gov Identifier: NCT00270647.

Topics: Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Dietary Supplements; Double-Blind Method; Humans; Longitudinal Studies; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Treatment Outcome; Vitamin E

Observational studies suggested that a diet high in fruits and vegetables, both of which are rich with antioxidants, may prevent cancer development. However, findings from randomized trials of the association between antioxidant use and cancer risk have been mostly negative.. From 8171 women who were randomly assigned in the Women's Antioxidant Cardiovascular Study, a double-blind, placebo-controlled 2 x 2 x 2 factorial trial of vitamin C (500 mg of ascorbic acid daily), natural-source vitamin E (600 IU of alpha-tocopherol every other day), and beta carotene (50 mg every other day), 7627 women who were free of cancer before random assignment were selected for this study. Diagnoses and deaths from cancer at a specific site were confirmed by use of hospital reports and the National Death Index. Cox proportional hazards regression models were used to assess hazard ratios (represented as relative risks [RRs]) of common cancers associated with use of antioxidants, either individually or in combination. Subgroup analyses were conducted to determine if duration of use modified the association of supplement use with cancer risk. All statistical tests were two-sided.. During an average 9.4 years of treatment, 624 women developed incident invasive cancer and 176 women died from cancer. There were no statistically significant effects of use of any antioxidant on total cancer incidence. Compared with the placebo group, the RRs were 1.11 (95% confidence interval [CI] = 0.95 to 1.30) in the vitamin C group, 0.93 (95% CI = 0.79 to 1.09) in the vitamin E group, and 1.00 (95% CI = 0.85 to 1.17) in the beta carotene group. Similarly, no effects of these antioxidants were observed on cancer mortality. Compared with the placebo group, the RRs were 1.28 (95% CI = 0.95 to 1.73) in the vitamin C group, 0.87 (95% CI = 0.65 to 1.17) in the vitamin E group, and 0.84 (95% CI = 0.62 to 1.13) in the beta carotene group. Duration and combined use of the three antioxidants also had no effect on cancer incidence and cancer death.. Supplementation with vitamin C, vitamin E, or beta carotene offers no overall benefits in the primary prevention of total cancer incidence or cancer mortality.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Incidence; Middle Aged; Neoplasms; Primary Prevention; Proportional Hazards Models; Risk Assessment; Risk Factors; United States; Vitamin E

Ascorbic acid is frequently administered intravenously by alternative health practitioners and, occasionally, by mainstream physicians. Intravenous administration can greatly increase the amount of ascorbic acid that reaches the circulation, potentially increasing the risk of oxalate crystallization in the urinary space. To investigate this possibility, we developed gas chromatography mass spectrometry methodology and sampling and storage procedures for oxalic acid analysis without interference from ascorbic acid and measured urinary oxalic acid excretion in people administered intravenous ascorbic acid in doses ranging from 0.2 to 1.5 g/kg body weight. In vitro oxidation of ascorbic acid to oxalic acid did not occur when urine samples were brought immediately to pH less than 2 and stored at -30 degrees C within 6 hours. Even very high ascorbic acid concentrations did not interfere with the analysis when oxalic acid extraction was carried out at pH 1. As measured during and over the 6 hours after ascorbic acid infusions, urinary oxalic acid excretion increased with increasing doses, reaching approximately 80 mg at a dose of approximately 100 g. We conclude that, when studied using correct procedures for sample handling, storage, and analysis, less than 0.5% of a very large intravenous dose of ascorbic acid is recovered as urinary oxalic acid in people with normal renal function.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Calcium Oxalate; Female; Humans; Hyperoxaluria; Injections, Intravenous; Male; Middle Aged; Neoplasms; Oxalic Acid; Urinary Calculi

The General Population Nutrition Intervention Trial was a randomized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991, in which 29,584 adult participants in Linxian, China, were given daily vitamin and mineral supplements. Treatment with "factor D," a combination of 50 microg selenium, 30 mg vitamin E, and 15 mg beta-carotene, led to decreased mortality from all causes, cancer overall, and gastric cancer. Here, we present 10-year follow-up after the end of active intervention.. Participants were assessed by periodic data collection, monthly visits by village health workers, and quarterly review of the Linxian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models.. Through May 31, 2001, 276 participants were lost to follow-up; 9727 died, including 3242 from cancer (1515 from esophageal cancer and 1199 from gastric cancer). Participants who received factor D had lower overall mortality (HR = 0.95, 95% CI = 0.91 to 0.99; P = .009; reduction in cumulative mortality from 33.62% to 32.19%) and gastric cancer mortality (HR = 0.89, 95% CI = 0.79 to 1.00; P = .043; reduction in cumulative gastric cancer mortality from 4.28% to 3.84%) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years. Esophageal cancer deaths between those who did and did not receive factor D were not different overall; however, decreased 17% among participants younger than 55 (HR = 0.83, 95% CI = 0.71 to 0.98; P = .025) but increased 14% among those aged 55 years or older (HR = 1.14, 95% CI = 1.00 to 1.30; P = .047) [corrected]. Vitamin A and zinc supplementation was associated with increased total and stroke mortality; vitamin C and molybdenum supplementation, with decreased stroke mortality.. The beneficial effects of selenium, vitamin E, and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants. Late effects of other supplementation regimens were also observed.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; China; Confounding Factors, Epidemiologic; Dietary Supplements; Diterpenes; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Malnutrition; Micronutrients; Middle Aged; Molybdenum; Neoplasms; Niacin; Odds Ratio; Retinyl Esters; Riboflavin; Risk Factors; Selenium; Vitamin A; Vitamins; Zinc Oxide

Ascorbic acid is a widely used and controversial alternative cancer treatment. In millimolar concentrations, it is selectively cytotoxic to many cancer cell lines and has in vivo anticancer activity when administered alone or together with other agents. We carried out a dose-finding phase I and pharmacokinetic study of i.v. ascorbic acid in patients with advanced malignancies.. Patients with advanced cancer or hematologic malignancy were assigned to sequential cohorts infused with 0.4, 0.6, 0.9 and 1.5 g ascorbic acid/kg body weight three times weekly.. Adverse events and toxicity were minimal at all dose levels. No patient had an objective anticancer response.. High-dose i.v. ascorbic acid was well tolerated but failed to demonstrate anticancer activity when administered to patients with previously treated advanced malignancies. The promise of this approach may lie in combination with cytotoxic or other redox-active molecules.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Neoplasms

Ascorbic acid is an essential nutrient commonly regarded as an antioxidant. In this study, we showed that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. To test this action in vivo, normal oral tight control was bypassed by parenteral ascorbate administration. Real-time microdialysis sampling in mice bearing glioblastoma xenografts showed that a single pharmacologic dose of ascorbate produced sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood. Moreover, a regimen of daily pharmacologic ascorbate treatment significantly decreased growth rates of ovarian (P < 0.005), pancreatic (P < 0.05), and glioblastoma (P < 0.001) tumors established in mice. Similar pharmacologic concentrations were readily achieved in humans given ascorbate intravenously. These data suggest that ascorbate as a prodrug may have benefits in cancers with poor prognosis and limited therapeutic options.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Female; Humans; Hydrogen Peroxide; Infusions, Intravenous; Mice; Mice, Nude; Neoplasms; Oxidants; Prodrugs; Xenograft Model Antitumor Assays

In April 2005 a phase III randomized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative stress in improving identified primary endpoints: increase of lean body mass, decrease of resting energy expenditure (REE), increase of total daily physical activity, decrease of interleukin-6 and tumor necrosis factor-alpha, and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF).. All patients were given as basic treatment polyphenols plus antioxidant agents alpha-lipoic acid, carbocysteine, and vitamins A, C, and E, all orally. Patients were then randomized to one of the following five arms: 1) medroxyprogesterone acetate/megestrol acetate; 2) pharmacologic nutritional support containing eicosapentaenoic acid; 3) L-carnitine; 4) thalidomide; or 5) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus L-carnitine plus thalidomide. Treatment duration was 4 mo. The sample comprised 475 patients.. By January 2007, 125 patients, well balanced for all clinical characteristics, were included. No severe side effects were observed. As for efficacy, an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3, 4, and 5, whereas arm 2 showed a significant worsening of lean body mass, REE, and MFSI-SF. Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1, 3, and 5 versus arm 2. A significant inferiority of arm 2 versus arms 3, 4, and 5 for the primary endpoints lean body mass, REE, and MFSI-SF was observed on the basis of t test for changes.. The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen. The study is still in progress and the final results should confirm these data.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antioxidants; Appetite Stimulants; Ascorbic Acid; Basal Metabolism; Cachexia; Carnitine; Dietary Supplements; Exercise; Fatigue; Female; Humans; Interleukin-6; Male; Medroxyprogesterone Acetate; Megestrol Acetate; Middle Aged; Muscle Proteins; Neoplasms; Nutritional Support; Oxidative Stress; Treatment Outcome; Tumor Necrosis Factor-alpha; Vitamin A; Vitamin E

To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support, antioxidants, and drugs, all given orally, in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress.. An open early-phase II study was designed according to the Simon two-stage design. The integrated treatment consisted of diet with high polyphenols content (400 mg), antioxidant treatment (300 mg/d alpha-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C), and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib. The treatment duration was 4 months. The following variables were evaluated: (a) clinical (Eastern Cooperative Oncology Group performance status); (b) nutritional [lean body mass (LBM), appetite, and resting energy expenditure]; (c) laboratory [proinflammatory cytokines and leptin, reactive oxygen species (ROS) and antioxidant enzymes]; (d) quality of life (European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D, and MFSI-SF).. From July 2002 to January 2005, 44 patients were enrolled. Of these, 39 completed the treatment and were assessable. Body weight increased significantly from baseline as did LBM and appetite. There was an important decrease of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha, and a negative relationship worthy of note was only found between LBM and IL-6 changes. As for quality of life evaluation, there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D(VAS), and multidimensional fatigue symptom inventory-short form scores. At the end of the study, 22 of the 39 patients were "responders" or "high responders." The minimum required was 21; therefore, the treatment was effective and more importantly was shown to be safe.. The efficacy and safety of the treatment have been shown by the study; therefore, a randomized phase III study is warranted.

Topics: Adult; Aged; Anorexia; Ascorbic Acid; Cachexia; Carbocysteine; Celecoxib; Dietary Supplements; Docosahexaenoic Acids; Female; Humans; Linear Models; Male; Medroxyprogesterone; Middle Aged; Neoplasms; Nutritional Support; Oxidative Stress; Pyrazoles; Statistics, Nonparametric; Sulfonamides; Thioctic Acid; Treatment Outcome; Vitamin A; Vitamin E

Elevated benzo(a)pyrene [B(a)P]-DNA adducts have been associated with 3-fold increased risk of lung cancer in current smokers. We assessed the chemopreventive effects of antioxidant supplementation using B(a)P-DNA adducts in leukocytes as an intermediate cancer risk marker.. Subjects were randomized to a double-blinded placebo-controlled clinical trial of antioxidant vitamin supplementation [500 mg vitamin C and 400 IU vitamin E (dl-alpha-tocopherol) daily] or placebo. Smokers with > or =10 cigarettes per day and serum cotinine > or =25 ng/mL were eligible for the study. B(a)P-DNA adduct level was the outcome. The randomization was stratified by gender and cigarettes per day (< or =20 or >20). Smoking habits and blood samples were collected every 3 months during the 15-month treatment period. Samples were analyzed for B(a)P-DNA adducts (high-performance liquid chromatography), plasma cotinine, vitamin levels, and GSTM1 genotype. The intent-to-treat model adjusted for B(a)P-DNA and cotinine at randomization.. Overall and among men, there was no effect of treatment on B(a)P-DNA adduct levels. Among treated women, B(a)P-DNA adducts decreased by 31% compared with women on placebo (P = 0.03). Among treated women with the GSTM1 genotype, there was a 43% decrease in adducts (P = 0.04).. Our primary hypothesis that the mean level of smoking-related B(a)P-DNA adducts would be lower in all subjects in the vitamin treatment group compared with all placebo-treated subjects was not substantiated. However, oursecondary gender-specific analysis found a significant reduction in B(a)P-DNA adducts in women with vitamin treatment, suggesting that antioxidant supplementation maymitigate some of the procarcinogenic effects of exposuretoB(a)P. The effect in GSTM1-null women suggeststhat certain subgroups may derive more benefit fromsupplementation. Although the results of this trial showthe potential chemopreventive role of antioxidants, thebest way for smokers to reduce their cancer risk remains smoking cessation.

Topics: Adult; Antioxidants; Ascorbic Acid; Benzo(a)pyrene; Chromatography, High Pressure Liquid; Cotinine; Dietary Supplements; DNA Adducts; Double-Blind Method; Female; Genotype; Glutathione Transferase; Humans; Male; Neoplasms; Polymerase Chain Reaction; Regression Analysis; Risk Factors; Smoking; Treatment Outcome; Vitamin E

The SUpplementation en VItamines et Mineraux AntioXydants (SU.VI.MAX) study, a randomised double-blind, primary-prevention trial showed that after 7.5 years, low-dose antioxidant supplementation lowered the total cancer incidence in men, but not in women. To explain this difference in the impact of antioxidant supplementation in men and women, we hypothesised that the effect of supplementation is dependent on initial antioxidant status; 12 741 French adults (7713 females aged 35--60 years; 5028 males aged 45--60 years) received daily antioxidant supplementation (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg Se, 20 mg Zn daily) or a matching placebo. Cut-off limits for baseline serum concentrations of the different antioxidant vitamins and minerals were defined as follows for both men and women: 0.3 micromol/l for beta-carotene, 11.4 micromol/l for vitamin C, 15 micromol/l for vitamin E, 0.75 micromol/l for Se and 10.7 micromol/l for Zn. The percentage of men with serum concentrations under cut-off limits was higher for vitamins C and E and beta-carotene in those who developed a cancer than in those who did not. The risk of cancer was higher in men with baseline concentrations of serum vitamin C or vitamin E under cut-off limits, but not in women. The effect of supplementation was greater in men with baseline serum concentrations of vitamin C, vitamin E and beta-carotene below the cut-off limits compared with those above it. This effect was maintained only for vitamin E after adjustment for age, tobacco, and alcohol consumption and BMI. No effect of supplementation could be seen in women. Baseline antioxidant status is related to the risk of cancer in men but not in women and therefore does not entirely explain the differences observed in the effect of antioxidant supplementation on cancer risk between sexes in the SU.VI.MAX study.

Topics: Adult; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Middle Aged; Neoplasms; Risk Factors; Selenium; Sex Factors; Vitamin E; Zinc

Case studies suggest that vitamin C, given intravenously at doses of 10-100 grams/day can improve patient well being and in some cases, reduce tumor size. While ascorbate is generally considered safe, clinical data on high intravenous doses is limited. Twenty-four late stage terminal cancer patients were given continuous infusions of 150 to 710 mg/kg/day for up to eight weeks. Blood chemistry and blood count profiles were obtained at roughly one-week intervals while patient health, adverse events and tumor progression were monitored. The majority of patients were vitamin C deficient prior to treatment. Intravenous infusions increased plasma ascorbate concentrations to a mean of 1.1 mM. The most common adverse events reported were nausea, edema, and dry mouth or skin; and these were generally minor. Two Grade 3 adverse events 'possibly related' to the agent were reported: one patient with a history of renal calculi developed a kidney stone after thirteen days of treatment and another patient experienced hypokalemia after six weeks of treatment. White blood cell counts were stable while hemoglobin and hematocrit levels dropped slightly during treatment, consistent with trends observed prior to therapy. Blood creatinine, BUN, glucose, and uric acid concentrations decreased or remained stable during therapy, suggesting that ascorbate infusions did not adversely affect renal function. One patient had stable disease and continued the treatment for forty-eight weeks. These data suggest that intravenous vitamin C therapy for cancer is relatively safe, provided the patient does not have a history of kidney stone formation.

Topics: Ascorbic Acid; Female; Humans; Infusions, Intravenous; Male; Neoplasms; Pilot Projects; Terminal Care; Vitamins

Cisplatin-induced toxicities are mainly caused by the formation of free radicals, leading to oxidative organ damage. Plasma concentrations of antioxidants decrease significantly during cisplatin chemotherapy for cancer. Forty-eight cancer patients treated with cisplatin-based chemotherapy were randomised in a double-blind manner to receive either supplementation with vitamin C, vitamin E and selenium dissolved in a beverage or to receive a placebo beverage. Primary outcome measures were the amount of nephrotoxicity and ototoxicity induced by cisplatin. No significant differences were found between the two study groups with respect to these primary outcome measures. However, patients who achieved the highest plasma concentrations of the three antioxidant micronutrients had significantly less loss of high-tone hearing. In addition, significant correlations were found between the reduced/oxidised vitamin C ratio and malondialdehyde (MDA), markers of oxidative stress, and cisplatin-induced ototoxicity and nephrotoxicity. The lack of protection against cisplatin-induced toxicities in patients in the intervention arm may be related to poor compliance and/or inadequate supplementation. Supplementation with a higher dose (intensity) and in combination with other antioxidants should be investigated further.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cisplatin; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Malondialdehyde; Micronutrients; Middle Aged; Neoplasms; Selenium; Vitamin E

It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer. To date, however, the published results of randomized, placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect. We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population.. The Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study is a randomized, double-blind, placebo-controlled primary prevention trial. A total of 13 017 French adults (7876 women aged 35-60 years and 5141 men aged 45-60 years) were included. All participants took a single daily capsule of a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 mug of selenium, and 20 mg of zinc, or a placebo. Median follow-up time was 7.5 years.. No major differences were detected between the groups in total cancer incidence (267 [4.1%] for the study group vs 295 [4.5%] for the placebo group), ischemic cardiovascular disease incidence (134 [2.1%] vs 137[2.1%]), or all-cause mortality (76 [1.2%] vs 98 [1.5%]). However, a significant interaction between sex and group effects on cancer incidence was found (P = .004). Sex-stratified analysis showed a protective effect of antioxidants in men (relative risk, 0.69 [95% confidence interval [CI], 0.53-0.91]) but not in women (relative risk, 1.04 [95% CI, 0.85-1.29]). A similar trend was observed for all-cause mortality (relative risk, 0.63 [95% CI, 0.42-0.93] in men vs 1.03 [95% CI, 0.64-1.63] in women; P = .11 for interaction).. After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Neoplasms; Selenium; Vitamin E; Zinc

It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes.. 20,536 UK adults (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) or matching placebo. Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants. An average of 83% of participants in each treatment group remained compliant during the scheduled 5-year treatment period. Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol, increased that of vitamin C by one-third, and quadrupled that of beta-carotene. Primary outcomes were major coronary events (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity.. There were no significant differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs 1389 [13.5%] placebo-allocated), or in deaths due to vascular (878 [8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%] vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058 [10.3%] vs 1086 [10.6%]). For the first occurrence of any of these "major vascular events", there were no material differences either overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI 0.94-1.06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause.. Among the high-risk individuals that were studied, these antioxidant vitamins appeared to be safe. But, although this regimen increased blood vitamin concentrations substantially, it did not produce any significant reductions in the 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cause of Death; Cholesterol; Coronary Disease; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Severity of Illness Index; Stroke; United Kingdom; Vitamin E

A total of 27 patients with various types of cancer were treated with cisplatin-based combination chemotherapy. Out of these, 13 patients were randomized to receive supplementation treatment with a beverage containing the antioxidants vitamins C and E, plus selenium, during chemotherapy. The antioxidant mixture was administered to investigate whether it could reduce the potential genotoxic and nephrotoxic effect of the applied chemotherapy. A placebo group of 14 cancer patients received a beverage without selenium or antioxidants. Micronuclei (MN) in cytochalasin B-blocked binucleate (BN) peripheral blood lymphocytes (PBLs) and hypoxanthine phosphoribosyl transferase (HPRT) mutants in PBLs were studied before, during and after chemotherapy as a measure for chemotherapy-induced genotoxic effects. Before chemotherapy, patients mean frequencies of MN and HPRT mutants did not differ from those in a group of 10 healthy subjects. The mean frequency of MN in patients increased significantly after one cycle of chemotherapy (P=0.002). This frequency was still elevated at 2 months after the completion of chemotherapy (not significantly). There was no significant difference in micronuclei frequency (MNF) between the antioxidant and placebo group of patients. Chemotherapy-induced frequencies of MN after three cycles of chemotherapy correlated significantly with the cumulative dose of cisplatin (r=0.58, P=0.012) and the cisplatin-mediated loss of renal function (r=0.53, P=0.03). No consistent change in HPRT mutant frequency following chemotherapy was observed in the placebo and antioxidant group of patients. In conclusion, cisplatin-combination chemotherapy resulted in a cisplatin dose-related increase of the frequency of chromosomal damage. Supplementation with antioxidants did not prevent or reduce this effect.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Ascorbic Acid; Chromosome Aberrations; Chromosome Disorders; Chromosomes; Cisplatin; Dietary Supplements; DNA Mutational Analysis; Female; Hearing; Humans; Hypoxanthine Phosphoribosyltransferase; Kidney; Lymphocytes; Male; Micronucleus Tests; Middle Aged; Mutagenicity Tests; Neoplasms; Selenium; Vitamin E

Low serum cholesterol has been associated with an increased risk of cancer mortality in various studies, which has led to uncertainty regarding the benefit of lower blood cholesterol.. The aim of our study was to evaluate the association between low blood cholesterol (<5.16 mmol/L) and cancer at sites that have rarely been evaluated. We placed special emphasis on the potential confounding effect of antioxidant vitamins.. Plasma concentrations of cholesterol and antioxidant vitamins were measured in 1971-1973 in 2974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed.. Two hundred ninety of the participants had died from cancer, 87 from lung, 30 from prostate, 28 from stomach, and 22 from colon cancer. Group means for plasma cholesterol concentrations did not differ significantly between survivors and those who died from cancer at any of the studied sites. With plasma cholesterol, vitamins C and E, retinol, carotene, smoking, and age accounted for in a Cox model, an increase in total cancer mortality in lung, prostate, and colon but not in stomach cancer mortality was observed in men >60 y of age with low plasma cholesterol. When data from the first 2 y of follow-up were excluded from the analysis, the relative risk estimates remained practically unchanged with regard to lung cancer but decreased for colon, prostate, and overall cancer.. Increased cancer mortality risks associated with low plasma cholesterol were not explained by the confounding effect of antioxidant vitamins, but were attributed in part to the effect of preexisting cancer.

Topics: Age Factors; Ascorbic Acid; Cholesterol; Cohort Studies; Colonic Neoplasms; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Prostatic Neoplasms; Risk Factors; Smoking; Stomach Neoplasms; Switzerland; Vitamin A; Vitamin E

To assess the balance of benefits and risks of supplementation with beta-carotene, vitamin E, vitamin C, and multivitamins on cancer, cardiovascular (CVD), and eye diseases.. Physicians' Health Study II (PHS II) is a randomized, double-blind, placebo-controlled trial enrolling 15,000 willing and eligible physicians aged 55 years and older. PHS II will utilize a 2 x 2 x 2 x 2 factorial design to test alternate day beta-carotene, alternate day vitamin E, daily vitamin C, and a daily multivitamin, in the prevention of total and prostate cancer, CVD, and the age-related eye diseases, cataract and macular degeneration. PRIOR RESULTS: The final results of the recently completed Physicians' Health Study I (PHS I), a randomized, double-blind, placebo-controlled trial in 22,071 healthy US male physicians, indicated that beta-carotene supplementation (50 mg on alternate days) had no significant benefit or harm on cancer or CVD during more than 12 years of treatment and follow-up. In regards to cancer, there were possible benefits on total and prostate cancer in those with low baseline levels assigned to beta-carotene, a finding compatible with the Chinese Cancer Prevention Study for combined treatment with beta-carotene, vitamin E, and selenium in a poorly nourished population. Further, with respect to CVD, there were apparent benefits of beta-carotene supplementation on subsequent vascular events among a small subgroup of 333 men with prior angina or revascularization. The currently available data from randomized trials of primary prevention are sparse and inconsistent for vitamin E and non-existent for vitamin C and multivitamins. For eye diseases, namely cataract and age-related macular degeneration, there are no completed large-scale randomized trials of antioxidant vitamins.. PHS II is unique in several respects. PHS II is the only primary prevention trial in apparently healthy men testing the balance of benefits and risks of vitamin E on cancer and CVD. In addition, PHS II is the only primary prevention trial in apparently healthy men to test the balance of benefits and risks of vitamin C, multivitamins, as well as any single antioxidant vitamin, alone and in combination, on cancer, CVD, and eye diseases. Finally, PHS II is the only trial testing a priori the hypotheses that beta-carotene and vitamin E may reduce the risks of prostate cancer. Thus, PHS II will add unique as well as importantly relevant and complementary information to the totality of evidence from other completed and ongoing large-scale randomized trials on the balance of benefits and risks of beta-carotene, vitamin E, vitamin C, and multivitamins alone and in combination on prevention of cancer, CVD and eye diseases.

Topics: Aged; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cataract; Double-Blind Method; Female; Follow-Up Studies; Humans; Macular Degeneration; Male; Middle Aged; Neoplasms; Sample Size; Vitamin E

The SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) Study is a randomized, double-blind, placebo-controlled, primary-prevention trial designed to test the efficacy of daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 microg; and zinc, 20 mg) at nutrition-level doses (one to three times the daily recommended dietary allowances) in reducing several major health problems in industrialized countries, especially the main causes of premature death, cancers and cardiovascular diseases. The present report describes the design, implementation, and baseline characteristics of participants in this 8-year cohort study, which started in 1994 in France; 12,735 eligible subjects (women aged 35-60, and men aged 45-60) were included in 1994 and will be followed for 8 years. Participants undergo a yearly visit consisting, every other year, of either biological sampling or clinical examination. They also regularly provide information on health events and dietary intake by filling out computerized questionnaires using the Minitel Telematic Network. Data on baseline characteristics of the participants suggest that the present sample is close to the national population in terms of geographic density, socioeconomic status, and the distribution of various major risk factors for the diseases under study. The choice of the study population should allow the results of this trial to apply to adult populations of both sexes in France and other industrialized countries.

Topics: Adult; Ascorbic Acid; beta Carotene; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Female; France; Humans; Male; Middle Aged; Mortality; Neoplasms; Selenium; Vitamin E; Zinc

The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids, and other antioxidants occurring in fruit and vegetables afford protection against heart disease and cancer by preventing oxidative damage to lipids and to DNA, respectively. To test elements of this hypothesis, we have measured blood levels of dietary antioxidants, and 8-oxodeoxyguanosine (8-oxo-dG) concentrations in lymphocyte DNA, in healthy men and women from five European countries: France, Ireland, The Netherlands, Spain, and the U.K. Volunteers, aged 25 45, all nonsmokers, gave blood samples before and after a 12-wk carotenoid supplementation regime. Vitamin C was measured in plasma and vitamin E and carotenoids were measured in serum by high-performance liquid chromatography (HPLC). 8-oxo-dG was assayed by HPLC (with coulometric detection) in DNA isolated from lymphocytes from the same blood samples. Mean values were calculated for groups of volunteers at each sampling time according to country, sex, and supplementation (between 9 and 24 individual samples contributing to each mean). We found that 8-oxo-dG levels in lymphocyte DNA vary significantly according to sex and country. A low mean 8-oxo-dG concentration is seen in DNA of women from all five countries, and of men from France and Spain. 8-oxo-dG is significantly higher (up to about threefold) in lymphocyte DNA from men in Ireland and the U.K. Oxidative DNA damage is not significantly affected by carotenoid supplementation; nor is there any association with mean baseline levels of antioxidants, which are generally similar in the five countries. The five countries sampled lie on an axis from northern to southern Europe with a steep gradient in terms of premature heart disease. There is a strong association between premature coronary heart disease mortality in men and the mean levels of 8-oxo-dG for the five countries (r = 0.95, P < 0.01). Women have low coronary heart disease mortality rates, which do not correlate with 8-oxo-dG. In terms of cancer deaths, only colorectal cancer in men shows a significant positive correlation (r = 0.91, P < 0.05), and stomach cancer in women is negatively correlated with DNA oxidation (r = -0.92, P = 0.01).

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Ascorbic Acid; Carotenoids; Chemoprevention; Deoxyguanosine; DNA Damage; Ethnicity; Europe; Female; Heart Diseases; Humans; Lutein; Lycopene; Lymphocytes; Male; Middle Aged; Neoplasms; Oxidation-Reduction; Palm Oil; Plant Oils; Reactive Oxygen Species; Sex Factors; Single-Blind Method; Vitamin E

The new anti-cancer drug zilascorb(2H) has shown promising activity in preclinical models. Its putative mechanism of action is reversible protein synthesis inhibition and long-term treatment is required. As a clinical treatment modality, long-term daily zilascorb(2H) infusions, as used in previous studies, are not regarded feasible. Therefore, an oral formulation of the drug was developed, and pharmacokinetic profile, toxicity and antitumor activity of zilascorb(2H) tablets were studied. Thirteen patients with advanced solid cancer not amenable to established therapy, but with adequate performance status and organ functions, were included. The treatment was given as a daily i.v. zilascorb(2H) infusion for 5 days, followed by zilascorb(2H) tablets twice daily for 3 months. Blood and urine sampling was performed when estimated plasma steady-state level was reached for each formulation, respectively. Analyses of drug concentrations in plasma and urine were performed by high performance liquid chromatography. Zilascorb(2H) in tablet formulation had a bioavailability of 32%, was quickly absorbed and slowly eliminated. Concomitant use of the H2-blocker ranitidine possibly enhanced bioavailability. Zilascorb(2H) was well tolerated. Two patients experienced drug-related fever, disturbing the treatment schedule for one of them. Moderate nausea was reported. One objective response was obtained. The bioavailability of zilascorb(2H) tablets was satisfactory. The principle of oral administration of zilascorb(2H) is feasible for long-term treatment and the side effects are acceptable. The mechanisms of action and the very low toxicity of the drug makes it a candidate for combination with other anticancer agents.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Area Under Curve; Ascorbic Acid; Benzylidene Compounds; Biological Availability; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged; Neoplasms

To assess the cardioprotective efficiency of an antioxidant regimen (vitamins E, C and N-acetylcysteine) in patients receiving high dose chemo- and/or radiotherapy for malignant disease.. Prospective, placebo controlled, randomized and double blinded pilot study involving 13 patients receiving chemotherapy and 12 patients receiving radiotherapy.. In patients receiving antioxidants, left ventricular ejection fraction did not change (63 +/- 4% to 63 +/- 4%). In the placebo group, ejection fraction changed from 67 +/- 6% to 61 +/- 4% (p = 0.03). No patient in the antioxidant group and 6/13 (46%) patients in the placebo group showed a fall of > 10% in the left ventricular ejection fraction. In the chemotherapy group, the left ventricular ejection fraction changed from 62% (+/- 2) to 63% (+/- 2) in the patients treated with antioxidants (ns) and from 63% (+/- 5) to 61% (+/- 5) in patients treated with placebo (ns). No patient showed a significant fall in ejection fraction in the antioxidant group, whereas 2/7 (29%) in the placebo group showed a reduction > or = 10%. In the radiotherapy group, left ventricular ejection fraction did not change ¿64% (+/- 6) to 64% (+/- 5)¿ in patients treated with antioxidants (ns) and changed from 70% (+/- 8) to 60% (+/- 4) in patients treated with placebo (p = 0.008). No patient in the antioxidant group, but 4/6 (66%) patients in the placebo group showed a fall of > or = 10% in ejection fraction.. The small number of patients in the study precludes a definitive statement. The preliminary results however suggest efficient cardioprotection by this nontoxic and inexpensive antioxidant combination, so larger studies are warranted for confirmation.

Topics: Acetylcysteine; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Double-Blind Method; Heart; Humans; Neoplasms; Pilot Projects; Prospective Studies; Radionuclide Ventriculography; Radiotherapy; Radiotherapy Dosage; Stroke Volume; Vitamin E

In the Western Electric Company Study, carried out in Chicago, Illinois, data on diet and other factors were obtained in 1958 and 1959 for a cohort of 1,556 employed, middle-aged men. Nutrients included vitamin C and beta-carotene. An index that summarized combined intake of both nutrients was constructed. Mean intakes of vitamin C in the lowest and highest tertiles of the index were 66 and 138 mg/day; corresponding values for beta-carotene were 2.3 and 5.3 mg/day. A total of 522 of 1,556 men died during 32,935 person-years of follow-up, 231 from coronary heart disease and 155 from cancer. After adjustment for potentially confounding factors, relative risks (95% confidence intervals) associated with an increment of 19 points in the index (difference between means of the lowest and highest tertiles) were 0.60 (0.39-0.93) for cancer mortality, 0.70 (0.49-0.98) for coronary disease mortality, and 0.69 (0.55-0.87) for all-cause mortality. These results support the hypothesis that consumption of foods rich in vitamin C and beta-carotene reduces risk of death in middle-aged men.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Chicago; Confidence Intervals; Confounding Factors, Epidemiologic; Coronary Disease; Diet; Humans; Male; Middle Aged; Mortality; Neoplasms; Pilot Projects; Risk Factors; Telephone

Conditioning therapy preceding bone marrow transplantation usually consists of high-dose chemotherapy and total body irradiation. This is associated with acute and delayed toxic effects for several tissues, possibly related to peroxidation processes and exhaustion of antioxidants. Therefore, plasma of 22 patients was examined for alpha- and gamma-tocopherol (vitamin E), the carotenoids beta-carotene and lycopene, retinol, and ascorbic acid before, during and after conditioning chemotherapy for bone marrow transplantation. 18 of the patients received total body irradiation as well. Retinol and ascorbic acid have been given intravenously in a multiple of the recommended doses (Deutsche Gesellschaft für Ernährung (DGE) and Recommended Dietary Allowance (RDA), respectively). The doses chosen were sufficient to maintain the initial plasma concentrations of these vitamins. However, alpha-tocopherol (in RDA doses) and beta-carotene (no RDA established) concentrations deteriorated after the conditioning therapy (20% and 50% loss, respectively). The loss of these lipid-soluble antioxidants has been considered to result from lipid peroxidation, since lipid peroxide concentrations in plasma increased concurrently. On the basis of these results we performed interventions studies in order to investigate the effect of high-dose supplementation on antioxidant status. We compared the loss of antioxidants and the toxicity in two groups of patients undergoing bone marrow transplantation: The first group without and the second group with oral supplementation of high doses of alpha-tocopherol (825 mg daily), ascorbic acid (450 mg daily) and beta-carotene (45 mg daily) for three weeks prior to chemo- and radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; beta Carotene; Bone Marrow Transplantation; Carotenoids; Combined Modality Therapy; Female; Humans; Lipid Peroxidation; Male; Neoplasms; Premedication; Vitamin E; Vitamins; Whole-Body Irradiation

A computerized data bank was created recording the details of all cancer patients attending three district general hospitals in West Central Scotland over a 4.5 year period 1978-1982. At the conclusion of the trial, the records of 2804 individual patients were available for study, of whom 1826 had reached an incurable stage. 294 of these incurable cancer patients had received supplemental ascorbate at some stage in their illness, whereas 1532 had not, and served as controls. Analysis showed that the ascorbate-supplemented patients had a median overall survival time (343 days) almost double that of the controls (180 days). Our difficulties in having this simple, but important, observation published are briefly recounted in the introduction.

Topics: Ascorbic Acid; Humans; Neoplasms; Scotland; Survival Analysis

Nutritional antioxidants support prostacyclin synthesis by preventing lipid hydroperoxide-mediated inhibition of prostacyclin synthetase. Recent preliminary clinical studies indicate that supplementary antioxidants exert antithrombotic effects in vivo that are most likely attributable to enhanced prostacyclin production. Optimal antioxidant nutrition may thus have preventive and therapeutic value for disorders in which inappropriate platelet aggregation plays an etiologic role, including MI, stroke, atherogenesis, pre-eclampsia, and the vascular complications of diabetes. In light of evidence that platelet aggregation encourages the implantation of hematogenous tumor metastases, supplemental antioxidants should also impede tumor dissemination--an effect which will be complemented by the immunostimulant actions of these nutrients. By exerting anticarcinogenic, immunostimulant and anti-metastatic effects, nutritional antioxidants should act to inhibit neoplasia at each stage of its development.

Topics: Adjuvants, Immunologic; Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Diet; Epoprostenol; Humans; Lipid Peroxides; Neoplasm Metastasis; Neoplasms; Neoplastic Cells, Circulating; Platelet Aggregation; Selenium; Thrombosis; Vitamin E

Topics: Adult; Ascorbic Acid; Calcium; Clinical Trials as Topic; Drug Therapy; Education, Nursing, Continuing; Female; Folic Acid; Humans; Male; Neoplasms; Oncology Nursing; Research; Retinoids; Selenium; Tamoxifen; Vitamin A; Vitamin D; Vitamin E

More research is needed to draw definitive conclusions on the relationship between vitamin C intake and cancer, but the following general statements can be made. The effectiveness of megadoses (greater than 1 gm/day) of vitamin C for the cure or prevention of cancer is still unproven; in fact, the safety of megadoses is still in question. Therefore, they are not recommended for the general public at present and, if used at all, should be used under medical supervision. Epidemiologic evidence suggests that vitamin C-rich foods may be beneficial in preventing cancer, and their consumption should be encouraged as a measure to reduce the incidence of cancer. Well-controlled studies should be undertaken to elucidate the relationship between vitamin C and cancer, using both vitamin-containing foods and vitamin C supplements at different intake levels.

Topics: Ascorbic Acid; Carcinogens; Clinical Trials as Topic; Diet; Double-Blind Method; Food, Fortified; Humans; Mutagens; Neoplasms; Nitrites; Prognosis; Random Allocation

Topics: Ascorbic Acid; Clinical Trials as Topic; Humans; Neoplasms

Clinical trials administering supplemental ascorbate to terminal cancer patients were conducted at two hospitals in Japan. During the period 1973-1977 there were 99 patients with terminal cancer at the Fukuoka Torikai Hospital. The average times of survival after the date of designation as terminal were 43 days for 44 low-ascorbate patients and 246 days for 55 high-ascorbate patients. Three of the high-ascorbate patients were still alive, their average survival being 1550 days, on April 1, 1980. Similar effectiveness of ascorbate was also observed at the Kamioka Kozan Hospital. There were 31 patients with terminal cancer during the period 1975-1979. The average survival times were 48 days for 19 control patients and 115 days for 6 high-ascorbate patients. One of the high-ascorbate patients was still alive, his survival being 215 days. In addition to the increase in survival times, the administration of large doses of ascorbate seemed to improve the quality of life.

Topics: Adult; Aged; Ascorbic Acid; Female; Humans; Male; Middle Aged; Neoplasms; Time Factors

Cameron and Pauling have reported large survival increases in terminal cancer patients treated with Vitamin C. Their trials, which have been criticised because not based on random, double-blind principles, are reviewed here using a broad inductive method that relies on diverse data of varying quality. Conclusions are offered both on the value of Vitamin C and on this broad method, as follows: There is a strong possibility that Vitamin C very approximately doubled survival time as measured from the start of Vitamin C treatment, regardless of whether this was after termination of conventional treatment or much earlier. A recent Mayo Clinic trial which concluded that Vitamin C is valueless in the terminal stage may be given an alternative interpretation which supports this view. Despite a speculative element because based only on the condensed, published data, these conclusions have sufficient possibility of validity as to call for full further investigation. The conclusions on method are that the broad, inductive approach may have potential value when the randomized method cannot be used; that it also may facilitate, to the public's benefit, the release of probably valuable, inexpensive, non-toxic treatments pending decisive proof; and a greater return on the research dollar might result from a formal acceptance of the probabilistic element in scientific proof.

Topics: Ascorbic Acid; Clinical Trials as Topic; Colonic Neoplasms; Follow-Up Studies; Humans; Models, Biological; Neoplasms; Placebos; Prognosis

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Mice; Neoplasms; Neoplasms, Experimental

One hundred and fifty patients with advanced cancer participated in a controlled double-blind study to evaluate the effects of high-dose vitamin C on symptoms and survival. Patients were divided randomly into a group that received vitamin C (10 g per day) and one that received a comparably flavored lactose placebo. Sixty evaluable patients received vitamin C and 63 received a placebo. Both groups were similar in age, sex, site of primary tumor, performance score, tumor grade and previous chemotherapy. The two groups showed no appreciable difference in changes in symptoms, performance status, appetite or weight. The median survival for all patients was about seven weeks, and the survival curves essentially overlapped. In this selected group of patients, we were unable to show a therapeutic benefit of high-dose vitamin C treatment.

Topics: Aged; Ascorbic Acid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Neoplasms; Placebos

The anti-cancer effect of high concentrations of ascorbic acid (AA) has been well established while its underlying mechanisms remain unclear. The association between iron and AA has attracted great attention but was still controversial due to the complicated roles of iron in tumors.. Our study aims to explore the anti-cancer mechanisms of AA and the interaction between AA and iron in cancer.. The MTT and ATP assays were used to evaluate the cytotoxicity of AA. Reactive oxygen species (ROS) generation, calcium (Ca. High concentrations of AA exhibited cytotoxicity in a panel of cancer cells. AA triggered ROS-dependent non-apoptotic cell death. AA-induced cell death was essentially mediated by the accumulated intracellular Ca. Our study elucidated the protective roles of iron in ROS/Ca

Topics: Animals; Ascorbic Acid; Humans; Iron; Mice; Neoplasms; Reactive Oxygen Species; Zebrafish

Topics: Adolescent; Anemia; Ascorbic Acid; Humans; Neoplasms; Scurvy; Thrombocytopenia

Pharmacological vitamin C (VC) is a potential natural compound for cancer treatment. However, the mechanism underlying its antitumor effects remains unclear. In this study, we found that pharmacological VC significantly inhibits the mTOR (including mTORC1 and mTORC2) pathway activation and promotes GSK3-FBXW7-mediated Rictor ubiquitination and degradation by increasing the cellular ROS. Moreover, we identified that HMOX1 is a checkpoint for pharmacological-VC-mediated mTOR inactivation, and the deletion of FBXW7 or HMOX1 suppresses the regulation of pharmacological VC on mTOR activation, cell size, cell viability, and autophagy. More importantly, it was observed that the inhibition of mTOR by pharmacological VC supplementation in vivo produces positive therapeutic responses in tumor growth, while HMOX1 deficiency rescues the inhibitory effect of pharmacological VC on tumor growth. These results demonstrate that VC influences cellular activities and tumor growth by inhibiting the mTOR pathway through Rictor and HMOX1, which may have therapeutic potential for cancer treatment.

Topics: Ascorbic Acid; F-Box-WD Repeat-Containing Protein 7; Glycogen Synthase Kinase 3; Heme Oxygenase-1; Humans; Mechanistic Target of Rapamycin Complex 1; Mechanistic Target of Rapamycin Complex 2; Neoplasms; Rapamycin-Insensitive Companion of mTOR Protein; TOR Serine-Threonine Kinases; Transcription Factors

Immunogenic cell death (ICD) induced by reactive oxygen species (ROS) represents a particular form of tumor cell death for approaching the problem of low immunogenicity of tumors in immunotherapy, while the oxidative damage to normal cells of current ICD inducers hinders their clinical application. Herein, a new ICD inducer VC@cLAV constructed solely by dietary antioxidants, lipoic acid (LA) and vitamin C (VC), is developed, which could promote heavy intracellular ROS production in cancer cells for ICD induction while acting as an anti-oxidant in non-cancer cells for cytoprotection, and thus hold high biosafety.

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; Humans; Immunotherapy; Nanoparticles; Neoplasms; Reactive Oxygen Species

Our study proposes a pharmacological strategy to target cancerous mitochondria via redox-cycling "mitocans" such as quinone/ascorbate (Q/A) redox-pairs, which makes cancer cells fragile and sensitive without adverse effects on normal cells and tissues. Eleven Q/A redox-pairs were tested on cultured cells and cancer-bearing mice. The following parameters were analyzed: cell proliferation/viability, mitochondrial superoxide, steady-state ATP, tissue redox-state, tumor-associated NADH oxidase (tNOX) expression, tumor growth, and survival. Q/A redox-pairs containing unprenylated quinones exhibited strong dose-dependent antiproliferative and cytotoxic effects on cancer cells, accompanied by overproduction of mitochondrial superoxide and accelerated ATP depletion. In normal cells, the same redox-pairs did not significantly affect the viability and energy homeostasis, but induced mild mitochondrial oxidative stress, which is well tolerated. Benzoquinone/ascorbate redox-pairs were more effective than naphthoquinone/ascorbate, with coenzyme Q0/ascorbate exhibiting the most pronounced anticancer effects in vitro and in vivo. Targeted anticancer effects of Q/A redox-pairs and their tolerance to normal cells and tissues are attributed to: (i) downregulation of quinone prenylation in cancer, leading to increased mitochondrial production of semiquinone and, consequently, superoxide; (ii) specific and accelerated redox-cycling of unprenylated quinones and ascorbate mainly in the impaired cancerous mitochondria due to their redox imbalance; and (iii) downregulation of tNOX.

Topics: Adenosine Triphosphate; Animals; Ascorbic Acid; Mice; Neoplasms; Oxidation-Reduction; Quinones; Superoxides

Cancer cells tend to have higher intracellular reactive oxygen species (ROS) levels and are more vulnerable to ROS-generating therapies such as ascorbic acid (H

Topics: Ascorbic Acid; Cell Line, Tumor; Glutathione; Humans; Hydrogen Peroxide; Neoplasms; Photochemotherapy; Reactive Oxygen Species

Detecting cancer biomarker levels in body fluids is essential for medical diagnosis. Enzyme-linked immunosorbent assay (ELISA) has been broadly used to detect cancer biomarkers. However, colorimetric ELISA based solely on nanoparticles (NPs) are susceptible to environmental influences, which often results in the detection inaccuracy, being limited in clinical applications. In this regard, the dual-mode approach would add signal diversity to the detection, making the results more reliable.. We present colorimetric and photothermal immunosensor that enables direct reading of the color and temperature of the solution. A core-satellite nanoprobe constructed by polydopamine (PDA) as the core and gold seeds as satellites is rationally designed as the signal reporter. When ascorbic acid is present in the solution, PDA can cooperate with ascorbic acid to reduce chloroauric acid and mediate the growth of gold seeds on the PDA surface, inducing a redshift of the localized surface plasmon resonance peak of the nanosensor and the change in photothermal conversion efficiency. The method is further combined with the sandwiched immunoassay to construct an alkaline phosphatase based colorimetric and photothermal ELISA for the highly sensitive and accurate evaluation and detection of prostate-specific antigen (PSA). The linear range was from 0.05 to 100 ng mL. The presented immunoassay allows straightforward, sensitive, and selective readout by color and temperature without advanced instrumentation. Particularly, the LOD was much lower than the threshold in clinical trials for PSA. Therefore, this method has a great prospect in the early diagnosis of cancer biomarkers based on a dual-mode multifunctional platform.

Topics: Ascorbic Acid; Biomarkers, Tumor; Biosensing Techniques; Colorimetry; Gold; Humans; Immunoassay; Limit of Detection; Male; Metal Nanoparticles; Neoplasms; Prostate-Specific Antigen

Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Ascorbic Acid; Combined Modality Therapy; Humans; Neoplasms; Vitamins

The epigenome delineates lineage-specific transcriptional programs and restricts cell plasticity to prevent non-physiological cell fate transitions. Although cell diversification fosters tumor evolution and therapy resistance, upstream mechanisms that regulate the stability and plasticity of the cancer epigenome remain elusive. Here we show that 2-hydroxyglutarate (2HG) not only suppresses DNA repair but also mediates the high-plasticity chromatin landscape. A combination of single-cell epigenomics and multi-omics approaches demonstrates that 2HG disarranges otherwise well-preserved stable nucleosome positioning and promotes cell-to-cell variability. 2HG induces loss of motif accessibility to the luminal-defining transcriptional factors FOXA1, FOXP1, and GATA3 and a shift from luminal to basal-like gene expression. Breast tumors with high 2HG exhibit enhanced heterogeneity with undifferentiated epigenomic signatures linked to adverse prognosis. Further, ascorbate-2-phosphate (A2P) eradicates heterogeneity and impairs growth of high 2HG-producing breast cancer cells. These findings suggest 2HG as a key determinant of cancer plasticity and provide a rational strategy to counteract tumor cell evolution.

Topics: Alcohol Oxidoreductases; Ascorbic Acid; Cell Differentiation; Cell Line, Tumor; Chromatin; DNA Repair; Epigenome; Forkhead Transcription Factors; Gene Expression; Gene Expression Regulation; Glutarates; Humans; Isocitrate Dehydrogenase; Neoplasms; Nucleosomes; Repressor Proteins

To evaluate the relations of dietary total antioxidant capacity (DTAC) with mortality outcomes in a Chinese population.. The study included 62,063 participants from the Singapore Chinese Health Study. The participants were 45-74 years at baseline (1993-1998) when dietary data were collected with a validated 165-item food frequency questionnaire. The DTAC was derived using two widely adopted scores of integrated dietary consumption of antioxidant nutrients, i.e., the Comprehensive Dietary Antioxidant Index (CDAI) and Vitamin C Equivalent Antioxidant Capacity (VCEAC). We used Cox proportional hazard model to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations with adjustment for potential confounders.. During 1,212,318 person-years of follow-up, 23,397 deaths [cardiovascular diseases (CVD): 7523; respiratory diseases: 4696; and cancer: 7713] occurred. In multivariable models, the HR (95% CI) comparing participants in the highest vs. lowest quartile of CDAI was 0.85 (0.82, 0.88) for all-cause mortality, 0.82 (0.76, 0.88) for CVD mortality, 0.76 (0.70, 0.83) for respiratory disease mortality (all P-trend < 0.001), and 0.94 (0.88, 1.00) for cancer mortality (P-trend = 0.16). Similar associations were found with the VCEAC index. Higher intakes of the DTAC components, i.e., vitamin C, vitamin E, carotenoids, and flavonoids, were all associated with lower mortality risk.. Diet with a higher antioxidant capacity in midlife was associated with a lower risk of all-cause, cardiovascular and respiratory disease mortality in the Singapore Chinese population, supporting the public health recommendation of consuming more plant-based foods that are rich in antioxidant nutrients.

Topics: Antioxidants; Ascorbic Acid; Cardiovascular Diseases; China; Diet; Humans; Neoplasms; Proportional Hazards Models; Prospective Studies; Risk Factors; Singapore; Vitamins

Despite extensive efforts to realize effective photodynamic therapy (PDT), there is still a lack of therapeutic approaches concisely structured to mitigate the major obstacles of PDT in clinical applications. Herein, we report a molecular strategy exploiting ascorbate chemistry to enhance the efficacy of PDT in cancer cells overexpressing glucose transporter 1 (GLUT1). AA-EtNBS, a 5-O-substituted ascorbate-photosensitizer (PS) conjugate, undergoes a reversible structural conversion of the ascorbate moiety in the presence of reactive oxygen species (ROS) and glutathione (GSH), thereby promoting its uptake in GLUT1-overexpressed KM12C colon cancer cells and perturbing tumor redox homeostasis, respectively. Due to the unique pro-oxidant role of ascorbate in tumor environments, AA-EtNBS effectively sensitized KM12C cancer cells prior to PS-mediated generation of superoxide radicals under near-infrared (NIR) illumination. AA-EtNBS successfully exhibited GLUT1-targeted synergistic therapeutic efficacy during PDT both in vitro and in vivo. Therefore, this study outlines a promising strategy employing ascorbate both as a targeting unit for GLUT1-overexpressed cancer cells and redox homeostasis destruction agent, thereby enhancing therapeutic responses towards anticancer treatment when used in conjunction with conventional PDT.

Topics: Ascorbic Acid; Cell Line, Tumor; Glucose Transporter Type 1; Glutathione; Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species

This work was carried out to compare the modifying roles of ascorbic and metformin during Ehrlich (ESC) tumor-bearing mice irradiation.. Fifty Swiss albino male mice were segmented into seven groups, including one control group and six Ehrlich induced tumors treated with ascorbic, ascorbic plus radiation, metformin, metformin plus radiation, and radiation only. Many tests, including behavioral, biochemical, immunohistochemistry, gene expression, DNA fragmentation, oxidative stress markers, and EPR, were performed to interrogate the modifying effects on tumor and liver tissues.. Remarkable apoptosis was found in metformin irradiated animals compared to irradiated ascorbic counterparts. The irradiated metformin mice showed the greatest reduction in PCNA. There was a significant reduction of DNA fragmentation in the liver tissues of the irradiated metformin group. Irradiated metformin and irradiated ascorbic acid animals showed a reduced signal of ERK as well as c-Fos genes. There was a tendency of metformin and metformin irradiated animals to reduce MDA levels in liver tissues. ESC-bearing mice treated with ascorbic or metformin showed an improvement in the spontaneous alternation percentage (SAP%) and improved short-term memory. There was also an improvement in long memory tests.. The study added more preclinical evidence on the utility of metformin in cancer treatment during radiotherapy. Metformin was shown to reduce lipid peroxidation in irradiated healthy tissues, increase tumor cytotoxicity, downregulate critical pathways involved in tumor progression and proliferation, and enhance tumor apoptosis. Controlled clinical trials using metformin are highly warranted.

Topics: Animals; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Lipid Peroxidation; Metformin; Mice; Neoplasms

Surface charge polarity and density influence the immune clearance and cellular uptake of intravenously administered lipid nanoparticles (LNPs), thus determining the efficiency of their delivery to the target. Here, we modified the surface charge with ascorbyl palmitate (AsP) used as a negatively charged lipid. AsP-PC-LNPs were prepared by dispersion and ultrasonication of AsP and phosphatidylcholine (PC) composite films at various ratios. AsP inserted into the PC film with its polar head outward. The pKa for AsP was 4.34, and its ion form conferred the LNPs with negative surface charge. Zeta potentials were correlated with the amount and distribution of AsP on the LNPs surface. DSC, Raman and FTIR spectra, and molecular dynamics simulations disclosed that AsP distributed homogeneously in PC at 1−8% (w/w), and there were strong hydrogen bonds between the polar heads of AsP and PC (PO2−), which favored LNPs’ stability. But at AsP:PC > 8% (w/w), the excessive AsP changed the interaction modes between AsP and PC. The AsP−PC composite films became inhomogeneous, and their phase transition behaviors and Raman and FTIR spectra were altered. Our results clarified the mechanism of surface charge modification by AsP and provided a rational use of AsP as a charged lipid to modify LNP surface properties in targeted drug delivery systems. Furthermore, AsP−PC composites were used as phospholipid-based biological membranes to prepare paclitaxel-loaded LNPs, which had stable surface negative charge, better tumor targeting and tumor inhibitory effects.

Topics: Ascorbic Acid; Humans; Liposomes; Nanoparticles; Neoplasms; Phosphatidylcholines; RNA, Small Interfering

While checkpoint blockade immunotherapy as a promising clinical modality has revolutionized cancer treatment, it is of benefit to only a subset of patients because of the tumor immunosuppressive microenvironment. Herein, we report that the specified delivery of vitamin C at the tumor site by responsive lipid nanoparticles can efficiently induce oxidative toxicity and the polarization of M1 macrophages, promoting the infiltration of activating cytotoxic T lymphocytes in the tumor microenvironment for intensive immune checkpoint blocking therapy. Both

Topics: Ascorbic Acid; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Ligands; Liposomes; Neoplasms; Programmed Cell Death 1 Receptor; Tumor Microenvironment; Tumor-Associated Macrophages

Topics: Anti-Inflammatory Agents; Ascorbic Acid; Hyperthermia, Induced; Ligands; Magnetite Nanoparticles; Nanoparticles; Neoplasms; Oxides; Temperature

Fasting and fasting mimicking diets extend lifespan and healthspan in mouse models and decrease risk factors for cancer and other age-related pathologies in humans. Normal cells respond to fasting and the consequent decrease in nutrients by down-regulating proto-oncogene pathways to enter a stress-resistant mode, which protects them from different cancer therapies. In contrast, oncogene mutations and the constitutive activation of pathways including RAS, AKT, and PKA allow cancer cells to disobey fasting-dependent anti-growth signal. Importantly, in different tumor types, fasting potentiates the toxicity of various therapies by increasing reactive oxygen species and oxidative stress, which ultimately leads to DNA damage and cell death. This effect is not limited to chemotherapy, since periodic fasting/FMD cycles potentiate the effects of tyrosine kinase inhibitors, hormone therapy, radiotherapy, and pharmacological doses of vitamin C. In addition, the anticancer effects of fasting/FMD can also be tumor-independent and involve an immunotherapy-like activation of T cell-dependent attack of tumor cells. Supported by a range of pre-clinical studies, clinical trials are beginning to confirm the safety and efficacy of fasting/FMD cycles in improving the potential of different cancer therapies, while decreasing side effects to healthy cells and tissues.

Topics: Animals; Ascorbic Acid; Fasting; Hormones; Humans; Mammals; Mice; Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Saccharomyces cerevisiae

Reactive oxygen species (ROS) homeostasis and mitochondrial metabolism are critical for the survival of cancer cells, including cancer stem cells (CSCs), which often cause drug resistance and cancer relapse. Auranofin is a mono-gold anti-rheumatic drug, and it has been repurposed as an anticancer agent working by the induction of both ROS increase and mitochondrial dysfunction. Hypothetically, increasing auranofin's positive charges via incorporating more gold atoms to enhance its mitochondria-targeting capacity could enhance its anti-cancer efficacy. Hence, in this work, both mono-gold and bi-gold compounds were designed and evaluated to test our hypothesis. The results showed that bi-gold compounds generally suppressed cancer cells proliferation better than their mono-gold counterparts. The most potent compound, BGC2a, substantially inhibited the antioxidant enzyme TrxR and increased the cellular ROS. BGC2a induced cell apoptosis, which could not be reversed by the antioxidant agent vitamin C, implying that the ROS induced by TrxR inhibition might not be the decisive cause of cell death. As expected, a significant proportion of BGC2a accumulated within mitochondria, likely contributing to mitochondrial dysfunction, which was further confirmed by measuring oxygen consumption rate, mitochondrial membrane potential, and ATP production. Moreover, BGC2a inhibited colony formation and reduced stem-like side population (SP) cells of A549. Finally, the compound effectively suppressed the tumor growth of both A549 and PANC-1 xenografts. Our study showed that mitochondrial disturbance may be gold-based compounds' major lethal factor in eradicating cancer cells, providing a new approach to developing potent gold-based anti-cancer drugs by increasing mitochondria-targeting capacity.

Topics: Adenosine Triphosphate; Antioxidants; Antirheumatic Agents; Apoptosis; Ascorbic Acid; Auranofin; Cell Line, Tumor; Cell Proliferation; Gold Compounds; Humans; Mitochondria; Neoplasms; Reactive Oxygen Species

Angiogenesis is the process of vascularization from preexisting blood vessels. It is essential for many physiological and pathological processes. Quinine is an anti-malarial agent belongs to the quinoline alkaloid that can inhibit angiogenesis. Vitamin C is also an important antioxidant and has been shown to reduce angiogenesis in tumor.. The study was aimed at investigating the effect of quinine alone and in combination with vitamin C on angiogenesis process.. 12 to 14 weeks old male albino rats were used for the study. Quinine was prepared by dissolving in DMSO and was serially diluted. The rat aorta ring assay was employed to investigate the antiangiogenic effect of quinine ex vivo. An in vivo chorioallantoic membrane (CAM) assay was used to measure the blood vessels inhibition zone by quinine. The zone of inhibition was calculated as the mean inhibition area of a blood vessel in mm±SD.The obtained data were statistically analyzed.. The results revealed that quinine has a significant dose-dependent inhibition effect on the growth of blood vessels by 98% ± 0.07 in concentration 100µg/ml when compared to the negative control. moreover, the inhibition of blood vessels growth as a measure of the antiangiogenic activity of quinine in combination with vitamin C shows a synergistic effect when the concentration that inhibit 50% of blood vessels growth (IC50) which equals to 5.05 µg/ml resulted in 85% of growth inhibition when combined with IC50 of vitamin C which equals to 22..87µg/ml.. The findings suggest that the activity of quinine with vitamin C synergism can greatly lower blood vessels growth in rat aorta rings and CAM assays. Quininehas an inhibitory effect on tumor and can be utilized as an antiangiogenic agent alone or in combination with vitamin C.

Topics: Angiogenesis Inhibitors; Animals; Ascorbic Acid; Chorioallantoic Membrane; Male; Neoplasms; Neovascularization, Pathologic; Quinine; Rats; Vitamins

This study aimed to compare the dietary intake of carotenoids, tocopherols, ascorbic acid, flavonoids, and dietary total antioxidant capacity (dTAC) and to evaluate relationship of dTAC with serum inflammatory biomarkers in patients with gastrointestinal system (GIS) and non-GIS cancer. In total, 104 adult cancer survivors (52 GIS and 52 non-GIS cancer cases) were included. 24-hour dietary recalls were obtained and dTAC was calculated on the basis of oxygen radical absorption capacity (ORAC), Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP), ferric reducing antioxidant potential (FRAP), and vitamin C equivalents (VCE). Serum C-reactive protein (CRP) level, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were used as inflammatory biomarkers. Routinely analyzed serum CRP, neutrophil, lymphocyte, and platelet levels every day in hospital biochemistry laboratory were obtained from patients' file. There was no significant difference between patients with GIS and non-GIS cancer in terms of dietary intake of carotenoids, tocopherols, and flavonoids. While there was no significant difference between groups in terms of the mean dietary ORAC, TEAC, and FRAP, the mean TRAP of patients with GIS cancer was significantly higher than patients with non-GIS cancer. Serum inflammatory markers (CRP and NLR) were found to have an inverse relationship with dTAC.

Topics: Adult; Antioxidants; Ascorbic Acid; Biomarkers; C-Reactive Protein; Cancer Survivors; Carotenoids; Flavonoids; Humans; Neoplasms; Reactive Oxygen Species; Tocopherols

Ascorbate is an important element of a variety of cellular processes including the control of reactive oxygen species levels. Since reactive oxygen species are implicated as a key factor in tumorigenesis and antitumor therapy, the injection of a large amount of ascorbate is considered beneficial in cancer therapy. Recent studies have shown that ascorbate can cross the plasma membrane through passive diffusion. In contrast to absorption by active transport, which is facilitated by transport proteins (SVCT1 and SVCT2). The passive diffusion of a weak acid across membranes depends on the electrostatic potential and the pH gradients. This has been used to construct a new theoretical model capable of providing steady-state ascorbate concentration in the intracellular space and evaluating the time needed to reach it. The main conclusion of the analysis is that the steady-state intracellular ascorbate concentration weakly depends on its serum concentration but requires days of exposure to saturate. Based on these findings, it can be hypothesized that extended oral ascorbate delivery is possibly more effective than a short intravenous infusion of high ascorbate quantities.

Topics: Ascorbic Acid; Cell Line, Tumor; Extracellular Space; Humans; Hydrogen-Ion Concentration; Intracellular Space; Membrane Potentials; Models, Biological; Neoplasms; Numerical Analysis, Computer-Assisted; Sodium-Coupled Vitamin C Transporters; Time Factors

Much attention has been put on antioxidants as potential preventive and therapeutic agents against cancer. Vitamin C, an important antioxidant with anti-inflammatory and immune system enhancement features, could provide protection against cancer. However, experimental and epidemiologic evidence on vitamin C and cancer risk are still indefinite. Substantial literature reports that cancer patients experience vitamin C deficiency associated with decreased oral intake, infection, inflammation, disease processes, and treatments such as radiation, chemotherapy, and surgery. Studies demonstrate associations between IVC and inflammation biomarkers and propose some amelioration in symptoms, with a possible advantage in quality of life (QoL) when intravenous vitamin C (IVC) alone or in combination with oral vitamin C is administered in oncologic care. While, the anticancer impact of high doses of IVC remains debatable in spite of growing evidence that high dose vitamin C shows anti-tumorigenic activity by elevating the amount of reactive oxygen species (ROS) in cancer cells without meaningful toxicities. Hence, there is an urgent requirement for rigorous and well-controlled assessments of IVC as an adjuvant therapy for cancer before clear conclusions can be drawn. Thus, more clinical trials are required to determine the additive impact of high dose vitamin C in cancer patients.

Topics: Antioxidants; Ascorbic Acid; Disease Progression; Humans; Neoplasms; Quality of Life; Vitamins

Vitamin C (ascorbic acid) is a normal liver metabolite in most animals, with humans being a notable exception due to random genetic mutations that have occurred during our evolution [...].

Topics: Ascorbic Acid; Bacterial Infections; Epigenesis, Genetic; Humans; Neoplasms; Sepsis

Topics: Animals; Antioxidants; Ascorbic Acid; Humans; Neoplasms; Oxidation-Reduction; Reactive Oxygen Species; Vitamins

Topics: Ascorbic Acid; Autophagy; Biomarkers; Disease Susceptibility; Energy Metabolism; Humans; Hydrogen Peroxide; Iron; Neoplasms; Polyamines

Topics: Allografts; Animals; Antineoplastic Agents; Ascorbic Acid; Cell Survival; Disease Models, Animal; Doxorubicin; Drug Carriers; Drug Liberation; Female; Fibroblasts; Humans; Hydrogen-Ion Concentration; MCF-7 Cells; Methacrylates; Mice; Mice, Inbred BALB C; Micelles; Neoplasms; Phosphorylcholine; Polymers; Surface Properties; Tumor Burden

The menadione/ascorbate (M/A) combination has attracted attention due to the unusual ability of pro-vitamin/vitamin combination to kill cancer cells without affecting the viability of normal cells. The aim of this study was to elucidate the role of M/A in targeting cancerous mitochondria.. Several cancer and normal cell lines of the same origin were used. Cells were treated with different concentrations of M/A for 24 h. The cell viability, mitochondrial superoxide, mitochondrial membrane potential, and succinate were analyzed using conventional analytical tests.. M/A exhibited a highly specific suppression on cancer cell growth and viability, without adversely affecting the viability of normal cells at concentrations attainable by oral or parenteral administration in vivo. This effect was accompanied by: (i) an extremely high production of mitochondrial superoxide in cancer cells, but not in normal cells; (ii) a significant dose-dependent depolarization of mitochondrial membrane and depletion of oncometabolite succinate in cancer cells.. The anticancer effect of M/A is related to the induction of severe mitochondrial oxidative stress in cancer cells only. Thus, M/A has a potential to increase the sensitivity and vulnerability of cancer cells to conventional anticancer therapy and immune system.

Topics: Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Apoptosis; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Cell Survival; Humans; Membrane Potential, Mitochondrial; Mitochondria; Neoplasms; Oxidative Stress; Superoxide Dismutase; Superoxides; Vitamin K 3

We report a strategy to boost Fenton reaction triggered by an exogenous circularly polarized magnetic field (MF) to enhance ferroptosis-like cell-death mediated immune response, as well as endow a responsive MRI capability by using a hybrid core-shell vesicles (HCSVs). HCSVs are prepared by loading ascorbic acid (AA) in the core and poly(lactic-co-glycolic acid) shell incorporating iron oxide nanocubes (IONCs). MF triggers the release of AA, resulting in the increase of ferrous ions through the redox reaction between AA and IONCs. A significant tumor suppression is achieved by Fenton reaction-mediated ferroptosis-like cell-death. The oxidative stress induced by the Fenton reaction leads to the exposure of calreticulin on tumor cells, which leads to dendritic cells maturation and the infiltration of cytotoxic T lymphocytes in tumor. Furthermore, the depletion of ferric ions during treatment enables monitoring of the Fe reaction in MRI-R2* signal change. This strategy provides a perspective on ferroptosis-based immunotherapy.

Topics: Animals; Ascorbic Acid; Calreticulin; Cell Line, Tumor; Drug Delivery Systems; Ferric Compounds; Ferroptosis; Immunotherapy; Magnetic Fields; Magnetic Resonance Imaging; Magnetite Nanoparticles; Mice; Nanomedicine; Nanoparticles; Neoplasms; Oxidative Stress; T-Lymphocytes, Cytotoxic

Vitamin C (ascorbate) acts as an antioxidant and enzyme cofactor, and plays a vital role in human health. Vitamin C status can be affected by illness, with low levels being associated with disease due to accelerated turnover. However, robust data on the ascorbate status of patients with cancer are sparse. This study aimed to accurately measure ascorbate concentrations in plasma from patients with cancer, and determine associations with patient or tumor characteristics. We recruited 150 fasting patients with cancer (of 199 total recruited) from two cohorts, either prior to cancer surgery or during cancer chemo- or immunotherapy. A significant number of patients with cancer had inadequate plasma ascorbate concentrations. Low plasma status was more prevalent in patients undergoing cancer therapy. Ascorbate status was higher in women than in men, and exercising patients had higher levels than sedentary patients. Our study may prompt increased vigilance of ascorbate status in cancer patients.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Breast Neoplasms; Colonic Neoplasms; Exercise; Female; Health Surveys; Humans; Male; Middle Aged; Neoplasms; Nutritional Status; Risk Factors; Sedentary Behavior; Vitamins

cis- and trans-Platinum(iv) complexes with diaminetetracarboxylate coordination spheres possess the highly desirable property of exhibiting unusual resistance to reduction by blood serum components and endogenous reductants such as ascorbate. At the same time they are rapidly reduced in the intracellular environment of cancer cells. Consequently, they can potentially be tuned to remain intact in vivo until arrival at the tumour target where they are rapidly reduced to yield the active platinum(ii) species. However, in order to achieve this, uptake must be largely restricted to tumour cells and therefore uptake by healthy cells including red blood cells must be prevented. In this proof of concept study, we report on the effect of net charge as a means of controlling the uptake by red blood cells. Using 1H NMR spectroscopy we found that modifying the net charge of the complex does not influence the rate of reduction of the complexes by an excess of ascorbate. Using XANES spectroscopy we found that modifying the net charge of the platinum(iv) complexes decreased the extent of reduction in whole blood, although probably not to the degree needed for the optimal delivery to tumours. Therefore, it is likely to be necessary to adopt higher charges and/or additional strategies to keep platinum(iv) prodrugs out of blood cells.

Topics: Antineoplastic Agents; Ascorbic Acid; Cell Line, Tumor; Humans; Neoplasms; Organoplatinum Compounds; Oxidation-Reduction; Prodrugs; Serum; Static Electricity

Topics: Antineoplastic Agents; Ascorbic Acid; Dietary Supplements; Humans; Neoplasms; Vitamins

The transcription factor hypoxia-inducible factor 1 (HIF1) is the crucial regulator of genes that are involved in metabolism under hypoxic conditions, but information regarding the transcriptional activity of HIF1 in normoxic metabolism is limited. Different tumor cells were treated under normoxic and hypoxic conditions with various drugs that affect cellular metabolism. HIF1α was silenced by siRNA in normoxic/hypoxic tumor cells, before RNA sequencing and bioinformatics analyses were performed while using the breast cancer cell line MDA-MB-231 as a model. Differentially expressed genes were further analyzed and validated by qPCR, while the activity of the metabolites was determined by enzyme assays. Under normoxic conditions, HIF1 activity was significantly increased by (i) glutamine metabolism, which was associated with the release of ammonium, and it was decreased by (ii) acetylation via acetyl CoA synthetase (ACSS2) or ATP citrate lyase (ACLY), respectively, and (iii) the presence of L-ascorbic acid, citrate, or acetyl-CoA. Interestingly, acetylsalicylic acid, ibuprofen, L-ascorbic acid, and citrate each significantly destabilized HIF1α only under normoxia. The results from the deep sequence analyses indicated that, in HIF1-siRNA silenced MDA-MB-231 cells, 231 genes under normoxia and 1384 genes under hypoxia were transcriptionally significant deregulated in a HIF1-dependent manner. Focusing on glycolysis genes, it was confirmed that HIF1 significantly regulated six normoxic and 16 hypoxic glycolysis-associated gene transcripts. However, the results from the targeted metabolome analyses revealed that HIF1 activity affected neither the consumption of glucose nor the release of ammonium or lactate; however, it significantly inhibited the release of the amino acid alanine. This study comprehensively investigated, for the first time, how normoxic HIF1 is stabilized, and it analyzed the possible function of normoxic HIF1 in the transcriptome and metabolic processes of tumor cells in a breast cancer cell model. Furthermore, these data imply that HIF1 compensates for the metabolic outcomes of glutaminolysis and, subsequently, the Warburg effect might be a direct consequence of the altered amino acid metabolism in tumor cells.

Topics: Acetylation; Ascorbic Acid; Carbonic Anhydrase IX; Cell Line, Tumor; Energy Metabolism; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Glutamine; Glycolysis; High-Throughput Nucleotide Sequencing; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; Protein Stability; RNA, Small Interfering

In order to assess the possibility of using liposomes to stabilize various antioxidant compounds, we investigated the effect of liposomes (1,2-palmitoyl-phosphatidic acid (DPPA) and dipalmitoylphosphatidylcholine (DPPC)) on the effectiveness of antioxidants, hydrophilic vitamin C and lipophilic vitamin E, in model systems of normal epithelial MDCK cells and tumor Jurkat T cells. The effect of vitamins C, E and (C + E) in combination with DPPC and DPPA liposomes on Jurkat and MDCK cells depends on the dissolution or integration of these liposomes with hydrophobic sections of the cellular membrane, as well as the subsequent release of vitamins from liposomes. Based on the results of the study, it can be concluded that the studied liposomes can modulate the effects of C and E vitamins on normal and tumor cells. These data can be used to study the possible selective regulation of the activity of various hydrophobic and hydrophilic antioxidants on normal and tumor cells, which is especially important for creating antitumor drugs, as well as effective radioprotectors that protect healthy tissues from radiation damage during radiotherapy.

Topics: Antioxidants; Ascorbic Acid; Humans; Liposomes; Neoplasms; Vitamin E; Vitamins

Intravenous ascorbic acid (IVAA) has been used extensively as part of the management plan for cancer patients in various medical clinics throughout the United States. The current research team has evaluated its effectiveness in patients with cancer as part of an ongoing research program. However, no data are available that support the chemical stability of intravenously injectable ascorbic acid (AA) to ensure its safety and efficacy in that patient population. Its clinical use as well as its use in research conducted in US Food and Drug Administration-approved clinical trials require validation of its stability.. The study intended to evaluate the chemical stability of the compounded IVAA that it prepares.. The research team conducted a stability analysis within a 6-h period, a period longer than the time required for most infusions, which typically take approximately 2 h. The study evaluated the stability of AA intravenous sets, which are compounded solutions for clinical or hospital use. The IVAA was prepared in sterile water, together with magnesium chloride (MgCl) and calcium gluconate (CaGluc) as buffers.. The study took place at the Marcus Institute of Integrative Health at Thomas Jefferson University (Philadelphia, PA, USA).. The study was performed for 2 dosages of an infusion set: 75 g and 100 g of IVAA. Interval testing included pH, particulate matter by light obscuration, and high-performance liquid chromatography assay. Analyses were performed at baseline and at 2-, 4-, and 6-h test intervals.. The results demonstrated that IVAA remained highly stable throughout the 6-h period. It also passed the US Pharmacopeia's criteria for pH and particulates when used with a 0.2 µ filter.. These data suggest that IVAA, when prepared with sterile water, in addition to MgCl and CaGluc, is highly stable and safe to use in patients for up to 6 h after preparation.

Topics: Ascorbic Acid; Drug Stability; Humans; Infusions, Intravenous; Neoplasms; Pharmaceutical Solutions; United States

Lipid intakes such as saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids have been widely studied regarding cardiovascular health, but their relevance to cancer is unclear. Inconsistent epidemiological results may be explained by varied mechanisms involving PUFAs and redox balance, inflammatory status and cell signalling, along with interactions with other dietary components such as antioxidants, dietary fibre and more generally fruits and vegetable intakes. Therefore, this study aimed to investigate the associations between lipid intakes and cancer risk, and their potential modulation by vitamin C, vitamin E, dietary fibre and fruit and vegetable intakes.. This prospective study included 44,039 participants aged ≥ 45 years from the NutriNet-Santé cohort (2009-2017). Dietary data were collected using repeated 24 h-dietary records. Multivariable Cox models were performed to characterize associations.. SFA intake was associated with increased overall [n = 1722 cases, HR. These findings suggested that SFA intake could increase overall and breast cancer risks while some unsaturated fatty acids could decrease digestive cancer risk. However, in line with mechanistic hypotheses, our results suggest that intakes of fruits and vegetables and their constituents (antioxidants, fibre) may interact with PUFAs to modulate these associations.

Topics: Ascorbic Acid; Cohort Studies; Diet; Diet Records; Dietary Fats; Dietary Fats, Unsaturated; Female; France; Fruit; Humans; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Prospective Studies; Risk Assessment; Vegetables; Vitamin E; Vitamins

Ascorbate administered intravenously gives a high plasma concentration of this drug. Clinical trials with pancreatic carcinoma patients revealed their prolonged survival if treated with intravenous ascorbate. On the other hand, high plasma ascorbate concentration leads to severe side effects, such as nephrotoxicity. In the present paper, we advocate to lower intravenous ascorbate dosage along with monothiol N-acetylcysteine pretreatment due to anticipation of the same therapeutic effect but less or none of side effects. We describe in detail molecular mechanism of ascorbate action to be potentiated by N-acetylcysteine, as observed under in vitro conditions. Providing further arguments, we believe that the same mechanism may be employed in vivo.

Topics: Acetylcysteine; Administration, Intravenous; Antioxidants; Ascorbic Acid; Copper; Electron Spin Resonance Spectroscopy; Free Radicals; Humans; Hyaluronic Acid; Immune System; Kidney; Neoplasms; Pancreatic Neoplasms; Sulfhydryl Compounds

To investigate the demographic and lifestyles factors associated with vitamin C deficiency and to examine the association between plasma vitamin C level and self-reported physical functional health.. A population-based cross-sectional study using the European Prospective Investigation into Cancer-Norfolk study. Plasma vitamin C level < 11 µmol/L indicated vitamin C deficiency. Unconditional logistic regression models assessed the association between vitamin C deficiency and potential risk factors. Associations between quartiles of vitamin C and self-reported functional health measured by the 36-item short-form questionnaire (SF-36) were assessed.. After adjustment, vitamin C deficiency was associated with older age, being male, lower physical activity, smoking, more socially deprived area (Townsend index) and a lower educational attainment. Compared to the highest, those in the lowest quartile of vitamin C were more likely to score in the lowest decile of physical function (adjusted odds ratio (aOR): 1.43 (95%CI: 1.21-1.70)), bodily pain (aOR: 1.29 (95% CI: 1.07-1.56)), general health (aOR: 1.4 (95%CI: 1.18-1.66)), and vitality (aOR: 1.23 (95%CI: 1.04-1.45)) SF-36 scores.. Simple public health interventions should be aimed at populations with risk factors for vitamin C deficiency. Poor self-reported functional health was associated with lower plasma vitamin C levels, which may reflect symptoms of latent scurvy.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Europe; Female; Humans; Life Style; Male; Middle Aged; Neoplasms; Risk Factors; Self Report; Socioeconomic Factors; United Kingdom

Intravenous ascorbic acid (IV AA) has been used extensively in cancer patients throughout the United States. Currently, there are limited data on the safety and clinical effects of IV AA. The purpose of this study was to expand the current literature using a retrospective analysis of adverse events and symptomatic changes of IV AA in a large sample of cancer patients.. We conducted a retrospective chart review of all patients receiving IV AA for cancer at the Thomas Jefferson University Hospital over a 7-year period. We assessed all reports of adverse events, laboratory findings, and hospital or emergency department admissions. We also reviewed quality-of-life data, including fatigue, nausea, pain, appetite, and mood.. There were 86 patients who received a total of 3034 doses of IV AA ranging from 50 to 150g. In all, 32 patients received only ascorbic acid as part of their cancer management (1197 doses), whereas 54 patients received ascorbic acid in conjunction with chemotherapy (1837 doses). The most common adverse events related to ascorbic acid were temporary nausea and discomfort at the injection site. All events reported in the ascorbic acid alone group were associated with less than 3% of the total number of infusions. Patients, overall, reported improvements in fatigue, pain, and mood while receiving ascorbic acid.. The results of this retrospective analysis support the growing evidence that IV AA is generally safe and well tolerated in patients with cancer, and may be useful in symptom management and improving quality of life.

Topics: Administration, Intravenous; Adult; Affect; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Appetite; Ascorbic Acid; Cancer Pain; Fatigue; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Quality of Life; Retrospective Studies; Young Adult

Oxidative stress, the imbalance between pro- and antioxidants, has been implicated in the etiology and pathophysiology of the incidence and mortality of many diseases. We aim to investigate the relations of dietary intakes of vitamin C and E and main carotenoids with all-cause mortality in Japanese men and women.. The Japan Collaborative Cohort Study for Evaluation of Cancer Risk had 22,795 men and 35,539 women, aged 40-79 years at baseline (1988-1990), who completed a valid food frequency questionnaire and were followed up to the end of 2009.. There were 6,179 deaths in men and 5,355 deaths in women during the median follow-up of 18.9 years for men and 19.4 years for women. Multivariate hazard ratios for the highest versus lowest quintile intakes in women were 0.83 (95% confidence interval [CI], 0.76-0.90; P for trend < 0.0001) for vitamin C, 0.85 (95% CI, 0.78-0.93; P for trend < 0.0001) for vitamin E, 0.88 (95% CI, 0.81-0.96; P for trend = 0.0006) for β-carotene, and 0.90 (95% CI, 0.82-0.98; P for trend = 0.0002) for β-cryptoxanthin. The joint effect of any two of these highly correlated micronutrients showed significant 12-17% reductions in risk in the high-intake group compared with the low-intake group in women. These significant associations were also observed in the highest quintile intakes of vitamin C, vitamin E, and β-carotene in female non-smokers but were not observed in female smokers, male smokers, and non-smokers.. Higher dietary intakes of antioxidant vitamins may reduce the risk of all-cause mortality in middle-aged Japanese women, especially female non-smokers.

Topics: Adult; Aged; Ascorbic Acid; Carotenoids; Cause of Death; Cohort Studies; Diet; Female; Humans; Japan; Male; Middle Aged; Neoplasms; Risk; Vitamin E

Magnetic iron oxide nanoparticles (MNPs) have been prepared and stabilized with three organic acids (tartaric, malic and ascorbic) in order to obtain biocompatible and water dispersible MNPs with potential to bind specifically to tumoral cancer cells. An in deep characterization was performed aiming to verify the presence and effect of the coating and stabilizer on MNPs surface. Besides the mechanisms followed by the different acids to bind MNPs were elucidated and used to justify the differences in the physicochemical properties of each formulation. Data related to characterization revealed that MNPs coated with ascorbic acid (MNPs-AA) resulted the most suitable in terms of their size, surface charge and stability along the time. Besides, ascorbic acid may be recognized by GLUTs receptors that are overexpressed in several kinds of tumoral cells. Therefore, MNPs-AA was selected to explore its performance in both MRI and in vitro assays using human colon cancer cells HCT 116. MRI experiments were performed in clinical equipment using a series of aqueous dispersions of MNPs-AA that were evaluated as T

Topics: Ascorbic Acid; Contrast Media; Ferric Compounds; Humans; Magnetic Resonance Imaging; Magnetite Nanoparticles; Neoplasms; Particle Size; Surface Properties

Dietary supplementation is becoming more and more common among both healthy and unhealthy people. The use of supplements is often unjustified, though in some groups of patients it is a necessary management for providing the required vitamins and minerals.. The aim of the study was to assess the frequency of using antioxidant vitamin supplements (A, C and E) among the patients of the oncology ward.. The study group included 78 patients aged 19-83 years. The dietary intake of vitamins as well as the intake of supplements was assessed based on the data from the Food Frequency Questionnaire (FFQ).. It was observed that 46.2% of patients used some kind of a dietary supplement and 77.8% of them used antioxidant vitamins. Among those taking vitamin A, C or E supplements, 72.2% of women and 80% of men used multivitamins. It was reported that the average fulfillment of the recommended daily intake for vitamin A was 303 ±136%, for vitamin C it was 282 ±166% and for vitamin E it was 199 ±80%. More than 25% of the patients whose diets contained at least the same level of vitamins as dietary recommendations were using antioxidant vitamin supplements at the same time.. Although the average dietary intake of antioxidant vitamins among the patients was not insufficient, the use of dietary supplements in different forms was common in our study. The results of other studies concerning the safety of using dietary supplements by cancer patients are not conclusive. Dietary supplementation in oncological patients should always be used after a medical consultation with a doctor and a dietician.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Dietary Supplements; Female; Humans; Male; Middle Aged; Neoplasms; Vitamin A; Vitamin E; Vitamins; Young Adult

Vitamin C insufficiency occurs across many countries and has been hypothesised to increase risk of various diseases. Few prospective studies with measured circulating vitamin C have related deficiency to disease mortality, particularly in low-income and middle-income countries.. We randomly selected 948 subjects (473 males and 475 females) aged 53-84 years from a Chinese cohort and measured meta-phosphoric acid-preserved vitamin C concentrations in plasma samples collected in 1999-2000. A total of 551 deaths were accrued from sample collection through 2016, including 141 from cancer, 170 from stroke and 174 from heart diseases. Vitamin C was analysed using season-specific quartiles, as a continuous variable and as a dichotomous variable based on sufficiency status (normal >28 µmol/L vs low ≤28 µmol/L). HRs and 95% CIs were estimated using Cox proportional hazards models.. We found significant inverse associations between higher plasma vitamin C concentrations and total mortality in quartile (HR. In this long-term prospective Chinese cohort study, higher plasma vitamin C concentration was associated with lower total mortality, heart disease mortality and cancer mortality. Our results corroborate the importance of adequate vitamin C to human health.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Biomarkers; Cardiovascular Diseases; Cause of Death; China; Female; Humans; Male; Middle Aged; Mortality; Neoplasms; Prospective Studies; Seasons

AMP-activated kinase (AMPK) is a major regulator of energy metabolism and a promising target for development of new treatments for type 2 diabetes and cancer. 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an adenosine analog, is a standard positive control for AMPK activation in cell-based assays. Some broadly used cell culture media, such as minimal essential medium α (MEMα), contain high concentrations of adenosine and other nucleosides. We determined whether such media alter AICAR action in skeletal muscle and cancer cells. In nucleoside-free media, AICAR stimulated AMPK activation, increased glucose uptake, and suppressed cell proliferation. Conversely, these effects were blunted or completely blocked in MEMα that contains nucleosides. Addition of adenosine or 2'-deoxyadenosine to nucleoside-free media also suppressed AICAR action. MEMα with nucleosides blocked AICAR-stimulated AMPK activation even in the presence of methotrexate, which normally markedly enhances AICAR action by reducing its intracellular clearance. Other common media components, such as vitamin B-12, vitamin C, and α-lipoic acid, had a minor modulatory effect on AICAR action. Our findings show that nucleoside-containing media, commonly used in AMPK research, block action of the most widely used pharmacological AMPK activator AICAR. Results of cell-based assays in which AICAR is used for AMPK activation therefore critically depend on media formulation. Furthermore, our findings highlight a role for extracellular nucleosides and nucleoside transporters in regulation of AMPK activation.

Topics: Adenosine; Aminoimidazole Carboxamide; AMP-Activated Protein Kinase Kinases; Ascorbic Acid; Cell Line, Tumor; Culture Media; Diabetes Mellitus, Type 2; Energy Metabolism; Glucose; Humans; Muscle, Skeletal; Neoplasms; Nucleosides; Protein Kinases; Ribonucleotides; Thioctic Acid; Vitamin B 12

Topics: Ascorbic Acid; Cardiovascular Diseases; China; Diet; Humans; Neoplasms; Seasons

Pharmacodynamic interactions of three anthracycline antibiotics namely doxorubicin (DXH), epirubicin (EpiDXH) and daunorubicin (DNR) with DNA in the absence and presence of ascorbic acid (AA) as natural additive were monitored under physiological conditions (pH = 7.4, 4.7 and T = 309.5K). Route-1 (Anthracycline-AA-DNA) and Route-2 (Anthracycline-DNA-AA) were adopted to see the interactional behavior by cyclic voltammetry (CV) and UV-visible spectroscopy. In comparison to Route-2; voltammetric and spectral responses as well as binding constant (Kb) and Gibb's free energy change (ΔG) values revealed strongest and more favorable interaction of anthracycline-AA complex with DNA via Route-1. Kb, s (binding site sizes) and ΔG evaluated from experimental (CV, UV-Vis) and theoretical (molecular docking) findings showed enhanced binding strength of tertiary complexes as compared to binary drug-DNA complexes. The results were found comparatively better at pH 7.4. Consistency was observed in binding parameters evaluated from experimental and theoretical techniques. Diffusion coefficients (Do) and heterogeneous electron transfer rate constant (ks,h) confirmed the formation of complexes via slow diffusion kinetics. Percent cell inhibition (%Cinh) of anthracyclines for non-small cell cancer cell lines (NSCCLs) H-1299 and H-157 were evaluated higher in the presence of AA which further complimented experimental and theoretical results.

Topics: Antibiotics, Antineoplastic; Antioxidants; Ascorbic Acid; Cardiotoxicity; Cell Line, Tumor; Cell Proliferation; Daunorubicin; DNA; Doxorubicin; Drug Interactions; Epirubicin; Humans; Hydrogen-Ion Concentration; Molecular Docking Simulation; Neoplasms

Topics: Ascorbic Acid; Humans; Leukemia; Neoplasms; Neoplastic Stem Cells; Stem Cells; Vitamins

The purpose of this study is to assess the efficacy of oral Vitamin C as an opioid-sparing agent when used in conjunction with opioids and standard adjuvant therapy in the management of chronic cancer pain.. An open-label pilot study of patients ≥18 years of age with chronic pain secondary to cancer and/or its treatment and a Brief Pain Inventory average pain score of ≥3/10. In addition to opioid analgesia, patients received 1 g of vitamin C twice daily over 3 days (total daily dose of 2 g). Patients' usual medications, including breakthrough medications, were continued throughout the study period. The primary endpoint was total daily opioid use during vitamin C administration compared with that immediately prior to study.. Thirty-four patients were enrolled in the study. Seven failed to complete the trial. Across the 17 evaluable patients, the median daily opioid consumption was 360 mg oral morphine equivalents (OME) on the days prior to vitamin C and 390 mg when administered with vitamin C.. This study failed to demonstrate any clinically significant benefit from vitamin C in conjunction with opioids in cancer-related pain and does not provide support for embarking on a larger randomised trial to determine efficacy.

Topics: Administration, Oral; Aged; Aged, 80 and over; Analgesics, Opioid; Ascorbic Acid; Chronic Pain; Female; Humans; Male; Middle Aged; Neoplasms; Pilot Projects

Water-soluble, biocompatible, and photoluminescent carbon nanodots have been obtained from the rationalized carbonization of vitamin C, a well-known antioxidant molecule in the presence of an amine co-reactant. Herein, we describe the positive influence of N-doping to induce a unique pH-dependent lifetime decay response that would be potentially attractive in biological backgrounds with intrinsic fluorescence fluctuations. In addition, the selectivity and sensitivity of the N-containing carbon nanoprobes towards the detection of copper ions at ppm levels is critically enhanced in comparison with the un-doped counterpart, especially in the near-infrared (NIR) range. Finally, the up-converting properties have been also successfully applied to image tumor cells in the visible range and remarkably, in the NIR region in which minimal tissue or water absorption and maximum penetration depth are expected.

Topics: Ascorbic Acid; Carbon; Cell Line, Tumor; Copper; Humans; Infrared Rays; Luminescent Agents; Luminescent Measurements; Nanoparticles; Neoplasms; Nitrogen; Optical Imaging

Cancer cell toxicity to therapeutic H2O2 varies widely depending on cell type. Interestingly, it has been observed that different cancer cell types have varying peroxiporin expression. We hypothesize that variation in peroxiporin expression can alter cell susceptibility to therapeutic H2O2 concentrations. Here, we silence peroxiporin aquaporin-3 (AQP3) on the pancreatic cancer cell line MIA PaCa-2 and compare clonogenic survival response to the wild-type. The results showed a significantly higher surviving fraction in the clonogenic response for siAQP3 MIA PaCa-2 cells at therapeutic H2O2 doses (P < 0.05). These results suggest that peroxiporin expression is significant in modulating the susceptibility of cancer cells to ascorbate therapy.

Topics: Aquaporin 3; Ascorbic Acid; Cell Line, Tumor; Cell Survival; Gene Silencing; Humans; Hydrogen Peroxide; Immunohistochemistry; Neoplasms

Few studies have evaluated dietary antioxidant vitamins intake in relation to risk of mortality in Asia.. We examined the associations between total carotene, vitamin C, and vitamin E from diet and risk of mortality from all causes, cancer, and cardiovascular disease in 134,358 participants (59,739 men and 74,619 women) from the Shanghai Men's Health Study and Shanghai Women's Health Study, two prospective cohort studies of middle-aged and elderly Chinese adults in urban Shanghai. Participants were followed up for a median period of 8.3 and 14.2 years for men and women, respectively. Hazard ratios (HRs) and 95% confidence interval (CIs) were estimated using Cox proportional hazards regression models.. During the 495,332 and 1,029,198 person-years of follow-up for men and women, respectively, there were 10,079 deaths (4170 men and 5909 women). For men, compared with the lowest quintiles, the multivariable-adjusted risk reductions in the highest categories were 17% (HR 0.83; 95% CI, 0.76-0.92) for dietary total carotene and 17% (HR 0.83; 95% CI, 0.75-0.91) for dietary vitamin C. Associations were weaker in women than in men, though they were still statistically significant (highest versus lowest quintiles of dietary total carotene, HR 0.87; 95% CI, 0.80-0.95; dietary vitamin C: HR 0.83; 95% CI, 0.77-0.91). Significant inverse associations were observed between dietary total carotene, vitamin C, and risk of cardiovascular disease mortality but not cancer mortality.. This study suggests that total carotene and vitamin C intake from diet were inversely associated with deaths from all causes and cardiovascular disease in middle-aged or elderly people in China.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Asian People; Cardiovascular Diseases; Carotenoids; Cause of Death; China; Cohort Studies; Diet; Dietary Supplements; Dose-Response Relationship, Drug; Female; Humans; Male; Neoplasms; Proportional Hazards Models; Prospective Studies; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires; Vitamin E; Vitamins

A rapid, facile and ultrasensitive fluorescence sensing system based on nitrogen-doped carbon dots (N-doped CDs) for the detection of ascorbic acid (AA) was developed. The highly photoluminescent N-doped CDs with excellent solubility in water and good biocompatibility were prepared by a one-step hydrothermal synthesis and gave the fluorescence quantum yield of 47%. The addition of AA can intensively suppress the fluorescence of the N-doped CDs through the synergistic effect of the inner filter effect (IFE) and the static quenching effect (SQE). Benefited from the remarkable synergistic effect of IFE and SQE, a facile and ultrasensitive sensor was constructed successfully for AA sensing. The detection procedure was achieved within 2min. The linear response range of AA was obtained from 10

Topics: Animals; Ascorbic Acid; Biosensing Techniques; Brain; Carbon; Case-Control Studies; Fluorescence; Fluorescent Dyes; Healthy Volunteers; Humans; Limit of Detection; Male; Microdialysis; Neoplasms; Quantum Dots; Rats; Rats, Sprague-Dawley; Spectrometry, Fluorescence

The aim of the study was to assess the relationships between individual-level dietary intakes of antioxidant vitamins C, E and beta-carotene with all-cause and cause-specific mortality in three Central and Eastern European (CEE) populations.. Data from the Health, Alcohol and Psychosocial factors in Eastern Europe cohort study were used. At the baseline survey, between 2002 and 2005, 28,945 men and women aged 45-69 years were examined in Novosibirsk (Russia), Krakow (Poland) and seven Czech towns. Deaths in the cohorts were identified through mortality registers. Cox regression was used to estimate the association between vitamin consumption and all-cause, cardiovascular (CVD) disease and cancer mortality.. In multivariable-adjusted analyses, there were no clear inverse associations between antioxidant vitamin intakes and mortality, although in some groups, several hazard ratios (HRs) were significant. For example, in men, compared with the lowest quintile of vitamin C intake, all-cause mortality in the third and fourth quintiles was lower by 28 % (HR 0.72; 95 % CI 0.61-0.85) and by 20 % (HR 0.80; 95 % CI 0.68-0.95), respectively. CVD mortality was lower by 35 % (HR 0.65; 95 % CI 0.50-0.84) and by 23 % (HR 0.77; 95 % CI 0.59-0.99) in third and fourth quintile of vitamin C intake, respectively. In women, the third and fourth quintiles of dietary intake of vitamin E were associated with reduced risk of all-cause death by 33 % (HR 0.67; 95 % CI 0.53-0.84) and by 23 % (HR 0.77; 95 % CI 0.61-0.97), respectively. Consumption of vitamin C, vitamin E and beta-carotene was not related to CVD mortality in women and to cancer mortality in either gender.. This large prospective cohort study in CEE populations with low prevalence of vitamin supplementation did not find a strong, dose-response evidence for protective effects of antioxidant vitamin intake.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cause of Death; Czech Republic; Dietary Supplements; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Poland; Proportional Hazards Models; Prospective Studies; Risk Factors; Russia; Socioeconomic Factors; Surveys and Questionnaires; Urban Population; Vitamin E; Vitamins

Here, I address the topic of suitability for redox research of common settings in cell cultures. This is done through the prism of in vitro anticancer effects of vitamin C. Cell culture media show lower concentrations of iron and a higher level of oxygen compared to interstitial fluid. Such a setup promotes ascorbate-mediated production and accumulation of hydrogen peroxide, which efficiently kills a variety of cancer cell lines. However, the anticancer effects are annihilated if the iron level is corrected to mimic in vivo concentrations. It appears that the potential benefits of application of vitamin C in cancer treatment have been significantly overestimated. This might be true for other pro-oxidative agents as well, such as some (poly)phenols. We urgently need to establish medium formula and culture maintenance settings that are optimal for redox research.

Topics: Animals; Antioxidants; Ascorbic Acid; Cells, Cultured; Culture Media; Humans; Iron; Neoplasms; Oxidation-Reduction; Oxidative Stress

Introduction Intravenous high-dose vitamin C therapy is widely used in naturopathic and integrative oncology; however, a study reviewing its effects has never been performed in Singapore. This article serves to document administration of supportive vitamin C therapy for cancer patients in Singapore.. The clinical response of 9 cancer patients of differing stages to the regular administration of large doses (25-100 g/d) of intravenous vitamin C (IVC; ascorbic acid) is outlined. Tumor pathology and patient health were verified by doctors who do not practice vitamin C treatment.. Cases suggesting survival beyond prognosis, improvement in quality of life, safe coadministration with and improved tolerance of conventional therapy, and deterioration in clinical condition following withdrawal of vitamin C therapy are documented clinically. Some patients experience the Jarisch-Herxheimer reaction-the release of endotoxin from microorganism death resulting in pimples, fever, and body odor-for a few hours after the therapy, but these are resolved quickly with no lasting effects.. Randomized trials of IVC therapy are recommended because it has minimal side effects and has shown promising results.

Topics: Adult; Aged; Ascorbic Acid; Female; Humans; Male; Middle Aged; Neoplasms; Prognosis; Quality of Life; Singapore

Cytokines play an important role in tumor angiogenesis and inflammation. There is evidence in the literature that high doses of ascorbate can reduce inflammatory cytokine levels in cancer patients. The objective of this study was to investigate the effect of treatment by intravenous vitamin C (IVC) on cytokines and tumor markers.. With the availability of protein array kits allowing assessment of many cytokines in a single sample, we measured 174 cytokines and additional 54 proteins and tumor markers in 12 cancer patients before and after a series of IVC treatments.. Presented results show for our 12 patients the effect of treatment resulted in normalization of many cytokine levels. Cytokines that were most consistently elevated prior to treatments included M-CSF-R, Leptin, EGF, FGF-6, TNF-α, β, TARC, MCP-1,4, MIP, IL-4, 10, IL-4, and TGF-β. Cytokine levels tended to decrease during the course of treatment. These include mitogens (EGF, Fit-3 ligand, HGF, IGF-1, IL-21R) and chemo-attractants (CTAC, Eotaxin, E-selectin, Lymphotactin, MIP-1, MCP-1, TARC, SDF-1), as well as inflammation and angiogenesis factors (FGF-6, IL-1β, TGF-1).. We are able to show that average z-scores for several inflammatory and angiogenesis promoting cytokines are positive, indicating that they are higher than averages for healthy controls, and that their levels decreased over the course of treatment. In addition, serum concentrations of tumor markers decreased during the time period of IVC treatment and there were reductions in cMyc and Ras, 2 proteins implicated in being upregulated in cancer.

Topics: Adult; Antineoplastic Agents; Ascorbic Acid; Biomarkers, Tumor; Case-Control Studies; Cytokines; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Infusions, Intravenous; Male; Middle Aged; Neoplasms; Neovascularization, Pathologic; Proto-Oncogene Proteins c-myc; ras Proteins; Up-Regulation

Owing to the excellent near infrared (NIR) light absorption and efficient passive targeting toward tumor tissue, two-dimensional (2D) core-shell PEGylated Pd@Au nanoplates have great potential in both photothermal therapy and drug delivery systems. In this work, we successfully conjugate Pd@Au nanoplates with a platinum(IV) prodrug c,c,t-[Pt(NH3)2Cl2(O2CCH2CH2CO2H)2] to obtain a nanocomposite (Pd@Au-PEG-Pt) for combined photothermal-chemotherapy. The prepared Pd@Au-PEG-Pt nanocomposite showed excellent stability in physiological solutions and efficient Pt(IV) prodrug loading. Once injected into biological tissue, the Pt(IV) prodrug was easily reduced by physiological reductants (e.g. ascorbic acid or glutathione) into its cytotoxic and hydrophilic Pt(II) form and released from the original nanocomposite, and the NIR laser irradiation could accelerate the release of Pt(II) species. More importantly, Pd@Au-PEG-Pt has high tumor accumulation (29%ID per g), which makes excellent therapeutic efficiency at relatively low power density possible. The in vivo results suggested that, compared with single therapy the combined thermo-chemotherapy treatment with Pd@Au-PEG-Pt resulted in complete destruction of the tumor tissue without recurrence, while chemotherapy using Pd@Au-PEG-Pt without irradiation or photothermal treatment using Pd@Au-PEG alone did not. Our work highlights the prospects of a feasible drug delivery strategy of the Pt prodrug by using 2D Pd@Au nanoplates as drug delivery carriers for multimode cancer treatment.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Cell Line; Cisplatin; Drug Carriers; Drug Delivery Systems; Drug Therapy; Female; Glutathione; Gold; HeLa Cells; Humans; Metal Nanoparticles; Mice; Mice, Inbred BALB C; Microscopy, Electron, Transmission; Nanocomposites; Nanotechnology; Neoplasms; Phototherapy; Platinum; Prodrugs; Spectroscopy, Near-Infrared

Supra-physiological concentrations of ascorbate, vitamin C, in blood, greater than 1mM, achieved through intravenous administration (IV), are being tested in clinical trials to treat human disease, e.g. cancer. These trials need information on the high levels of ascorbate achieved in blood upon IV administration of pharmacological ascorbate so appropriate clinical decisions can be made.. Here we demonstrate that in the complex matrix of human blood plasma supra-physiological levels of ascorbate can be quantified by direct UV spectroscopy with use of a microvolume UV-vis spectrophotometer.. Direct quantitation of ascorbate in plasma in the range of 2.9mM, lower limit of detection, up to at least 35mM can be achieved without any sample processing, other than centrifugation.. This approach is rapid, economical, and can be used to quantify supraphysiological blood levels of ascorbate associated with the use of IV administration of pharmacological ascorbate to treat disease.

Topics: Administration, Intravenous; Ascorbic Acid; Humans; Neoplasms; Spectrophotometry, Ultraviolet

The discovery that oxidized vitamin C, dehydroascorbate (DHA), can induce oxidative stress and cell death in cancer cells has rekindled interest in the use of high dose vitamin C (VC) as a cancer therapy. However, high dose VC has shown limited efficacy in clinical trials, possibly due to the decreased bioavailability of oral VC. Because human erythrocytes express high levels of Glut1, take up DHA, and reduce it to VC, we tested how erythrocytes might impact high dose VC therapies. Cancer cells are protected from VC-mediated cell death when co-cultured with physiologically relevant numbers of erythrocytes. Pharmacological doses of VC induce oxidative stress, GSH depletion, and increased glucose flux through the oxidative pentose phosphate pathway (PPP) in erythrocytes. Incubation of erythrocytes with VC induced hemolysis, which was exacerbated in erythrocytes from glucose-6-phosphate dehydrogenase (G6PD) patients and rescued by antioxidants. Thus, erythrocytes protect cancer cells from VC-induced oxidative stress and undergo hemolysis in vitro, despite activation of the PPP. These results have implications on the use of high dose VC in ongoing clinical trials and highlight the importance of the PPP in the response to oxidative stress.

Topics: Ascorbic Acid; Cell Line, Tumor; Dehydroascorbic Acid; Erythrocytes; Glucose; Glucose Transporter Type 1; Glucosephosphate Dehydrogenase; Glutathione; Hemolysis; Humans; Neoplasms; Oxidation-Reduction; Oxidative Stress; Pentose Phosphate Pathway

Psidium guajava (Myrtaceae) is an evergreen shrub growing extensively throughout the tropical and subtropical areas. Four new compounds, guavinoside C, D, E and F (1-3, 10) were isolated from the leaves of P. guajava, along with six known ones (4-9). Their structures were elucidated by spectroscopic analysis. Compounds 1, 4 and 10 showed significant cytotoxic activities on HeLa, SGC-7901 and A549 cell lines, respectively. Compounds 1 and 4-10 showed antioxidant activities in DPPH, ABTS and FRAP assays, and five of them (1, 4-6, 10) exhibited stronger activities than that of vitamin C.

Topics: Antineoplastic Agents; Antioxidants; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; HeLa Cells; Humans; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Neoplasms; Plant Extracts; Plant Leaves; Psidium

We assessed the prevalence, patterns and predictors of dietary supplement use among participants of the databank and biorepository (DBBR) at a comprehensive cancer centre in western New York.. Archived epidemiological questionnaire data were obtained from the DBBR at Roswell Park Cancer Institute. Descriptive statistics and logistic regression explored the prevalence, patterns and predictors of lifetime use of four common supplements (multivitamins, vitamin C, vitamin E and calcium) and use of multivitamins, sixteen single vitamins/minerals and eighteen herbal/specialty supplements within the previous 10 years.. Western New York, USA.. DBBR participants (n 8096) enrolled between December 2003 and July 2012 were included in these analyses: 66.9 % (n 5418) with cancer, 65.6 % (n 5309) women, mean age for patients v. cancer-free controls 59.9 (SD 12.6) years and 50.7 (SD 15.4) years, respectively.. Overall, 54.4 % of DBBR participants reported lifetime use of one or more supplements and 63.1 % reported use of one or more supplements within the previous 10 years (excluding multivitamins). Multivitamin use was high in this sample (lifetime: 64.1 %; 10 years: 71.3 %; current: 51.8 %). Supplementation was higher among cancer-free controls than cancer patients. Vitamin C, calcium and fish oil were the most common single vitamin, mineral and specialty product, respectively.. A consistently high and increasing proportion of dietary supplement use over time remains clear. Supplementation is prevalent among cancer patients and may even be higher than predicted in cancer-free individuals. Further studies should assess the safety and efficacy of specific supplements in reducing disease risk.

Topics: Adult; Aged; Ascorbic Acid; Biological Specimen Banks; Calcium, Dietary; Cancer Care Facilities; Cohort Studies; Cross-Sectional Studies; Databases, Factual; Dietary Supplements; Female; Fish Oils; Humans; Logistic Models; Male; Middle Aged; Neoplasms; New York; Nutrition Policy; Patient Compliance; Prospective Studies; Surveys and Questionnaires; Vitamin E; Vitamins

Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner.

Topics: Ascorbic Acid; Cell Death; Cytotoxins; HCT116 Cells; Humans; MCF-7 Cells; Neoplasms; Nuclear Proteins; Proteolysis; Trans-Activators; Transcription Factors; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases; Ubiquitination

Potential risk of high-dose vitamin C consumption is often ignored. Recently, gram-dose vitamin C is being intravenously injected for the treatment of cancer, which can expose circulating blood cells to extremely high concentrations of vitamin C. As well as platelets, red blood cells (RBCs) can actively participate in thrombosis through procoagulant activation. Here, we examined the procoagulant and prothrombotic risks associated with the intravenous injection of gram-dose vitamin C. Vitamin C (0.5-5 mM) increased procoagulant activity of freshly isolated human RBCs via the externalization of phosphatidylserine (PS) to outer cellular membrane and the formation of PS-bearing microvesicles. PS exposure was induced by the dysregulation of key enzymes for the maintenance of membrane phospholipid asymmetry, which was from vitamin C-induced oxidative stress, and resultant disruption of calcium and thiol homeostasis. Indeed, the intravenous injection of vitamin C (0.5-1.0 g/kg) in rats in vivo significantly increased thrombosis. Notably, the prothrombotic effects of vitamin C were more prominent in RBCs isolated from cancer patients, who are at increased risks of thrombotic events. Vitamin C-induced procoagulant and prothrombotic activation of RBCs, and increased thrombosis in vivo. RBCs from cancer patients exhibited increased sensitivity to the prothrombotic effects of vitamin C, reflecting that intravenous gram-dose vitamin C therapy needs to be carefully revisited.

Topics: Adenosine Triphosphate; Animals; Ascorbic Acid; Blood Coagulation; Calcium; Erythrocytes; Flow Cytometry; Glutathione; Hemolysis; Humans; Injections, Intravenous; Leukemia; Male; Microscopy, Electron, Scanning; Neoplasms; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Thrombosis; Vitamins

Intravenous administration of high-dose vitamin C has recently attracted attention as a cancer therapy. High-dose vitamin C induces pro-oxidant effects and selectively kills cancer cells. However, the anticancer mechanisms of vitamin C are not fully understood. Here, we analyzed metabolic changes induced by vitamin C in MCF7 human breast adenocarcinoma and HT29 human colon cancer cells using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The metabolomic profiles of both cell lines were dramatically altered after exposure to cytotoxic concentrations of vitamin C. Levels of upstream metabolites in the glycolysis pathway and tricarboxylic acid (TCA) cycle were increased in both cell lines following treatment with vitamin C, while adenosine triphosphate (ATP) levels and adenylate energy charges were decreased concentration-dependently. Treatment with N-acetyl cysteine (NAC) and reduced glutathione (GSH) significantly inhibited vitamin C-induced cytotoxicity in MCF7 cells. NAC also suppressed vitamin C-dependent metabolic changes, and NAD treatment prevented vitamin C-induced cell death. Collectively, our data suggests that vitamin C inhibited energy metabolism through NAD depletion, thereby inducing cancer cell death.

Topics: Ascorbic Acid; Cell Survival; Energy Metabolism; Humans; Hydrogen Peroxide; MCF-7 Cells; Metabolome; Metabolomics; NAD; Neoplasms; Oxidative Stress

Despite the fact that Au-Ag hollow nanoparticles (HNPs) have gained much attention as ablation agents for photothermal therapy, the instability of the Ag element limits their applications. Herein, excess Au atoms were deposited on the surface of a Au-Ag HNP by improving the reduction power of l-ascorbic acid (AA) and thereby preventing the reaction between HAuCl4 and the Ag element in the Au-Ag alloy nanostructure. Significantly, the obtained Au-Ag@Au HNPs show excellent chemical stability in an oxidative environment, together with remarkable increase in extinction peak intensity and obvious narrowing in peak width. Moreover, finite-difference time-domain (FDTD) was used to simulate the optical properties and electric field distribution of HNPs. The calculated results show that the proportion of absorption cross section in total extinction cross section increases with the improvement of Au content in HNP. As predicted by the theoretical calculation results, Au-Ag@Au nanocages (NCs) exhibit a photothermal transduction efficiency (η) as high as 36.5% at 808 nm, which is higher than that of Au-Ag NCs (31.2%). Irradiated by 808 nm laser at power densities of 1 W/cm(2), MCF-7 breast cancer cells incubated with PEGylated Au-Ag@Au NCs were seriously destroyed. Combined together, Au-Ag@Au HNPs with enhanced chemical stability and improved photothermal transduction efficiency show superior competitiveness as photothermal agents.

Topics: Alloys; Antineoplastic Agents; Ascorbic Acid; Cell Survival; Drug Stability; Gold; Humans; MCF-7 Cells; Metal Nanoparticles; Nanostructures; Neoplasms; Phototherapy; Silver

Topics: Animals; Ascorbic Acid; Biological Transport; Free Radicals; Glucose; Glucose Transporter Type 1; Mice; Mutation; Neoplasms; Proto-Oncogene Proteins; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); ras Proteins; Vitamins

Megadose vitamin C (Vc) is one of the most enduring alternative treatments for diverse human diseases and is deeply engrafted in popular culture. Preliminary studies in the 1970s described potent effects of Vc on prolonging the survival of patients with terminal cancer, but these claims were later criticized. An improved knowledge of the pharmacokinetics of Vc and recent reports using cancer cell lines have renewed the interest in this subject. Despite these findings, using Vc as an adjuvant for anticancer therapy remains questionable, among other things because there is no proper mechanistic understanding. Here, we show that a Warburg effect triggered by activation of the hypoxia-inducible factor (HIF) pathway greatly enhances Vc-induced toxicity in multiple cancer cell lines, including von Hippel-Lindau (VHL)-defective renal cancer cells. HIF increases the intracellular uptake of oxidized Vc through its transcriptional target glucose transporter 1 (GLUT1), synergizing with the uptake of its reduced form through sodium-dependent Vc transporters. The resulting high levels of intracellular Vc induce oxidative stress and massive DNA damage, which then causes metabolic exhaustion by depleting cellular ATP reserves. HIF-positive cells are particularly sensitive to Vc-induced ATP reduction because they mostly rely on the rather inefficient glycolytic pathway for energy production. Thus, our experiments link Vc-induced toxicity and cancer metabolism, providing a new explanation for the preferential effect of Vc on cancer cells.

Topics: Ascorbic Acid; Basic Helix-Loop-Helix Transcription Factors; Cytotoxins; DNA Damage; Glucose Transporter Type 1; HeLa Cells; Humans; Neoplasms; Oxidative Stress; Signal Transduction; Von Hippel-Lindau Tumor Suppressor Protein

Strong clinical and experimental evidence demonstrates association of elevated levels of matrix metalloproteinase MMP-9 with cancer progression, metastasis and shortened patient survival, as it plays a key role in tumor cell invasion and metastasis by digesting the basement membrane and ECM components. MMP-9 is secreted in both the monomeric and dimeric form. Although there is little research on MMP-9 dimers, some studies have shown the dimer to be associated with more aggressive tumor progression. Our objective was to study the relative secretion patterns of MMP-9 monomer and dimer in a variety of cancer cell lines and the effect of a nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract on MMP-9 secretion. The cancer cell lines were grown in their respective media, supplemented with 10% FBS, penicillin (100 U/ml) and streptomycin (100 µg/ml) in 24-well tissue culture plates. At near confluence, the cells were treated with NM at 0,10, 50, 100, 500 and 1000 µg/ml. Parallel sets of cultures were treated with PMA (100 ng/ml) for induction of MMP-9. Cell MMP-9 secretion was assayed by gelatinase zymography. MMP-9 dimer secretion patterns of cancer cells fell into different categories. We observed no MMP-9 dimer in prostate DU-145 and PC-3, pancreatic MIA-Pa-Ca2, colon HCT-116, bladder T-24, head and neck FaDu, glioblastoma A-172, T-98 and LN-18 and leukemia HL-60, Jurkat, and Raji cell lines. MMP-dimer secretion only with PMA induction was seen in breast MCF-7 and MDA-MB-231, uterine SK-UT-1, lung A-549, tongue SC-25, melanoma A2058, osteosarcoma U-2OS, rhabdomyosarcoma, fibrosarcoma HT-1080, chondrosarcoma SW-1350 and liposarcoma SW-872. Cervical HeLa and DoTc 2 4510, renal 786-0 and HCC SK-Hep-1 cells exhibited MMP-9 dimer without PMA treatment and increased secretion with PMA treatment. Sarcomas had the highest levels of MMP-9 monomer and dimer with and without PMA among these cancer cell lines. Cervical, uterine and male breast cancer cell lines showed the next highest levels of MMP-9, followed by breast cancer cell lines. Melanoma, renal, lung, head and neck and HCC showed lower levels and prostate, glioblastoma, bladder and leukemia cell lines the lowest. NM showed dose-dependent inhibition of MMP-9 monomer and dimer in all cell lines tested. In conclusion, high MMP-9 and dimer secretion levels correlated with the most aggressive cancer cell lines. NM was effective in inhibiting MMP-9 and dimer secretion in all cell line

Topics: Antioxidants; Ascorbic Acid; Dimerization; Gelatinases; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Lysine; Matrix Metalloproteinase 9; Neoplasms; Proline; Urokinase-Type Plasminogen Activator

The addition of high-dose ascorbate to existing anticancer treatment strategies can improve efficacy and decrease toxicity--but not in all patients or with all combination therapies (Ma et al., this issue).

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Drug Synergism; Humans; Neoplasms

Topics: Adult; Ascorbic Acid; Feeding Behavior; Female; Health Surveys; Healthy Volunteers; Humans; Male; Middle Aged; Neoplasms; New Zealand; Recommended Dietary Allowances; Vitamins

Topics: Aged, 80 and over; Ascorbic Acid; Fatigue; Humans; Male; Neoplasms; Pain; Palliative Care; Quality of Life; Terminally Ill

Xanthohumol (1) and xanthohumol D (2) were isolated from spent hops. Isoxanthohumol (3) was obtained from xanthohumol by isomerisation in alkaline solution. Six metabolites were obtained as a result of transformation of xanthohumol (1) by selected fungal cultures. Their structures were established on the basis of their spectral data. One of them: 2″-(2'''-hydroxyisopropyl)-dihydrofurano-[4″,5″:3',4']-4',2-dihydroxy-6'-methoxy-α,β-dihydrochalcone (6) has not been previously reported in the literature. The antioxidant properties of hops flavonoids and xanthohumol derivatives were investigated using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. The effects of these compounds on proliferation of MCF-7, PC-3 and HT-29 human cancer cell lines were determined by the SRB assay. With the exception of one metabolite, all tested compounds showed antiproliferative activity against the tested human cancer lines. α,β-Dihydroxanthohumol (4), obtained through the biotransformation of xanthohumol, showed higher antiproliferative activity against MCF-7 human breast carcinoma cell line than cisplatin, a widely used anticancer therapeutic agent, and a comparably high activity against PC-3 human prostate cancer cell line.

Topics: Antineoplastic Agents; Antioxidants; Biotransformation; Cell Line, Tumor; Cell Proliferation; Flavonoids; Fungi; Humans; Humulus; Neoplasms; Propiophenones

Nanobubbles and microbubbles are non-invasive ultrasound imaging contrast agents that may potentially enhance diagnosis of tumors. However, to date, both nanobubbles and microbubbles display poor in vivo tumor-selectivity over non-targeted organs such as liver. We report here cyanine 5.5 conjugated nanobubbles (cy5.5-nanobubbles) of a biocompatible chitosan-vitamin C lipid system as a dual ultrasound-fluorescence contrast agent that achieved tumor-selective imaging in a mouse tumor model. Cy5.5-nanobubble suspension contained single bubble spheres and clusters of bubble spheres with the size ranging between 400-800 nm. In the in vivo mouse study, enhancement of ultrasound signals at tumor site was found to persist over 2 h while tumor-selective fluorescence emission was persistently observed over 24 h with intravenous injection of cy5.5-nanobubbles. In vitro cell study indicated that cy5.5-flurescence dye was able to accumulate in cancer cells due to the unique conjugated nanobubble structure. Further in vivo fluorescence study suggested that cy5.5-nanobubbles were mainly located at tumor site and in the bladder of mice. Subsequent analysis confirmed that accumulation of high fluorescence was present at the intact subcutaneous tumor site and in isolated tumor tissue but not in liver tissue post intravenous injection of cy5.5-nanobubbles. All these results led to the conclusion that cy5.5-nanobubbles with unique crosslinked chitosan-vitamin C lipid system have achieved tumor-selective imaging in vivo.

Topics: Animals; Ascorbic Acid; Carbocyanines; Cell Line, Tumor; Contrast Media; Diagnostic Imaging; Female; Mice; Mice, Inbred BALB C; Microbubbles; Neoplasms; Ultrasonography

A method based on combining inductively coupled plasma mass spectrometry (ICP-MS) with capillary electrophoresis (CE) or an ultrafiltration step was developed to study the speciation of the serum-protein adducts of a ruthenium anticancer drug under in vitro intracellular conditions. The formation of a reactive Ru species in the cell, following the metal release from the protein, is thought to play an important role in the drug's mode of action. Glutathione and ascorbic acid at their cancer cytosol concentrations were shown to be capable of altering the metal speciation in the drug adduct with holo-transferrin but not that with albumin. The appearance of the additional peaks in ICP-MS electropherograms (by recording both Ru- and Fe-specific signals) was found to be dependent on time which allowed for kinetic assessment of the evolution of novel metal species. On the contrary, after the addition of citric acid the ruthenium ion (within the appropriately complexed scaffold) remained sequestered in the adduct. This was inferred as a proof of the speciation changes taking place by a virtue of a redox mechanism rather than due to ligand-exchange transformations. The protein-bound metallodrug was further characterized by direct ICP-MS assaying so as to confirm a partial release of ruthenium induced by glutathione.

Topics: Antineoplastic Agents; Ascorbic Acid; Blood Proteins; Cell Proliferation; Cytosol; Drug Design; Electrophoresis, Capillary; Glutathione; Humans; Ligands; Mass Spectrometry; Neoplasms; Oxidation-Reduction; Protein Binding; Ruthenium; Time Factors; Transferrin

A simple method of using fingerstick blood glucose (FSBG) monitors to estimate blood ascorbate values after high-dose intravenous (IV) ascorbate infusion is evaluated as a substitution for high-performance liquid chromatography (HPLC) measurement.. In 33 participants, readings from FSBG monitors were taken before and after IV ascorbate infusions at various time points, with the postinfusion FSBG readings subtracted from the baseline glucose readings. The results of the subtractions (AAFSBG) were correlated with ascorbate concentrations detected by HPLC (AAHPLC).. A linear regression was found between ascorbate concentrations detected by the fingerstick method (AAFSBG) and by HPLC (AAHPLC). The linear correlations were identical in healthy subjects, diabetic subjects, and cancer patients. Analysis of variance obtained an AAFSBG/AAHPLC ratio of 0.90, with a 90% confidence interval of (0.69, 1.20). The corrections of AAFSBG improved similarity to AAHPLC but did not significantly differ from the uncorrected values.. The FSBG method can be used as an approximate estimation of high blood ascorbate concentration after IV ascorbate (>50 mg/dL, or 2.8 mM) without correction. However, this measurement is not accurate in detecting lower or baseline blood ascorbate. It is also important to highlight that in regard to glucose monitoring, FSBG readings will be erroneously elevated following IV ascorbate use and insulin should not be administered to patients based on these readings.

Topics: Ascorbic Acid; Blood Glucose; Chromatography, High Pressure Liquid; Diabetes Mellitus; Dose-Response Relationship, Drug; Humans; Infusions, Intravenous; Linear Models; Neoplasms; Reproducibility of Results

Observational studies have suggested that antioxidant nutrients may reduce cancer and overall mortality risks. However, most randomized trials have failed to show survival benefits. Examining nonlinear associations between antioxidant levels and health outcomes may help to explain these discrepant findings.. We evaluated all-cause, cancer, and cardiovascular mortality risks associated with quintiles (Q1-Q5) of serum antioxidant (vitamins C and E, β-carotene, and selenium) and vitamin A levels, in 16,008 adult participants of The Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994).. Over a median follow-up period of 14.2 years, there were 4,225 deaths, including 891 from cancer and 1,891 from cardiovascular disease. We observed a dose-response decrease in cancer and overall mortality risks with higher vitamin C levels. In contrast, for vitamin A, risk of cancer death decreased from Q1-Q2, with no further decline in risk at higher levels. For vitamin E, having levels in Q4 was associated with the lowest cancer mortality risk. Both vitamin A and E had U-shaped associations with all-cause mortality. Cancer mortality risks decreased from Q1-Q2 for β-carotene and from Q1-Q4 for selenium. However, for β-carotene and selenium, overall mortality risks decreased from Q1-Q2 but then did not change significantly with higher levels.. Antioxidant supplement use should be studied in the context of overall mortality and other competing mortality risks.. These data suggest the need for novel intervention studies where doses of these agents are individualized based on their serum levels, and possibly, markers of oxidative stress and systemic inflammatory response.

Topics: Adult; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Male; Neoplasms; Nutrition Surveys; Selenium; United States; Vitamin A; Young Adult

Ascorbic acid (vitamin C, ascorbate) is a key water soluble antioxidant that, when administered in doses well above its recommended dietary allowance, may have preventative and therapeutic value against a number of pathologies. The intravenous administration of high dose ascorbate (IVC) has increased in popularity among complementary and alternative medicine practitioners: thousands of patients received IVC, at an average dose of 0.5 g/kg, without significant side effects. While IVC may have a variety of possible applications, it has generated the most interest for its potential use in treating cancer.. Medical records of patients with cancer treated with IVC at the Riordan Clinic were retrospectively reviewed. Cancer patients, for whom plasma ascorbate concentration data before and after treatment were available, along with C-reactive protein (CRP) measurements, were chosen for analysis.. The results of the analysis can be summarized as follows. IVC produces peak plasma ascorbate concentrations on the order of ten millimolars with lower peak plasma concentrations obtained in cancer patients as compared to healthy subjects. Cancer patients who are deficient in vitamin C prior to therapy tend to achieve lower plasma levels post infusion. High inflammation or tumor burdens, as measured by CRP or tumor antigen levels, tend to lower peak plasma ascorbate levels after IVC. When compared to patients with localized tumors, patients with metastatic tumors tend to achieve lower post infusion plasma ascorbate concentrations.. The data indicate that, while potentially therapeutic plasma ascorbate concentrations can be achieved with IVC, levels attained will vary based on tumor burden and degree of inflammation (among other factors). Evidence suggests that IVC may be able to modulate inflammation, which in turn might improve outcomes for cancer patients. IVC may serve as a safe, adjunctive therapy in clinical cancer care.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Biomarkers, Tumor; C-Reactive Protein; Female; Humans; Inflammation; Male; Middle Aged; Neoplasms

Topics: Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Female; Humans; Male; Neoplasms; Selenium; Vitamin A

In this paper, a simple and sensitive sandwich-type photoelectrochemical (PEC) immunosensor for measurement of biomarkers on a gold nanoparticle-modified indium tin oxide (ITO) electrode through electrodeposition for point-of-care testing was developed by using a tin dioxide quantum dot-graphene nanocomposite (G-SnO2) as an excellent label with amplification techniques. The capture antibody (Ab1) was firstly immobilized on the gold nanoparticle-modified ITO electrode due to the covalent conjugation, then the antigen and the AuNP/PDDA-G-SnO2 nanocomposite nanoparticle labeled signal antibody (Ab2) were conjugated successively to form a sandwich-type immunocomplex through a specific interaction. Under irradiation with a common ultraviolet lamp (∼365 nm, price $50), the SnO2 NPs were excited and underwent charge-separation to yield electrons (e(-)) and holes (h(+)). As the holes were scavenged by ascorbic acid (AA), the electrons were transferred to the ITO electrode through RGO to generate a photocurrent. The photocurrents were proportional to the CEA concentrations, and the linear range of the developed immunosensor was from 0.005 to 10 ng mL(-1) with a detection limit of 0.036 pg mL(-1). The proposed sensor shows high sensitivity, stability, reproducibility, and can become a promising platform for other biomolecular detection.

Topics: Ascorbic Acid; Electrochemical Techniques; Gold; Graphite; Light; Metal Nanoparticles; Microscopy, Electron, Transmission; Neoplasms; Photochemical Processes; Quantum Dots; Tin Compounds; Ultraviolet Rays

Several phenylaminopyrimidoisoquinolinequinones (APIQs) were tested for their cytotoxicity against different cancer cell lines (K562, T24, HepG2) in the presence or absence of ascorbate. Ascorbate enhanced the toxic effects of quinones with first half-wave potential E(I) (1/2) values in the range of -480 to -660 mV. Phenylaminoquinones that were unsubstituted at position 6 exhibited greater cytotoxic activity than did their 6-methyl-substituted analogues. Two groups of compounds were further selected, namely 8-10 and 20-22, to study the cellular mechanisms involved in quinone cytotoxicity. Indeed, these compounds have the same range of redox potentials but differed considerably in their capacity to induce cell death. In the presence of ascorbate, the cell demise induced by compounds 8-10 was not caspase-3 dependent, as shown by the lack of activation of caspase-3 and the absence of cleaved PARP fragments. In addition, an index of ER stress (eIF2α phosphorylation) was activated by these compounds. Quinones 8-10 decreased the cellular capacity to reduce MTT dye and caused marked ATP depletion. Taken together, our results show that ascorbate enhances quinone redox-cycling and leads to ROS formation that inhibits cell proliferation and provokes caspase-independent cell death. Interestingly, we also observed that quinone 8 had a rather selective effect given that freshly isolated peripheral blood leukocytes from human healthy donors were more resistant than human leukemia K562 cells.

Topics: Adult; Ascorbic Acid; Caspase 3; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cells, Cultured; Cytostatic Agents; Female; Humans; L-Lactate Dehydrogenase; Leukocytes; Male; Middle Aged; Necrosis; Neoplasms; Oxidation-Reduction; Oxidative Stress; Poly(ADP-ribose) Polymerases; Quinolones; Reactive Oxygen Species

Oral mucositis (OM) is known to be a significant complication of chemotherapy preceding haematopoietic cell transplantation (HCT). Antioxidants (AOX) scavenge free radicals, which play a major role in the initiation of OM and may reduce the OM risk.. The primary objective of this prospective study was to investigate the association between the incidence and severity of OM (WHO oral toxicity scale) and the AOX status in buccal mucosa cells (BMC) and plasma. The α-tocopherol, ascorbic acid and ß-carotene concentrations in BMC and plasma were assessed at admission in 70 patients with a median age of 58 years before undergoing allogeneic HCT.. Severe OM (III-IV), ulcerative OM (II-IV) and no or mild OM (0-I) were documented in 14 (20.0%), 32 (45.7%) and 38 (54.3%) patients, respectively. We observed no significant differences in baseline AOX concentrations in plasma or BMC among the OM groups. However, between patients with at least one plasma AOX beneath the normal range (39/70) and those with all plasma AOX in the normal range (31/70), we noted a trend towards longer duration of parenteral nutrition (PN) during the study period (10 vs. 8 days; p = 0.066).. No single AOX, either in plasma or BMC (α-tocopherol, ascorbic acid and ß-carotene), revealed predictive value for the incidence or severity of OM. However, patients with an overall good plasma AOX status tended to require less PN, a common clinical marker for OM, which may be more relevant than any one AOX at reducing the risk of OM.

Topics: Adult; Aged; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Middle Aged; Mouth Mucosa; Neoplasms; Prospective Studies; Severity of Illness Index; Stomatitis; Transplantation Conditioning; Transplantation, Homologous

The commercial development of plants as sources of antioxidants that can be used to enhance the properties of foods, for nutritional purposes and preservation as well as for prevention of oxidation-related diseases, is currently of major interest. Rosehip (Rosa canina L.) is a rich source of vitamin C and polyphenols.. Phytochemicals in rosehip tea were separated into three fractions: Fr1 (vitamin C, 39.17 mg kg(-1)), Fr2 (flavonoids, 451.05 µg kg(-1)) and Fr3 (phenolic acids, 504.69 µg kg(-1)). Quercetin and ellagic acid were the most abundant polyphenolic compounds. Rosehip fractions, primarily rosehip flavonoids (EC(50) = 49 mg L(-1)), showed high antioxidant activity towards 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH(•)). Cell growth effects of rosehip fractions were assessed in HeLa, MCF7 and HT-29 cell lines, with the lowest IC(50) values being determined for rosehip flavonoids, (80.63, 248.03 and 363.95 mg L(-1) respectively). However, the vitamin C fraction did not inhibit the growth of tested tumour cells.. The results of this study confirm that vitamin C and flavonoids are responsible for the antioxidant activity of rosehip tea, while only polyphenols contribute to its antiproliferative activity.

Topics: Antineoplastic Agents, Phytogenic; Antioxidants; Ascorbic Acid; Biphenyl Compounds; Cell Line, Tumor; Ellagic Acid; Flavonoids; Free Radicals; Fruit; HeLa Cells; Humans; Inhibitory Concentration 50; Neoplasms; Phytotherapy; Picrates; Plant Extracts; Polyphenols; Quercetin; Rosa

Tumor establishment and penetration consists of a series of complex processes involving multiple changes in gene expression and protein modification. Proteome changes of tumor tissue were investigated after intraperitoneal administration of a high concentration of ascorbic acid in BALB/C mice implanted with CT-26 cancer cells using two-dimensional gel electrophoresis and mass spectrometry. Eighteen protein spots were identified whose expression was different between control and ascorbic acid treatment groups. In particular, eukaryotic translation initiation factor 3 subunit 1, nucleophosmin, latexin, actin-related protein 2/3 complex subunit 5, M2-type pyruvate kinase, vimentin, tumor protein translationally-controlled 1, RAS oncogene family Ran, plastin 3 precursor, ATPase, Rho GDT dissociation inhibitor β, and proteasome activator subunit 2 expression were quantitatively up-regulated. The increase in the level of these proteins was accompanied by an increase in mRNA level. The cytoskeleton protein actin, vimentin, and tumor protein translationally-controlled 1 showed quantitative expression profile differences. A change in actin cytoskeleton distribution, functionally relevant to the proteome result, was observed after treatment with ascorbic acid. These results suggest a previously undefined role of ascorbic acid in the regulation of cytoskeleton remodeling in tumor tissues.

Topics: Actin Cytoskeleton; Animals; Ascorbic Acid; Cell Line, Tumor; Electrophoresis, Gel, Two-Dimensional; Gene Expression Regulation; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; Neoplasms; Proteome; RNA, Messenger; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

The molecular basis of interaction of selected carotenoids and xanthophylls with ascorbic acid on cancer cells was studied to determine their anticancer effects.. Drug accumulation was measured in a human ABCB1 gene-transfected mouse lymphoma cell line and in a human lung cancer cell line by flow cytometry; furthermore, their anticancer effects were determined in mice in vivo.. Several carotenoids inhibited the multidrug resistance of cancer cells. Ascorbic acid improved the effect of certain xanthophylls, but the effect of capsanthin was not modified. Capsanthin had weak (12%) but capsorubin (85%) had a remarkable antiproliferative effect on A549 lung cancer cells. Capsorubin reduced immediate-early tumor antigen expression, while capsanthin was not effective. Capsorubin accumulates selectively in the nuclei of cancer cells.. The Authors suggest a special complex formation between membrane-bound capsorubin and ascorbic acid, which can be exploited in experimental chemotherapy.

Topics: Animals; Ascorbic Acid; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Humans; Lung Neoplasms; Lymphoma, T-Cell; Male; Mice; Mice, Inbred CBA; Neoplasms; Pancreatic Neoplasms; Transfection; Xanthophylls; Xenograft Model Antitumor Assays

Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS) involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L). The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress.. Effective concentration (EC(50)) values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA) in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay.. The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC(50) > 20 mmol/L and fifty-five percent had an EC(50) < 20 mmol/L. With an EC(50) of 2.6-5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC(50): 94,9 mmol/L), was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT) became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L).. Fifty-five percent of the human cancer cell lines tested were unable to protect themselves against oxidative stress mediated by ascorbic acid induced hydrogen peroxide production. The antioxidative enzyme catalase is important to protect cancer cells against cytotoxic hydrogen peroxide. Silenced catalase expression increased the susceptibility of the formerly resistant cancer cell line BT-20 to oxidative stress.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Breast Neoplasms; Carcinoma; Catalase; Cell Line, Tumor; Gene Silencing; Glioblastoma; Humans; Hydrogen Peroxide; Neoplasms; Oxidants; Oxidative Stress; RNA, Small Interfering; Vitamins

The altered energy metabolism of tumor cells provides a viable target for a non toxic chemotherapeutic approach. An increased glucose consumption rate has been observed in malignant cells. Warburg (Nobel Laureate in medicine) postulated that the respiratory process of malignant cells was impaired and that the transformation of a normal cell to malignant was due to defects in the aerobic respiratory pathways. Szent-Györgyi (Nobel Laureate in medicine) also viewed cancer as originating from insufficient availability of oxygen. Oxygen by itself has an inhibitory action on malignant cell proliferation by interfering with anaerobic respiration (fermentation and lactic acid production). Interestingly, during cell differentiation (where cell energy level is high) there is an increased cellular production of oxidants that appear to provide one type of physiological stimulation for changes in gene expression that may lead to a terminal differentiated state. The failure to maintain high ATP production (high cell energy levels) may be a consequence of inactivation of key enzymes, especially those related to the Krebs cycle and the electron transport system. A distorted mitochondrial function (transmembrane potential) may result. This aspect could be suggestive of an important mitochondrial involvement in the carcinogenic process in addition to presenting it as a possible therapeutic target for cancer. Intermediate metabolic correction of the mitochondria is postulated as a possible non-toxic therapeutic approach for cancer.

Topics: Animals; Ascorbic Acid; Cell Differentiation; Cell Membrane; Energy Metabolism; Fermentation; Glycolysis; Humans; Hydrogen-Ion Concentration; Mitochondria; Models, Biological; Neoplasms; Oxygen

Ascorbate is an important natural antioxidant that can selectively kill cancer cells at pharmacological concentrations. Despite its benefit, it is quite difficult to predict the antitumor effects of ascorbate, because the relative cytotoxicity of ascorbate differs between cancer cell lines. Therefore, it is essential to examine the basis for this fundamental disagreement. Because p53 is activated by DNA-damaging stress and then regulates various cellular conditions, we hypothesized that p53 can sensitize cancer cells to ascorbate. Using isogenic cancer cells, we observed that the presence of p53 can affect ascorbate cytotoxicity, and also reactivation of p53 can make cancer cells sensitive to ascorbate. p53-dependent enhancement of ascorbate cytotoxicity is caused by increased reactive oxygen species generation via a differentially regulated p53 transcriptional network. We also found that transcriptionally activated p53 was derived from MDM2 ubiquitination by ascorbate and subsequently its signaling network renders cancer cells more susceptible to oxidative stress. Similar to the p53 effect on in vitro ascorbate cytotoxicity, inhibition of tumor growth is also stronger in p53-expressing tumors than in p53-deficient ones in vivo. This is the first observation that ascorbate cytotoxicity is positively related to p53 expression, activating its transcriptional network to worsen intracellular oxidative stress and consequently enhancing its cytotoxicity. Based on our study, reactivation of p53 may help to achieve more consistent cytotoxic effects of ascorbate in cancer therapies.

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Blotting, Western; Cell Proliferation; Humans; Hydrogen Peroxide; Immunoprecipitation; Male; Mice; Mice, Nude; Neoplasms; Oxidative Stress; Proto-Oncogene Proteins c-mdm2; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Ubiquitination

In this work, we reported a sandwiched luminol electrochemiluminescence (ECL) immunosensor using ZnO nanoparticles (ZnONPs) and glucose oxidase (GOD) decorated graphene as labels and in situ generated hydrogen peroxide as coreactant. In order to construct the base of the immunosensor, a hybrid architecture of Au nanoparticles and graphene by reduction of HAuCl(4) and graphene oxide (GO) with ascorbic acid was prepared. The resulted hybrid architecture modified electrode provided an excellent platform for immobilization of antibody with good bioactivity and stability. Then, ZnONPs and GOD functionalized graphene labeled secondary antibody was designed for fabricating a novel sandwiched ECL immunosensor. Enhanced sensitivity was obtained by in situ generating hydrogen peroxide with glucose oxidase and the catalysis of ZnONPs to the ECL reaction of luminol-H(2)O(2) system. The as-prepared ECL immunosensor exhibited excellent analytical property for the detection of carcinoembryonic antigen (CEA) in the range from 10 pg mL(-1) to 80 ng mL(-1) and with a detection limit of 3.3 pg mL(-1) (SN(-1)=3). The amplification strategy performed good promise for clinical application of screening of cancer biomarkers.

Topics: Ascorbic Acid; Biomarkers, Tumor; Biosensing Techniques; Carcinoembryonic Antigen; Electrochemical Techniques; Electrodes; Glucose Oxidase; Gold; Graphite; Humans; Hydrogen Peroxide; Immunoassay; Limit of Detection; Luminescent Measurements; Luminol; Nanostructures; Neoplasms; Zinc Oxide

An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are associated with poor prognosis and decreased survival in many types of cancer.Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels.Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients.. 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g) after standard treatments by conventional methods.CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests.. According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment.There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in the levels of C-reactive protein.Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments.. The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels.In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients. Our results suggest that further investigations into the use of IVC to reduce inflammation in diseases where inflammation is relevant are warranted.

Topics: Ascorbic Acid; Dose-Response Relationship, Drug; Humans; Inflammation; Neoplasms

The present study assess the effect of consumption of alcohol on oxidative stress and antioxidant status in patients suffering from different types of cancer.. This hospital based case control study conducted in the Western part of Nepal covered a total of 93 cancer patients with or without alcohol intake and smoking habits, along with 94 age, sex and habit-matched individuals serving as controls. Plasma thiobarbituric acid reacting substances (TBARS), total antioxidant activity (TAA), vitamin C, α-tocopherol and erythrocyte reduced glutathione (GSH) were estimated and compared.. The TBARS level was found to be significantly higher (p≤0.001) in all types of cancer patients when compared to controls, being aggravated in alcoholics with a smoking habit. No statistical significance (p≥0.05) was observed in the level of vitamin C and α-tocopherol. GSH and TAA level were significantly decreased (p≤0.001) in all the groups except those who consumed both branded as well as homemade alcohol and non-alcoholics without smoking habit.. Alcohol, irrespective of its commercial brand, increases oxidative stress in all types of cancer patients. This is even higher when alcohol intake is combined with a smoking habit. Decreased TAA and GSH are major risk factors for cancer development.

Topics: Alcohol Drinking; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Case-Control Studies; Erythrocytes; Ethanol; Glutathione; Humans; Middle Aged; Neoplasms; Nepal; Oxidative Stress; Risk Factors; Smoking; Thiobarbituric Acid Reactive Substances

Approximately 30% of the adult Czech population smokes. Previous studies of smokers have documented diet sufficient in energy, but inadequate intake of dietary fibre, vitamins A, E, calcium and proteins.. Nutrition was assessed between the groups of the probands (over 18 years aged, 667 smokers, 1044 nonsmokers, 428 past smokers) from 1% random sample of the Czech population. All volunteers completed a one day dietary recall after instruction from a nutrition expert. The dietary recall calculated energy, proteins, fats, vitamins C and E, cholesterol, fibre, calcium and iron intake using the Nutridan programme.. Smokers had higher consumption of animal (p=0.0034), and total fat (p=0.0315), cholesterol (p=0.005), and lower intake of vitamin E (p=0.004) than nonsmokers. No other differences were found. The differences between past smokers and other groups were insignificant.. The smokers consumed more total and animal fat, cholesterol and less of vitamin E than nonsmokers.

Topics: Adult; Ascorbic Acid; Calcium, Dietary; Cardiovascular Diseases; Czech Republic; Dietary Fats; Dietary Proteins; Feeding Behavior; Female; Humans; Iron, Dietary; Male; Middle Aged; Neoplasms; Nutrition Surveys; Risk Factors; Smoking; Vitamin E

Numerous studies suggest that generation of oxidative stress could be useful in cancer treatment. In this study, we evaluated, in vitro and in vivo, the antitumor potential of oxidative stress induced by ascorbate/menadione (asc/men). This combination of a reducing agent (ascorbate) and a redox active quinone (menadione) generates redox cycling leading to formation of reactive oxygen species (ROS). Asc/men was tested in several cell types including K562 cells (a stable human-derived leukemia cell line), freshly isolated leukocytes from patients with chronic myeloid leukemia, BaF3 cells (a murine pro-B cell line) transfected with Bcr-Abl and peripheral blood leukocytes derived from healthy donors. Although these latter cells were resistant to asc/men, survival of all the other cell lines was markedly reduced, including the BaF3 cells expressing either wild-type or mutated Bcr-Abl. In a standard in vivo model of subcutaneous tumor transplantation, asc/men provoked a significant delay in the proliferation of K562 and BaF3 cells expressing the T315I mutated form of Bcr-Abl. No effect of asc/men was observed when these latter cells were injected into blood of mice most probably because of the high antioxidant potential of red blood cells, as shown by in vitro experiments. We postulate that cancer cells are more sensitive to asc/men than healthy cells because of their lack of antioxidant enzymes, mainly catalase. The mechanism underlying this cytotoxicity involves the oxidative cleavage of Hsp90 with a subsequent loss of its chaperone function thus leading to degradation of wild-type and mutated Bcr-Abl protein.

Topics: Animals; Ascorbic Acid; Cell Death; Cell Line, Tumor; Cytoprotection; Erythrocytes; Fusion Proteins, bcr-abl; Humans; Hydrogen Peroxide; K562 Cells; Mice; Mice, Nude; Mutant Proteins; Neoplasms; Oxidative Stress; Vitamin K 3; Xenograft Model Antitumor Assays

In the cell Mn porphyrins (MnPs) likely couple with cellular reductants which results in a drop of total charge from 5+ to 4+ and dramatically increases their lipophilicity by up to three orders of magnitude depending upon the length of alkylpyridyl chains and type of isomer. The effects result from the interplay of solvation, lipophilicit and stericity. Impact of ascorbate on accumulation of MnPs was measured in E. coli and in Balb/C mouse tumours and muscle; for the latter measurements, the LC/ESI-MS/MS method was developed. Accumulation was significantly enhanced when MnPs were co-administered with ascorbate in both prokaryotic and eukaryotic systems. Further, MnTnHex-2-PyP(5+) accumulates 5-fold more in the tumour than in a muscle. Such data increase our understanding of MnPs cellular and sub-cellular accumulation and remarkable in vivo effects. The work is in progress to understand how coupling of MnPs with ascorbate affects their mechanism of action, in particular with respect to cancer therapy.

Topics: Animals; Ascorbic Acid; Biological Availability; Chromatography, Liquid; Escherichia coli; Female; Hydrophobic and Hydrophilic Interactions; Ion Transport; Isomerism; Manganese; Mass Spectrometry; Metalloporphyrins; Mice; Molecular Mimicry; Muscles; Neoplasms; Oxidation-Reduction; Solubility; Static Electricity; Superoxide Dismutase

Strong evidence indicates that reactive oxygen species (ROS) play an important role in the initiation as well as the promotion phase of carcinogenesis. Studies support the role of ROS in cancer, in part, by showing that dietary antioxidants act as cancer-preventive agents. Although results are promising, the research on this topic is still controversial. Thus, the aim of this study was to investigate whether vitamins C, E and pequi oil can, individually, provide prevention and/or be used afterward as an adjuvant in cancer therapy. Ehrlich solid tumor-bearing mice received antioxidant as follows: before tumor inoculation, before and after tumor inoculation (continuous administration), and after tumor inoculation; morphometric analyses of tumor, genotoxicity and hematology were then carried out. Antioxidant administrations before tumor inoculation effectively inhibited its growth in the three experimental protocols, but administrations after the tumor's appearance accelerated tumor growth and favored metastases. Continuous administration of pequi oil inhibited the tumor's growth, while the same protocol with vitamins E and C accelerated it, favoring metastasis and increasing oxidative stress on erythrocytes. Except for continuous administration with vitamin E, the development of ascites tumor metastases was linked with increased inflammation. Results suggest that the efficiency and applicability of antioxidants in the medical clinic can depend not only on the nature of the antioxidant, the type and stage of cancer being treated and the prevailing oxygen partial pressure in the tissues, but also on the type of antioxidant therapy chosen.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Cell Count; Carcinoma, Ehrlich Tumor; Carotenoids; Comet Assay; Ericales; Female; Mice; Neoplasms; Plant Oils; Reactive Oxygen Species; Vitamin E

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Endothelium; Humans; Immunity; Injections, Intravenous; Neoplasms; Sepsis

Humans are exposed to preformed N-nitroso compounds (NOCs) and endogenous NOCs. Several NOCs are potential human carcinogens, including N-nitrosodimethylamine (NDMA), but evidence from population studies is inconsistent.. We examined the relation between dietary NOCs (NDMA), the endogenous NOC index, and dietary nitrite and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, United Kingdom, study.. This was a prospective study of 23,363 men and women, aged 40-79 y, who were recruited in 1993-1997 and followed up to 2008. The baseline diet was assessed with food-frequency questionnaires.. There were 3268 incident cancers after a mean follow-up of 11.4 y. Dietary NDMA intake was significantly associated with increased cancer risk in men and women [hazard ratio (HR): 1.14; 95% CI: 1.03, 1.27; P for trend = 0.03] and in men (HR: 1.24; 95% CI: 1.07, 1.44; P for trend = 0.005) when the highest quartile was compared with the lowest quartile in age- and sex-adjusted analyses but not in multivariate analyses (HR: 1.10; 95% CI: 0.97, 1.24; HR for men: 1.18; 95% CI: 1.00, 1.40; P for trend ≥ 0.05). When continuously analyzed, NDMA was associated with increased risk of gastrointestinal cancers (HR: 1.13; 95% CI: 1.00, 1.28), specifically of rectal cancer (HR: 1.46; 95% CI: 1.16, 1.84) per 1-SD increase after adjustment for age, sex, body mass index, cigarette smoking status, alcohol intake, energy intake, physical activity, education, and menopausal status (in women). The endogenous NOC index and dietary nitrite were not significantly associated with cancer risk. There was a significant interaction between plasma vitamin C concentrations and dietary NDMA intake on cancer incidence (P for interaction < 0.00001).. Dietary NOC (NDMA) was associated with a higher gastrointestinal cancer incidence, specifically of rectal cancer. Plasma vitamin C may modify the relation between NDMA exposure and cancer risk.

Topics: Adult; Aged; Ascorbic Acid; Carcinogens; Diet; Dimethylnitrosamine; Europe; Female; Gastrointestinal Neoplasms; Humans; Incidence; Iron, Dietary; Male; Meat; Middle Aged; Neoplasms; Nitrites; Nitroso Compounds; Prospective Studies; Rectal Neoplasms; Risk; United Kingdom

There is growing evidence that oxidative stress (OS) has a causal relationship with cancer and a weak antioxidant defense can aggravate it further. We therefore, undertook this study to examine lipid peroxidation (TBARS), total antioxidant activity (TAA), ascorbic acid (vitamin C) and α- tocopherol levels in cancer patients, with special attention to the influence of smoking.. The study subjects were 42 patients (61.19 ± 10.1 yrs) suffering from cancer and 43 normal subjects (NS) (56.69 ± 19.1 yrs). Plasma levels of TBARS, TAA, vitamin C and ?- tocopherol were estimated.. TAA and α-tocopherol levels were significantly lower and TBARS levels significantly higher in cancer patients when compared to NS. In smoking cancer patient's ?-tocopherol levels were significantly low and TBARS significantly raised.. Our observations indicate that increased lipid peroxidation, reduced total antioxidant activity and ?-tocopherol levels are associated with cancer development, with and without smoking. However, a greater reduction of TAA in smokers may be due to increased oxidants introduced by smoking.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Case-Control Studies; Humans; Lipid Peroxidation; Middle Aged; Neoplasms; Nepal; Oxidative Stress; Smoking; Thiobarbituric Acid Reactive Substances

The effect of fruit and vegetable consumption and blood pressure is unclear. A population-based cross-sectional study was conducted in 20 926 men and women aged 40 to 79 years participating in the European Prospective Investigation Into Cancer-Norfolk who completed a health questionnaire and attended a clinic from 1993 to 1997. The relationship between plasma vitamin C concentrations, as an indicator of fruit and vegetable intake, and systolic BP was examined. The magnitude of their association was assessed using dichotomized values of high (≥140 mm Hg) and low (<140 mm Hg) systolic blood pressure. A total of 20 926 participants (46% men; mean [SD] 58.5 years [9.2 years]) were included after excluding participants with any missing data for variables of interest. People with high vitamin C concentrations had lower clinic blood pressure. The likelihood of having high blood pressure was 22% lower (odds ratio: 0.78 [95% CI: 0.71 to 0.86]) for those who were in the top quartiles of plasma vitamin C levels compared with the bottom quartiles after adjusting for age, sex, body mass index, cholesterol, prevalent medical conditions, smoking, physical activity, alcohol consumption, social class, education, use of vitamin C-containing supplement, and antihypertensive medication. Sex-specific analysis, as well as repeated analysis after exclusion of people who used vitamin C-containing supplements or who were taking antihypertensive medication, did not alter the results. There appears to be a strong association between vitamin C concentrations, an indicator of fruit and vegetable consumption, and a lower level of blood pressure. This may provide further evidence for health benefits of dietary patterns with higher fruit and vegetable consumption.

Topics: Adult; Age Factors; Aged; Ascorbic Acid; Blood Pressure; Cross-Sectional Studies; Europe; Female; Humans; Hypertension; Linear Models; Male; Middle Aged; Multivariate Analysis; Neoplasms; Prospective Studies; Risk Factors; Surveys and Questionnaires; United Kingdom

Reduction and oxidation (redox) chemistry is involved in both normal and abnormal cellular function, in processes as diverse as circadian rhythms and neurotransmission. Intracellular redox is maintained by coupled reactions involving NADPH, glutathione (GSH), and vitamin C, as well as their corresponding oxidized counterparts. In addition to functioning as enzyme cofactors, these reducing agents have a critical role in dealing with reactive oxygen species (ROS), the toxic products of oxidative metabolism seen as culprits in aging, neurodegenerative disease, and ischemia/ reperfusion injury. Despite this strong relationship between redox and human disease, methods to interrogate a redox pair in vivo are limited. Here we report the development of [1-(13)C] dehydroascorbate [DHA], the oxidized form of Vitamin C, as an endogenous redox sensor for in vivo imaging using hyperpolarized (13)C spectroscopy. In murine models, hyperpolarized [1-(13)C] DHA was rapidly converted to [1-(13)C] vitamin C within the liver, kidneys, and brain, as well as within tumor in a transgenic prostate cancer mouse. This result is consistent with what has been previously described for the DHA/Vitamin C redox pair, and points to a role for hyperpolarized [1-(13)C] DHA in characterizing the concentrations of key intracellular reducing agents, including GSH. More broadly, these findings suggest a prognostic role for this new redox sensor in determining vulnerability of both normal and abnormal tissues to ROS.

Topics: Animals; Anisotropy; Ascorbic Acid; Brain; Carbon Isotopes; Dehydroascorbic Acid; Glutathione; Kidney; Kinetics; Liver; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mice; Neoplasms; Oxidation-Reduction; Reactive Oxygen Species; Tissue Distribution

Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR) associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK) and phosphoinositol-3 kinase (PI3K)/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1)/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential) due to the elevated level of reactive oxygen species (ROS) is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers.

Topics: Ascorbic Acid; Cell Death; Cell Line, Tumor; Computer Simulation; Enzyme Activation; ErbB Receptors; Extracellular Signal-Regulated MAP Kinases; Gefitinib; Gene Silencing; Humans; Models, Biological; Neoplasms; Oncogenes; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Quinazolines; Reactive Oxygen Species; Reproducibility of Results; Signal Transduction; Systems Biology

Many cancers are deficient in catalase activity, and maintain a moderate level of oxidative stress to aid their proliferation and survival. It may prove feasible to achieve substantial selective tumor kill with a three-pronged strategy for acutely exacerbating oxidative stress in cancer cells: inducing increased production of oxidants in tumors with sustained high-dose infusions of sodium ascorbate and menadione, while concurrently undercutting the antioxidant defenses of cancer cells by imposing glucose deprivation - as with 2-deoxyglucose administration or a hypoglycemic insulin clamp - and by suppressing hypoxia-inducible factor-1 activity with available agents such as salicylate, rapamycin, and irinotecan. Inhibition of pyruvate dehydrogenase-1 with dichloroacetate may also promote oxidative stress in hypoxic cancer cells. Cell culture studies could be employed to devise effective protocols that could be tested in xenografted rodents and, ultimately, in exploratory clinical trials.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Glucose; Humans; Hypoxia-Inducible Factor 1; Models, Biological; Neoplasms; Oxidative Stress; Protein Serine-Threonine Kinases; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Vitamin K 3

Topics: Animals; Ascorbic Acid; Folic Acid; Humans; Neoplasms; Randomized Controlled Trials as Topic; Riboflavin; Vitamin A; Vitamin D; Vitamin E; Vitamins

Type IV collagenase matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, have been found to promote invasion and metastasis of malignant tumors. Extracellular matrix (ECM) degradation by MMPs and increased expression of MMPs in cancer cells and tumor microvascular endothelial cells make MMPs an attractive target for cancer. Focused on a common pathomechanism of cancer growth and invasion, the disintegration of connective tissue, we used natural approaches to increase the integrity and strength of connective tissues. Utilizing the principle of nutrition synergy, we developed a novel micronutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract. This study evaluates the potency of the components EGCG and green tea extract independently compared to that of NM on modulation of patterns of MMP-2 and MMP-9 expression in four cancer cell lines expressing MMP-2, MMP-9 or both. Human fibrosarcoma (HT-1080), hepatocellular carcinoma (SK-Hep-1), glioblastoma (T-98G), uterine leiomyosarcoma (SK-UT-1) cell lines were obtained from ATCC and grown in minimum essential medium (MEM) supplemented with 10% FBS, penicillin (100 U/ml) and streptomycin (100 mg/ml) in 24-well tissue culture plates. At near confluence, the cells were treated with agents dissolved in media and tested at concentrations indicated in triplicate at each dose. Cells were also treated with PMA 100 ng/ml to study enhanced expression of MMP-9. MMP expression was assessed by gelatinase zymography. Fibrosarcoma and hepatocellular carcinoma cells expressed both MMP-2 and MMP-9. Glioblastoma cells expressed MMP-2 and PMA treatment induced MMP-9 expression. Uterine leimyosarcoma cells expressed no MMPs but PMA induced MMP-9. NM was the most potent dose-dependent inhibitor of MMPs, followed by green tea extract and EGCG. In conclusion, these results suggest the enhanced efficacy of nutrients working in synergy to modulate complex pathways such as MMP expression.

Topics: Antineoplastic Agents, Phytogenic; Ascorbic Acid; Camellia sinensis; Catechin; Cell Line, Tumor; Dose-Response Relationship, Drug; Humans; Lysine; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Micronutrients; Neoplasm Invasiveness; Neoplasms; Plant Extracts; Proline; Protease Inhibitors; Tetradecanoylphorbol Acetate

Topics: Ascorbic Acid; Dose-Response Relationship, Drug; Humans; Influenza, Human; Information Dissemination; Neoplasms; New Zealand; Prognosis; Vitamins

Topics: Ascorbic Acid; Humans; Neoplasms; Time Factors; Vitamins

Topics: Ascorbic Acid; Humans; Neoplasms; Time Factors; Vitamins

Three triterpene saponins isolated from the roots of Physospermum verticillatum and identified as saikosaponin a (1), buddlejasaponin IV (2), and songarosaponin D (3) were investigated in vitro for their cytotoxic activity against a panel of seven different cancer cell lines including ACHN, C32, Caco-2, COR-L23, A375, A549, and Huh-7D12 cell lines. The hydrolysis of sugar unit was performed on saikosaponin a (1) to obtain saikosapogenin a (4). All isolated saponins exhibited strong cytotoxic activity against COR-L23 cell line with IC(50) values ranged from 0.4 to 0.6 microM. A similar activity was recorded for saikogenin a (4). None of the tested compounds affected the proliferation of skin fibroblasts 142BR suggesting a selective action against cancer cells. Moreover, buddlejasaponin IV (2) and songarosaponin D (3) exerted significant inhibition of NO production in LPS induced RAW 264.7 macrophages with IC(50) of 4.2 and 10.4 microM, respectively.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apiaceae; Cell Line, Tumor; Cell Survival; Drug Screening Assays, Antitumor; Humans; Macrophages; Mice; Neoplasms; Nitric Oxide; Oleanolic Acid; Plant Roots; Saponins; Triterpenes

Topics: Antioxidants; Ascorbic Acid; Dietary Supplements; Humans; Male; Neoplasms; Prostatic Neoplasms; Selenium; Vitamin E

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Colorectal Neoplasms; Confounding Factors, Epidemiologic; Dietary Supplements; Female; Folic Acid; Humans; Incidence; Lung Neoplasms; Male; Neoplasms; Primary Prevention; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Selenium; United States; Vitamin B 12; Vitamin B 6; Vitamin E

Taking into account the importance role of lipid peroxidation and antioxidants in the prevention and incidence of cancer, the present study was carried out to determine oxidative stress, serum total antioxidant (TAS), and vitamin C levels in cancer patients. Malondialdehyde(MDA), total antioxidant status, and vitamin C levels of 57cancer patients aged 19-80 years and 22 healthy subjects (control group) aged 22-76 years were evaluated. Serum concentrations of MDA as thiobarbitaric acid complexes were measured by fluorometry method, the serum TAS by using commercial test kits from Randox Laboratories, and vitamin C by using spectrocolorimetric method. The mean serum MDA concentrations of all cancer groups except lung cancer were significantly higher than control group (P < 0.004). The mean total antioxidant status was insignificantly higher than control group. The mean serum vitamin C level was significantly lower in patients as compared to the healthy subjects (PV < 0.0001). In conclusion, an alteration in the lipid peroxidation with concomitant changes in antioxidant defense system in cancer patients may be due to excessive oxidative stress. Serum low levels of vitamin C in the different type of cancer patients in spite of adequate daily intake may be due to increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Female; Humans; Male; Malondialdehyde; Middle Aged; Neoplasms; Oxidative Stress

Ascorbic acid (AA), or Vitamin C, is most well known as a nutritional supplement with antioxidant properties. Recently, we demonstrated that high concentrations of AA act on PMP22 gene expression and partially correct the Charcot-Marie-Tooth disease phenotype in a mouse model. This is due to the capacity of AA, but not other antioxidants, to down-modulate cAMP intracellular concentration by a competitive inhibition of the adenylate cyclase enzymatic activity. Because of the critical role of cAMP in intracellular signalling, we decided to explore the possibility that ascorbic acid could modulate the expression of other genes.. Using human pangenomic microarrays, we found that AA inhibited the expression of two categories of genes necessary for cell cycle progression, tRNA synthetases and translation initiation factor subunits. In in vitro assays, we demonstrated that AA induced the S-phase arrest of proliferative normal and tumor cells. Highest concentrations of AA leaded to necrotic cell death. However, quiescent cells were not susceptible to AA toxicity, suggesting the blockage of protein synthesis was mainly detrimental in metabolically-active cells. Using animal models, we found that high concentrations of AA inhibited tumor progression in nude mice grafted with HT29 cells (derived from human colon carcinoma). Consistently, expression of tRNA synthetases and ieF2 appeared to be specifically decreased in tumors upon AA treatment.. AA has an antiproliferative activity, at elevated concentration that could be obtained using IV injection. This activity has been observed in vitro as well in vivo and likely results from the inhibition of expression of genes involved in protein synthesis. Implications for a clinical use in anticancer therapies will be discussed.

Topics: Animals; Ascorbic Acid; Cell Cycle; Cell Division; Cell Line; Cell Proliferation; Cell Survival; Disease Progression; Female; Gene Expression Regulation; HT29 Cells; Humans; Mice; Mice, Nude; Neoplasms; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction

Topics: Aged; Ascorbic Acid; Cardiovascular Diseases; Clinical Protocols; Clinical Trials as Topic; Data Interpretation, Statistical; Humans; Male; Middle Aged; Neoplasms; Oxidative Stress; Patient Compliance; Prostatic Neoplasms; Vitamin E

Topics: Aged; Anticarcinogenic Agents; Ascorbic Acid; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Dietary Supplements; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Physicians; Prostatic Neoplasms; Randomized Controlled Trials as Topic; United States; Vitamin E

Mexican American men living in the United States who are more acculturated exhibit higher rates of cancer compared to those less acculturated. This study explored the association between acculturation and serum levels of nutrients thought to be involved with cancer prevention among Mexican American men.. Our sample included 2,479 Mexican American men from the Third National Health and Nutrition Examination Survey (1988-1994). Outcomes were serum levels of micronutrients. Acculturation in Mexican American men was assessed by a combined measure including country of origin, language of interview, and years of residence in the United States and was categorized as follows: (1) foreign-born, 0-5 years in the United States (lowest acculturation), (2) foreign-born, 6-15 years in the United States, (3) foreign-born, > 15 years in the United States, (4) US-born Spanish-speaking, and (5) US-born English-speaking (highest acculturation).. Adjusted analyses showed that acculturation decreased the serum levels for vitamin E, vitamin C, and folate and also for some carotenoids (alpha and beta carotenes, beta cryptoxanthin, and lutein-zeaxanthin). By contrast, acculturation increased the serum levels for selenium and lycopene.. With the exception of selenium and lycopene, acculturation among Mexican American men decreased the serum levels for most carotenoids and for vitamin E, vitamin C, and folate. These changes in nutrient profiles, reflecting altered patterns in food consumption or other behaviors, may explain in part why Mexican American men who are more acculturated have an increased risk for diet-related cancer

Topics: Acculturation; Adolescent; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Carotenoids; Diet; Folic Acid; Food; Humans; Lycopene; Male; Mexican Americans; Micronutrients; Middle Aged; Neoplasms; Risk Factors; Selenium; United States; Vitamin D; Vitamin E

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Cell Death; Cell Growth Processes; Clinical Trials as Topic; Drug Synergism; Humans; Mice; Mice, Knockout; Neoplasms; Nutrition Policy; Organic Anion Transporters, Sodium-Dependent; Sodium-Coupled Vitamin C Transporters; Symporters

In this cohort study, the authors evaluated how supplemental use of multivitamins, vitamin C, and vitamin E over a 10-year period was related to 5-year total mortality, cancer mortality, and cardiovascular disease (CVD) mortality. Participants (n = 77,719) were Washington State residents aged 50-76 years who completed a mailed self-administered questionnaire in 2000-2002. Adjusted hazard ratios and 95% confidence intervals were computed using Cox regression. Multivitamin use was not related to total mortality. However, vitamin C and vitamin E use were associated with small decreases in risk. In cause-specific analyses, use of multivitamins and use of vitamin E were associated with decreased risks of CVD mortality. The hazard ratio comparing persons who had a 10-year average frequency of multivitamin use of 6-7 days per week with nonusers was 0.84 (95% confidence interval: 0.70, 0.99); and the hazard ratio comparing persons who had a 10-year average daily dose of vitamin E greater than 215 mg with nonusers was 0.72 (95% confidence interval: 0.59, 0.88). In contrast, vitamin C use was not associated with CVD mortality. Multivitamin and vitamin E use were not associated with cancer mortality. Some of the associations we observed were small and may have been due to unmeasured healthy behaviors that were more common in supplement users.

Topics: Aged; Ascorbic Acid; Cardiovascular Diseases; Cohort Studies; Dietary Supplements; Follow-Up Studies; Humans; Middle Aged; Mortality; Neoplasms; Proportional Hazards Models; Vitamin E; Vitamins; Washington

To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 x 10(-4) mol high dose concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high dose concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 x 10(-4) mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high dose concentration ascorbic acid occurred through inhibition of angiogenesis.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascites; Ascorbic Acid; Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Drug; Fibroblast Growth Factor 2; Gene Expression Regulation, Neoplastic; Matrix Metalloproteinase 2; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplasms; Neovascularization, Pathologic; NIH 3T3 Cells; Sarcoma; Survival Rate; Vascular Endothelial Growth Factor A

In traditional Korean medicine, lotus (Nelumbo nucifera Gaertn) roots have been used as an antidiabetic and an antiproliferative remedy. However, scientific publications on lotus properties are very limited. Therefore, it was decided to investigate the Korean white lotus cultivars in order to find out their bioactivity. It was found that all lotus cultivars (Inchisa, Muan, Garam, and Chungyang) possess high amounts of bioactive compounds: total phenols, between 7.95 +/- 0.8 and 4.21 +/- 0.3 mg of gallic acid equivalents (GAE)/g dry weight (DW); ascorbic acid, between 15.8 +/- 1.1 and 22.3 +/- 1.7 mg of ascorbic acid/g DW; and amino acids, between 15.05 +/- 0.82% and 16.62 +/- 0.90% DW. The highest contents of polyphenols (7.95 +/- 0.8 mg of GAE/g DW) and the highest levels of antioxidant [by 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and 1,1-diphenyl-2-picrylhydrazyl assays, 54.27 +/- 6.1 and 21.98 +/- 2.5 microM Trolox equivalents/g DW, respectively] and antiproliferative activities on both human cancer cell lines (Calu-6 for human pulmonary carcinoma and SMU-601 for human gastric carcinoma, 59.75 +/- 3.99% and 71.21 +/- 2.79% cell viability, respectively) were found in the Chungyang cultivar. Fluorometry and Fourier transform infrared spectroscopy can be applied as rapid methods for determination of bioactive compounds, such as polyphenols. The correlation between the bioactive compounds and the antioxidant activity was high. In conclusion, all Korean white lotus cultivars are valuable medicinal foods, and in order to receive the best results a combination of lotus cultivars has to be consumed.

Topics: Amino Acids; Antineoplastic Agents, Phytogenic; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Cell Survival; Fluorometry; Gallic Acid; Humans; Lung Neoplasms; Nelumbo; Neoplasms; Phenols; Plant Extracts; Plant Roots; Spectroscopy, Fourier Transform Infrared; Stomach Neoplasms

In exercise, as well as cancer and ischemia, hypoxia-inducible factor 1 (HIF1) transcriptionally activates hundreds of genes vital for cell homeostasis and angiogenesis. While potentially beneficial in ischemia, upregulation of the HIF1 transcription factor has been linked to inflammation, poor prognosis in many cancers, and decreased susceptibility of tumors to radiotherapy and chemotherapy. Considering HIF1's function, HIF1alpha protein and its hydroxylation cofactors look increasingly attractive as therapeutic targets. Independently, antioxidants have shown promise in lowering the risk of some cancers and improving neurological and cardiac function following ischemia. The mechanism of how different antioxidants and reactive oxygen species influence HIF1alpha expression has drawn interest and intense debate. Here we present an experimentally based computational model of HIF1alpha protein degradation that represents how reactive oxygen species and antioxidants likely affect the HIF1 pathway differentially in cancer and ischemia. We use the model to demonstrate effects on HIF1alpha expression from combined doses of five potential therapeutically targeted compounds (iron, ascorbate, hydrogen peroxide, 2-oxoglutarate, and succinate) influenced by cellular oxidation-reduction and involved in HIF1alpha hydroxylation. Results justify the hypothesis that reactive oxygen species work by two opposite ways on the HIF1 system. We also show how tumor cells and cells under ischemic conditions would differentially respond to reactive oxygen species via changes to HIF1alpha expression over the course of hours to days, dependent on extracellular hydrogen peroxide levels and largely independent of initial intracellular levels, during hypoxia.

Topics: Animals; Ascorbic Acid; Cell Hypoxia; Down-Regulation; Humans; Hydrogen Peroxide; Hypoxia-Inducible Factor 1, alpha Subunit; Iron; Ischemia; Jurkat Cells; Ketoglutaric Acids; Models, Biological; Neoplasms; Rats; Reactive Oxygen Species; Succinic Acid; Up-Regulation

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Female; Humans; Hydrogen Peroxide; Infusions, Intravenous; Mice; Mice, Nude; Neoplasms; Oxidants; Prodrugs; Xenograft Model Antitumor Assays

Vitamin C is an antioxidant vitamin that has been hypothesized to antagonize the effects of reactive oxygen species-generating antineoplastic drugs. The therapeutic efficacy of the widely used antineoplastic drugs doxorubicin, cisplatin, vincristine, methotrexate, and imatinib were compared in leukemia (K562) and lymphoma (RL) cell lines with and without pretreatment with dehydroascorbic acid, the commonly transported form of vitamin C. The effect of vitamin C on viability, clonogenicity, apoptosis, P-glycoprotein, reactive oxygen species (ROS), and mitochondrial membrane potential was determined. Pretreatment with vitamin C caused a dose-dependent attenuation of cytotoxicity, as measured by trypan blue exclusion and colony formation after treatment with all antineoplastic agents tested. Vitamin C given before doxorubicin treatment led to a substantial reduction of therapeutic efficacy in mice with RL cell-derived xenogeneic tumors. Vitamin C treatment led to a dose-dependent decrease in apoptosis in cells treated with the antineoplastic agents that was not due to up-regulation of P-glycoprotein or vitamin C retention modulated by antineoplastics. Vitamin C had only modest effects on intracellular ROS and a more general cytoprotective profile than N-acetylcysteine, suggesting a mechanism of action that is not mediated by ROS. All antineoplastic agents tested caused mitochondrial membrane depolarization that was inhibited by vitamin C. These findings indicate that vitamin C given before mechanistically dissimilar antineoplastic agents antagonizes therapeutic efficacy in a model of human hematopoietic cancers by preserving mitochondrial membrane potential. These results support the hypothesis that vitamin C supplementation during cancer treatment may detrimentally affect therapeutic response.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Cytoprotection; Dehydroascorbic Acid; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Humans; K562 Cells; Mice; Mice, Inbred ICR; Mice, SCID; Neoplasms; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Topics: Animals; Antioxidants; Ascorbic Acid; Humans; Mice; Neoplasms; Randomized Controlled Trials as Topic

Topics: Adult; Aged; Ascorbic Acid; Asthma; beta Carotene; Clinical Trials as Topic; Clinical Trials, Phase I as Topic; Coronary Disease; Disease; Disease Susceptibility; Epidemiologic Factors; Female; Heart Transplantation; Humans; Incidence; Male; Men; Middle Aged; Neoplasms; Pregnancy; Prognosis; Pulmonary Disease, Chronic Obstructive; Risk Factors; Sex Factors

Evidence exists that a more acidic diet is detrimental to bone health. Although more precise methods exist for measurement of acid-base balance, urine pH reflects acid-base balance and is readily measurable but has not been related to habitual dietary intake in general populations. The present study investigated the relationship between urine pH and dietary acid-base load (potential renal acid load; PRAL) and its contributory food groups (fruit and vegetables, meats, cereal and dairy foods). There were 22,034 men and women aged 39-78 years living in Norfolk (UK) with casual urine samples and dietary intakes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk FFQ. A sub-study (n 363) compared pH in casual samples and 24 h urine and intakes from a 7 d diary and the FFQ. A more alkaline diet (low PRAL), high fruit and vegetable intake and lower consumption of meat was significantly associated with a more alkaline urine pH before and after adjustment for age, BMI, physical activity and smoking habit and also after excluding for urinary protein, glucose, ketones, diagnosed high blood pressure and diuretic medication. In the sub-study the strongest relationship was found between the 24 h urine and the 7 d diary. In conclusion, a more alkaline diet, higher fruit and vegetable and lower meat intake were related to more alkaline urine with a magnitude similar to intervention studies. As urine pH relates to dietary acid-base load its use to monitor change in consumption of fruit and vegetables, in individuals, warrants further investigation.

Topics: Adult; Age Distribution; Aged; Ascorbic Acid; Biomarkers; Diet; Europe; Feeding Behavior; Female; Fruit; Health Surveys; Humans; Hydrogen-Ion Concentration; Male; Meat; Middle Aged; Neoplasms; Prospective Studies; Regression Analysis; Sex Distribution; Smoking; Urine; Vegetables; White People

TNF-related apoptosis-inducing ligand (TRAIL/ Apo-2L) is a member of the TNF family of apoptosis-inducing proteins that initiates apoptosis in a variety of neoplastic cells while displaying minimal or absent cytotoxicity to most normal cells. Therefore, TRAIL is currently considered a promising target to develop anti-cancer therapies. TRAIL-receptor ligation recruits and activates pro-caspase-8, which in turn activates proteins that mediate disruption of the mitochondrial membranes. These events lead to the nuclear and cytosolic damage characteristic of apoptosis. Here we report that TRAIL-induced apoptosis is mediated by oxidative stress and that vitamin C (ascorbic acid), a potent nutritional antioxidant, protects cancer cell lines from apoptosis induced by TRAIL. Vitamin C impedes the elevation of reactive oxygen species (ROS) levels induced by TRAIL and impairs caspase-8 activation. We found that the removal of hydrogen peroxide by extracellular catalase during TRAIL-induced apoptosis also impairs caspase-8 activation. These data suggest that hydrogen peroxide is produced during TRAIL-receptor ligation, and that the increase of intracellular ROS regulates the activation of caspase-8 during apoptosis. Additionally we propose a mechanism by which cancer cells might resist apoptosis via TRAIL, by the intake of the nutritional antioxidant vitamin C.

Topics: Apoptosis; Ascorbic Acid; Caspase 8; Caspase Inhibitors; Catalase; Cell Line, Tumor; Humans; K562 Cells; Membrane Potential, Mitochondrial; Neoplasms; Reactive Oxygen Species; Recombinant Proteins; TNF-Related Apoptosis-Inducing Ligand; U937 Cells

Man, with other primates, lost the ability to synthesize vitamin C through an inactivating mutation of the gene encoding gulonolactone oxidase (GULO) millions of years ago. Though the consequences of this prehistoric loss must have been favorable (and thus selected for) at the population level, the inability to produce vitamin C may have serious health implications for modern humans, especially for those conditions in which antioxidants (like vitamin C) have been implicated as potential therapeutic agents. Two general types of recent findings regarding vitamin C have made re-evaluation of this important nutrient imperative. First, vitamin C is now known to be involved in several novel physiological phenomena including stem cell differentiation and respiratory development, which likely require pharmacological levels of vitamin C. Secondly, the growing recognition that many ageing-related diseases, including heart disease, neural degeneration and cancer, may have a contributing oxidative damage factor that might be reduced by dietary antioxidants such as vitamin C. In this paper, we hypothesize that high serum-level vitamin C provides important, broad-ranging therapeutic benefits in treating ageing-related degenerative diseases. This hypothesis can be readily tested using traditional and newly-developed genetically-engineered animal models.

Topics: Aging; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Humans; Models, Biological; Neoplasms; Nerve Degeneration

Over the years there has been a great deal of controversy on the effect of vitamin C on cancer. To investigate the effects of vitamin C on cancer patients' health-related quality of life, we prospectively studied 39 terminal cancer patients. All patients were given an intravenous administration of 10 g vitamin C twice with a 3-day interval and an oral intake of 4 g vitamin C daily for a week. And then we investigated demographic data and assessed changes in patients' quality of life after administration of vitamin C. Quality of life was assessed with EORTC QLQ-C30. In the global health/quality of life scale, health score improved from 36+/-18 to 55+/-16 after administration of vitamin C (p=0.001). In functional scale, the patients reported significantly higher scores for physical, role, emotional, and cognitive function after administration of vitamin C (p<0.05). In symptom scale, the patients reported significantly lower scores for fatigue, nausea/vomiting, pain, and appetite loss after administration of vitamin C (p<0.005). The other function and symptom scales were not significantly changed after administration of vitamin C. In terminal cancer patients, the quality of life is as important as cure. Although there is still controversy regarding anticancer effects of vitamin C, the use of vitamin C is considered a safe and effective therapy to improve the quality of life of terminal cancer patients.

Topics: Adult; Aged; Ascorbic Acid; Female; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Terminal Care

In many cancers, a chronic increase in oxidant stress - associated with elevated levels of hydrogen peroxide - contributes to the increased proliferative rate, diminished apoptosis, increased angiogenic and metastatic capacity, and chemoresistance that often characterize advanced malignancies. This oxidant stress often reflects up-regulation of expression and activity of NADPH oxidase, and/or decreased activity of catalase, which functions as suppressor gene in oxidant-dependent cancers. These characteristics of oxidant-dependent cancers suggest a dual strategy for treatment of these cancers. Since ascorbate can react spontaneously with molecular oxygen to generate hydrogen peroxide, high-dose intravenous ascorbate should be selectively toxic to tumors that are low in catalase activity - as suggested by numerous cell culture studies. Measures which concurrently improve the oxygenation of hypoxic tumor regions would be expected to boost the efficacy of such therapy; calcitriol and high-dose selenium might also be useful in this regard. Secondly, during the intervals between sessions of ascorbate therapy, administration of agents which can safely inhibit NADPH oxidase would be expected to slow the proliferation and spread of surviving tumor cells - while providing selection pressure for a further decline in catalase activity. In effect, cancers treated in this way would be whipsawed between lethally excessive and inadequately low oxidant stress. An additional possibility is that ascorbate-induced oxidant stress in tumors might potentiate the cell kill achieved with concurrently administered cytotoxic drugs, inasmuch as oxidant mechanisms appear to play a mediating role in the apoptosis induced by many such drugs, largely via activation of c-Jun NH(2)-terminal kinase; cell culture studies would be useful for evaluating this possibility.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Catalase; Humans; Hydrogen Peroxide; Models, Biological; NADPH Oxidases; Neoplasms; Oxidants; Oxygen

Topics: Ascorbic Acid; Clinical Trials, Phase I as Topic; Humans; Injections, Intravenous; Neoplasms

The effects of extracts from five cultivars of strawberries on the proliferation of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated, and possible correlations with the levels of several antioxidants were analyzed. In addition, the effects of organic cultivation compared to conventional cultivation on the content of antioxidants in the strawberries and strawberry extracts on the cancer cell proliferation were investigated. The ratio of ascorbate to dehydroascorbate was significantly higher in the organically cultivated strawberries. The strawberry extracts decreased the proliferation of both HT29 cells and MCF-7 cells in a dose-dependent way. The inhibitory effect for the highest concentration of the extracts was in the range of 41-63% (average 53%) inhibition compared to controls for the HT29 cells and 26-56% (average 43%) for MCF-7 cells. The extracts from organically grown strawberries had a higher antiproliferative activity for both cell types at the highest concentration than the conventionally grown, and this might indicate a higher content of secondary metabolites with anticarcinogenic properties in the organically grown strawberries. For HT29 cells, there was a negative correlation at the highest extract concentration between the content of ascorbate or vitamin C and cancer cell proliferation, whereas for MCF-7 cells, a high ratio of ascorbate to dehydroascorbate correlated with a higher inhibition of cell proliferation at the second highest concentration. The significance of the effect of ascorbate on cancer cell proliferation might lie in a synergistic action with other compounds.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; Cell Division; Cell Line, Tumor; Food, Organic; Fragaria; Fruit; HT29 Cells; Humans; Neoplasms

Topics: Ascorbic Acid; Cell Death; Dose-Response Relationship, Drug; Female; Forecasting; Humans; Male; Neoplasms; Research; Treatment Outcome; Tumor Cells, Cultured; United States

Topics: Ascorbic Acid; Clinical Trials as Topic; Complementary Therapies; Evidence-Based Medicine; Humans; Neoplasms; Prognosis; Vitamins

Several decades back ascorbic acid was proposed as an effective anticancer agent. However, this idea remained controversial and the mechanism of action unclear. In this paper, we show that ascorbic acid at a concentration reported to be achievable through high doses of oral consumption is capable of cytotoxic action against normal cells. Several antioxidants of both animal as well as plant origin including ascorbic acid also possess prooxidant properties. Copper is an essential component of chromatin and can take part in redox reactions. Previously we have proposed a mechanism for the cytotoxic action of plant antioxidants against cancer cells that involves mobilization of endogenous copper ions and the consequent generation of reactive oxygen species. Using human peripheral lymphocytes and Comet assay we show here that ascorbic acid is able to cause oxidative DNA breakage in normal cells at a concentration of 100-200 microM. Neocuproine, a Cu(I) specific sequestering agent inhibited DNA breakage in a dose dependent manner indicating that Cu(I) is an intermediate in the DNA cleavage reaction. The results are in support of our above hypothesis that involves events that lead to a prooxidant action by antioxidants. The results would support the idea that even a plasma concentration of around 200 microM. would be sufficient to cause pharmacological tumor cell death particularly when copper levels are elevated. This would account for the observation of several decades back by Pauling and co-workers where oral doses of ascorbic acid in gram quantities were found to be effective in treating some cancers.

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; Comet Assay; Copper; DNA Damage; Drug Screening Assays, Antitumor; Free Radical Scavengers; Humans; Hydrogen Peroxide; Lymphocytes; Neoplasms; Oxidants; Oxidation-Reduction; Phenanthrolines; Tannins

The new platinum(IV) complex cis,trans,cis-[PtCl(2)(CH(3)COO)(2)-(NH(3))(1-adamantylamine)] [adamplatin(IV)] seems promising for the perspective application in therapy of corresponding tumors. It is therefore of great interest to understand details of mechanisms underlying its biological efficacy. Cellular uptake of the drug, alterations in the target DNA induced by platinum drugs along with processing of platinum-induced damage to DNA and drug inactivation by sulfur-containing compounds belong to major pharmacological factors affecting antitumor effects of platinum compounds. We examined in the present work the significance of these factors in the mechanism of antitumor effects of adamplatin(IV) and compared the results with those of the parallel studies performed with "conventional" cisplatin. The results show that deactivation of adamplatin(IV) by sulfur-containing compounds (such as glutathione or metallothioneins) is likely to play a less significant role in the mechanism of resistance of tumor cells to adamplatin(IV) in contrast to the role of these reactions in the effects of cisplatin. Moreover, the treatment of tumor cells with adamplatin(IV) does not result in DNA modifications that would be markedly different from those produced by cisplatin. In contrast, the effects of other factors, such as enhanced accumulation of the drug in cells, strong inhibition of DNA polymerization by these adducts, lowered DNA repair, and DNA-protein cross-linking are different from the effects of these factors in the mechanism underlying activity of cisplatin. Hence, the differences between effects of adamplatin(IV) and cisplatin observed in the present work on molecular level may help understand the unique activity of adamplatin(IV).

Topics: Adamantane; Animals; Antineoplastic Agents; Ascorbic Acid; Base Sequence; Cell Line, Tumor; Cell-Free System; Cross-Linking Reagents; DNA; DNA Adducts; DNA Repair; DNA-Directed RNA Polymerases; HeLa Cells; High Mobility Group Proteins; HIV-1; Humans; Molecular Sequence Data; Neoplasms; Organoplatinum Compounds; Plasmids; Platinum; Rats; RNA-Directed DNA Polymerase; Sulfur Compounds; Viral Proteins

The discussions on interval estimation of the proportion ratio (PR) of responses or the relative risk (RR) of a disease for multiple matching have been generally focused on the odds ratio (OR) based on the assumption that the latter can approximate the former well. When the underlying proportion of outcomes is not rare, however, the results for the OR would be inadequate for use if the PR or RR was the parameter of our interest. In this paper, we develop five asymptotic interval estimators of the common PR (or RR) for multiple matching. To evaluate and compare the finite sample performance of these estimators, we apply Monte Carlo simulation to calculate the coverage probability and the average length of the resulting confidence intervals in a variety of situations. We note that when we have a constant number of matching, the interval estimator using the logarithmic transformation of the Mantel-Haenszel estimator, the interval estimator derived from the quadratic inequality given in this paper, and the interval estimator using the logarithmic transformation of the ratio estimator can consistently perform well. When the number of matching varies between matched sets, we find that the interval estimator using the logarithmic transformation of the ratio estimator is probably the best among the five interval estimators considered here in the case of a small number (=20) of matched sets. To illustrate the use of these interval estimators, we employ the data studying the supplemental ascorbate in the supportive treatment of terminal cancer patients.

Topics: Ascorbic Acid; Biometry; Confidence Intervals; Controlled Clinical Trials as Topic; Humans; Likelihood Functions; Models, Statistical; Monte Carlo Method; Neoplasms; Odds Ratio; Probability; Proportional Hazards Models; Risk

Topics: Antioxidants; Ascorbic Acid; Humans; Neoplasms

To assess the prevalence of vitamin C deficiency within a group of hospice patients. To assess the relationship between plasma vitamin C, dietary intake and subsequent survival.. Patients with advanced cancer were recruited from a large hospice. Data were collected on demographic details, physical functioning and smoking history. An estimate was obtained of the number of weekly dietary portions consumed equivalent to 40 mg of vitamin C, the recommended daily intake. Plasma vitamin C was measured by a single blood sample. The study had local ethical approval.. Fifty patients were recruited (mean age 65.2 years, 28 female). Plasma vitamin C deficiency was found in 15 (30%). Dietary intake of vitamin C was correlated to plasma vitamin C (r=0.518, P<0.0001). Low dietary intake, low albumin, high platelet count, high CRP level and shorter survival were all significantly associated with low plasma vitamin C concentrations (<11 micromol/L). There was no correlation between plasma vitamin C, smoking history or physical functioning.. Vitamin C deficiency is common in patients with advanced cancer and the most important factors determining plasma levels are dietary intake and markers of the inflammatory response. Patients with low plasma concentrations of vitamin C have a shorter survival.

Topics: Acute Disease; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; England; Female; Hospice Care; Humans; Male; Middle Aged; Neoplasms; Nutritional Status; Prevalence; Serum Albumin

Since raised oxidative stress (OS) or weak antioxidant defence or both are considered to be important players in multimechanistic pathogenesis of cancer, the present study was undertaken to evaluate their possible involvement in the pathogenesis of this disease in the local population. Levels of plasma vitamin C, vitamin E, total antioxidant activity (TAA) and thiobarbituric acid reacting substances (TBARS) as a marker of OS were measured in 20 cancer patients (Mean age 63.1 + 9.3 yr.) and 20 age, sex and socioeconomically matched healthy subjects (Mean age 63.7+7.8 yr.). Significantly low level of vitamin C (p <0.001), vitamin E (p <0.001) and TAA (p <0.003) were observed in cancer patients, whereas OS was significantly increased in patients as compared to control (p <0.003). Smokers had significantly lowered TAA and significantly raised OS than non-smokers, in both case and control groups. Tobacco chewer patients had raised OS as compared to control. This study supports the thesis that OS is a risk factor in carcinogenesis and that smoking, an established risk factor in cancer, at least partly appears through it.

Topics: Aged; Ascorbic Acid; Case-Control Studies; Female; Humans; Male; Middle Aged; Neoplasms; Oxidative Stress; Risk Assessment; Risk Factors; Thiobarbiturates; Vitamin E

Daylilies (Hemerocallis) are used medicinally in eastern Asia and extracts of the plant had been shown to inhibit cell proliferation and induce cancer cells to undergo differentiation. In our studies of the constituents of Hemerocallis fulva var. 'Kwanzo' roots, we isolated a series of new [kwanzoquinones A (1), B (2), C (4), D (5), E (6), F (7), G (9)] and known [2-hydroxychrysophanol (3) and rhein (8)] anthraquinones. These compounds were tested in order to determine their potential roles as cancer cell growth inhibitors. Kwanzoquinones A-C and E, kwanzoquinone A and B monoacetates (1a and 2a), 2-hydroxychrysophanol, and rhein inhibited the proliferation of human breast, CNS, colon, and lung cancer cells with GI50 values between 1.8 to 21.1 microg/mL. However, upon exposure of the cancer cells to the GI50 concentrations of the bioactive anthraquinones, most of the cancer cell lines exhibited higher than anticipated levels of cell viability. Co-incubation of the anthraquinones with vitamins C and E increased the viability of breast cancer cells. In contrast, vitamins C and E potentiated the cytotoxic effects of the anthraquinones against the colon cancer cells. None of the anthraquinones inhibited the activity of topoisomerase.

Topics: Anthraquinones; Antineoplastic Agents; Ascorbic Acid; Cell Division; Cell Line, Tumor; Cell Survival; Drug Combinations; Drug Screening Assays, Antitumor; Hemerocallis; Humans; Neoplasms; Plant Extracts; Vitamin E

The aim of this study was to prospectively assess the relation between red meat intake and incidence of type 2 diabetes.. Over an average of 8.8 years, we evaluated 37,309 participants in the Women's Health Study aged >/=45 years who were free of cardiovascular disease, cancer, and type 2 diabetes and completed validated semiquantitative food frequency questionnaires in 1993.. During 326,876 person-years of follow-up, we documented 1,558 incident cases of type 2 diabetes. After adjusting for age, BMI, total energy intake, exercise, alcohol intake, cigarette smoking, and family history of diabetes, we found positive associations between intakes of red meat and processed meat and risk of type 2 diabetes. Comparing women in the highest quintile with those in the lowest quintile, the multivariate-adjusted relative risks (RRs) of type 2 diabetes were 1.28 for red meat (95% CI 1.07-1.53, P < 0.001 for trend) and 1.23 for processed meat intake (1.05-1.45, P = 0.001 for trend). Furthermore, the significantly increased diabetes risk appeared to be most pronounced for frequent consumption of total processed meat (RR 1.43, 95% CI 1.17-1.75 for >/=5/week vs. <1/month, P < 0.001 for trend) and two major subtypes, which were bacon (1.21, 1.06-1.39 for >/=2/week vs. <1/week, P = 0.004 for trend) and hot dogs (1.28, 1.09-1.50 for >/=2/week vs. <1/week, P = 0.003 for trend). These results remained significant after further adjustment for intakes of dietary fiber, magnesium, glycemic load, and total fat. Intakes of total cholesterol, animal protein, and heme iron were also significantly associated with a higher risk of type 2 diabetes.. Our data indicate that higher consumption of total red meat, especially various processed meats, may increase risk of developing type 2 diabetes in women.

Topics: Ascorbic Acid; Aspirin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Energy Intake; Feeding Behavior; Female; Humans; Life Style; Male; Meat; Middle Aged; Neoplasms; Prospective Studies; Risk Assessment

A series of seven cases are presented in which intravenous vitamin C has been used as antineoplastic agent in the treatment of different types of cancers. The cancers cases reviewed are the following: Renal cell carcinoma (2), Colorectal cancer (1), Pancreatic cancer (1), Non-Hodgkin's lymphoma (2) and breast cancer (1). Toxic reactions were not observed at these high doses of intravenous Vitamin C. All patients were prescreened for Glucose 6--phosphate dehydrogenase deficiency before administering intravenous Vitamin C in order to prevent hemolysis.

Topics: Aged; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Female; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasms; Treatment Outcome

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Butylated Hydroxytoluene; Diet; Dietary Fats; Dietary Supplements; Drug Interactions; Energy Intake; Free Radicals; Humans; Neoplasms; Oxidants; Vitamin E

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Breast Neoplasms; Dietary Supplements; Female; Humans; Middle Aged; Neoplasms; Survival Rate; Survivors; Vitamin E

Higher intake of fruits, vegetables, and antioxidants may help protect against oxidative damage, thus lowering cancer and cardiovascular disease risk. This Washington County, Maryland, prospective study examined the association of fruit, vegetable, and antioxidant intake with all-cause, cancer, and cardiovascular disease death. CLUE participants who donated a blood sample in 1974 and 1989 and completed a food frequency questionnaire in 1989 (N = 6,151) were included in the analysis. Participants were followed to date of death or January 1, 2002. Compared with those in the bottom fifth, participants in the highest fifth of fruit and vegetable intake had a lower risk of all-cause (cases = 910; hazard ratio (HR) = 0.63, 95% confidence interval (CI): 0.51, 0.78; p-trend = 0.0004), cancer (cases = 307; HR = 0.65, 95% CI: 0.45, 0.93; p-trend = 0.08), and cardiovascular disease (cases = 225; HR = 0.76, 95% CI: 0.54, 1.06; p-trend = 0.15) mortality. Higher intake of cruciferous vegetables was associated with lower risk of all-cause mortality (HR = 0.74, 95% CI: 0.60, 0.91; p-trend = 0.04). No statistically significant associations were observed between dietary vitamin C, vitamin E, and beta-carotene intake and mortality. Overall, greater intake of fruits and vegetables was associated with lower risk of all-cause, cancer, and cardiovascular disease death. These findings support the general health recommendation to consume multiple servings of fruits and vegetables (5-9/day).

Topics: Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Body Mass Index; Cardiovascular Diseases; Cause of Death; Cohort Studies; Diet; Female; Fruit; Humans; Male; Maryland; Middle Aged; Neoplasms; Smoking; Vegetables

Hypoxia-inducible factor (HIF) plays an important role in determining patterns of gene expression in cancer. HIF is down-regulated in oxygenated cells by a series of Fe (II) and 2-oxoglutarate dependent dioxygenases that hydroxylate specific residues in the regulatory HIF-alpha subunits. Because these enzymes require ascorbate for activity in vitro we analyzed the effects of ascorbate on HIF in human cancer cell lines. Ascorbate at physiological concentrations (25 micro M) strikingly suppressed HIF-1alpha protein levels and HIF transcriptional targets, particularly when the system was oncogenically activated in normoxic cells. Similar results were obtained with iron supplementation. These results indicate that both ascorbate and iron availability have major effects on HIF, and imply that the system is commonly regulated by limiting hydroxylase activity under normoxic tissue culture conditions.

Topics: Adenocarcinoma; Ascorbic Acid; Breast Neoplasms; Cell Hypoxia; Endothelial Growth Factors; Female; Ferrous Compounds; Glucose Transporter Type 1; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intercellular Signaling Peptides and Proteins; Lymphokines; Male; Monosaccharide Transport Proteins; Neoplasms; Ovarian Neoplasms; Procollagen-Proline Dioxygenase; Prostatic Neoplasms; RNA, Messenger; Transcription Factors; Transcriptional Activation; Transferrin; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Our previous study showed that tumor invasion of human fibrosarcoma cells HT-1080 is hardly inhibited by ascorbic acid itself (Asc), but inhibited by 2-O-phosphorylated Asc-6-O-palmitylester (Asc2P6Plm) more markedly than 2-O-phosphorylated Asc or Asc-6-O-palmitylester, and that the inhibitory effect may be attributed to an increase in intracellular Asc derived from Asc2P6Plm. In the present study, the mechanism underlying the inhibitory effect of Asc2P6Plm on tumor invasion was analyzed. Migratory ability of the tumor cells was shown to be inhibited in a dose-dependent manner by either treatment with Asc2P6Plm at 50-300 micro M for 1 h or at 10-50 micro M for 18 h as assessed by cell sheet scratching assay. Hydroxyl radicals in homogenates of Asc2P6Plm-treated HT-1080 cells were markedly diminished relative to those of non-treated cells as evaluated by electron spin resonance method using the spin trapping agent DMPO. This may be closely related to attenuation of intracellular gross reactive oxygen species by Asc2P6Plm as was shown with the redox indicator CDCFH-DA. Actin was localized in the vicinity of the cell membrane abundantly in non-treated cells, but was diminished in a time-dependent manner in Asc2P6Plm-treated cells together with disappearance of pseudopods as shown with the actin-directed agent NBD-phallacidin and by immunocytochemical stain. The cell adhesion-controling molecule RhoA was increased time-dependently in the cytoplasm of Asc2P6Plm-treated cells as shown by Western blots. Thus the inhibition of tumor invasion by Asc2P6Plm was shown to be attributed to decrease in both the cell migratory ability and the actin localization near the cell membrane, which may result from an increase in cytoplasmic RhoA and reduction of intracellular ROS that is achieved by enrichment of intracellular Asc derived from Asc2P6Plm.

Topics: Actins; Ascorbic Acid; Blotting, Western; Cell Line, Tumor; Cell Movement; Cyclic N-Oxides; Dose-Response Relationship, Drug; Electron Spin Resonance Spectroscopy; Humans; Hydroxyl Radical; Immunohistochemistry; Microscopy, Fluorescence; Neoplasm Invasiveness; Neoplasms; Reactive Oxygen Species; rhoA GTP-Binding Protein; Spin Labels; Time Factors

High dose intravenous(i.v.) ascorbic acid (AA) has been used as therapy for infectious disease from bacterial and viral origin and adjuvant therapy for cancer. In this publication we describe a clinical protocol that has been developed over the past twenty years utilizing high dose i.v. AA as therapy for cancer. This includes principles of treatment, rationale, baseline workup, infusion protocol, precautions and side effects.

Topics: Anti-Infective Agents; Antineoplastic Agents; Ascorbic Acid; Bacterial Infections; Clinical Protocols; Dose-Response Relationship, Drug; Humans; Infusions, Intravenous; Neoplasms; Neoplastic Stem Cells; Virus Diseases

Tobacco and alcohol consumption are strongly related to other cardiovascular and cancer risk factors. The aim of the present study was to analyse the association of nutrient intake, blood lipid variables and leisure-time physical activity with tobacco and alcohol consumption status. Participants were recruited in a cross-sectional population-based survey, including cardiovascular risk factor measurements and evaluation of physical activity and diet intake in a Mediterranean population (n 1748). Multiple linear regression analysis, adjusted for several confounders, showed a direct association of saturated fatty acids (g and % total energy intake), dietary cholesterol intakes and serum triacylglycerol with smoking. An inverse association was observed for smoking and unsaturated fatty acids (% energy intake), vitamin C, alpha-tocopherol and beta-carotene intakes, leisure-time physical activity and HDL-cholesterol. These associations were not observed for alcohol drinking. After adjusting for the confounders earlier mentioned, low dietary intakes of vitamin C and dietary fibre were more likely in heavy-smokers as compared with non-smokers (odds ratio 1.74 (95 % CI 1.07, 2.73) and 1.94 (95 % CI 1.29, 2.92) of low vitamin C (<60 mg/d) and dietary fibre intakes (<10 g/d) respectively). Alcohol consumption was directly associated with HDL-cholesterol and triacylglycerol, and attenuated the effects of smoking on HDL-cholesterol. These results suggest that the dietary intake of fibre and several antioxidant components of the Mediterranean diet is reduced in smokers, who also show an adverse lipid profile. However, the worst triacylglycerol levels are associated with the combination of heavy smoking and heavy alcohol drinking. Moderate alcohol consumption was not associated with an unhealthy diet pattern or adverse lipid profile. The health benefits of the Mediterranean diet appear to be strongly counteracted by smoking.

Topics: Adult; Aged; Alcohol Drinking; Ascorbic Acid; Cardiovascular Diseases; Cross-Sectional Studies; Dietary Fiber; Energy Intake; Exercise; Feeding Behavior; Female; Humans; Linear Models; Lipids; Male; Middle Aged; Neoplasms; Nutritional Status; Risk Factors; Smoking; Spain

Vitamins are essential components of a normal diet, and sufficient amounts are always needed. Occasionally, multivitamin supplements may make sense in cancer patients. However, because of the balance of (antioxidant) vitamins, coenzymes, trace elements and secondary phytochemicals it offers, a varied diet of fresh fruits and vegetables is--wherever possible--to be preferred to supplements of single or combinations of vitamins. Although preclinical studies have confirmed the positive effects of high-dose vitamins on cancer, there is currently no evidence that increased consumption of vitamins benefits cancer patients--nor is the dose necessary to achieve a possible therapeutic impact known. Since a number of clinical and epidemiological studies fail to show any benefit, and adverse effects have even been reported, high-dose vitamins can at present be recommended only for short-term substitution in known vitamin deficiencies. Before a definitive pronouncement can be made, therefore, further clinical studies of megavitamins in cancer patients are needed.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Diet; Female; Fruit; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Time Factors; Vegetables; Vitamin E; Vitamins

Topics: Aged; Antioxidants; Ascorbic Acid; Cause of Death; Cohort Studies; Diet Surveys; Female; Humans; Incidence; Male; Middle Aged; Neoplasms; Prospective Studies; Registries; Risk Factors; Sex Factors; United Kingdom

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Ascorbic Acid; Cell Differentiation; Cell Division; Connexin 43; Connexins; Disease Models, Animal; Drug Evaluation, Preclinical; Free Radical Scavengers; Humans; Neoplasms; Phosphorylation; Primary Prevention; Rats

Topics: Antioxidants; Ascorbic Acid; Bias; Evidence-Based Medicine; Humans; Neoplasms; Remission Induction; Research Design

Topics: Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Complementary Therapies; Evidence-Based Medicine; Guidelines as Topic; Humans; Neoplasms; Remission Induction; Reproducibility of Results; Research Design

Ascorbic acid (vitamin C) might be protective for several chronic diseases. However, findings from prospective studies that relate ascorbic acid to cardiovascular disease or cancer are not consistent. We aimed to assess the relation between plasma ascorbic acid and subsequent mortality due to all causes, cardiovascular disease, ischaemic heart disease, and cancer.. We prospectively examined for 4 years the relation between plasma ascorbic acid concentrations and mortality due to all causes, and to cardiovascular disease, ischaemic heart disease, and cancer in 19 496 men and women aged 45-79 years. We recruited individuals by post using age-sex registers of general practices. Participants completed a health and lifestyle questionnaire and were examined at a clinic visit. They were followed-up for causes of death for about 4 years. Individuals were divided into sex-specific quintiles of plasma ascorbic acid. We used the Cox proportional hazard model to determine the effect of ascorbic acid and other risk factors on mortality.. Plasma ascorbic acid concentration was inversely related to mortality from all-causes, and from cardiovascular disease, and ischaemic heart disease in men and women. Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile (p<0.0001). The relation with mortality was continuous through the whole distribution of ascorbic acid concentrations. 20 micromol/L rise in plasma ascorbic acid concentration, equivalent to about 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality (p<0.0001), independent of age, systolic blood pressure, blood cholesterol, cigarette smoking habit, diabetes, and supplement use. Ascorbic acid was inversely related to cancer mortality in men but not women.. Small increases in fruit and vegetable intake of about one serving daily has encouraging prospects for possible prevention of disease.

Topics: Age Distribution; Aged; Ascorbic Acid; Cardiovascular Diseases; Cause of Death; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Neoplasms; Proportional Hazards Models; Prospective Studies; Registries; Risk Factors; Sex Distribution; Surveys and Questionnaires

We present a new protocol for the preparation of nucleic acids for microarray hybridization. DNA is fragmented quantitatively and reproducibly by using a hydroxyl radical-based reaction, which is initiated by hydrogen peroxide, iron(II)-EDTA and ascorbic acid. Following fragmentation, the nucleic acid fragments are densely biotinylated using a biotinylated psoralen analog plus UVA light and hybridized on microarrays. This non-enzymatic protocol circumvents several practical difficulties associated with DNA preparation for microarrays: the lack of reproducible fragmentation patterns associated with enzymatic methods; the large amount of labeled nucleic acids required by some array designs, which is often combined with a limited amount of starting material; and the high cost associated with currently used biotinylation methods. The method is applicable to any form of nucleic acid, but is particularly useful when applying double-stranded DNA on oligonucleotide arrays. Validation of this protocol is demonstrated by hybridizing PCR products with oligonucleotide-coated microspheres and PCR amplified cDNA with Affymetrix Cancer GeneChip microarrays.

Topics: Ascorbic Acid; Biotinylation; Cost Savings; DNA Probes; DNA, Complementary; Edetic Acid; Ferrous Compounds; Ficusin; Flow Cytometry; Furocoumarins; Gene Deletion; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, p53; Humans; Hydrogen Peroxide; Hydroxyl Radical; Microspheres; Neoplasms; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; Oligonucleotides; Photochemistry; Polymerase Chain Reaction; Reproducibility of Results; Tumor Cells, Cultured; Ultraviolet Rays

To examine the relation between serum ascorbic acid (SAA), a marker of dietary intake (including supplements), and cause-specific mortality.. We analyzed data from a probability sample of 8,453 Americans age > or = 30 years at baseline enrolled in the Second National Health and Nutrition Examination Survey (NHANES II), who were followed for mortality endpoints. We calculated relative hazard ratios as measures of disease association comparing the mortality rates in three biologically relevant SAA categories.. Participants with normal to high SAA levels had a marginally significant 21% to 25% decreased risk of fatal cardiovascular disease (CVD) (p for trend = 0.09) and a 25% to 29% decreased risk of all-cause mortality (p for trend <0.001) compared to participants with low levels. Because we determined that gender modified the association between SAA levels and cancer death, we analyzed these associations stratified by gender. Among men, normal to high SAA levels were associated with an approximately 30% decreased risk of cancer deaths, whereas such SAA levels were associated with an approximately two-fold increased risk of cancer deaths among women. This association among women persisted even after adjustment for baseline prevalent cancer and exclusion for early cancer death or exclusion for prevalent cancer.. Low SAA levels were marginally associated with an increased risk of fatal CVD and significantly associated with an increased risk for all-cause mortality. Low SAA levels were also a risk factor for cancer death in men, but unexpectedly were associated with a decreased risk of cancer death in women. If the association between low SAA levels and all-cause mortality is causal, increasing the consumption of ascorbic acid, and thereby SAA levels, could decrease the risk of death among Americans with low ascorbic acid intakes.

Topics: Adult; Aged; Ascorbic Acid; Cardiovascular Diseases; Cause of Death; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Neoplasms; Nutrition Surveys; Risk Factors; Sex Factors; United States

Topics: Ascorbic Acid; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Fibrinogen; Humans; Neoplasms; Risk Factors

Topics: Ascorbic Acid; Cardiovascular Diseases; Humans; Neoplasms; Risk Factors

Topics: Ascorbic Acid; Cardiovascular Diseases; Humans; Neoplasms; Risk Factors

Topics: Ascorbic Acid; Cardiovascular Diseases; Humans; Neoplasms; Risk Factors

Topics: Ascorbic Acid; Cardiovascular Diseases; Humans; Neoplasms; Risk Factors

We assessed the accuracy of a 141-item food frequency questionnaire as a screening test to detect high or low consumption of nutrients associated with cancer. Fifty-five men and 58 women participating in two population-based cohort studies in Miyagi, Japan, provided four three-day diet records over a one-year period and subsequently completed the questionnaire twice with a one-year interval. Pearson correlation coefficients between 17 nutrients measured by the diet records and the first questionnaire ranged from 0.24 to 0.85 (median 0.43), and those between the two questionnaires ranged from 0.47 to 0.91 (median 0.68). The sensitivity and specificity of the questionnaire for detecting high-alcohol, high-fat, low-calcium, and low-ascorbic acid consumers were 86.7% and 96.7%, 50.0% and 85.7%, 48.8% and 76.4%, and 61.9% and 70.0%, respectively. Receiver operating characteristic curves indicated comparable performance of the questionnaire and a three-day diet record, regarded as another screening test. The questionnaire performed poorly for other nutrients. The results indicate that our questionnaire is reasonably reproducible, comparable with the diet records, and useful as a screening test to detect high or low consumers of several nutrients associated with cancer for subsequent enrollment in dietary intervention trials or dietary counseling.

Topics: Alcohol Drinking; Ascorbic Acid; Calcium, Dietary; Cohort Studies; Diet Records; Diet Surveys; Dietary Fats; Female; Humans; Male; Mass Screening; Middle Aged; Neoplasms; Reproducibility of Results; Risk Factors; ROC Curve; Sensitivity and Specificity; Surveys and Questionnaires

The number of cancer survivors in the United States is increasing, but little is known about this population, including its use of vitamin/mineral supplements. We combined data on vitamin/mineral use from the 1987 and 1992 National Health Interview Survey Cancer Epidemiology Supplement (CES) for cancer survivors: persons reporting a diagnosis of cancer other than nonmelanoma skin cancer > 5 yr before their interviews [n = 461 (1987) and 228 (1992)] and persons reporting no history of cancer [n = 20,851 (1987) and 11,186 (1992)]. For both groups, we calculated gender-specific proportions (adjusted for age, race/ethnicity, education, smoking status, and poverty index) for use of multivitamins, vitamins A, C, and E, and calcium during the year before each survey. Supplement use was similar in survivors and persons reporting no history of cancer. Among survivors, calcium use was significantly higher among women (34.9%) than men (13.8%), and vitamin A use was higher among men than women (P < 0.05). Over three-fourths of both groups used multivitamins, and about one-half used vitamin C. No differences were found in vitamin/mineral use between male survivors and men with no cancer history or between female survivors and women with no cancer history. These first nationally representative estimates suggest that persons who have survived cancer and those who report that they never had the disease do not differ appreciably in their use of vitamin/mineral supplements. Results were based on small numbers of survivors, however, and require replication.

Topics: Adult; Ascorbic Acid; Calcium, Dietary; Dietary Supplements; Educational Status; Female; Health Surveys; Humans; Male; Middle Aged; Minerals; Neoplasms; Sex Factors; Smoking; Survivors; Vitamin A; Vitamin E; Vitamins

To examine the cross-sectional association between plasma vitamin C, self-reported diabetes, and HbA1c.. Data from a population-based study of diet, cancer, and chronic disease were analyzed. A total of 2,898 men and 3,560 women 45-74 years of age who were registered with general practices in Norfolk, U.K., were recruited to the European Prospective Investigation Into Cancer-Norfolk study between 1995 and 1998.. Mean plasma vitamin C levels were significantly higher in individuals with HbA1c levels < 7% than in those with self-reported diabetes or prevalent undiagnosed hyperglycemia (HbA1c > or = 7%). An inverse gradient of mean plasma vitamin C was found in both sexes across quintiles of HbA1c distribution < 7%. The odds ratio (95% CI) of having prevalent undiagnosed hyperglycemia per 20 micromol/l (or 1 SD) increase in plasma vitamin C was 0.70 (0.52-0.95) (adjusted for sex, age, BMI, waist-to-hip ratio, tertiary education, any use of dietary supplements, vegetarian diet, alcohol consumption, physical activity, dietary vitamin E, dietary fiber, dietary saturated fat, and smoking history). The unadjusted change in HbA1c per 20 micromol/l increase in vitamin C estimated by linear regression was -0.12% (-0.14 to -0.09) in men and -0.09% (-0.11 to -0.07) in women. After adjusting for the possible confounders, these values were -0.08% (-0.11 to -0.04) in men and -0.05% (-0.07 to -0.03) in women.. An inverse association was found between plasma vitamin C and HbA1c. Dietary measures to increase plasma vitamin C may be an important public health strategy for reducing the prevalence of diabetes.

Topics: Aged; Ascorbic Acid; Chronic Disease; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus; Diet; England; Europe; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Male; Middle Aged; Neoplasms; Odds Ratio; Prevalence

Topics: Agaricales; Antioxidants; Ascorbic Acid; Complementary Therapies; Drugs, Chinese Herbal; Electroacupuncture; Humans; Neoplasms; Quality Control; United States

Low vitamin C status may increase the risk of mortality from cancer and cardiovascular disease.. The objective was to test whether an association existed between serum ascorbate concentrations and mortality and whether the association was modified by cigarette smoking status or sex.. Serum ascorbate concentrations were measured in adults as part of the second National Health and Nutrition Examination Survey (1976-1980). Vital status was ascertained 12-16 y later.. The relative risk (RR) of death, adjusted for potential confounders, was estimated by using Cox proportional hazards models. Men in the lowest (<28.4 micromol/L) compared with the highest (>/=73.8 micromol/L) serum ascorbate quartile had a 57% higher risk of dying from any cause (RR: 1.57; 95% CI: 1.21, 2.03) and a 62% higher risk of dying from cancer (RR: 1.62; 95% CI: 1.01, 2.59). In contrast, there was no increased risk among men in the middle 2 quartiles for these outcomes and no increased risk of cardiovascular disease mortality in any quartile. There was no association between serum ascorbate quartile and mortality among women. These findings were consistent when analyses were limited to nonsmokers or further to adults who never smoked, suggesting that the observed relations were not due to cigarette smoking.. These data suggest that men with low serum ascorbate concentrations may have an increased risk of mortality, probably because of an increased risk of dying from cancer. In contrast, serum ascorbate concentrations were not related to mortality among women.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Neoplasms; Nutrition Surveys; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Factors; Smoking; United States

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; Combined Modality Therapy; Dietary Fats; Dietary Fiber; Exercise; Humans; Neoplasms; Nutrition Policy; Selenium; United States; Vitamin E; Vitamins

To determine the relation between multivitamin use and death from heart disease, cerebrovascular disease, and cancer, the authors examined a prospective cohort of 1,063,023 adult Americans in 1982-1989 and compared the mortality of users of multivitamins alone; vitamin A, C, or E alone; and multivitamin and vitamin A, C, or E in combination with that of vitamin nonusers by using multivariate Cox proportional hazard models. Multivitamin users had heart disease and cerebrovascular disease mortality risks similar to those of nonusers, whereas combination users had mortality risks that were 15% lower than those of nonusers. Multivitamin and combination use had minimal effect on cancer mortality overall, although mortality from all cancers combined was increased among male current smokers who used multivitamins alone (relative risk (RR) = 1.13, 95% confidence interval (CI): 1.05, 1.23) or in combination with vitamin A, C, or E (RR = 1.16, 95% CI: 1.06, 1.26), but decreased in male combination users who had never (RR = 0.86, 95% CI: 0.74, 0.99) or had formerly (RR = 0.90, 95% CI: 0.82, 0.98) smoked. No such associations were seen in women. These observational data provide limited support for the hypothesis that multivitamin use in combination with vitamin A, C, or E may reduce heart disease and cardiovascular disease mortality, but add to concerns raised by randomized studies that some vitamin supplements may adversely affect male smokers.

Topics: Aged; Ascorbic Acid; Coronary Disease; Female; Humans; Male; Middle Aged; Mortality; Neoplasms; Proportional Hazards Models; Prospective Studies; Risk Factors; Smoking; Stroke; Vitamin A; Vitamin E; Vitamins

Free radicals have been implicated in over a hundred disease conditions in humans, including arthritis, hemorrhagic shock, atherosclerosis, advancing age, ischemia and reperfusion injury of many organs, Alzheimer and Parkinson's disease, gastrointestinal dysfunctions, tumor promotion and carcinogenesis, and AIDS. Antioxidants are potent scavengers of free radicals and serve as inhibitors of neoplastic processes. A large number of synthetic and natural antioxidants have been demonstrated to induce beneficial effects on human health and disease prevention. However, the structure-activity relationship, bioavailability and therapeutic efficacy of the antioxidants differ extensively. Oligomeric proanthocyanidins, naturally occurring antioxidants widely available in fruits, vegetables, nuts, seeds, flowers and bark, have been reported to possess a broad spectrum of biological, pharmacological and therapeutic activities against free radicals and oxidative stress. We have assessed the concentration- or dose-dependent free radical scavenging ability of a novel IH636 grape seed proanthocyanidin extract (GSPE) both in vitro and in vivo models, and compared the free radical scavenging ability of GSPE with vitamins C, E and beta-carotene. These experiments demonstrated that GSPE is highly bioavailable and provides significantly greater protection against free radicals and free radical-induced lipid peroxidation and DNA damage than vitamins C, E and beta-carotene. GSPE was also shown to demonstrate cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal human gastric mucosal cells. The comparative protective effects of GSPE, vitamins C and E were examined on tobacco-induced oxidative stress and apoptotic cell death in human oral keratinocytes. Oxidative tissue damage was determined by lipid peroxidation and DNA fragmentation, while apoptotic cell death was assessed by flow cytometry. GSPE provided significantly better protection as compared to vitamins C and E, singly and in combination. GSPE also demonstrated excellent protection against acetaminophen overdose-induced liver and kidney damage by regulating bcl-X(L) gene, DNA damage and presumably by reducing oxidative stress. GSPE demonstrated excellent protection against myocardial ischemia-reperfusion injury and myocardial infarction in rats. GSPE was also shown to upregulate bcl(2) gene and downregulate the oncogene c-myc. Topical application of GS

Topics: Animals; Anthocyanins; Antioxidants; Apoptosis; Ascorbic Acid; beta Carotene; Biological Availability; Cardiovascular Diseases; Dose-Response Relationship, Drug; Flow Cytometry; Free Radical Scavengers; Free Radicals; Humans; Keratinocytes; Kidney Diseases; Liver Diseases; Neoplasms; Plant Extracts; Proanthocyanidins; Seeds; Vitamin E

Some clinicians and alternative therapy practitioners advocate megadose intravenous and oral ascorbate treatment of cancer. Randomized control studies using oral ascorbate showed no benefit. Recent data show that intravenous but not oral administration of ascorbate can produce millimolar plasma concentrations, which are toxic to many cancer cell lines. We propose that ascorbate treatment of cancer should be reexamined by rigorous scientific scrutiny in the light of new evidence.

Topics: Administration, Oral; Antioxidants; Ascorbic Acid; Humans; Injections, Intravenous; Neoplasms; Tumor Cells, Cultured

Rates of vitamin-mineral supplement use by US female physicians are unknown but are of particular interest for several epidemiologic and clinical reasons.. The objective was to determine rates of and variations in vitamin-mineral supplement use among US female physicians.. We used data from the Women Physicians' Health Study, a large (n = 4501) national, randomly sampled mail survey of female physicians aged 30-70 y.. Half of the physicians took a multivitamin-mineral supplement; 35.5% of these did so regularly. However,

Topics: Adult; Aged; Ascorbic Acid; Calcium; Cohort Studies; Coronary Disease; Diabetes Mellitus; Dietary Supplements; Female; Humans; Marital Status; Middle Aged; Minerals; Neoplasms; Osteoporosis; Physicians, Women; Social Class; Surveys and Questionnaires; Vitamin A; Vitamin E; Vitamins

One striking paradox in epidemiologic research is the strong association between diet and cancer in ecologic studies compared with the weaker associations reported in many within-country case-control and cohort studies. However, most ecologic studies have relied on indirect measures of dietary intake, such as food disappearance data. The objectives of our study were to assess the feasibility of collecting dietary and biomarker data from individuals living in countries having markedly different dietary patterns and cultures and to examine the magnitude of the between-country variation in their measurement. Adults surveyed in Shanghai (China), Costa Rica and King County (Washington, USA) completed a 24-hr dietary recall, a cancer risk factor survey, and provided a blood sample. We analyzed a subset of the blood specimens for vitamins C, E, carotenoids and phospholipid fatty acids. We observed substantial differences in nutrient intakes and in mean plasma concentrations of dietary biomarkers across the study populations. For example, King County participants had the highest daily intake of vitamin C (mean 78.3 +/- 12.2 mg compared with 42.6 +/- 38.3 mg in Shanghai and 34.8 +/- 43.8 mg in Costa Rica). The mean plasma vitamin C level in King County was also the highest of the 3 study sites: 927.9 +/- 43.9 microg/dl in King County, 585.7 +/- 35.9 microg/dl in Shanghai and 461.1 +/- 33.1 microg/dl in Costa Rica. Plasma trans fatty acids (a biomarker of a diet high in hydrogenated fats) were highest in King County and lowest in Shanghai.

Topics: Adult; Aged; Ascorbic Acid; Biomarkers; China; Costa Rica; Diet; Fatty Acids; Female; Humans; Male; Middle Aged; Neoplasms; Risk; United States

Many constituents present in the human diet may inhibit endogenous formation of N-nitroso compounds (NOC). Studies with human volunteers showed inhibiting effects of intake of ascorbic acid and green tea consumption on nitrosation using the N-nitrosoproline test. The aim of the present study was to evaluate the effects of ascorbic acid and green tea on urinary excretion of carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) in humans. Twenty-five healthy female volunteers consumed a fish meal rich in amines as nitrosatable precursors in combination with intake of nitrate-containing drinking water at the Acceptable Daily Intake level during 7 consecutive days. During 1 week before and after nitrate intake a diet low in nitrate was consumed. Using the same protocol, the effect of two different doses of ascorbic acid (250 mg and 1 g/day) and two different doses of green tea (2 g and 4 g/day) on formation of NDMA and NPIP was studied. Mean nitrate excretion in urine significantly increased from control (76+/-24) to 167+/-25 mg/24 h. Intake of nitrate and fish resulted in a significant increase in mean urinary excretion of NDMA compared with the control weeks: 871+/-430 and 640+/-277 ng/24 h during days 1-3 and 4-7, respectively, compared with 385+/-196 ng/24 h (p<0.0002). Excretion of NPIP in urine was not related to nitrate intake and composition of the diet. Intake of 250 mg and 1 g of ascorbic acid per day resulted in a significant decrease in urinary NDMA excretion during days 4-7 (p=0.0001), but not during days 1-3. Also, consumption of four cups of green tea per day (2 g) significantly decreased excretion of NDMA during days 4-7 (p=0.0035), but not during days 1-3. Surprisingly, consumption of eight cups of green tea per day (4 g) significantly increased NDMA excretion during days 4-7 (p=0.0001), again not during days 1-3. This increase is probably a result of catalytic effects of tea polyphenols on nitrosation, or of another, yet unknown, mechanism. These results suggest that intake of ascorbic acid and moderate consumption of green tea can reduce endogenous NDMA formation.

Topics: Adolescent; Adult; Ascorbic Acid; Carcinogens; Diet; Dimethylnitrosamine; Female; Humans; Middle Aged; Neoplasms; Nitrosamines; Tea

Topics: Antioxidants; Ascorbic Acid; Humans; Neoplasms; Radiation Injuries

Environmental tobacco smoke (ETS) is a pervasive contaminant in the workplace. Our objective was to determine the oxidative stress effects of ETS on employees who are exposed. The results provide information that is useful to the resolution of risk assessment questions associated with ETS. We analyzed two blood draws from volunteers in our control and exposed groups. The level of exposure to ETS was determined through plasma cotinine measurements, which showed a 65% increase from the control group to the exposed group. Exposure to ETS resulted in a statistically significant increase of 63% of the oxidative DNA mutagen 8-hydroxy-2'-deoxyguanosine in the blood of exposed subjects. This oxidative DNA damage has been linked to an increased risk of developing several degenerative chronic diseases, including coronary heart disease and cancer. The exposed subjects also had increased levels of superoxide dismutase, catalase, glutathione peroxidase (GPOX), and glutathione reductase. However, these increases were only statistically significant in catalase and GPOX. Catalase levels were 13% higher in the exposed group, and GPOX levels were 37% higher in exposed volunteers. The biochemical evidence suggests that exposure to ETS causes oxidative stress, resulting in DNA damage that may increase the risk of certain diseases.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Air Pollution, Indoor; Ascorbic Acid; beta Carotene; Catalase; Coronary Disease; Cotinine; Deoxyguanosine; Female; Glutathione Reductase; Humans; Male; Middle Aged; Neoplasms; Oxidative Stress; Risk Factors; Superoxide Dismutase; Tobacco Smoke Pollution; Vitamin E; Workplace

The National University of Singapore Heart Study measured cardiovascular risk factors, including selected plasma vitamins, on a random sample of the general population aged 30 to 69 years. Plasma vitamins A and E were normal and similar by ethnic group. Mean plasma vitamin A levels were: Chinese (males 0.68 and females 0.52 mg/L), Malays (males 0.67 and females 0.54 mg/L), and Indians (males 0.66 and females 0.51 mg/L). Mean plasma vitamin E levels were: Chinese (males 12.6 and females 12.6 mg/L), Malays (males 13.6 and females 13.3 mg/L), and Indians (males 12.9 and females 12.8 mg/L). No person had plasma vitamin A deficiency (< 0.01 mg/L) and only 0.1% had vitamin E deficiency (< 5.0 mg/L). In contrast, plasma vitamin C was on the low side and higher in Chinese than Malays and Indians. Mean plasma vitamin C levels were: Chinese (males 6.3 and females 8.4 mg/L), Malays (males 5.1 and females 6.4 mg/L), and Indians (males 5.7 and females 6.9 mg/L). Likewise, the proportions with plasma vitamin C deficiency (< 2.0 mg/L) were lower in Chinese (males 14.4 and females 0.7%), than Malays (males 19.7 and females 7.2%), and Indians (males 17.8 and females 11.0%). Relatively low levels of plasma vitamin C may contribute to the high rates of coronary heart disease and cancer in Singapore. In particular, lower plasma vitamin C in Malays and Indians than Chinese may contribute to their higher rates of coronary heart disease. However, plasma vitamin C does not seem to be involved in the higher rates of cancer in Chinese than Malays and Indians. The findings suggest a relatively low intake of fresh fruits and a higher intake is recommended. Also, food sources of vitamin C may be destroyed by the high cooking temperatures of local cuisines, especially the Malay and Indian ones.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; China; Cooking; Coronary Disease; Ethnicity; Feeding Behavior; Female; Fruit; Heart Diseases; Humans; India; Malaysia; Male; Middle Aged; Neoplasms; Risk Factors; Singapore; Smoking; Vitamin A; Vitamin E; Vitamin E Deficiency

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; Attitude to Health; Canada; Clinical Trials as Topic; Complementary Therapies; Cooperative Behavior; Government Agencies; Humans; Hydrazines; Neoplasms; Voluntary Health Agencies

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Coronary Disease; Humans; Neoplasms; Risk Factors; Treatment Outcome; Vitamin E

The Food and Drug Administration (FDA) is issuing an interim final rule to prohibit the use on foods of a claim relating to the relationship between antioxidant vitamins C and E and the risk in adults of atherosclerosis, coronary heart disease, certain cancers, and cataracts. This rule is in response to a notification of a health claim submitted under section 303 of the FDA Modernization Act of 1997 (FDAMA). FDA has reviewed statements that the petitioner submitted in that notification, and, in conformity with the requirements of FDAMA, the agency is prohibiting the claim because the statements submitted as the basis of the claim are not "authoritative statements" of a scientific body, as required by FDAMA; therefore, section 303 of FDAMA does not authorize use of this claim. As provided for in section 301 of FDAMA, this rule is effective immediately upon publication.

Topics: Adult; Arteriosclerosis; Ascorbic Acid; Cataract; Coronary Disease; Drug Approval; Food Labeling; Humans; Neoplasms; Risk Factors; United States; United States Food and Drug Administration; Vitamin E

The purpose of this study was to investigate the association of health and dietary characteristics with the use of vitamin and mineral supplements in community-dwelling, cognitively intact elders aged in their 60s (n = 89), 80s (n = 92), and 100s (n = 76) who resided in Georgia in the southeastern United States. Elders who were physically active (p = 0.008), had stomach problems (p = 0.042), or used arthritis medication (p = 0.015) were more likely to take a nutritional supplement than elders without these characteristics. Physically active elders were more likely to take calcium (p = 0.004), vitamin E (p = 0.022), and vitamin C (p = 0.046) than non-physically active elders. Compared to non-users, supplement users were also more likely to comply with nutritional health seeking behaviors such as avoiding too much salt, fat, cholesterol, sugar, caffeine, and eating enough fiber, vitamins and minerals from food or supplements, and calcium in foods or supplements. The observation that the use of certain vitamin or mineral supplements is associated with dietary fat intakes, dietary protein intakes, and patterns of alcohol, decaffeinated coffee, and tea consumption suggests that supplement use is one of a cluster of health behaviors. Thus, it may be important that future investigations concerning the impact of supplement use on diseases, such as heart disease or cancer, control for the effects of dietary patterns and physical activity.

Topics: Aged; Aged, 80 and over; Aging; Alcohol Drinking; Ascorbic Acid; Caffeine; Calcium, Dietary; Cardiovascular Diseases; Cohort Studies; Diet; Dietary Fats; Dietary Proteins; Exercise; Female; Food, Fortified; Georgia; Health Status; Humans; Male; Minerals; Neoplasms; Risk Factors; Surveys and Questionnaires; Vitamin E; Vitamins

The aim of this study was to determine the kinetics of the reactions between the gaseous free-radical pollutant, nitrogen dioxide (NO2), and the water-soluble antioxidants present in respiratory tract lining fluid (RTLF). Samples of RTLF, recovered from 12 subjects (mean age 54.1+/-16.3 years; eight male, four female) as bronchoalveolar lavage (BAL) fluid were exposed ex vivo to NO2 [50-1000 parts per billion (ppb)] for 4 h. For comparison, similar exposures were carried out with single and composite solutions with relevant RTLF antioxidant concentrations. Ascorbic acid (AA), uric acid (UA), GSH depletion, and GSSG and malondialdehyde (MDA) formation were determined with time. In the three models, UA and AA were consumed in a time- and NO2-concentration-related fashion. In addition, their rate of depletion correlated positively with their initial concentration (UA, r=0.92, P<0.05; AA, r=0.94, P<0.05). Little difference was found between the rate of loss of AA (2.2+/-0. 2; 1.9+/-0.5; 1.4+/-0.3 nmol.l-1.h-1.ppb-1), and that of UA (2.4+/-0. 2; 2.1+/-0.6; 1.3+/-0.2 nmol.l-1.h-1.ppb-1) in the three RTLF models examined (single, composite, BAL fluid respectively). GSH loss from BAL fluid (0.2+/-0.1) was significantly less than that seen in either single (1.4+/-0.3) or composite (1.2+/-0.5 nmol.l-1.h-1. ppb-1) antioxidant solutions. In all cases, GSH consumption was significantly less than AA or UA. As model complexity increased, the rate of individual antioxidant loss decreased, such that in BAL fluid, AA, UA and GSH consumption rates were significantly less (P<0. 05) than in the pure or composite antioxidant mixtures. In BAL fluid, little GSSG production was observed at any NO2 concentration. MDA concentration, determined as a measure of lipid peroxidation, did not change following exposure to 50, 150 or 400 ppb NO2, but increased MDA was seen in BAL fluid from 8/12 subjects following exposure to 1000 ppb NO2 for 1 h or more. In conclusion, NO2, at environmentally relevant concentrations, depletes BAL fluid of the antioxidant defences, UA and AA, but not GSH.

Topics: Antioxidants; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Female; Glutathione; Glutathione Disulfide; Humans; Kinetics; Male; Malondialdehyde; Middle Aged; Neoplasms; Nitrogen Dioxide; Regression Analysis; Uric Acid

Biomarkers of nutrition intake were used to validate the dietary assessments proposed for use in the European prospective study of diet and cancer (EPIC). In the UK validation studies, the accuracy of several tested methods was assessed with weighed food records and biomarkers, 24 h urine nitrogen, potassium and plasma carotenoids and vitamin C. Correlations between dietary nitrogen intake from weighed food records and 24 h urine excretion were high (0.78-0.87). The correlations between nitrogen from estimated food diaries and urinary nitrogen were r = 0.60-0.70. Correlations with other methods were lower, but improved by energy adjustment, using residuals for those nutrients correlated with total energy, such as nitrogen and potassium, but not for nutrients not correlated with energy intake--for example, beta-carotene. Hence, the correlation between urinary nitrogen and unadjusted nitrogen from a food frequency questionnaire (FFQ) was 0.24 but improved with energy adjustment to 0.49. UK EPIC uses three methods (diary, improved FFQ and 24 h recall) to assess diet, with repeated measures from the food diary at 18 months and four years. Ninety-three percent of first food diaries are returned completed by participants. Results from 200 subjects randomly selected from the first 2,000 recruits suggest that differences between methods with improved FFQ design are less obvious than in the initial validation study. Results from the diary are more closely correlated with plasma carotenoids and vitamin C than other methods, although supplements of vitamin C are the main determinant of the magnitude of correlations. More detailed biomarker studies are in progress among EPIC participants.

Topics: Aged; Anthropometry; Ascorbic Acid; beta Carotene; Biomarkers; Carotenoids; Cohort Studies; Diet; Europe; Female; Humans; Incidence; Middle Aged; Neoplasms; Nitrogen; Nutrition Assessment; Patient Compliance; Prospective Studies; Random Allocation; Reproducibility of Results; Risk Factors

Topics: Ascorbic Acid; Humans; Neoplasms

Plasma vitamins C, E, retinol and carotene were measured in 1971-1973 in 2,974 men working in Basel Switzerland. In 1990, the vital status of all participants was assessed. A total of 290 men had died from cancer during the 17 years of follow-up, including 87 with lung cancer, 30 with prostate cancer, 28 with stomach cancer and 22 with colon cancer. Overall mortality from cancer was associated with low mean plasma levels of carotene (adjusted for cholesterol) and of vitamin C. Lung and stomach cancers were associated with low mean plasma carotene level. After calculation of the relative risk, using the Cox model, with exclusion of mortality during the first 2 years of follow-up, simultaneously low levels of plasma carotene (below quartile I) and lipid-adjusted retinol were related to a significantly increased mortality risk for all cancers and for lung cancer. Simultaneously, low levels of plasma vitamin C and lipid-adjusted vitamin E also were associated with a significantly increased risk for lung cancer. Additionally, low vitamin E levels in smokers were related to an increased risk for prostate cancer. It is concluded that low plasma levels of the vitamins C, E, retinol and carotene are related to increased risk of subsequent overall and lung-cancer mortality and that low levels of vitamin E in smokers are related to an increased risk of prostate-cancer mortality.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Carotenoids; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Prostatic Neoplasms; Vitamin A; Vitamin E; Vitamins

Topics: Ascorbic Acid; Humans; Neoplasms

We examined vitamin E and vitamin C supplement use in relation to mortality risk and whether vitamin C enhanced the effects of vitamin E in 11,178 persons aged 67-105 y who participated in the Established Populations for Epidemiologic Studies of the Elderly in 1984-1993. Participants were asked to report all nonprescription drugs currently used, including vitamin supplements. Persons were defined as users of these supplements if they reported individual vitamin E and/or vitamin C use, not part of a multivitamin. During the follow-up period there were 3490 deaths. Use of vitamin E reduced the risk of all-cause mortality [relative risk (RR) = 0.66; 95% CI: 0.53, 0.83] and risk of coronary disease mortality (RR = 0.53; 95% CI: 0.34, 0.84). Use of vitamin E at two points in time was also associated with reduced risk of total mortality compared with that in persons who did not use any vitamin supplements. Effects were strongest for coronary heart disease mortality (RR = 0.37; 95% CI: 0.15, 0.90). The RR for cancer mortality was 0.41 (95% CI: 0.15, 1.08). Simultaneous use of vitamins E and C was associated with a lower risk of total mortality (RR = 0.58; 95% CI: 0.42, 0.79) and coronary mortality (RR = 0.47; 95% CI: 0.25, 0.87). Adjustment for alcohol use, smoking history, aspirin use, and medical conditions did not substantially alter these findings. These findings are consistent with those for younger persons and suggest protective effects of vitamin E supplements in the elderly.

Topics: Aged; Aged, 80 and over; Aging; Ascorbic Acid; Coronary Disease; Female; Humans; Male; Mortality; Neoplasms; Risk; Vitamin E

Topics: Ascorbic Acid; Clinical Trials as Topic; Humans; Neoplasms

The proton spin-lattice relaxation rate (1/T1) in malignant and non-malignant ascites was measured with an FT NMR spectrometer operating at 60 MHz. The mean relaxation rate in non-malignant ascites was significantly smaller than that of malignant ascites. However, the 1/T1 of malignant ascites overlaps with that of non-malignant ascites over all concentrations of total protein (TP) in samples. The 1/T1 in non-malignant ascites correlates strongly with TP, whilst the 1/T1 in malignant ascites shows only a moderate correlation. T1 measurements before and after addition of ascorbic acid (reductant) suggest that there is a small paramagnetic contribution of ions to the 1/T1 in malignant ascites. The least-squares fitting of 1/T1 versus TP for non-malignant data gives a linear relationship, and suggests that the T1 mechanism in non-malignant ascites is caused by a fast chemical exchange of water molecules between protein-bound water and free water.

Topics: Ascites; Ascorbic Acid; Biophysical Phenomena; Biophysics; Copper; Humans; In Vitro Techniques; Iron; Magnetic Resonance Spectroscopy; Neoplasm Proteins; Neoplasms; Oxidation-Reduction; Proteins; Protons

We investigated whether the consumption of fruit and vegetables lowered cancer mortality in a cohort of 2112 Welsh men ages 45-69 years (The Caerphilly Study), which was followed-up for 13.8 years. At baseline (between 1979 and 1983), participants completed a 56-item food frequency questionnaire from which the consumption of fruit and vegetables was calculated. Relative risks (RR) were estimated with Cox proportional hazard analysis, with death from various types of cancer as a dependent variable, and fruit, vegetables, vitamin C, beta-carotene, dietary fiber, and potential confounders as independent variables. Mean consumption of vegetables and fruit at baseline was 118 g/day and 83 g/day, respectively. During follow-up 114 men died from cancer, including 51 men who died from respiratory tract cancer and 45 men who died from digestive tract cancer. Fruit consumption and the intake of dietary fiber were inversely related to respiratory tract cancer, but after adjustment for potential confounders including age, smoking, and social class, the association with fruit consumption became nonsignificant. Vegetable and fruit consumption was, independently from other risk factors, inversely related to mortality from cancer of the digestive tract (P for trend = 0.021), mainly due to an inverse association with fruit consumption (RR for the highest quartile versus the lowest was 0.3; 95% CI, 0.1-0.8). Vitamin C, beta-carotene, and dietary fiber were not significantly associated with cancers of the digestive tract. Vegetable and fruit consumption was also inversely related to all-cause cancer mortality, and the strongest association was observed for fruit consumption (RR in the highest versus lowest quartile was 0.5; 95% CI, 0.3-1.0). Consumption of vegetables and particularly the consumption of fruit could considerably lower the risk of dying from cancer in middle-aged men.

Topics: Age Factors; Antioxidants; Ascorbic Acid; beta Carotene; Cause of Death; Cohort Studies; Confounding Factors, Epidemiologic; Diet; Dietary Fiber; Digestive System Neoplasms; Feeding Behavior; Follow-Up Studies; Fruit; Humans; Longitudinal Studies; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Respiratory Tract Neoplasms; Risk Factors; Smoking; Social Class; Vegetables; Wales

Topics: Acquired Immunodeficiency Syndrome; Ascorbic Acid; Cytotoxicity, Immunologic; HIV; HIV Infections; Humans; In Vitro Techniques; Neoplasms; T-Lymphocytes

Differentiation from the neoplastic state can be a dynamic adaptation to the localized stress of increasing cohesive forces in tissue. Repulsive forces, occurring within and between cells, are seen as leading to de-differentiation into the neoplastic state or neoplasm. During early development, especially where and when mitosis occurs frequently, cohesive and repulsive forces may necessarily coexist in oscillating degrees. Correspondingly, cohesive-force and repulsive-force generating metabolites may co-exist in oscillating concentrations. Cancer or neoplasia occurs, according A. Szent-Gyorgyi, when cohesiveness breaks down locally, probably thru the conversion of methylglyoxal into lactic acid. Cancer may also occur due to the accumulation of such putatively, repulsion-generating factors as lactic acid. Plant tumors in vitro respond adaptively to cohesion-generating chemicals, such as ascorbic acid and methylglyoxal, by generating buds, embryos, and plantlets.

Topics: Adaptation, Physiological; Animals; Ascorbic Acid; Biological Evolution; Culture Media; Culture Techniques; Embryonic and Fetal Development; Fabaceae; Humans; Lactic Acid; Mammals; Mice; Mutagenesis; Neoplasms; Nicotiana; Plant Development; Plant Tumors; Plants; Plants, Medicinal; Plants, Toxic; Pyruvaldehyde; Temperature; Time Factors

Antioxidant nutrients have been hypothesized to be protective against cancer. Vitamin C is a major circulating water-soluble antioxidant, and vitamin E is a major lipid-soluble antioxidant. Many case-control and cohort studies have related cancer risk to estimates of nutrient intake derived from food intake reports. Diets high in fruit and vegetables, and hence high in vitamin C, have been found to be associated with lower risk for cancers of the oral cavity, esophagus, stomach, colon, and lung. Diets high in added vegetable oils, and hence high in vitamin E, have been less consistently shown to be associated with cancer protection. This may be because vitamin E offers less protection against cancer or because the estimation of vitamin E intake is less accurate than is the estimation of vitamin C intake. In contrast with the findings from epidemiologic studies based on foods, observational studies of nutrients consumed in supplements and recent experimental trials provide little support for a strong protective role for vitamins C or E against cancer. If vitamins C or E are indeed protective against cancer, that protection may derive from their consumption in complex mixtures with other nutrients and with other bioactive compounds as found in the matrix provided by whole foods.

Topics: Ascorbic Acid; Fruit; Humans; Neoplasms; Risk; Vegetables; Vitamin E

Ascorbic acid and its salts (AA) are preferentially toxic to tumor cells in vitro and in vivo. Given in high enough doses to maintain plasma concentrations above levels that have been shown to be toxic to tumor cells in vitro, AA has the potential to selectively kill tumor cells in a manner similar to other tumor cytotoxic chemotherapeutic agents. Most studies of AA and cancer to date have not utilized high enough doses of AA to maintain tumor cytotoxic plasma concentrations of AA. Data are presented which demonstrate the ability to sustain plasma levels of AA in humans above levels which are toxic to tumor cells in vitro and suggests the feasibility of using AA as a cytotoxic chemotherapeutic agent.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Cell Line; Cell Survival; Humans; Infusions, Intravenous; Lung Neoplasms; Mice; Neoplasms; Tumor Cells, Cultured

This ecologic study aimed to investigate whether differences in population mortality from lung, stomach and colorectal cancer among the 16 cohorts of the Seven Countries Study could be explained by differences in the average intake of anti-oxidant (pro)vitamins. In the 1960s, detailed dietary information was collected in small sub-samples of the cohorts by the dietary record method. In 1987, food-equivalent composites representing the average food intake of each cohort at baseline were collected locally and analyzed in a central laboratory. The vital status of all participants was verified after 25 years of follow-up. The average intake of vitamin C was strongly inversely related to the 25-year stomach-cancer mortality (r = -0.66, p = 0.01), also after adjustment for smoking and intake of salt or nitrate. The average intake of alpha-carotene, beta-carotene, and alpha-tocopherol were not independently related to mortality from lung, stomach or colorectal cancer, nor was vitamin C related to lung and colorectal cancer.

Topics: Adult; Analysis of Variance; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cohort Studies; Diet; Europe; Follow-Up Studies; Humans; Japan; Male; Middle Aged; Neoplasms; United States; Vitamin E; Vitamins

6-Amino-6-deoxyascorbic acid was found to inhibit human tumor cell growth. The antitumor effect depends on the tumor type and concentration of the acid. After cell treatment with 6-amino-6-deoxyascorbic acid, drastic morphological changes were found. Although image analysis did not show a difference in p53 and c-myc gene expression, the appearance of chromatin aggregation and DNA fragmentation points to apoptosis or programmed cell death.

Topics: Antineoplastic Agents; Apoptosis; Ascorbic Acid; DNA; Humans; Neoplasms; Proto-Oncogene Proteins c-myc; Tumor Cells, Cultured; Tumor Suppressor Protein p53

Topics: Aging; Ascorbic Acid; Beverages; Bone Diseases; Citrates; Citric Acid; Diabetes Mellitus; Drug Synergism; Fruit; Hemosiderosis; Humans; Iron; Neoplasms; Oxidative Stress

We measured the levels of serum carotenoids (beta-carotene), total tocopherol (vitamin E), ascorbic acid and malondialdehyde (MDA) in newly diagnosed cancer cases. Levels of the antioxidants and MDA in serum samples from 208 subjects with cancer affecting different sites (59 breast, 38 head and neck, 46 genitourinary, 12 lung, 20 gastrointestinal and 33 other sites) were compared with levels in 156 controls. Cases and controls were compared with respect to a number of potentially confounding factors: age, sex, smoking status, Quetelet index (kg/m2), diet and alcohol intake. Mean (+/- SD) levels of beta-carotene, vitamin E and vitamin C were significantly lower among the cases than the controls (49.35 +/- 36.55 micrograms/l, 0.60 +/- 0.14 mg/dl, 0.40 +/- 0.27 mg/dl and 75.31 +/- 28.59 mg/dl, 0.98 +/- 0.13 mg/dl, 0.88 +/- 0.47 mg/dl, respectively) (P < 0.05). On the other hand, mean levels of MDA were significantly higher among the cases than the controls (6.79 +/- 1.22 nmol/ml and 3.52 +/- 0.97 nmol/ml, respectively) (P < 0.05). The results obtained suggest that measurement of serum antioxidants and MDA levels may provide further useful information when evaluating cancer patients.

Topics: Adult; Aged; Aging; Alcohol Drinking; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cohort Studies; Diet; Female; Humans; Male; Malondialdehyde; Menopause; Middle Aged; Neoplasms; Sex Factors; Smoking; Vitamin E

This hypothesis suggests that psychosocial stress is the pivotal determinator of many modern day disorders in consequence to consuming today's nutritional intakes of ascorbic acid and sodium. For it seems, as a result of our tropical African evolution, present day intakes of these essential nutrients are incompatible with the maintenance of bodily homeostasis when the body is subjected to any form of stress. In addition, the climatic conditions under which most of us live are seemingly ill-suited to experiencing stress, since it appears that a constituent part of the bodily stress response remains exclusively designed to be effective in a hot tropical environment, where the stress can be expected to be accompanied by thermoregulation sweating and an overheated body. For without such an occurrence coinciding with stress, the stress response itself appears to have been transposed into a reaction that inhibits the body's ability to resist infection and disease.

Topics: Ascorbic Acid; Biological Evolution; Common Cold; Humans; Life Style; Neoplasms; Sodium, Dietary; Stress, Psychological

Topics: Aged; Aging; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Carotenoids; DNA Damage; Female; Humans; Male; Middle Aged; Neoplasms; Reactive Oxygen Species; Selenium; Vitamin E

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Food, Fortified; Humans; Iron; Neoplasms; Oxidation-Reduction; Vitamin E

Topics: Antineoplastic Agents; Ascorbic Acid; Humans; Hydrazines; Male; Neoplasms; Smoking

There is extensive epidemiologic evidence suggesting a protective role for micronutrients in cancer incidence. This evidence comes from studies of fruit and vegetable intake and serum levels of specific micronutrients. There also is limited in vitro evidence demonstrating that micronutrients can influence the first step in carcinogenesis, binding of chemical carcinogens to DNA. These in vitro studies allow the determination of specific effects of individual micronutrients. The influence of micronutrients on DNA binding of aflatoxin B1 (AFB1), a potent hepatocarcinogen, in mammalian cells is unknown. Woodchuck hepatocytes were used as a model to investigate the effects of vitamin A (all-trans retinol), C (ascorbic acid), ascorbyl palmitate (a synthetic lipophilic derivative of ascorbic acid), vitamin E (alpha-tocopherol), and beta-carotene on AFB1-DNA binding.. Woodchuck hepatocytes were treated with 4 doses (0.080, 0.40, 2.0, and 10 microM) of [3H]AFB1 or with different combinations of AFB1 and the vitamins for 6 hours, and adduct levels determined. Western blot analysis of protein extracts of treated cells was used to determine the effects of vitamin A and beta-carotene on glutathione-S- transferase M1 levels.. Vitamin A inhibited formation of AFB1-DNA adducts in a dose-dependent manner throughout a concentration range of 34-122 microM by 40-80%. Vitamin C (0.080-10 mM) was much less effective than vitamin A as an inhibitor of AFB1-DNA binding. Treatment with 6.0-48.3 microM ascorbyl palmitate reduced adduct levels at lower AFB1 concentrations but had no significant effect at higher AFB1 concentrations. beta-Carotene and vitamin E enhanced covalent binding of AFB1 to DNA. Enhancement with beta-carotene was observed when both tetrahydrofuran or liposomes were used as the administration vehicle. Western blot analysis indicated that neither the vitamin A nor beta-carotene treatment affected glutathione-S-transferase M1 protein levels.. These results demonstrate that micronutrients play a complex role in the process of chemical carcinogenesis. Although protective effects were seen with several antioxidant vitamins, increased DNA adduct formation was observed with beta-carotene and vitamin E. This antioxidant activity may be unrelated to the inhibition of DNA adduct formation. Additional studies are needed to understand the mechanism of enhanced adduct formation.

Topics: Aflatoxin B1; Animals; Ascorbic Acid; beta Carotene; Carotenoids; Cells, Cultured; Depression, Chemical; DNA; Dose-Response Relationship, Drug; Glutathione Transferase; Liposomes; Liver; Marmota; Neoplasms; Stimulation, Chemical; Vitamin A; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Base Sequence; DNA Damage; Glutathione; Glutathione Transferase; Humans; Molecular Sequence Data; NAD(P)H Dehydrogenase (Quinone); Neoplasms; Reactive Oxygen Species; Superoxide Dismutase

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Drug Synergism; Humans; Neoplasms; Neoplasms, Experimental

Topics: Ascorbic Acid; Breast Neoplasms; Cholecalciferol; Fatty Acids; Feeding Behavior; Female; Humans; Neoplasms; Nutritional Requirements; Risk Factors; Vitamin A

A cohort of 11,580 residents of a retirement community initially free from cancer were followed from 1981 to 1989. A total of 1,335 incident cancer cases were diagnosed during the period. Relative risks of cancer were calculated for baseline consumption of vegetables, fruits, beta-carotene, dietary vitamin C, and vitamin supplements. After adjustment for age and smoking, no evidence of a protective effect was found for any of the dietary variables in men. However, an inverse association was observed between vitamin C supplement use and bladder cancer risk. In women, reduced cancer risks of all sites combined and of the colon were noted for combined intake of all vegetables and fruits, fruit intake alone, and dietary vitamin C. Supplemental use of vitamins A and C showed a protective effect on colon cancer risk in women. There was some suggestion that beta-carotene intake and supplemental use of vitamin A, C, and E were associated with reduced risk of lung cancer in women, but none of these results were statistically significant. These inverse associations observed in women seem to warrant further investigation, although there was inconsistency in results between the sexes.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; beta Carotene; Carotenoids; Diet; Diet Surveys; Fruit; Humans; Incidence; Neoplasms; Prospective Studies; Sex Factors; Vegetables; Vitamins

There is accumulating evidence that free radicals may contribute to various diseases such as cancer or cardiovascular disease. Possible health hazards can to some extent be prevented by the body's multilevel defense system against free radicals, which comprises, besides others, antioxidant vitamins. The 12-year mortality follow-up of 2,974 participants of the Basal Study allowed to test the hypothesis that low antioxidant vitamin plasma concentrations (vitamin A, C, E and carotene) were associated with increased death from cancer of various sites and death from atherosclerosis such as ischemic heart disease and stroke, respectively. For the analysis 204 cancer cases, 132 fatalities from ischemic heart disease (IHD) and 31 deaths from cerebral vascular disease were available. Cancer mortality. Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer had also lower mean vitamin C and lipid-adjusted vitamin A levels than survivors (p less than 0.05). Calculating the relative risk with exclusion of mortality during the first two years of follow-up, low plasma carotene was associated with an increased risk for bronchus cancer (RR 1.8, p less than 0.05), and the small number of stomach cancer cases (RR 2.95, p less than 0.05) low plasma levels of carotene and vitamin A with all cancer types (RR 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than 60 years) with lung cancer (RR 2.17, p less than 0.05). Studies in other cohorts with a poor vitamin E status revealed an increased risk of subsequent cancer at low vitamin E levels as well. It is concluded that low plasma levels of all major essential antioxidants are associated with an increased risk of subsequent cancer mortality. Cardio-vascular mortality. Plasma carotene concentration below quartile 1 was associated with an increased risk for IHD (RR 1.53, p = 0.02). The same was true for low levels of both carotene and vitamin C (RR = 1.96, p = 0.022). The risk of cerebrovascular death was elevated in subjects with low carotene in the presence of low vitamin C plasma concentration (RR 4.17, p less than 0.01). These data confirm and extend recent findings on an inverse correlation of beta-carotene and vitamin C respectively to CVD.(ABSTRACT

Topics: Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Carotenoids; Cerebrovascular Disorders; Cholesterol; Female; Follow-Up Studies; Free Radicals; Humans; Male; Myocardial Ischemia; Neoplasms; Prospective Studies; Risk Factors; Switzerland; Vitamin A; Vitamin E; Vitamins

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Heart Diseases; Humans; Male; Neoplasms

Topics: Ascorbic Acid; Carcinogens; Colonic Neoplasms; Feeding Behavior; Humans; Neoplasms; Vitamin A; Vitamin D; Vitamin E

Topics: Ascorbic Acid; Cohort Studies; Diet; Eating; Heart Diseases; Humans; Neoplasms; Odds Ratio; United States

We examined the relation between vitamin C intake and mortality in the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study cohort. This cohort is based on a representative sample of 11,348 noninstitutionalized U.S. adults age 25-74 years who were nutritionally examined during 1971-1974 and followed up for mortality (1,809 deaths) through 1984, a median of 10 years. An index of vitamin C intake has been formed from detailed dietary measurements and use of vitamin supplements. The relation of the standardized mortality ratio (SMR) for all causes of death to increasing vitamin C intake is strongly inverse for males and weakly inverse for females. Among those with the highest vitamin C intake, males have an SMR (95% confidence interval) of 0.65 (0.52-0.80) for all causes, 0.78 (0.50-1.17) for all cancers, and 0.58 (0.41-0.78) for all cardiovascular diseases; females have an SMR of 0.90 (0.74-1.09) for all causes, 0.86 (0.55-1.27) for all cancers, and 0.75 (0.55-0.99) for all cardiovascular diseases. Comparisons are made relative to all U.S. whites, for whom the SMR is defined to be 1.00. There is no clear relation for individual cancer sites, except possibly an inverse relation for esophagus and stomach cancer among males. The relation with all causes of death among males remains after adjustment for age, sex, and 10 potentially confounding variables (including cigarette smoking, education, race, and disease history).

Topics: Adult; Aged; Ascorbic Acid; Cohort Studies; Diet; Eating; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Middle Aged; Neoplasms; Nutrition Surveys; Population Surveillance; Prospective Studies; Sex Factors; Survival Rate; United States

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Combined Modality Therapy; Enzymes; Humans; In Vitro Techniques; Neoplasms

Topics: Animals; Ascorbic Acid; Humans; Neoplasms

A protocol for the use of vitamin C in the treatment of cancer, developed over a number of years in Vale of Leven Hospital, Scotland, is presented. Clinical experience has shown this protocol to be both safe and efficient. It need not be followed 'to the letter', but provides general guidance to physicians unfamiliar with this therapeutic approach. It recommends that all cancer patients treated in this fashion be given an initial course of intravenous ascorbate followed by a maintenance oral dose to be continued indefinitely thereafter. The importance of continuous as opposed to intermittent administration is emphasized.

Topics: Administration, Oral; Ascorbic Acid; Clinical Protocols; Humans; Infusions, Intravenous; Kidney; Neoplasms

Topics: Animals; Ascorbic Acid; Humans; Neoplasms

In 1971-1973 at the third examination of the Basel Study started in 1959, the major antioxidant vitamins and carotene were measured in the plasma of 2974 men. A subsample and their families were reinvestigated in 1977-79. During the 12-y observation period (1973-85) 553 men died, 204 of cancer (lung cancer 68, stomach cancer 20; colon cancer 17, all other malignancies 99). We found significantly lower mean carotene levels for all cancer, bronchus cancer, and stomach cancer (all P less than 0.01) compared with the 2421 survivors. The relative risk of subjects with low carotene (less than 0.23 mumol/L) was significantly elevated (P less than 0.05) for lung cancer (Cox's model). Higher risks were noted for all cancer (P less than 0.01) if both carotene and retinol were low. Low plasma carotene which is known to reflect carotene intake is in our study associated with increased cancer risk.

Topics: Adult; Age Factors; Ascorbic Acid; beta Carotene; Carotenoids; Cholesterol; Cohort Studies; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Sex Factors; Smoking; Stomach Neoplasms; Switzerland; Triglycerides; Vitamin A; Vitamin E

The effect of methylglyoxal (MG), ascorbic acid and lactaldehyde has been tested on the in vitro respiration of Ehrlich ascites carcinoma (EAC) cells and several normal and malignant human tissues. Methylglyoxal inhibited the respiration of each type of malignant cell and tissue tested, but it had practically no inhibitory effect on the respiration of any of the normal cells and tissues. Ascorbic acid exhibited a synergistic effect with MG in inhibiting the respiration of all the neoplastic cells. In the presence of lactaldehyde, a catabolite of MG, the inhibitory effect of MG on the respiration of tumor cells was significantly reduced. Lactaldehyde can exert a similar protective effect on the loss of viability and transplantability of MG-treated EAC cells.

Topics: Aldehydes; Animals; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Cell Survival; Female; Humans; In Vitro Techniques; Leukemia; Mice; Neoplasms; Oxygen Consumption; Pyruvaldehyde; Uterus

Topics: Ascorbic Acid; Humans; Neoplasms; Nitrosamines

Plasma antioxidant vitamins A, C, and E and carotene were measured in a group of 2,974 men participating in the third examination of the prospective Basel Study in 1971-1973. In 1985, the vital status and mortality of all participants were assessed. A total of 204 men had died from cancer, including 68 with bronchus cancer and 37 with gastrointestinal cancer (20 with stomach cancer and 17 with large bowel cancer excluding cancer of the rectum). Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer also had lower mean vitamin C and lipid-adjusted vitamin A levels than did survivors (p less than 0.05). After calculation of the relative risk using the Cox model with exclusion of mortality during the first 2 years of follow-up, low plasma carotene (below quartile 1) was associated with a significantly increased risk for bronchus cancer (relative risk (RR) = 1.8, p less than 0.05), low plasma levels of carotene and vitamin A with all cancers (RR = 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than age 60 years) with lung cancer (RR = 2.17, p less than 0.05). Low levels of vitamin C increased the risk of stomach cancer (RR = 2.38) and gastrointestinal cancer (RR = 2.46) in older subjects, but only significantly with the inclusion of the first 2 years. The authors conclude that low plasma levels of antioxidant vitamins are associated with an increased risk of subsequent cancer mortality. This effect was stronger in men above age 60 years at blood sampling, and the effect seems to be site-specific.

Topics: Adult; Age Factors; Aged; Antioxidants; Ascorbic Acid; Bronchial Neoplasms; Carotenoids; Female; Follow-Up Studies; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Stomach Neoplasms; Time Factors; Vitamin A; Vitamin E; Vitamins

Topics: Animals; Ascorbic Acid; Humans; Neoplasms; Rats; Retinoids; Vitamin A; Vitamin E; Vitamins

The concept that lipoprotein(a) [Lp(a)] is a surrogate for ascorbate is suggested by the fact that this lipoprotein is found generally in the blood of primates and the guinea pig, which have lost the ability to synthesize ascorbate, but only rarely in the blood of other animals. Properties of Lp(a) that are shared with ascorbate, in accordance with this hypothesis, are the acceleration of wound healing and other cell-repair mechanisms, the strengthening of the extracellular matrix (e.g., in blood vessels), and the prevention of lipid peroxidation. High plasma Lp(a) is associated with coronary heart disease and other forms of atherosclerosis in humans, and the incidence of cardiovascular disease is decreased by elevated ascorbate. Similar observations have been made in cancer and diabetes. We have formulated the hypothesis that Lp(a) is a surrogate for ascorbate in humans and other species and have marshaled the evidence bearing on this hypothesis.

Topics: Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Biological Evolution; Cardiovascular Diseases; Diabetes Mellitus; Disease Models, Animal; Humans; Lipoprotein(a); Lipoproteins; Neoplasms; Wound Healing

Topics: Ascorbic Acid; Humans; National Institutes of Health (U.S.); Neoplasms; United States

Supplementation with 1 g of vitamin C (ascorbic acid) per day decreased the amount of chromosome damage induced in lymphocytes by an exposure to bleomycin during the last 5 h of cell culture. We did not see such changes in lymphocytes from control individuals samples at the same time but not taking vitamin C supplements. This bleomycin assay has been proposed as a test for cancer susceptibility. A similar assay for genetic instability may be useful in detecting heterozygotes for chromosome-breakage syndromes (for example, Fanconi anemia or ataxia telangiectasia). Even though our sample size is small and our results should be interpreted cautiously, statistically significant effects were found with vitamin C supplementation. It would, therefore, be prudent to consider dietary and perhaps other lifestyle factors when interpreting of results from this bleomycin assay and related assays for genetic instability.

Topics: Ascorbic Acid; Bleomycin; Cells, Cultured; Chromosome Fragility; Disease Susceptibility; Humans; Lymphocytes; Neoplasms

Cancer epidemiologists rely heavily on the frequency of food use technique to assess dietary risk factors. We found that the accepted procedures for arraying individuals along a continuum, based on their positions within distributions of intakes of specific nutrients, simultaneously array them on other dietary characteristics. A unidimensional approach to dietary assessment could confound cancer risk assessments, and the effects could differ for men and women. We found that men consumed more calories and energy-containing nutrients than women, who were more likely to consume larger amounts of vitamins A and C. Dietary variety was similar for men and women, despite compositional differences in diet. Diets of men contained proportionately more meats, grains and nuts, and alcohol. Diets of women contained more fruits, vegetables, and poultry and fish. Among men, we found stronger intercorrelations among energy intake and intakes of fat, fiber, and vitamin C and among fat intake and intakes of fiber and vitamins A and C. Compositional differences in diet across quartiles of nutrient intake were not consistent for men and women, suggesting that the constellation of dietary risk factors may differ for the two sexes. Men in the lowest quartiles of energy, fiber, and vitamin A intakes had the greatest percent contribution of alcohol to the diet. This pattern was not observed for fat intake levels. Measures of dietary patterns may be needed for more accurate descriptions of the associations of cancer risk and diet.

Topics: Alcohol Drinking; Ascorbic Acid; Diet; Dietary Fats; Dietary Fiber; Energy Intake; Female; Food; Humans; Male; Neoplasms; Nutritional Physiological Phenomena; Risk Factors; Sex Factors; Vitamin A

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Bronchial Neoplasms; Carotenoids; Colonic Neoplasms; Humans; Lipids; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Stomach Neoplasms; Vitamin A; Vitamin E

Nutrition surveys suggest an association between the low intake of vitamin A, beta-carotene and cancer death. The prospective Basel study included as a part of its third investigation (1971-1973) the immediate analysis of all plasma vitamins. 2974 men were evaluated and all cancer deaths registered in a first phase until 1980 (n = 102) and in a second period until 1985 (total n = 204). In the completely analyzed seven years follow up we found a strong inverse relationship for beta-carotene and all cancers, lung cancer and stomach cancer (p less than .01). Vitamin A (p less than .01) and vitamin C (p less than .05) were both on the average lower in subsequent stomach cancer death cases compared to non cases. Vitamin E was lower in death by all cancers and by stomach cancer (p less than .05). The first results of the twelve years follow up confirm the significant association for beta-carotene, vitamin A and C and cancer death.

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Humans; Male; Neoplasms; Nutrition Surveys; Prospective Studies; Switzerland; Vitamin A Deficiency; Vitamin E; Vitamins

With the assumption of the validity of the Hardin Jones principle that the death rate of members of a homogeneous cohort of cancer patients is constant, three criteria for the validity of clinical trials of cancer treatments are formulated. These criteria are satisfied by most published clinical trials, but one trial was found to violate all three, rendering the validity of its reported results uncertain.

Topics: Ascorbic Acid; Clinical Trials as Topic; Cohort Studies; Colonic Neoplasms; Colorectal Neoplasms; Double-Blind Method; Humans; Models, Statistical; Neoplasms

Topics: Ascorbic Acid; Diet; Dietary Fiber; Energy Intake; Humans; Meat; Neoplasms; Risk Factors; Selenium; Vitamin A; Vitamin E

Topics: Ascorbic Acid; Drug and Narcotic Control; Humans; Neoplasms; Orthomolecular Therapy; Switzerland

Ascorbate ions induced a polarization peak in the intracellular fluorescein fluorescence polarization spectra of asynchronous populations of a variety of cancer cell types from human and animal biopsy material or in cells grown in vivo and/or in vitro. The appearance of this polarization peak at 510 nm on excitation at 470 nm (P510 peak) indicates the transition of mitochondria from the condensed (active) into orthodox (resting) conformation. In contrast, no effects of ascorbate ions were observed in the polarization spectra of various normal cell lines. This apparent differential response seems to be caused by the effects of ascorbate ions on several steps of the altered energy metabolism in cancer cells. It appeared not to be due to a defective mechanism responsible for the conformational changes in the mitochondria. In YMDR cells resistant to the antitumor drug methylene-dimethanesulphonate (MDMS), HeLa cells pretreated with colcemid, and YMDS cells pretreated with cytochalasin B, the transition of mitochondria into orthodox conformation could not be induced by ascorbate ions. Thus, it is possible that tumors also pretreated with other drugs become resistant to growth inhibitory effects of ascorbate ions. Induction of the fluorescein emission polarization peak at 510 nm in cells from biopsies or from in vitro-induced malignancies could be used as an additional criterion for malignant transformation.

Topics: 2,4-Dinitrophenol; Ascorbic Acid; Calcium; Cell Line; Cyclic AMP; Cytochalasin B; Demecolcine; Dinitrophenols; Energy Metabolism; Fluorescence Polarization; Glycolysis; Humans; Hydrogen-Ion Concentration; Interphase; Methyl Methanesulfonate; Mitochondria; Neoplasms

Certain dietary practices are valid methods of lowering the risk of disease. Others, while popular, have unproven benefits or may even be associated with risks of their own. Careful evaluation of hypercholesterolemia is necessary. Persons with a high level of low-density lipoprotein (LDL) cholesterol and a low level of high-density lipoprotein (HDL) cholesterol need diet therapy, because they are at increased risk of cardiovascular disease. Weight reduction and fat restriction can lower blood pressure, help control hyperglycemia, and improve the LDL cholesterol-HDL cholesterol ratio. Some evidence indicates a protective role of beta carotene against cancer in animals. However, hypervitaminosis A is dangerous and relatively easy to accomplish, so supplementation beyond a multivitamin tablet is discouraged. Data about inhibition of cancer in humans through use of high doses of vitamin E or C or selenium are inconclusive, and studies of effects of long-term ingestion are not available. In general, megadoses of even healthy substances are thought to be dangerous. Decreased consumption of fat, increased consumption of foods high in fiber, and elimination of alcohol and tobacco are sensible recommendations. Consumption of cruciferous vegetables has not been proven to reduce the incidence of cancer, but a moderate amount of them in the diet would seem reasonable.

Topics: Adult; Aged; Ascorbic Acid; Diet; Dietary Fats; Dietary Fiber; Humans; Hypercholesterolemia; Middle Aged; Neoplasms; Selenium; Vegetables; Vitamin A; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Cytochrome P-450 Enzyme System; DNA Repair; Free Radicals; Glutathione; Humans; Mutation; NADPH-Ferrihemoprotein Reductase; Neoplasms

Topics: Aged; Ascorbic Acid; beta Carotene; Carotenoids; Colonic Neoplasms; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Rectal Neoplasms; Smoking; Stomach Neoplasms; Switzerland; Vitamin A; Vitamin E

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coronary Disease; Cross-Cultural Comparison; Cross-Sectional Studies; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Vitamin A; Vitamin E; Vitamins

Adoptive immunotherapy of human cancer was investigated in our institution as part of a National Cancer Institute extramural group study. This treatment, for patients with metastatic malignant melanoma, hypernephroma, and colon carcinoma, consisted of three phases: (a) 5 days of i.v. high-dose (10(5) units/kg every 8 h) interleukin 2, (b) 6 1/2 days of rest plus leukapheresis; and (c) 4 days of high-dose interleukin 2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Ascorbic acid is known to be important to cell-mediated immunity, and it has been reported to be depleted during physiologically stressful events. Therefore, we determined plasma ascorbic acid levels in patients (n = 11) before adoptive immunotherapy and before and after Phases 1, 2, and 3 of treatment. Patients entering the trial were not malnourished. Mean plasma ascorbic acid levels were normal (0.64 +/- 0.25 mg/dl) before therapy. Mean levels dropped by 80% after the first phase of treatment with high-dose interleukin 2 alone (0.13 +/- 0.08 mg/dl). Mean plasma ascorbic acid levels remained severely depleted (0.08 to 0.13 mg/dl) throughout the remainder of the treatment, becoming undetectable (less than 0.05 mg/dl) in eight of 11 patients during this time. Values obtained from 24-h urine collections on two of two patients indicated that ascorbate was not excreted in the urine. Plasma ascorbic acid normalized in three of three patients tested 1 mo after the completion of treatment. Unlike the results for ascorbic acid, blood pantothenate and plasma vitamin E remained within normal limits in all 11 patients throughout the phases of therapy. Responders (n = 3) differed from nonresponders (n = 8) in that plasma ascorbate levels in the former recovered to at least 0.1 mg/dl (frank clinical scurvy) during Phases 2 and 3, whereas levels in the latter fell below this level.

Topics: Adult; Ascorbic Acid; Evaluation Studies as Topic; Female; Humans; Immunization, Passive; Immunotherapy; Interleukin-2; Killer Cells, Natural; Male; Middle Aged; Neoplasms; Pantothenic Acid; Scurvy; Vitamin E

The role of vitamins A, E, C, D, folates and selenium in the chemical prevention of tumours and/or precancerous conditions is examined in the light of epidemiological studies and experimental observations. Particular mention is made of significant clinical studies that provide valuable indications about the use of vitamin A and its derivates in particular for the treatment of precancerous and cancerous conditions. Vitamin A and its derivates apparently play a fundamental role not only in the treatment of proliferating malignancies of the skin (carcinomas, severe aclinic keratosis) or involving the skin (fungoid mycosis, skin metastases of solid tumours) but also in the prevention of recurring bladder tumours and the treatment of several bronchial dysplasias.

Topics: Ascorbic Acid; Folic Acid; Humans; Neoplasms; Retinoids; Selenium; Skin Diseases; Vitamin A; Vitamin D; Vitamin E; Vitamins

We collected information on dietary intake from 9230 participants aged 40 years old or more by means of self-administered food frequency questionnaire in Fujieda city in order to conduct prospective study to examine the relationship between dietary VA, C and carotene intakes and subsequent risk of cancer in August 1985. To estimate VA, C, and carotene intakes from this questionnaire we multiplied food frequency scores for individual items (25 foods rich in VA, C, and carotene) by the nutrient contents of the standard portion, after adjustments were made for the seasonal availability of some foods.

Topics: Adult; Aged; Alcohol Drinking; Ascorbic Acid; Carotenoids; Diet; Diet Surveys; Female; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Risk; Smoking; Surveys and Questionnaires; Vitamin A

The involvement of certain micronutrients (vitamin C, vitamin E, beta-carotene, selenium) in the antioxidant defense system against free radical cell damage, and of vitamin A in the differentiation of epithelial cells, has raised the question whether intakes of these nutrients in excess of their recommended daily allowances should be recommended to the general public for cancer prevention. The considerations surrounding this question are discussed, and it is concluded that such measures are unjustified by present epidemiological and experimental evidence. Any such action should await the outcome of ongoing intervention trials.

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Diet; Humans; Neoplasms; Nutritional Physiological Phenomena; Selenium; Vitamin A; Vitamin E; Vitamins

Samples of 12-h overnight urine were collected from approximately 40 male adults in each of the 26 counties of China. Two urine specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids, nitrite and nitrate were measured in urine samples and correlated with cancer mortality per 100,000 male subjects in the truncated age range 35-64 years. Preliminary results show no clear correlation between presence of stomach cancer or liver cancer and nitrosation potential [as measured by the urinary level of N-nitrosoproline (NPRO) after the proline load test or of nitrate]. There was a moderate, although not clearly significant, tendency for oesophageal cancer mortality rates to be associated positively with nitrosation potential and negatively with background ascorbate levels in plasma. This result was due chiefly to the inclusion of one county (Song Xian) in which there is a fairly high oesophageal mortality rate, an average nitrosation potential three times greater than that of any other county, and the lowest ascorbate index of any county. Further study of this county is planned.

Topics: Adult; Ascorbic Acid; China; Humans; Male; Middle Aged; Neoplasms; Nitrosamines; Nitroso Compounds

A group of 30 coal-tar workers was treated with 1 g of ascorbic acid (AA) orally five times a week for 3 months. The effect of this treatment was assessed on serum IgG, IgM, IgA, alpha 1-antitrypsin, prealbumin, orosomucoid, transferrin, alpha 2-macroglobulin, C-reactive protein, ceruloplasmin, the latex fixation test and cancer serum index (CSI). After 3 months treatment the concentration of AA in the blood increased from 9.52 to 60.75 mumol l-1 (i.e. from 0.15 to 1.07 mg 100 ml-1), prealbumin increased from 0.37 +/- 0.08 g l-1 to 0.48 +/- 0.08 g l-1 (P less than 0.01), CSI decreased from 2.28 +/- 0.88 to 1.76 +/- 0.50 (P less than 0.01) and alpha 2-macro-globulin decreased from 3.40 +/- 0.95 to 2.06 +/- 0.39 g l-1 (P less than 0.01). These findings, together with reports that AA is a strong stimulator of xenobiotics biotransformation in the liver, support the use of AA as a prophylactic agent for coal-tar exposed workers.

Topics: Adult; alpha-Macroglobulins; Ascorbic Acid; Coal Tar; Humans; Immunoglobulins; Male; Neoplasms; Occupational Diseases; Orosomucoid; Prealbumin; Time Factors

Topics: Ascorbic Acid; Diet; Dietary Fiber; Humans; Neoplasms; Risk; Smoking; Vitamin A

Topics: Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Diet; Food Additives; Humans; Neoplasms; Selenium; Vitamin A; Vitamin E

Vitamin C is an essential nutrient whose protective role in carcinogenesis has been discussed for more than 50 years. Epidemiologic studies suggest that the consumption of vitamin C-rich foods is associated with a lower risk of cancers of the esophagus and stomach. The observation that cancer patients have low leukocyte vitamin C levels led to therapeutic trials the results of which are controversial; the hypothesis that vitamin C acts like a drug must be questioned. On the other hand, ascorbic acid interacts with various tumor-inducing compounds, such as the precursors of N-nitroso compounds, to prevent the formation of tumors. Experiments with animals and cell cultures indicate that ascorbic acid can interfere with the metabolism of tumor promoters. It has also been postulated that ascorbic acid helps to prevent cancer by enhancing cellular immunity. In general, evidence suggests that vitamin C can inhibit the formation of some carcinogens.

Topics: Animals; Ascorbic Acid; Carcinogens; Diet; Humans; Leukocytes; Neoplasms; Neoplasms, Experimental

The properties of N-nitroso compounds (NNC) and of vitamins C and E are briefly described. The author reviews the ability of vitamins C and E to inhibit NNC formation in chemical systems, in nitrite-preserved meat, in experimental animals and in humans. Dietary vitamins C and E both produced 30% to 60% inhibitions in most carcinogenesis experiments employing preformed carcinogens. Vitamin C reversed transformation in an in vitro system. Carcinogenicity tests of the vitamins are reviewed (vitamin C can promote bladder carcinogenesis). Intake of fresh fruits and vegetables (which contain vitamin C) is negatively correlated with cancer of the stomach, esophagus, larynx, mouth and cervix. For gastric and esophageal cancer, there is evidence that this association is due to an inhibition of in vivo NNC formation. Vitamin C is apparently not a useful treatment for cancer. The author supports the recommendation that fresh fruit and vegetable intake be increased to lower the risk of cancer.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinogens; Food Preservatives; Humans; Neoplasms; Nitrites; Nitroso Compounds; Vitamin E

Topics: Ascorbic Acid; Carcinogens; Humans; Neoplasms; Nitroso Compounds; Polycyclic Compounds; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Humans; Neoplasms; Orthomolecular Therapy; Vitamin A; Vitamin E; Vitamins

Topics: Ascorbic Acid; beta Carotene; Blood Pressure; Body Composition; Carotenoids; Colonic Neoplasms; Diet; Female; Humans; Life Style; Lipids; Lung Neoplasms; Male; Neoplasms; Prospective Studies; Risk; Smoking; Stomach Neoplasms; Vitamin B Complex; Vitamin E; Vitamins

Topics: Ascorbic Acid; Humans; Neoplasms

Topics: Ascorbic Acid; Complementary Therapies; Evaluation Studies as Topic; Human Experimentation; Humans; Neoplasms; Quality of Health Care

The multiple-step model of carcinogenesis discussed here identifies the two major stages of initiation and promotion. A more recent research development proposes that oncogenes present in chromosomes are activated by viral, chemical, or physical agents and cause cancer. A great variety of natural mutagens and carcinogens find their way into the modern US diet. Excessive fat and alcohol consumption have been studied in relation to many kinds of malignancies. Dietary anticarcinogens include vitamins A, C, and E, although under certain conditions some generally inhibitive substances can actually enhance carcinogenesis. A provocative hypothesis argues that a high-fiber diet can substantially reduce the likelihood of carcinoma of the colon.

Topics: Aflatoxins; Ascorbic Acid; Carcinogens; Diet; Dietary Fats; Dietary Fiber; Ethanol; Humans; Liver Neoplasms; Neoplasms; Nitrogen Oxides; Nutritional Physiological Phenomena; Oncogenes; Retinoids

Topics: Ascorbic Acid; Humans; Neoplasms

Several major factors may influence the micronutrient requirements of the patient with cancer. These factors include the metabolic state of the malignancy and its effects on host metabolism, the catabolic effects of antineoplastic therapy, and other physiologic stresses commonly associated with the treatment of cancer, i.e., surgery, fever and infection. Although the nutritional importance of vitamins, minerals and trace elements is recognized, the optimal daily dose that will preserve lean body mass without enhancing tumor growth, is not known. Recommended Dietary Allowances (RDAs), where established, are based on populations with nonmalignant diseases. However, supplementation with vitamins, minerals, and certain trace elements is recommended for the cancer patient who requires prolonged parenteral support, since clinically relevant deficiency states have been described. The effect of malignancy on the metabolism of several of these micronutrients (iron, ascorbic acid, alpha tocopherol, selenium, zinc, copper) is discussed.

Topics: Adult; Antineoplastic Agents; Ascorbic Acid; Cachexia; Child; Copper; Female; Humans; Iron; Male; Minerals; Neoplasms; Nutritional Requirements; Parenteral Nutrition; Selenium; Trace Elements; United States; United States Food and Drug Administration; Vitamin E; Vitamins; Zinc

A comparative study has been made on the levels of vitamins A and C in normal and malignant conditions in human and murine subjects. Further, the effect of supplemental vitamins A and C on tumor take, host-survival and tumor growth have been studied in a number of transplantable and induced tumors in mice. The vitamins were assayed in sera samples from normal subjects, patients with cancer of the uterine cervix or ovary, and leukemia and lymphoma patients. Among the murine group the tumors included sarcoma 180 in solid and ascitic form, benzo[a]pyrene-induced fibrosarcoma, Dalton's ascitic lymphoma and Schwartz lymphoblastic leukemia. The serum level of vitamin C was found to be lower than that of the normal controls in all cases studied. The level of vitamin A was found to be higher in cancer patients in the human group and lower in the murine group when compared with their normal controls. Studies on murine tumors showed that supplementary vitamins administered at the initial phase of tumor development reduced the percentage tumor take and the rate of tumor growth, and improved host survival, indicating that these vitamins have a protective role in the murine system.

Topics: Animals; Ascorbic Acid; Humans; Mice; Neoplasms; Neoplasms, Experimental; Vitamin A

Topics: Ascorbic Acid; Humans; Neoplasms

Topics: Amygdalin; Ascorbic Acid; Humans; Immunotherapy; Neoplasms

The influence of external abdominal irradiation and cytostatic therapy on the vitamin status was studied in patients with cancer of the uterus, bladder or prostate and in patients with malignant lymphoma. It was found that the vitamin status of these patients at the beginning of therapy in general was adequate, though vitamin A and vitamin D levels were reduced. During radiotherapy decreases of vitamin E, vitamin C, vitamin B12 and folic acid levels were observed. Chemotherapy caused a decrease of the folic acid levels after a few months. No clinical symptoms of vitamin deficiency were observed.

Topics: Ascorbic Acid; Calcifediol; Female; Humans; Lymphoma; Male; Neoplasms; Prostatic Neoplasms; Urinary Bladder Neoplasms; Uterine Neoplasms; Vitamin A; Vitamin B 12; Vitamin E; Vitamins

Topics: Adolescent; Adult; Aged; Animals; Ascorbic Acid; Cadmium Poisoning; Child; Environmental Exposure; Female; Food Analysis; Humans; Kinetics; Lead Poisoning; Middle Aged; Neoplasms; Nitrosamines; Nitroso Compounds; Pesticide Residues; Pregnancy; Rats; Risk

There may be a considerable potential for the prevention of cancer through dietary modifications or chemo-prevention strategies. The epidemiological methods which have been used in the study of the relation between diet and cancer are briefly reviewed and the scientific basis for major hypotheses linking diet to cancer are summarized. Clinical trials, now being considered to assess the potential for the prevention of cancer by dietary supplementation or modification, do not have many of the uncertainities of other methods, yet there are many potential difficulties in both the conduct and interpretation of such trials. These limitations are discussed as well as the problem in making general dietary recommendations for the prevention of cancer based on current knowledge. A more complete understanding of the effect of diet on cancer risk will likely emerge only through a more integrated and interdisciplinary approach in future studies.

Topics: Ascorbic Acid; Diet; Dietary Fats; Dietary Fiber; Epidemiologic Methods; Ethanol; Feeding Behavior; Food Additives; Humans; Neoplasms; Nutritional Physiological Phenomena; Risk

Topics: Adolescent; Adult; Ascorbic Acid; Back Pain; Bone Diseases; Child; Fractures, Bone; Humans; Muscular Diseases; Neoplasms; Osteogenesis Imperfecta; Pain

Comparison of 9 and 35 GHz spectra, obtained from frozen and lyophilized tissues, with those from model systems containing ascorbic acid, confirm that the major component of the "lyophilization signal" of tissue is the ascorbyl radical, stabilized by adsorption on an inert matrix. The magnitude of the signal under anoxic conditions is shown to be a measure of cellular damage, which allows intracellular ascorbic acid to be oxidized. On exposure of lyophilized samples to air, the signal increases due to autoxidation of the available tissue ascorbic acid. Under moist atmospheric conditions the ascorbyl radicals readily decay, leaving other radicals, which appear to be formed by interaction of ascorbic acid or ascorbyl radicals with some tissue component. The results show that, although widely studied, the free radical ESR signal of lyophilized tissue is not unique to tumour and has no relevance to malignancy.

Topics: Animals; Ascorbic Acid; Electron Spin Resonance Spectroscopy; Free Radicals; Freeze Drying; Male; Muscles; Neoplasms; Rats; Rats, Inbred Strains

High but well-tolerated doses of the nutritional antioxidants selenium and vitamins E and C have significant immunostimulant, anti-inflammatory, and anti-carcinogenic effects which are well documented in the existing biomedical literature. In addition, these antioxidants help to protect the structural integrity of ischemic or hypoxic tissues, and may have useful anti-thrombotic actions as well. Supplementation with high-dose nutritional antioxidants may eventually gain a broad role in the prevention, treatment, or palliation of cancer, cardiovascular disease, infection, inflammatory disorders, and certain diabetic complications.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis; Ascorbic Acid; Cardiovascular Diseases; Diabetes Mellitus; Free Radicals; Humans; Hypoxia; Ischemia; Mice; Neoplasms; Rabbits; Rats; Selenium; Superoxides; Thrombosis; Vitamin E

Accumulating evidence suggests that a number of micronutrients may decrease the incidence of cancer of epithelial cell origin. These include vitamins A, C and E, beta-carotene and selenium. Few lines of research, apart from means to reduce cigarette smoking or heavy alcohol consumption, are as promising in terms of substantially decreasing human cancer incidence as studies of such micronutrients as dietary inhibitors of cancer. In this paper, we review the mechanisms by which these micronutrients may act to inhibit carcinogenesis, as well as the current animal and epidemiologic evidence supporting their role as chemopreventive agents. With respect to areas of future study, valuable information can be obtained from basic research as well as observational analytic epidemiologic studies utilizing dietary questionnaires which are more specifically focused and have been more rigorously evaluated than those previously employed. Another promising avenue of epidemiologic research is prospective studies of cancer incidence in relation to biochemical parameters in stored blood samples collected at baseline. The most reliable way to test directly whether a micronutrient prevents the development of human cancer is a large, randomized placebo-controlled trial among individuals with no previous history of the disease. The timely conduct of such trials is particularly important, since regular intake of nutritional supplements is already widespread in the United States, despite the lack of reliable evidence as to their benefits.

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Humans; Neoplasms; Nutritional Physiological Phenomena; Random Allocation; Selenium; Vitamin A; Vitamin E; Vitamins

Carcinogenicity of sodium erythorbate, a widely used antioxidant food additive, was evaluated using a total of 306 eight-week-old male and female F344/DuCrj rats. Test rats were given 1.25 or 2.5% aqueous solution as drinking water for 104 weeks. Controls were given tap water. All the rats were fed commercial pellets. None of the tumors observed was attributable to sodium erythorbate in drinking water. Neither concentration of sodium erythorbate changed the pattern of spontaneous tumor development in both sexes, except for a slight reduction in aggregate tumor incidence in the 2.5% Group females. Additionally, 2.5% solution suppressed body weight gains in both males and females. These results and prior data by others together suggest that weak mutagens may be noncarcinogenic under certain conditions.

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Body Weight; Female; Food Additives; Male; Neoplasms; Rats; Rats, Inbred F344

Three methods of estimating vitamin A and C intakes from food frequency data obtained in June 1981 were compared with estimates obtained from dietary histories taken in September 1982, in 50 elderly residents of a Southern California retirement community. The first method of estimating vitamin A and C intakes (Af and Cf) was to add the products of the frequency of use of foods and the vitamin content of an average serving. The second method of estimating the intakes of these vitamins (Ai and Ci) was to develop an index based on the sum of frequencies of consumption of foods rich in these vitamins. This was then converted to absolute amounts using a regression equation. The third method (Ar and Cr) was to use stepwise multiple regression with the estimated intakes from the history (Ah and Ch) as dependent variables and to develop an equation with a small number of foods as the independent variables. When intakes from food alone were examined, the Spearman correlations between Ah and Af, Ai, and Ar, respectively, were 0.03, 0.16, and 0.43; the correlations between Ch and Cf, Ci, and Cr were 0.29, 0.36, and 0.38. When supplemental vitamin intakes were included, the correlations were between 0.35 and 0.44 for vitamin A and between 0.62 and 0.64 for vitamin C. The results demonstrated the importance of including the contribution of supplemental vitamins in estimating total vitamin A and C intake and suggested that the index and regression approaches may be superior to Af and Cf for estimating dietary vitamin intakes from food frequency questionnaires.

Topics: Aged; Ascorbic Acid; California; Diet Surveys; Feeding Behavior; Female; Humans; Male; Methods; Middle Aged; Neoplasms; Prospective Studies; Surveys and Questionnaires; Vitamin A

Topics: Adenocarcinoma; Adenoma; Animals; Ascorbic Acid; Carcinogens; Humans; Neoplasms; Neoplasms, Experimental; Nitrosamines; Orthomolecular Therapy; Palliative Care; Rats

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Fluorouracil; Humans; Lung Neoplasms; Mice; Neoplasms; Neoplasms, Experimental; Orthomolecular Therapy; Thiamine; Thiamine Pyrophosphate; Transketolase; Vitamin A

Topics: Ascorbic Acid; Chemotaxis, Leukocyte; Humans; In Vitro Techniques; Macrophages; Monocytes; Neoplasms

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Gastrointestinal Neoplasms; Humans; Neoplasms; Neoplasms, Experimental

Topics: Ascorbic Acid; Cardiovascular Diseases; Humans; Longevity; Neoplasms

Topics: Adenocarcinoma; Animals; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Male; Methylnitronitrosoguanidine; Neoplasms; Rats; Rats, Inbred F344; Sarcoma; Stomach Neoplasms

Incidence rates for many sites of cancer show wide variations among the main ethnic groups in Hawaii (Caucasians, Japanese, Chinese, Filipinos, and Hawaiians). Major shifts in cancer rates among migrants to the islands suggest that environmental factors are at least in part responsible for these variations. One prominent area of difference among these ethnic populations is their diets, which can vary substantially, not only in the consumption of particular food items but also in mean nutrient intakes. In aggregate correlational analyses based on data from representative samples of these ethnic groups and corresponding population-based cancer incidence rates, we found significant associations between ethnic-sex-specific intakes of dietary fat (including total fat, as well as animal, saturated, and unsaturated fats) and breast, endometrial, and prostate cancers. Animal protein intake showed associations similar to those for dietary fat, but these two nutrients were highly correlated in the data. Cholesterol intake showed significant correlations with lung and laryngeal cancers. Analyses of both nutrient and food item data suggested an association of stomach cancer incidence with the consumption of fish products, particularly dried/salted fish, and with a lower intake of vitamin C. Preliminary findings from ongoing case-control studies showed the following relationships: an inverse association between lung cancer risk and the intake of food sources of vitamin A, especially foods containing carotenes; an inverse association between cancers of the lower urinary tract and vitamin A consumption, especially from supplements; a positive association between prostate cancer risk and dietary fat intake in men above age 69, but not in younger men; and a positive association between breast cancer risk and the intake of dietary fat (particularly saturated fat) and animal protein in postmenopausal women, especially the Japanese. Two large cohorts (50,000 and 5,000 subjects) on whom dietary information was collected between 1975 and 1980 are being followed prospectively for their occurrence of cancer.

Topics: Age Factors; Aged; Ascorbic Acid; Breast Neoplasms; Diet; Dietary Fats; Ethnicity; Female; Hawaii; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Risk; Urologic Neoplasms; Vitamin A

Topics: Antioxidants; Ascorbic Acid; Carcinogens; Humans; Mutagens; Neoplasms; Selenium; Vitamin A

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Humans; Immunity; Interferons; Neoplasms

Topics: Ascorbic Acid; Humans; Neoplasms; Protein Deficiency; Protein-Energy Malnutrition; Vitamin A

Topics: Aged; Ascorbic Acid; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Neoplasms; Orthomolecular Therapy

Topics: Animals; Ascorbic Acid; Cats; Common Cold; Diet Fads; Humans; Mental Disorders; Neoplasms; Niacin; Orthomolecular Therapy; Receptors, Cholinergic; Thiamine

Topics: Ascorbic Acid; Cooking; Food; Humans; Neoplasms; Nitrates; Nitrosamines; Vitamin E

Topics: Ascorbic Acid; Cell Biology; History, 19th Century; History, 20th Century; Humans; Hungary; London; Massachusetts; Neoplasms; Nobel Prize

C3H/10T 1/2 mouse embryo cells were transformed with 3-methylcholanthrene. Several type III morphologically transformed cell lines were selected with morphologies that either could or could not be reverted back to normal at passage 1 by daily addition of ascorbic acid (1 or 5 microgram/ml). Those transformed cell lines with morphologies that could be caused to revert to normal did not produce colonies in agarose or tumors in nude mice at early passages. Such transformed cell lines at later passages all formed colonies in agarose, but only 2 of 8 lines produced tumors at any passage tested. Subsequently, clones of transformed cells from each cell line have been isolated which are tumorigenic. In contrast, the transformed cell lines which were unresponsive to ascorbic acid at passage 1 were able to form colonies and to produce tumors in early passages. The reversion of the transformed morphology by ascorbic acid is apparently not caused by cytotoxicity since no cell kill was observed following exposure to ascorbate in any newly transformed cell lines at the concentrations used. Thus, the use of ascorbic acid allowed morphologically transformed cell lines to be isolated which appeared to be at different stages in the progression of an initiated cell from a morphologically transformed cell to a highly tumorigenic one. These studies also suggest that low concentrations of ascorbic acid in C3H/10T 1/2/CL8 cells can be effective in suppressing oncogenic progression only prior to a stage where an initiated cell achieves the capacity to grow in semisolid medium and to produce tumors in immunosuppressed animals. The importance of these cell lines for elucidating key changes required for the promotion and/or progression of cells to a tumorigenic phenotype is also presented.

Topics: Animals; Ascorbic Acid; Cell Division; Cell Line; Cell Survival; Cell Transformation, Neoplastic; Embryo, Mammalian; Methylcholanthrene; Mice; Mice, Inbred C3H; Mice, Nude; Mutation; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Phenotype

A systematic study of vitamin C blood levels in patients with cancer and an evaluation of their modifications when the patients were orally treated with daily large doses of ascorbic acid (5g/day) have been carried out. For excluding any interference on intestinal vitamin C absorption, all patients with digestive tract cancer have been excluded. Our first results concern 24 lung cancer and 35 bladder cancer patients, operable or not, of different sex and age. The study has shown hypovitaminosis C subclinic conditions for the greater part of subjects: in fact the average haematic rate of ascorbic acid approaches to lower level of physiologic range, appearing very low particularly for the younger patients. Periodic haematic dosages of vitamin C of unoperable and operated patients treated with large doses of ascorbic acid, have shown a rapid increase of its blood concentration which frequently has been very over 1500 micrograms%, the higher level of normal range. These high vitamin haematic levels, generally constant during the time, appear usefull in increasing the defence reactions of the cancerous patient.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Urinary Bladder Neoplasms

Topics: Adolescent; Adult; Aged; Amniocentesis; Amniotic Fluid; Arteriosclerosis; Ascorbic Acid; Child; Child, Preschool; Chromosome Aberrations; Dementia; Female; Folic Acid; Glutathione; Humans; Infant; Middle Aged; Mutagens; Neoplasms; Pregnancy; Tretinoin

Topics: Ascorbic Acid; Carcinogens; Female; Free Radicals; Humans; Leukocytes; Lung Neoplasms; Male; Neoplasms; Nicotiana; Plants, Toxic; Smoke; Smoking; Sodium; Stomach Neoplasms; Vascular Diseases; Vitamin A; Vitamin E

Topics: Ascorbic Acid; Humans; Neoplasms

Topics: Aging; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Carcinogens, Environmental; Carotenoids; Cooking; Dietary Fats; Ethanol; Food Analysis; Humans; Lipid Peroxides; Mutagens; Neoplasms; Plants; Vitamin E

Topics: Ascorbic Acid; Humans; Interferons; Neoplasms; Orthomolecular Therapy; Virus Diseases

During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.

Topics: Adult; Aging; Animals; Antioxidants; Ascorbic Acid; Biological Evolution; Brain; Digestive System; Erythrocyte Membrane; Female; Free Radicals; Hemoglobins; Humans; Male; Neoplasms; Oxidation-Reduction; Peroxides; Uric Acid

A certain amount of resistance to new ideas is normal and functional in science providing the innovations have a means of being tested. A number of differences between medicine and pure science are noted which can result in some medical innovations being ignored or rejected without an adequate assessment. Historical and current instances of resistance to innovation are given. Social-organizational factors in medicine appear to favor the acceptance of theoretically glamorous, pharmaceutical, and high technology innovations over simpler and less profitable ones.

Topics: Ascorbic Acid; Communication; Diffusion of Innovation; Female; Food Hypersensitivity; History, 19th Century; History, 20th Century; Humans; Medicine; Neoplasms; Poliomyelitis; Pregnancy; Puerperal Infection; Sociology, Medical; Therapeutics

Topics: Adult; Animals; Ascorbic Acid; Child; Female; Humans; Infant; Male; Mental Disorders; Neoplasms; Orthomolecular Therapy; Pregnancy; Rats; Reproduction; Vitamin A; Vitamin E

Based on a consideration of biochemical mechanisms, rational methods for the prevention of cancer and for its positive regression are presented. It is demonstrated that the means employed are fundamentally opposed so that if the preventive method were to be used after the onset of cancer, it would only accelerate its development. The solution to these subtle questions rests notably on the established fact that a spontaneous cancer is nothing else but a phenomenon of anti-ageing. Thus, it is evident that all living beings that attain maximal longevity would necessarily die of cancer. Nevertheless, the malignant tumour is, from a certain aspect, hereditarily linked, since its early appearance in young children can only be explained by premature tissue ageing which is itself genetically derived.

Topics: Aging; Animals; Ascorbic Acid; Chemical Phenomena; Chemistry; Child, Preschool; Humans; Mice; Neoplasms; Oxidation-Reduction; Rats; Vitamin A; Vitamin E

Topics: Ascorbic Acid; Dietary Fats; Dietary Fiber; Energy Intake; Feeding Behavior; Female; Humans; Male; Neoplasms; Nutritional Physiological Phenomena

Most inanimate systems are build of closed-shell molecules in which electrons lack excitability and mobility. These electrons can be rendered reactive and mobile by taking out some of them, desaturating the system electronically. Single electrons can be taken out of molecules by transfer to an external acceptor, creating two radicals that form a biradical having no net charge. The living state is such an electronically desaturated state. The universal electron acceptor of the biosphere is oxygen. Before light and O2 appeared, a weak electron acceptor could occur through linkage of two C=O groups to glyoxal and addition of a methyl group. The resulting methylglyoxal, being a weak acceptor, could lead to only a low degree of desaturation and thus to formation of only the simple life forms extant during this dark and anaerobic period--the alpha period. During the subsequent aerobic beta period, more highly differentiated life forms could develop because of occurrence of O2, a strong electron acceptor leading to a greater degree of desaturation. When dividing, however, beta-type cells return partially to the proliferative alpha state. The process of electron (charge) transfer, described here in two models, depends on the dielectric constant of the medium and the relative concentration of SH and methylglyoxal. Structure-building proteins that perform the main biological functions carry with them this chemical mechanism of their desaturation. Central to the mechanism is the NH2 of lysine that attaches a methylglyoxal. Through folding of the side chain, the CO groups of resulting Schiff bases can come in touch with the NH's of the peptide chain and accept electrons from it, desaturating it. Ascorbic acid is the catalyst of this charge transfer, which brings protein into the living state. Purified protein is inanimate matter. Manganese and oxygen form part of the chemical mechanism of desaturation, and the charge transfer reactions studied were found to be autocatalytic. It follows from the above observations that a cancer cell is a cell trapped in the alpha state.

Topics: Aldehydes; Ascorbic Acid; Biological Evolution; Chemical Phenomena; Chemistry; Electric Conductivity; Electron Spin Resonance Spectroscopy; Electron Transport; Ethylenediamines; Glutathione; Lysine; Methylamines; Mixed Function Oxygenases; Neoplasms; Origin of Life; Oxygen; Proteins; Pyruvaldehyde

Topics: 2-Acetylaminofluorene; Animals; Aryl Hydrocarbon Hydroxylases; Ascorbic Acid; Butylated Hydroxytoluene; Carcinogens; Dimethylhydrazines; Hydroxyacetylaminofluorene; In Vitro Techniques; Liver Neoplasms; Male; Methylazoxymethanol Acetate; Mutation; Neoplasms; Neoplasms, Experimental; p-Dimethylaminoazobenzene; Rats; Selenium; Sister Chromatid Exchange

Topics: Ascorbic Acid; Humans; Neoplasms

Topics: Animals; Antioxidants; Ascorbic Acid; Carcinogens; Humans; Neoplasms

Topics: Ascorbic Acid; Humans; Neoplasms; Research Design

Topics: Ascorbic Acid; Humans; Neoplasms; Self Medication

Topics: Ascorbic Acid; Humans; Neoplasms; Placebos

Topics: Ascorbic Acid; Humans; Neoplasms

Topics: Ascorbic Acid; Humans; Neoplasms

Topics: Amygdalin; Animals; Ascorbic Acid; Calcium; Cyanides; Diet Therapy; Dietary Proteins; Humans; Iron Deficiencies; Neoplasms; Vitamin A; Vitamin B 12 Deficiency; Vitamin B Complex

Topics: Adult; Aged; Ascorbic Acid; Humans; Middle Aged; Neoplasms

Topics: Animals; Ascorbic Acid; Haplorhini; Herpes Simplex; History of Medicine; Humans; Neoplasms

Three cases are described, 2 of Hodgkin's disease and a further case of bronchial carcinoma, where high dosage ascorbic acid treatment appeared to be associated with the development of potentially dangerous symptoms. It is suggested that mega ascorbic acid therapy should be given with caution in malignant disease, with a slow build-up over several days to high levels of dosage.

Topics: Adult; Aged; Animals; Antineoplastic Agents; Ascorbic Acid; Bronchial Neoplasms; Carcinoma, Small Cell; Dyspnea; Fever; Hodgkin Disease; Humans; Lung Neoplasms; Male; Neoplasms; Orthomolecular Therapy

Prostaglandin (PG) E1 plays a major role in the regulation of thymus development and T lymphocyte function and the evidence for this is reviewed. The production of PGE1 is dependent on nutritional factors with linoleic acid, gamma-linolenic acid, pyridoxine, zinc and vitamin C playing key roles. Inadequate intake of any one of these will lead to inadequate PGE1 formation and defective T lymphocyte function. Megadoses of any one are likely to be only minimally effective in the absence of adequate intakes of the others. By careful attention to diet it should be possible to activate T lymphocyte function in the large number of diseases including rheumatoid arthritis, various auto-immune diseases, multiple sclerosis, and cancer in which such function is defective. It is possible that T lymphocytes may require both endogenous and exogenous PGE1 in order to function adequately. It is therefore of particular interest that many cancer cells and virally infected cells are unable to make PGE1 because they cannot convert linoleic acid to gamma-linolenic acid. The direct provision of gamma-linolenic or dihomo-gammalinolenic acids in these situations is worthy of full investigation.

Topics: Animals; Ascorbic Acid; Diet; Fatty Acids, Nonesterified; Glucocorticoids; Humans; Immunity, Cellular; Inflammation; Lithium; Neoplasms; Nutritional Physiological Phenomena; Prostaglandins E; T-Lymphocytes; Thymus Gland; Virus Diseases; Zinc

Vitamin C stimulates the formation of PGE1 in human platelets. The effect occurs over the physiologically relevant range of concentrations. PGE1 is required for T lymphocyte function and plays a major part in the regulation of immune responses. PGE1 is also important in the regulation of collagen and ground substance metabolism, in cholesterol metabolism and in regulation of responsiveness to insulin. It is proposed that defective formation of PGE1 could account for many of the features of scurvy and for many of the reported therapeutic effects of vitamin C. If correct, vitamin C will be of value only in conjunction with an adequate supply of dihomogammalinolenic acid, the precursor of PGE1. Essential fatty acids, pyridoxine and zinc are all required to achieve this.

Topics: Animals; Arachidonic Acids; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Platelets; Cats; Cholesterol; Collagen; Dental Caries; Drug Therapy, Combination; Glycosaminoglycans; Humans; Linolenic Acids; Neoplasms; Platelet Aggregation; Prostaglandins E; Salivation; Scurvy; Sjogren's Syndrome; Stimulation, Chemical

The dominant role of the physical and chemical environment in the development of cancer is challenged. Analyses of the etiology of skin, bladder, respiratory and gastric cancers are presented which demonstrate the considerable extent to which one's health status may modify the initiation and promotion of environmentally associated cancers. It is concluded that although environmental factors may initiate and/or promote 85 to 90 percent of all cancers this is misleading since it neglects the critical role of the individual's health status as a factor modifying carcinogenesis.

Topics: Ascorbic Acid; Benzopyrenes; Carcinogens, Environmental; Carcinoma, Bronchogenic; Diet; Humans; Hydrocarbons; Neoplasms; Neoplasms, Radiation-Induced; Racial Groups; Riboflavin; Skin Neoplasms; Smoking; Stomach Neoplasms; Ultraviolet Rays; Urinary Bladder Neoplasms; Vitamin A

Homo sapiens' gene pool contains a defective gene for the synthesis of the active enzyme protein, L-gulonolactone oxidase(GLO). The absence of GLO in the human liver blocks the normal mammalian conversion of blood sugar into ascorbate, leading to the potentially-fatal "inborn error of carbohydrate metabolism", the genetic disease, Hypoascorbemia (in the older nomenclature- scurvy). To survive, humans need exogenous sources of daily ascorbate. Most mammals have the intact gene for GLO synthesis and produce generous daily amounts of the liver metabolite, ascorbate; for instance, an unstressed 70 Kg goat is capable of producing over 13 grams of ascorbate daily and much more under stress. The recommended dietary allowance of 45 milligrams of ascorbate a day for human adults, now proposed and used by nutritionists, is grossly inadequate to restore Homo sapiens to a normal mammalian ascorbate physiology. To correct fully this human genetic defect and banish epidemic chronic subclinical scurvy requires daily intakes of ascorbate equivalent to, at least, the amounts synthesized by the other mammals. Humans kept on a long term regime of full correction of this birth defect show great salutary benefits in health maintenance, disease therapy and slowing of the aging process. This can be regarded as the creation of a new and more robust, longer-living, tough human sub-species, Homo sapiens ascorbicus, by the biochemical reversal of a primate mutation occurring some 60 million years ago. Some of the practical benefits and pathways of future clinical research are discussed.

Topics: Aging; Alcohol Oxidoreductases; Ascorbic Acid; Ascorbic Acid Deficiency; Genes; Heart Diseases; Humans; Neoplasms; Substance-Related Disorders; Sudden Infant Death; Virus Diseases

Topics: Ascorbic Acid; Child, Preschool; Encephalitis, Arbovirus; Family; Female; Humans; Neoplasms; Physician-Patient Relations

Topics: Ascorbic Acid; Humans; Neoplasms

Individuals who have a reduced capacity to detoxify cyanide to thiocyanate are at increased risk to experience adverse side effects from laetrile, a cyanide containing substance used in cancer treatment. Since megadoses of ascorbic acid may markedly diminish body stores of cysteine, a sulfur containing amino acid which facilitates the detoxification of cyanide, it is predicted that persons consuming megadoses of ascorbic acid will be at increased risk to experience the adverse side effects from laetrile treatment.

Topics: Amygdalin; Ascorbic Acid; Cyanides; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Neoplasms

Topics: Ascorbic Acid; Bacteria; Humans; Neoplasms; Palliative Care; Viruses

Topics: Ascorbic Acid; Humans; Neoplasms

HeLa cells in culture do not accumulate ascorbic acid unless ascorbic acid or dehydroascorbic acid is available in the medium. Collagen peptidase corresponding to the activity found in the invasive zone of tumours, and acid phosphatase, in HeLa cells cultured under normal conditions, are unaffected by ascorbic acid, but are reduced in cells deprived of carbohydrate. These reduced collagen-peptidase levels, but not acid phosphatase, are restored to the values of normal HeLa cells by ascorbic acid. The relevance of these findings is considered in the context of tumour growth and spread.

Topics: Acid Phosphatase; Ascorbic Acid; Dehydroascorbic Acid; Glucose; HeLa Cells; Microbial Collagenase; Neoplasms

The results of ab initio 'supermolecule' calculations of the charge transfer between formamide and methylglyoxal, dimethylglyoxal and ethylglyoxal are compared for several different relative conformations of the constituent molecules. The extent and sign of the charge transfer is similar for all three molecules; the ketoaldehyde acts as an electron acceptor only for the stacked conformation. Similar calculations on alpha-hydroxytetronic acid as a model for ascorbic acid show that it can act as either an acceptor from formamide or a donor to glyoxal.

Topics: Animals; Ascorbic Acid; Diacetyl; Electron Transport; Energy Transfer; Formamides; Humans; Molecular Conformation; Neoplasms; Pyruvaldehyde; Quantum Theory; Thermodynamics

The surrounding world can be divided into two parts: alive and inanimate. What makes the difference is the subtle reactivity of living systems. The difference is so great that it is reasonable to suppose that what underlies life is a specific physical state, 'the living state'. Living systems are built mainly of nucleic acids and proteins. The former are the guardians of the basic blueprint while the business of life is carried on by proteins. Proteins thus have to share the subtle reactivity of living systems. A closed-shell protein molecule, however, has no electronic mobility, and has but a low chemical reactivity. Its orbitals are occupied by electron pairs which are held firmly. The situation can be changed by taking single electrons out of the system. This unpairs electrons, leaves half-occupied orbitals with positive electron holes, making the molecules into highly reactive paramagnetic free radicals. The reactivity of the system depends on the degree of its electronic desaturation. Electrons can be taken out of protein molecules by 'electron aceptors' in 'cahrge transfer'. When life began, our globe was covered by dense water vapour. There was no light and no free oxygen. Electron acceptors could be made out of trioses by concentrating their carbon atoms as carbonyls at one end of the molecule. The resulting methylglyoxal is a weak acceptor which made a low level of development possible. When light appeared, free oxygen was generated by the energy of photons. Oxygen is a strong electron acceptor. Its appearance opened the way to the present level of development. The transfer of electrons from protein to oxygen is effected by a complex chemical mechanism which involves ascorbic acid.

Topics: Animals; Ascorbic Acid; Biological Evolution; Electrons; Free Radicals; Humans; Molecular Biology; Neoplasms; Oxygen Consumption; Proteins; Pyruvaldehyde

A study has been made of the survival times of 100 terminal cancer patients who were given supplemental ascorbate, usually 10 g/day, as part of their routine management and 1000 matched controls, similar patients who had received the same treatment except for the ascorbate. The two sets of patients were in part the same as those used in our earlier study [Cameron, E. & Pauling, L. (1976) Proc. Natl. Acad. Sci. USA 73, 3685-3689]. Tests confirm that the ascorbate-treated patients and the matched controls are representative subpopulations of the same population of "untreatable" patients. Survival times were measured not only from the date of "untreatability" but also from the precisely known date of first hospital attendance for the cancer that eventually reached the terminal stage. The ascorbate-treated patients were found to have a mean survival time about 300 days greater than that of the controls. Survival times greater than 1 yr after the date of untreatability were observed for 22% of the ascorbate-treated patients and for 0.4% of the controls. The mean survival time of these 22 ascorbate-treated patients is 2.4 yr after reaching the apparently terminal stage; 8 of the ascorbate-treated patients are still alive, with a mean survival time after untreatability of 3.5 yr.

Topics: Adult; Aged; Ascorbic Acid; Female; Humans; Male; Methods; Middle Aged; Neoplasms; Prognosis

Topics: Ascorbic Acid; Humans; Neoplasms; Research Design

Topics: Ascorbic Acid; Humans; Neoplasms

Topics: Adolescent; Adult; Arteriosclerosis; Ascorbic Acid; Cholesterol; Common Cold; Double-Blind Method; Humans; Middle Aged; Neoplasms; Placebos

Topics: Ascorbic Acid; Diet; Humans; Lymphoma, Large B-Cell, Diffuse; Neoplasms

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Breast Neoplasms; Female; Humans; Hydroxyproline; Lipid Metabolism; Neoplasm Metastasis; Neoplasms; Thiamine Deficiency; Vitamin A; Vitamin A Deficiency

Patients receiving BCNU [1,3-bis(2 chloroethyl)-1-nitrosourea] acquire a profound deficiency of erythrocytic oxidized glutathione reductase (GSSG-R) within minutes after the first intravenous injection of a single therapeutic dose (75 mg/M.2) of the drug. This effect is not accompanied by changes in the activites of 19 additional erythrocytic enzymes tested, is reproducible in vitro in a dose-related manner, and is not caused by the antitumor agents administered concurrently with the nitrosourea. The inactivation of erythrocytic GSSG-R results in decreased levels of reduced glutathione (GSH), marked GSH instability and disturbed hydrogen peroxide removal with a positibe ascorbate cyanide test and leads to increased susceptibility to oxidative hemolysis, particularly in glucose-6-phosphate dehydrogenase (G-6-D)-deficient patients. BCNU inhibits GSSG-R irreversibly, probably through alkylation rather than carbamylation, and the reappearance of enzyme activity in vivo after each chemotherapy pulse depends on the capacity of the marrow to release erythrocytes with normal activity formed during the drug-free interval. BCNU inhibits GSSG-R not only in erythrocytes but also in human leukocytes and platelets, as well as in yeast, monkey erythrocytes, and all the organs tested in the mouse. This generalized, severe, and specific GSSG-R deficiency caused by therapeutic doses of BCNU may enhance or mediate the toxic and antitumor effects of the nitrosourea and provides a simple yet sensitive biochemical means of monitoring bone marrow reserve in patients receiving multiple courses of chemotherapy with this agent.

Topics: Animals; Ascorbic Acid; Carmustine; Dose-Response Relationship, Drug; Erythrocytes; Female; Glutathione Reductase; Humans; Male; Mice; Neoplasms

Topics: Adult; Aged; Ascorbic Acid; Female; Humans; Leukocytes; Middle Aged; Neoplasms

Topics: Adult; Ascorbic Acid; Breast Neoplasms; Child; Female; Humans; Leukocytes; Lung Neoplasms; Mouth Neoplasms; Neoplasms; Rectal Neoplasms; Skin Neoplasms; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms

Ascorbic acid metabolism is associated with a number of mechanisms known to be involved in host resistance to malignant disease. Cancer patients are significantly depleted of ascorbic acid, and in our opinion this demonstrable biochemical characteristic indicates a substantially increased requirement and utilization of this substance to potentiate these various host resistance factors. The results of a clinical trial are presented in which 100 terminal cancer patients were given supplemental ascorbate as part of their routine management. Their progress is compared to that of 1000 similar patients treated identically, but who received no supplemental ascorbate. The mean survival time is more than 4.2 times as great for the ascorbate subjects (more than 210 days) as for the controls (50 days). Analysis of the survival-time curves indicates that deaths occur for about 90% of the ascorbate-treated patients at one-third the rate for the controls and that the other 10% have a much greater survival time, averaging more than 20 times that for the controls. The results clearly indicate that this simple and safe form of medication is of definite value in the treatment of patients with advanced cancer.

Topics: Adult; Aged; Ascorbic Acid; Breast Neoplasms; Bronchial Neoplasms; Colonic Neoplasms; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Rectal Neoplasms; Stomach Neoplasms; Terminal Care; Urinary Bladder Neoplasms

In a study of the vitamin C status of 50 patients with malignant disease, 46 had leucocyte levels less than the lower limit of the normal range (18-50,μg/10(8) W.B.C.) and of these 30 had very low levels (< 12.5 μg/10(8) W.B.C.). Physical signs compatible with subclinical scurvy were frequently recorded and there was a significant decrease in capillary fragility in those with the lowest levels. Most patients had an inadequate dietary intake of ascorbic acid-containing foods and this was felt to be the major factor in producing the vitamin depletion.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Bronchial Neoplasms; Capillary Fragility; Colonic Neoplasms; Diet; Humans; Leukocytes; Lymphatic Diseases; Neoplasms; Rectal Neoplasms; Scurvy; Stomach Neoplasms

Topics: Administration, Oral; Ascorbic Acid; Breast Neoplasms; Carcinoma; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Evaluation; Drug Stability; Female; Fibrosarcoma; Humans; Injections, Intravenous; Neoplasms; Papilloma; Rectal Neoplasms; Stomach Neoplasms; Time Factors; Urinary Bladder Neoplasms

Topics: Adolescent; Aged; Ascorbic Acid; Carcinoma; Child; Child, Preschool; Humans; Leukemia, Lymphoid; Leukocytes; Lung Neoplasms; Male; Middle Aged; Neoplasms; Skin; Skin Neoplasms

Normal and tumour tissues from rats, blood from normal and tumour bearing rats, and normal human blood were examined using the electron paramagnetic resonance (epr) technique. At low temperature a triplet epr signal, which is known to be produced by a NO-haemoprotein complex, was detected in some tumour samples and in decaying normal liver. At room temperature all of the tumour samples examined gave a doublet signal. This signal was also detected in blood but not in other normal tissues. The signal has a g value of 2·0054 ± 0·0002 and a hyperfine splitting of 1·80 ± 0·05 G and is assigned to the ascorbyl free radical. Model experiments suggest that the appearance of detectable concentrations of this radical result from a disturbance of the normal state of the ascorbic acid, dehydroascorbic acid redox system. It was verified that cell division is not responsible for the ascorbyl radical although autolysis may be involved. A possible relationship between the formation of ascorbyl radicals and other paramagnetic species in tumours is discussed.

Topics: Animals; Ascorbic Acid; Autolysis; Blood Proteins; Carcinoma 256, Walker; Carcinoma, Hepatocellular; Cell Division; Electron Spin Resonance Spectroscopy; Liver Neoplasms; Lung Neoplasms; Methods; Models, Biological; Models, Chemical; Neoplasms; Nitric Oxide; Oxidation-Reduction; Rats; Sarcoma, Yoshida; Temperature

Topics: Animals; Ascorbic Acid; Cysteamine; Dose-Response Relationship, Radiation; Electron Spin Resonance Spectroscopy; Ferricyanides; Flavin Mononucleotide; Free Radicals; Male; Neoplasms; Organ Specificity; Radiation Effects; Rats; Temperature; Testis; Thymus Gland; Uranium

Topics: Ascorbic Acid; Cell Division; Humans; Hyaluronoglucosaminidase; Neoplasms

Topics: Adolescent; Adult; Age Factors; Aged; Aneurysm; Ascorbic Acid; Cholecystectomy; Creatinine; Digestive System Surgical Procedures; Female; Fructose; Fucose; Gastrectomy; Glycosaminoglycans; Herniorrhaphy; Hexosamines; Hexoses; Humans; Male; Middle Aged; Neoplasms; Neuraminic Acids; Pneumonectomy; Surgical Procedures, Operative; Thyroidectomy; Time Factors; Wound Healing

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Chlorides; Colorimetry; Evaluation Studies as Topic; In Vitro Techniques; Iodoacetates; Mice; Neoplasms; Succinate Dehydrogenase; Tetrazolium Salts

Topics: Ascorbic Acid; Blood; Carcinoma; Catalase; Conductometry; Dialysis; Edetic Acid; Erythrocytes; Ethylmaleimide; Hemolysis; Hot Temperature; Humans; Kidney; Liver; Lung Neoplasms; Male; Neoplasms; Prostatic Neoplasms; Stomach Neoplasms; Tissue Extracts; Triazoles

Topics: Ascorbic Acid; Female; Humans; Menopause; Neoplasms; Uterine Hemorrhage

Topics: Adolescent; Adult; Ascorbic Acid; Biological Assay; Child; Drowning; Female; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Luteinizing Hormone; Male; Middle Aged; Neoplasms; Ovary; Pituitary Hormone-Releasing Hormones; Poisoning; Uremia; Vascular Diseases; Wounds and Injuries

Topics: Aged; Ascorbic Acid; Dietary Proteins; Female; Hematopoiesis; Humans; Leukopenia; Male; Middle Aged; Neoplasms; Thiotepa; Vitamin B Complex

Topics: Adult; Amino Acids; Ascorbic Acid; Cystamine; Female; Humans; Male; Middle Aged; Neoplasms; Proteins; Vitamin B Complex

Topics: Animals; Ascorbic Acid; Chick Embryo; Congenital Abnormalities; Hot Temperature; Humans; Neoplasms

Topics: Aging; Alcohol Oxidoreductases; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Collagen; Humans; Liver; Neoplasms

Topics: Ascorbic Acid; Humans; Leukocytes; Neoplasms

Topics: Ascorbic Acid; Body Weight; Calcium; Calcium, Dietary; California; Cardiovascular Diseases; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Follow-Up Studies; Geriatrics; Humans; Iron; Morbidity; Mortality; Neoplasms; Nutrition Surveys; Vitamin A; Vitamin B Complex

Topics: Ascorbic Acid; Histocytochemistry; Macrophages; Mast Cells; Neoplasms; Neoplasms, Experimental; Rats; Research

Topics: Ascorbic Acid; Cyclophosphamide; Leadership; Leukocyte Disorders; Leukopenia; Muramidase; Neoplasms; Propionates; Radiation-Protective Agents; Testosterone; Toxicology

Topics: Ascorbic Acid; Blood Transfusion; Brazil; Breast Neoplasms; Cyclophosphamide; Female; Humans; Neoplasms; Ovarian Neoplasms; Thyroid Hormones; Urethral Neoplasms; Uterine Cervical Neoplasms; Vaginal Neoplasms; Vitamin B 12; Vitamin B Complex

This series presents further evidence for an association between reticulosis of the intestine and steatorrhoea. Although some patients have a definite past history of gluten enteropathy, it seems likely that in certain patients the reticulosis itself is the primary cause of the steatorrhoea.

Topics: Ascorbic Acid; Blood Transfusion; Body Weight; Bone Marrow Examination; Celiac Disease; Diet; Diet Therapy; Fats; Feces; Folic Acid; Humans; Intestinal Neoplasms; Intestinal Perforation; Intestine, Small; Iron; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Nandrolone; Neomycin; Neoplasms; Pathology; Prednisone; Sarcoma; Steatorrhea; Surgical Procedures, Operative; Vitamin A; Vitamin B 12; Vitamin B Complex; Vitamins; Water-Electrolyte Balance

Topics: Animals; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Liver; Liver Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Metabolism; Mice; Microsomes; Microsomes, Liver; Neoplasms; Neoplasms, Experimental; Oxidoreductases; Research

Topics: Alcoholism; Ascorbic Acid; Drug Synergism; Drug Therapy; Fatigue; Geriatrics; Humans; Neoplasms; Pyridoxine; Tuberculosis

Topics: Ascorbic Acid; Carcinogens; Citrus; Dietary Fats; Fruit; Humans; Intestinal Neoplasms; Neoplasms; Netherlands; Nutrition Surveys; Nutritional Status; Stomach Neoplasms

Topics: Ascorbic Acid; Body Fluids; Cachexia; Endotoxins; Glucuronates; Iron; Iron-Dextran Complex; Liver; Metabolism; Neoplasms; Nitrogen; Pharmacology; Urine

Topics: Ascorbic Acid; Humans; Neoplasms; Research; Vitamins

Topics: Ascorbic Acid; Chronic Disease; Hematologic Diseases; Humans; Lymphatic Diseases; Neoplasms; Vitamins

Topics: Ascorbic Acid; Carbohydrate Metabolism; Humans; Neoplasms

Topics: Ascorbic Acid; Carbohydrate Metabolism; Glutarates; Humans; Neoplasms

Topics: Ascorbic Acid; Neoplasms; Vitamin A; Vitamin K; Vitamins

Topics: Ascorbic Acid; Neoplasms; Penicillin V; Penicillins; Potassium; Salts

Topics: Ascorbic Acid; Carrageenan; Collagen; Encephalomyelitis; Granuloma; Hydroxyproline; Neoplasms; Proline; Vitamins

Topics: Adrenalectomy; Animals; Ascorbic Acid; Neoplasms; Neoplasms, Experimental; Rats; Sarcoma; Vitamins

Topics: Ascorbic Acid; Dehydroascorbic Acid; Humans; Neoplasms; Vitamins

Topics: Animals; Ascorbic Acid; Dehydroascorbic Acid; Humans; Neoplasms; Neoplasms, Experimental; Vitamins

Topics: Ascorbic Acid; Leukemia; Mechlorethamine; Neoplasms; Nitrogen Mustard Compounds; Vitamin A

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; DNA; Glucose; Humans; Neoplasms; Neoplasms, Experimental; Nucleic Acids

Topics: Animals; Ascorbic Acid; Dehydroascorbic Acid; Neoplasms; Neoplasms, Experimental; Vitamins

Topics: Animals; Ascorbic Acid; Humans; Neoplasms; Neoplasms, Experimental; Sarcoma; Sarcoma, Experimental

Topics: Ascorbic Acid; Carcinoma; Humans; Neoplasms; Vitamin A; Vitamins

Topics: Ascorbic Acid; Biochemical Phenomena; Humans; Neoplasms; Nutrition Therapy; Skin Tests; Vitamin A; Vitamins

Topics: Ascorbic Acid; Humans; Neoplasms

Topics: Adrenocorticotropic Hormone; Ascorbic Acid; Humans; Neoplasms; Vitamins

Topics: Ascorbic Acid; Carcinoma; Female; Genitalia; Genitalia, Female; Humans; Neoplasms; Vitamin A; Vitamins

Topics: Ascorbic Acid; Diet; Humans; Neoplasms; Radiotherapy; Vitamins

Topics: Ascorbic Acid; Heptoses; Neoplasms; Nucleic Acids; Vitamins

Topics: Ascorbic Acid; Humans; Neoplasms; Nutrition Therapy; Vitamin A; Vitamins

Topics: Ascorbic Acid; Carcinoma; Humans; Neoplasms; Vitamin A; Vitamins

Topics: Ascorbic Acid; Folic Acid; Humans; Neoplasms; Niacin; Nicotinic Acids; Vitamin A; Vitamin B Complex; Vitamin K; Vitamins

Topics: Animals; Ascorbic Acid; Neoplasms; Neoplasms, Experimental; Organic Chemicals; Vitamins

Topics: Ascorbic Acid; Female; Humans; Neoplasms; Uterine Neoplasms; Vitamin A; Vitamins

Topics: Animals; Ascorbic Acid; Mice; Neoplasms; Neoplasms, Experimental

Topics: Ascorbic Acid; Chronic Disease; Humans; Leukocyte Count; Leukocytes; Neoplasms; Vitamins

Topics: Ascorbic Acid; Estradiol Congeners; Estrogens; Female; Fibroma; Guinea Pigs; Humans; Neoplasms; Neoplasms, Fibrous Tissue; Vitamin A; Vitamins

Topics: Ascorbic Acid; Hematologic Diseases; Humans; Iron; Iron Compounds; Neoplasms; Penicillins; Vitamins

Topics: Animals; Ascorbic Acid; Dehydroascorbic Acid; Humans; Melanoma; Mice; Neoplasms

Topics: Ascorbic Acid; Humans; Indoles; Neoplasms; Urine; Vitamins

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Fibrosarcoma; Humans; Neoplasms; Sarcoma

Topics: Ascorbic Acid; Breast Neoplasms; Cells; Glutathione; Humans; Neoplasms