beta-carotene and Neoplasms

According to National Health and Nutrition Examination Survey data, 52% of surveyed US adults reported using at least 1 dietary supplement in the prior 30 days and 31% reported using a multivitamin-mineral supplement. The most commonly cited reason for using supplements is for overall health and wellness and to fill nutrient gaps in the diet. Cardiovascular disease and cancer are the 2 leading causes of death and combined account for approximately half of all deaths in the US annually. Inflammation and oxidative stress have been shown to have a role in both cardiovascular disease and cancer, and dietary supplements may have anti-inflammatory and antioxidative effects.. To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the efficacy of supplementation with single nutrients, functionally related nutrient pairs, or multivitamins for reducing the risk of cardiovascular disease, cancer, and mortality in the general adult population, as well as the harms of supplementation.. Community-dwelling, nonpregnant adults.. The USPSTF concludes with moderate certainty that the harms of beta carotene supplementation outweigh the benefits for the prevention of cardiovascular disease or cancer. The USPSTF also concludes with moderate certainty that there is no net benefit of supplementation with vitamin E for the prevention of cardiovascular disease or cancer. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of supplementation with multivitamins for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of supplementation with single or paired nutrients (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined.. The USPSTF recommends against the use of beta carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of multivitamin supplements for the prevention of cardiovascular disease or cancer. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of single- or paired-nutrient supplements (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. (I statement).

Topics: Adult; Advisory Committees; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Mass Screening; Minerals; Neoplasms; Nutrition Surveys; Risk Assessment; Vitamin E; Vitamins

Cardiovascular disease and cancer are the 2 leading causes of death in the US, and vitamin and mineral supplementation has been proposed to help prevent these conditions.. To review the benefits and harms of vitamin and mineral supplementation in healthy adults to prevent cardiovascular disease and cancer to inform the US Preventive Services Task Force.. MEDLINE, PubMed (publisher-supplied records only), Cochrane Library, and Embase (January 2013 to February 1, 2022); prior reviews.. English-language randomized clinical trials (RCTs) of vitamin or mineral use among adults without cardiovascular disease or cancer and with no known vitamin or mineral deficiencies; observational cohort studies examining serious harms.. Single extraction, verified by a second reviewer. Quantitative pooling methods appropriate for rare events were used for most analyses.. Mortality, cardiovascular disease events, cancer incidence, serious harms.. Eighty-four studies (N=739 803) were included. In pooled analyses, multivitamin use was significantly associated with a lower incidence of any cancer (odds ratio [OR], 0.93 [95% CI, 0.87-0.99]; 4 RCTs [n=48 859]; absolute risk difference [ARD] range among adequately powered trials, -0.2% to -1.2%) and lung cancer (OR, 0.75 [95% CI, 0.58-0.95]; 2 RCTs [n=36 052]; ARD, 0.2%). However, the evidence for multivitamins had important limitations. Beta carotene (with or without vitamin A) was significantly associated with an increased risk of lung cancer (OR, 1.20 [95% CI, 1.01-1.42]; 4 RCTs [n=94 830]; ARD range, -0.1% to 0.6%) and cardiovascular mortality (OR, 1.10 [95% CI, 1.02-1.19]; 5 RCTs [n=94 506] ARD range, -0.8% to 0.8%). Vitamin D use was not significantly associated with all-cause mortality (OR, 0.96 [95% CI, 0.91-1.02]; 27 RCTs [n=117 082]), cardiovascular disease (eg, composite cardiovascular disease event outcome: OR, 1.00 [95% CI, 0.95-1.05]; 7 RCTs [n=74 925]), or cancer outcomes (eg, any cancer incidence: OR, 0.98 [95% CI, 0.92-1.03]; 19 RCTs [n=86 899]). Vitamin E was not significantly associated with all-cause mortality (OR, 1.02 [95% CI, 0.97-1.07]; 9 RCTs [n=107 772]), cardiovascular disease events (OR, 0.96 [95% CI, 0.90-1.04]; 4 RCTs [n=62 136]), or cancer incidence (OR, 1.02 [95% CI, 0.98-1.08]; 5 RCTs [n=76 777]). Evidence for benefit of other supplements was equivocal, minimal, or absent. Limited evidence suggested some supplements may be associated with higher risk of serious harms (hip fracture [vitamin A], hemorrhagic stroke [vitamin E], and kidney stones [vitamin C, calcium]).. Vitamin and mineral supplementation was associated with little or no benefit in preventing cancer, cardiovascular disease, and death, with the exception of a small benefit for cancer incidence with multivitamin use. Beta carotene was associated with an increased risk of lung cancer and other harmful outcomes in persons at high risk of lung cancer.

Topics: Adult; Advisory Committees; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Lung Neoplasms; Minerals; Neoplasms; Primary Prevention; United States; Vitamin A; Vitamins

Epidemiological studies have observed the association between dietary patterns and the risk of certain types of cancer. Extensive studies have been conducted on the cancer preventive activities of constituents from food and beverages. While laboratory research has shown impressive and promising results, such promising cancer preventive activities have not been demonstrated in many human intervention trials. This article analyzes the major differences between these different types of studies and the limitations of these studies. Animal and cell line studies usually use optimal conditions in order to demonstrate the hypothesized effects, sometimes without considering the human relevance. On the other hand, some clinical trials were designed without a good understanding of the biochemical and pharmacological properties of the agents used. Lessons learned from these studies will be illustrated using vitamin E, β-carotene and selenium as examples for nutrients, and green tea polyphenols as an example for non-nutritive dietary constituents. From the lessons learned, we believe that more interdisciplinary collaboration and integration of laboratory and human studies would effectively advance the field of cancer prevention.

Topics: Animals; Antioxidants; beta Carotene; Cell Line; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Neoplasms; Nutritional Status; Phytochemicals; Randomized Controlled Trials as Topic; Selenium; Vitamin E

Observational studies evaluating the relation between dietary or circulating level of beta-carotene and risk of total mortality yielded inconsistent results. We conducted a comprehensive search on publications of PubMed and EMBASE up to 31 March 2016. Random effect models were used to combine the results. Potential publication bias was assessed using Egger's and Begg's test. Seven studies that evaluated dietary beta-carotene intake in relation to overall mortality, indicated that a higher intake of beta-carotene was related to a significant lower risk of all-cause mortality (RR for highest vs. lowest group = 0.83, 95%CI: 0.78-0.88) with no evidence of heterogeneity between studies (I(2) = 1.0%, P = 0.416). A random-effect analysis comprising seven studies showed high beta-carotene level in serum or plasma was associated with a significant lower risk of all-cause mortality (RR for highest vs. lowest group = 0.69, 95%CI: 0.59-0.80) with low heterogeneity (I(2) = 37.1%, P = 0.145). No evidence of publication bias was detected by Begg's and Egger's regression tests. In conclusion, dietary or circulating beta-carotene was inversely associated with risk of all-cause mortality. More studies should be conducted to clarify the dose-response relationship between beta-carotene and all-cause mortality.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Cardiovascular Diseases; Diet; Female; Humans; Male; Metabolic Diseases; Middle Aged; Neoplasms; Phytochemicals; Prospective Studies; Survival Analysis

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

Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. When ingested, it is metabolized mainly to fucoxanthinol by digestive enzymes of the gastrointestinal tract. These compounds have been shown to have many beneficial health effects, including anti-mutagenic, anti-diabetic, anti-obesity, anti-inflammatory and anti-neoplastic actions. In every cancer tested, modulatory actions of fucoxanthinol on viability, cell-cycle arrest, apoptosis and members of the NF-κB pathway were more pronounced than that of fucoxanthin. Anti-proliferative and cancer preventing influences of fucoxanthin and fucoxanthinol are mediated through different signalling pathways, including the caspases, Bcl-2 proteins, MAPK, PI3K/Akt, JAK/STAT, AP-1, GADD45, and several other molecules that are involved in cell cycle arrest, apoptosis, anti-angiogenesis or inhibition of metastasis. In this review, we address the mechanisms of action of fucoxanthin and fucoxanthinol according to different types of cancers. Current findings suggest that these compounds could be effective for treatment and/or prevention of cancer development and aggressiveness.

Topics: Animals; Antineoplastic Agents; Apoptosis; beta Carotene; Humans; Neoplasms; Signal Transduction; Xanthophylls

Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs.

Topics: Abietanes; Alkaloids; Allyl Compounds; Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; Benzodioxoles; beta Carotene; Biflavonoids; Capsaicin; Catechin; Catechols; Curcumin; Dietary Supplements; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Fatty Alcohols; Furocoumarins; Humans; Indoles; Limonins; Neoplasms; Phytotherapy; Piperidines; Polyunsaturated Alkamides; Proanthocyanidins; Quercetin; Resveratrol; Stilbenes; Sulfides; Tea; Triterpenes; Xanthophylls

Oxidative damage to cells and tissues is considered involved in the aging process and in the development of chronic diseases in humans, including cancer and cardiovascular diseases, the leading causes of death in high-income countries. This has stimulated interest in the preventive potential of antioxidant supplements. Today, more than one half of adults in high-income countries ingest antioxidant supplements hoping to improve their health, oppose unhealthy behaviors, and counteract the ravages of aging.. Older observational studies and some randomized clinical trials with high risks of systematic errors ('bias') have suggested that antioxidant supplements may improve health and prolong life. A number of randomized clinical trials with adequate methodologies observed neutral or negative results of antioxidant supplements. Recently completed large randomized clinical trials with low risks of bias and systematic reviews of randomized clinical trials taking systematic errors ('bias') and risks of random errors ('play of chance') into account have shown that antioxidant supplements do not seem to prevent cancer, cardiovascular diseases, or death. Even more, beta-carotene, vitamin A, and vitamin E may increase mortality. Some recent large observational studies now support these findings. According to recent dietary guidelines, there is no evidence to support the use of antioxidant supplements in the primary prevention of chronic diseases or mortality.. Antioxidant supplements do not possess preventive effects and may be harmful with unwanted consequences to our health, especially in well-nourished populations. The optimal source of antioxidants seems to come from our diet, not from antioxidant supplements in pills or tablets.

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Chronic Disease; Dietary Supplements; Dose-Response Relationship, Drug; Humans; Meta-Analysis as Topic; Neoplasms; Observational Studies as Topic; Randomized Controlled Trials as Topic; Vitamin A; Vitamin E

Topics: Alzheimer Disease; Animals; Antioxidants; Apoptosis; beta Carotene; Carotenoids; Humans; Metabolic Diseases; Neoplasms; Reactive Oxygen Species; Receptors, Cytoplasmic and Nuclear; Retinoids; Tretinoin; Vitamin A

Cancer remains the second leading cause of death in the United States, and the number of cases is expected to continue to rise worldwide. Cancer prevention strategies are crucial for reducing the cancer burden. The carcinogenic potential of dietary acrylamide exposure from cooked foods is unknown. Acrylamide is a by-product of the common Maillard reaction where reducing sugars (i.e., fructose and glucose) react with the amino acid, asparagine. Based on the evidence of acrylamide carcinogenicity in animals, the International Agency for Research on Cancer has classified acrylamide as a group 2A carcinogen for humans. Since the discovery of acrylamide in foods in 2002, a number of studies have explored its potential as a human carcinogen. This article outlines a systematic review of dietary acrylamide and human cancer, acrylamide exposure and internal dose, exposure assessment methods in the epidemiologic studies, existing data gaps, and future directions. A majority of the studies reported no statistically significant association between dietary acrylamide intake and various cancers, and few studies reported increased risk for renal, endometrial, and ovarian cancers; however, the exposure assessment has been inadequate leading to potential misclassification or underestimation of exposure. Future studies with improved dietary acrylamide exposure assessment are encouraged.

Topics: Acrylamide; alpha-Tocopherol; Animals; beta Carotene; Carcinogens; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Epidemiologic Studies; Evidence-Based Practice; Female; Humans; Male; Neoplasms

Topics: Administration, Ophthalmic; Antioxidants; beta Carotene; Carotenoids; Cryptoxanthins; Eye Diseases; Female; Fruit; Humans; Lutein; Lycopene; Male; Neoplasms; Osteoporosis; Vegetables; Xanthophylls; Zeaxanthins

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

This meta-analysis aimed to investigate the effects of beta-carotene supplements alone on cancer prevention as reported by randomized controlled trials (RCTs). We searched PubMed, EMBASE, and CENTRAL. Among the 848 articles searched, 6 randomized controlled trials, including 40,544 total participants, 20,290 in beta-carotene supplement groups, and 20,254 in placebo groups, were included in the final analysis. In a meta-analysis of 6 RCTs, beta-carotene supplements had no preventive effect on either cancer incidence [relative risk (RR) = 1.08, 95% confidence interval (CI) = 0.99-1.18] or cancer mortality (RR = 1.00, 95% CI = 0.87-1.15). Similar findings were observed in both primary prevention trials and secondary prevention trials. Subgroup analyses by various factors revealed no preventive effect of beta-carotene supplementation on cancer prevention and that it significantly increased the risk of urothelial cancer, especially bladder cancer (RR = 1.52, 95% CI = 1.03-2.24) and marginally increased the risk of cancer among current smokers (RR = 1.07, 95% CI = 0.99-1.17). The current meta-analysis of RCTs indicated that there is no clinical evidence to support the overall primary or secondary preventive effect of beta-carotene supplements on cancer. The potential effects, either beneficial or harmful, of beta-carotene supplementation on cancer should not be overemphasized.

Topics: Anticarcinogenic Agents; Antioxidants; beta Carotene; Databases, Factual; Dietary Supplements; Dose-Response Relationship, Drug; Humans; Incidence; Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Smoking

The effect of beta-carotene supplementation on cancer incidence has been investigated in several randomized controlled trials. The objective was to review the effect of beta-carotene supplementation on cancer incidence in randomized trials by cancer site, beta-carotene supplementation characteristics and study population. Relevant trials were retrieved by searching PubMed (up to April 2009). Authors involved in selected studies were contacted for additional information. Thirteen publications reporting results from 9 randomized controlled trials were included. Overall, no effect of beta-carotene supplementation was observed on the incidence of all cancers combined (RR, 1.01; 95% CI, 0.98-1.04), pancreatic cancer (RR, 0.99; 95% CI, 0.73-1.36), colorectal cancer (RR, 0.96; 95% CI, 0.85-1.09), prostate cancer (RR, 0.99; 95% CI, 0.91-1.07), breast cancer (RR, 0.96; 95% CI, 0.85-1.10), melanoma (RR, 0.98; 95% CI, 0.65-1.46) and non melanoma skin cancer (RR, 0.99; 95% CI, 0.93-1.05). The incidence of lung and stomach cancers were significantly increased in individuals supplemented with beta-carotene at 20-30 mg day(-1) (RR, 1.16; 95% CI, 1.06-1.27 and RR, 1.34; 95% CI, 1.06-1.70), in smokers and asbestos workers (RR, 1.20; 95% CI, 1.07-1.34 and RR, 1.54; 95% CI, 1.08-2.19) compared to the placebo group. Beta-carotene supplementation has not been shown to have any beneficial effect on cancer prevention. Conversely, it was associated with increased risk not only of lung cancer but also of gastric cancer at doses of 20-30 mg day(-1), in smokers and asbestos workers. This study adds to the evidence that nutritional prevention of cancer through beta-carotene supplementation should not be recommended.

Topics: beta Carotene; Humans; Neoplasms; Randomized Controlled Trials as Topic; Risk Factors

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

"Second cancers" can be thought of in two general categories: (a) those occurring as a consequence of cancer treatment and (b) primary cancers that are thought to develop largely as a consequence of prior lifestyle habits (e.g., chronic smoking, drinking, sun exposures), genetic susceptibility, or interactions of the two. Because there has been limited work on chemoprevention of treatment-related secondary cancers, this minireview will focus on chemoprevention of second cancers with lifestyle/genetic origins.. Trials aimed at preventing second cancers in patients with tobacco-related cancers (head and neck, lung), skin cancers, breast cancer, and colorectal adenomatous polyps have been completed with some success. However, one finding that has emerged is that, across several cancer sites, subgroups are found with differential response to the chemopreventive agent. For example, smoking status, alcohol consumption, nutritional status, and host tumor characteristics seem to modify chemopreventive efficacy. Stratum-specific (subgroup) findings may occur by chance, requiring a need for supportive evidence from observational epidemiologic studies of the agent (where available), mechanistic studies, or results of other related trials.. Although chemoprevention of second cancers has been realized, it has become increasingly apparent that not all benefit equally. The finding of subgroup effects in completed trials results in the need to consider such subgroup effects in the design of future trials, by either restricting enrollment to particular subgroups (e.g., never or former smokers), or by increasing sample size requirements to allow for variation in response in subgroups in a statistically powerful way.

Topics: Alcohol Drinking; Anticarcinogenic Agents; beta Carotene; Breast Neoplasms; Clinical Trials as Topic; Female; Genetic Predisposition to Disease; Humans; Neoplasms; Neoplasms, Second Primary; Nutritional Status; Smoking

Based on extensive epidemiological observation, fruits and vegetables that are a rich source of carotenoids are thought to provide health benefits by decreasing the risk of various diseases, particularly certain cancers and eye diseases. The carotenoids that have been most studied in this regard are beta-carotene, lycopene, lutein and zeaxanthin. In part, the beneficial effects of carotenoids are thought to be due to their role as antioxidants. beta-Carotene may have added benefits due its ability to be converted to vitamin A. Additionally, lutein and zeaxanthin may be protective in eye disease because they absorb damaging blue light that enters the eye. Food sources of these compounds include a variety of fruits and vegetables, although the primary sources of lycopene are tomato and tomato products. Additionally, egg yolk is a highly bioavailable source of lutein and zeaxanthin. These carotenoids are available in supplement form. However, intervention trials with large doses of beta-carotene found an adverse effect on the incidence of lung cancer in smokers and workers exposed to asbestos. Until the efficacy and safety of taking supplements containing these nutrients can be determined, current dietary recommendations of diets high in fruits and vegetables are advised.

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Carotenoids; Diet; Eye Diseases; Free Radicals; Fruit; Humans; Lutein; Lycopene; Neoplasms; Vegetables; Xanthophylls; Zeaxanthins

Early studies demonstrating the ability of dietary carotenes to prevent infections have left open the possibility that the action of these carotenoids may be through their prior conversion to vitamin A. Subsequent studies to demonstrate the specific action of dietary carotenoids have used carotenoids without provitamin A activity such as lutein, canthaxanthin, lycopene and astaxanthin. In fact, these nonprovitamin A carotenoids were as active, and at times more active, than beta-carotene in enhancing cell-mediated and humoral immune response in animals and humans. Another approach to study the possible specific role of dietary carotenoids has used animals that are inefficient converters of carotenoids to vitamin A, for example the domestic cat. Results have similarly shown immuno-enhancement by nonprovitamin A carotenoids, based either on the relative activity or on the type of immune response affected compared to beta-carotene. Certain carotenoids, acting as antioxidants, can potentially reduce the toxic effects of reactive oxygen species (ROS). These ROS, and therefore carotenoids, have been implicated in the etiology of diseases such as cancer, cardiovascular and neurodegenerative diseases and aging. Recent studies on the role of carotenoids in gene regulation, apoptosis and angiogenesis have advanced our knowledge on the possible mechanism by which carotenoids regulate immune function and cancer.

Topics: Animals; beta Carotene; Carotenoids; Diet; Humans; Immunity; Neoplasms; Reactive Oxygen Species; Vitamin A

Beta-carotene and other carotenoids have been thought to have anti-cancer activity, either because of antioxidant activity or because of their ability to be converted to vitamin A. Nevertheless, two large scale intervention studies in humans using high doses of beta-carotene found that beta-carotene supplementation resulted in more lung cancer rather than less lung cancer among smoking and asbestos exposed populations. Studies conducted in the ferret have elucidated molecular mechanisms behind this observation, in that high-dose beta-carotene and smoke exposure in these animals leads to squamous metaplasia, a pre-cancerous lesion in the lung. High dose beta-carotene in the smoke exposed animals was found to give rise to a number of transient oxidative metabolites, which include P450 enzymes that result in the destruction of retinoic acid, and diminished retinoid signaling, and enhanced cell proliferation. In addition, eccentric cleavage beta-carotene metabolites facilitate the binding of smoke derived carcinogens to DNA. In other ferret studies low dose beta-carotene smoke exposure provided mild protection against squamous metaplasia. Thus, it appears that the explanation of the apparent paradoxical effects of beta-carotene on lung cancer is related to dose. The metabolism and breakdown of natural products should be thoroughly investigated in animal models before embarking on large scale intervention trials, particularly when using unusually high doses that greatly exceed normal dietary levels.

Topics: Animals; Asbestos; beta Carotene; Cytochrome P-450 Enzyme System; Dietary Supplements; Dose-Response Relationship, Drug; Ferrets; Humans; Lung; Lung Neoplasms; Neoplasms; Smoking; Tretinoin

Beta-carotene is a strong singlet oxygen quencher and antioxidant. Epidemiologic studies have implied that an above average intake of the carotenoid might reduce cancer risks. Earlier studies found that the carotenoid, when added to commercial closed-formula rodent diets, provided significant photoprotection against UV-carcinogenesis in mice. Clinical intervention trials found that beta-carotene supplementation evoked no change in incidence of nonmelanoma skin cancer. However, when smokers were supplemented with the carotenoid a significant increase in lung cancer resulted. Recently, employing a beta-carotene supplemented semi-defined diet, not only was no photoprotective effect found, but significant exacerbation of UV-carcinogenesis occurred. Earlier, a mechanism, based upon redox potential of interacting antioxidants, was proposed in which beta-carotene participated with vitamins E and C to efficiently repair oxy radicals and, thus, thought to provide photoprotection. In this schema, alpha-tocopherol would first intercept an oxy radical. In terminating the radical-propagating reaction, the tocopherol radical cation is formed which, in turn, is repaired by beta-carotene to form the carotenoid radical cation. This radical is repaired by ascorbic acid (vitamin C). As the carotenoid radical cation is a strongly oxidizing radical, unrepaired it could contribute to the exacerbating effect on UV-carcinogenesis. Thus, vitamin C levels could influence the levels of the pro-oxidant carotenoid radical cation. However, when hairless mice were fed beta-carotene supplemented semi-defined diet with varying levels of vitamin C (0-5590 mg kg(-1) diet) no effect on UV-carcinogenesis was observed. Lowering alpha-tocopherol levels did result in further increase of beta-carotene exacerbation, suggesting beta-carotene and alpha-tocopherol interaction. It was concluded that the non-injurious or protective effect of beta-carotene found in the closed-formula rations might depend on interaction with other dietary factors that are absent in the semi-defined diet. At present, beta-carotene use as a dietary supplement for photoprotection should be approached cautiously.

Topics: Animals; beta Carotene; Carcinogens; Dietary Supplements; Humans; Neoplasms; Radiation-Protective Agents; Smoking

Pro-oxidants, reactive species and free radicals, are toxic substances that can cause oxidative damage to major constituents of biological systems. In contradistinction, antioxidants are defined as any substance that significantly prevents the pro-oxidant-initiated oxidation of a substrate. Consequently, it was suggested that it might be possible to reduce free radical damage and thus cancer risk through 3 dietary changes: (1) caloric reduction, that is, lowering the level of free radical reactions arising in the course of normal metabolism; (2) minimize dietary components that increase the level of free radical reactions (eg, polyunsaturated fats); and (3) supplement the diet with one or more free radical reaction inhibitors (antioxidants). Lipid peroxidation exemplifies the type of chain reaction initiated by free radicals in (2) and (3). Both the phenolic antioxidant butylated hydroxytoluene (BHT) and the carotenoid beta-carotene can terminate such reactions and have been shown to influence ultraviolet (UV) carcinogenesis. However, there is a lack of correlation between physicochemical and patho-physiological responses in both instances. Whereas the influence on UV carcinogenesis of both antioxidants has been reported to diminish as the level of dietary fat decreases, pointing to the involvement of lipid peroxidative reactions, the mode of BHT's action in inhibiting UV carcinogenesis appears to be related to UV dose diminution through increased spectral absorbance of the stratum corneum. beta-carotene has no such effect and may actually exacerbate UV carcinogenesis under certain dietary conditions. This paradox points to the complex relationship between chemical mechanisms and biological mode of action of antioxidants. Recent clinical and experimental data suggest that antioxidant supplementation of the complex and intricately balanced natural antioxidant defense system as a cancer prevention strategy will demand extreme caution.

Topics: Animals; Antioxidants; beta Carotene; Delivery of Health Care, Integrated; Free Radicals; Humans; Lipid Peroxidation; Mice; Neoplasms; Oxidative Stress; Primary Prevention; Prognosis; Rats; Risk Factors; Skin Neoplasms; Ultraviolet Rays

Lutein and zeaxanthin are xanthophyll carotenoids found particularly in dark-green leafy vegetables and in egg yolks. They are widely distributed in tissues and are the principal carotenoids in the eye lens and macular region of the retina. Epidemiologic studies indicating an inverse relationship between xanthophyll intake or status and both cataract and age-related macular degeneration suggest these compounds can play a protective role in the eye. Some observational studies have also shown these xanthophylls may help reduce the risk of certain types of cancer, particularly those of the breast and lung. Emerging studies suggest as well a potential contribution of lutein and zeaxanthin to the prevention of heart disease and stroke. Even as the evidence for a role of lutein and zeaxanthin in disease prevention continues to evolve, particularly from human studies directed to their bioavailability, metabolism, and dose-response relationships with intermediary biomarkers and clinical outcomes, it is worth noting that recommendations to consume foods rich in xanthophylls are consistent with current dietary guidelines.

Topics: Aging; Anticarcinogenic Agents; beta Carotene; Cataract; Coronary Disease; Humans; Lutein; Macular Degeneration; Neoplasms; Primary Prevention; Stroke; Xanthophylls; Zeaxanthins

The carotenoid pigment astaxanthin has important applications in the nutraceutical, cosmetics, food and feed industries. Haematococcus pluvialis is the richest source of natural astaxanthin and is now cultivated at industrial scale. Astaxanthin is a strong coloring agent and a potent antioxidant - its strong antioxidant activity points to its potential to target several health conditions. This article covers the antioxidant, UV-light protection, anti-inflammatory and other properties of astaxanthin and its possible role in many human health problems. The research reviewed supports the assumption that protecting body tissues from oxidative damage with daily ingestion of natural astaxanthin might be a practical and beneficial strategy in health management.

Topics: Adjuvants, Immunologic; Administration, Oral; Antioxidants; Arteriosclerosis; beta Carotene; Biological Availability; Blindness; Chlorophyta; Diet Therapy; Humans; Inflammation; Macular Degeneration; Neoplasms; Neurodegenerative Diseases; Nutritional Physiological Phenomena; Photosensitivity Disorders; Radiation-Sensitizing Agents; Species Specificity; Xanthophylls

Lutein is one of the most widely found carotenoids distributed in fruits and vegetables frequently consumed. Its presence in human tissues is entirely of dietary origin. Distribution of lutein among tissues is similar to other carotenoids but, along with zeaxanthin, they are found selectively at the centre of the retina, being usually referred to as macular pigments. Lutein has no provitamin A activity in man but it displays biological activities that have attracted great attention in relation to human health. Epidemiological studies have shown inconsistent associations between high intake or serum levels of lutein and lower risk for developing cardiovascular disease, several types of cancer, cataracts and age-related maculopathy. Also, lutein supplementation has provided both null and positive results on different biomarkers of oxidative stress although it is effective in increasing macular pigment concentration and in improving visual function in some, but not all, subjects with different eye pathologies. Overall, data suggest that whereas serum levels of lutein have, at present, no predictive, diagnostic or prognostic value in clinical practice, its determination may be very helpful in assessing compliance and efficacy of intervention as well as potential toxicity. In addition, available evidence suggests that a serum lutein concentration between 0.6 and 1.05 micromol/l seems to be a safe, dietary achievable and desirable target potentially associated with beneficial impact on visual function and, possibly, on the development of other chronic diseases. The use of lutein as a biomarker of exposure in clinical practice may provide some rationale for assessing its relationship with human health as well as its potential use within the context of evidence-based medicine.

Topics: beta Carotene; Biological Availability; Biomarkers; Cardiovascular Diseases; Cataract; Diet; Dietary Supplements; Fruit; Humans; Lutein; Macular Degeneration; Neoplasms; Nutritional Physiological Phenomena; Retina; Vegetables; Xanthophylls; Zeaxanthins

Chemoprevention of cancer is reviewed from the viewpoints of action mechanisms and methodology of clinical trials in order to introduce promising agents discovered by in vitro and/or in vivo studies to applications in humans. The clinical trial procedure essentially follows the phase study which has been employed for chemotherapeutic drugs. Chemoprevention of bladder cancer, prostate cancer, gastric cancer, hepatocellular carcinoma, breast cancer, head and neck cancer, colorectal cancer and lung cancer is reviewed, mainly focusing on clinical trials. Previous clinical trials have shown the effectiveness of the following: polyprenoic acid (acyclic retinoid) for hepatocellular carcinoma; tamoxifen for breast cancer; retinoic acids for head and neck tumor; and aspirin, a COX-2 inhibitor, for colorectal cancer. Despite the advantageous effects of some of these agents, their toxic effects must also be of concern at the same time. For example, in a chemoprevention trial of lung cancer, beta-carotene was unexpectedly found to increase the risk of lung cancer among high-risk groups. It is also noted that large-scale clinical trials demand large research grants, which may not be affordable in Japan. Chemoprevention is still an emerging field of oncology where researchers in both basic and clinical sciences face great challenges.

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; beta Carotene; Breast Neoplasms; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Neoplasms; Prostatic Neoplasms; Tamoxifen; Tretinoin; Urinary Bladder Neoplasms

Randomized controlled trials are generally regarded as the gold standard of study designs to determine causality. The inclusion of a placebo group in these trials, when appropriate, is critical to access the efficacy of a drug or supplement. The placebo response itself has received some attention in the medical literature over the past fifty years. The recent increasing utilization of dietary supplements and herbal medications by patients makes it imperative to reevaluate the placebo response in conventional and alternative medicine. This article will review some of the negative and positive results from randomized trials utilizing dietary supplements (androstenedione, beta-carotene, CoQ10, garlic, soy, vitamin C and E...) for a number of non-urologic and urologic conditions, including cancer.

Topics: Androstenedione; Antioxidants; beta Carotene; Coenzymes; Complementary Therapies; Dehydroepiandrosterone; Garlic; Heart Failure; Hot Flashes; Humans; Libido; Neoplasms; Placebo Effect; Randomized Controlled Trials as Topic; Ubiquinone; Vitamin E

Cancer is the culmination of the chronic disease process, and can be attributed the interactions of environment and genes. An optimistic message for 35% cancer prevention may be in dietary constituents, food supply. Carotenoids are isoprenoid compounds synthesized in plants and microorganisms, but not in animals. Human tissue contains only a fraction of the total number of carotenoids(nearly 600 have been identified in nature) present in food supply such as fruit and vegetables. People with high intake of beta-Carotene have a reduced risk of cancer. This outcome seems to bear relation to the chemical to quench singlet oxygen and inhibit peroxyl free radical reaction. But the ATBC and CARET cancer prevention study found the increase in lung cancer incidence in smokers and asbestos. This adverse effect may be explained by beta-Carotene prooxidant when tobacco smoke exposure and oxidative stress occurs, and cellular DNA damage was further aggrevated. Phase I enzymes were induced. Cell transformation was enhanced.

Topics: Animals; Antineoplastic Agents; Antioxidants; beta Carotene; DNA Damage; Humans; Neoplasms

Recent evidence introduces the possibility that lutein and zeaxanthin may protect against the development of the two common eye diseases of aging, cataract and macular degeneration. This potential and the lack of other effective means to slow the progression of macular degeneration have fueled high public interest in the health benefits of lutein and zeaxanthin and the proliferation of supplements containing them on pharmacy shelves. An understanding of the biologic consequences of limiting or supplementing with these carotenoids is only beginning to emerge. Some epidemiologic evidence supports a role in eye disease and, to a lesser extent, cancer and cardiovascular disease. However, the overall body of evidence is insufficient to conclude that increasing levels of lutein and zeaxanthin, specifically, will confer an important health benefit. Future advances in scientific research are required to gain a better understanding of the biologic mechanisms of their possible role in preventing disease. Additional research is also required to understand the effect of their consumption, independent of other nutrients in fruits and vegetables, on human health. The newly advanced ability to measure levels of lutein and zeaxanthin in the retina in vivo creates a unique opportunity to contribute some of this needed evidence.

Topics: Aging; beta Carotene; Cataract; Chronic Disease; Fruit; Heart Diseases; Humans; Lutein; Macular Degeneration; Neoplasms; Stroke; Tissue Distribution; Vegetables; Xanthophylls; Zeaxanthins

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Carcinogens; Carotenoids; Diet; Dietary Supplements; Epidemiologic Research Design; Humans; Lycopene; Neoplasms; Randomized Controlled Trials as Topic; Structure-Activity Relationship

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: Antineoplastic Agents; Antioxidants; beta Carotene; Carotenoids; Clinical Trials as Topic; Epidemiologic Studies; Fruit; Humans; Neoplasms; Safety; Treatment Outcome; Vegetables

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

The growth of our knowledge of carotenoid biochemistry has opened new and divergent paths for research. The earliest role established for beta-carotene in animals was as a vitamin A precursor, a role it shares with several other pro-vitamin A carotenoids. Additional studies have continued to refine our understanding of this function. Because carotenoids are excellent scavengers of singlet oxygen and respectable scavengers for other reactive oxygen species, substantial work was done concerning their potential role as antioxidants. In an unexpected twist, the ability of radicals in cigarette smoke to degrade carotenoids might be responsible for the finding that high-dose dietary beta-carotene increased the incidence of lung cancer in smokers. A new role for the polar carotenoids lutein and zeaxanthin was identified, when those carotenoids were found to constitute the macular pigment (the yellow spot at the center of the human retina). Many different carotenoids can be metabolized to products with retinoid activity, which might affect gene expression and cell differentiation. The formation of retinoids from diverse carotenoids might account for a portion of their activities as anticancer agents. Studies of lycopene in prostate cancer prevention have been very promising, and clinical studies of lycopene are underway. Carotenoids have emerged as the best single tissue marker for a diet rich in fruits and vegetables, and measurements of plasma and tissue carotenoids have an important role in defining the optimal diets for humans.

Topics: Animals; Antioxidants; beta Carotene; Carotenoids; Fruit; Humans; Lung Neoplasms; Macular Degeneration; Neoplasms; Reactive Oxygen Species; Smoking; Vegetables; Vitamin A

The colorful group of compounds known as carotenoids are present in many plants, where they provide photoprotection and act as accessory pigments in photosynthesis. Many epidemiologic studies have shown strong associations between diets rich in carotenoids and a reduced incidence of many forms of cancer, and that finding led to the suggestion that the antioxidant properties of those compounds might help protect immune cells from oxidative damage, thus enhancing their ability to detect and eliminate tumor cells. Since the early 1980s, there have been reports supporting that hypothesis. However, more recently, after large prospective studies did not show protective effects of beta-carotene supplementation, more attention has been given to studies defining optimal levels of intake that can be achieved within a well-balanced diet. The latest intervention studies have suggested that, in well-nourished, healthy individuals, a moderate level of carotenoid supplementation is neither beneficial nor harmful. However, supplementation might be appropriate in undernourished or less healthy individuals, particularly if they are elderly. Future studies comparing supplements with real foodstuffs, combined with postgenomic technologies, will help define optimal intakes for different sectors of the population.

Topics: Antioxidants; beta Carotene; Carotenoids; Dietary Supplements; Humans; Immune System; Immunity; Neoplasms; Oxidation-Reduction; Oxidative Stress

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

Topics: beta Carotene; Cardiovascular Diseases; Carotenoids; Dietary Supplements; Gallic Acid; Humans; Macular Degeneration; Neoplasms

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

Observational studies indicate a lower incidence of chronic diseases, including various cancers and cardiovascular disease, related to higher intakes of carotenoid containing foods (fruits and vegetables). Beta-carotene, one of the large number of naturally occurring carotenoids, thus appears to actively participate in health. However, recent intervention trials indicate that beta-carotene supplements are not efficacious in the prevention of cardiovascular disease and major cancers occurring in well-nourished populations. In fact, supplemental beta-carotene appears to increase, rather than to reduce, lung cancer incidence and deaths from cardiovascular disease in current smokers and in asbestos exposed workers. In order to resolve these paradoxes, we need to better understand the underlying biology, identify interactions, develop mechanistic hypotheses and test them in clinical trials in humans. Until that time, we should confine any premature enthusiasm for chemopreventive supplementation.

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Chemoprevention; Diet; Dose-Response Relationship, Drug; Humans; Neoplasms

If one were to wait for the perfect set of experimental results before launching a multi-agent chemoprevention or large risk reduction study, the trial would never be launched. On the other hand, non-scientific considerations have led to the premature launching of at least three prominent studies (CARET, Carotene and Retinol Efficacy Trial; ATBC, Apha Tocopherol Beta Carotene; PCPT, Prostate Cancer Prevention Trial) and the much delayed start-up of another, BCPT, the Breast Cancer Prevention Trial. Strong epidemiologic data by itself should not be adequate to justify starting a large trial; experimental and/or clinical data should be developed. On the other hand fear of secondary adverse events that are of low incidence should not be enough to delay a trial if the overall health benefit could be high. The development of multiagent chemoprevention trials requires that each agent is active and additively or synergistically so in combination in preclinical models. Additionally, side effects of each agent should be non-overlapping and low to non-existent, preferably a feature determined in formal phase IIa and IIb trials. These principles will be discussed in the context of prior (CARET, ATBC) and ongoing (EUROSCAN, acetylcysteine/retinol), as well as proposed future trials (difluromethyl/sulindac).

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Clinical Protocols; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Neoplasms; Vitamin A

The objective of the article is to provide a concise overview of the conclusions of most important studies assessing the role of beta-carotene in the prevention of civilization diseases. Beta-carotene seemed to be a very promising agent in the prevention of civilization diseases in the early 1980s. However, several large-scale studies concluded that the preventive effects of beta-carotene may have been overestimated or that beta-carotene may even have harmful effects previously not anticipated. Current nutritional recommendations promote increased consumption of vegetables and fruits, but beta-carotene supplementation is not recommended.

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Humans; Neoplasms

Until recently, protein kinase GSK3 (glycogen synthase kinase 3), an essential component for cell-fate specification, had been considered a constitutively activated enzyme subject to developmentally regulated inhibition through hierarchical, linear signaling paths. Data from various systems now indicate more complex scenarios involving activating as well as inhibiting circuits, and the differential formation of multi-protein complexes that antagonistically affect GSK3 function.

Topics: Animals; beta Carotene; Calcium-Calmodulin-Dependent Protein Kinases; Cell Differentiation; Dictyostelium; Drosophila; Embryo, Nonmammalian; Embryonic Development; Glycogen Synthase Kinase 3; Glycogen Synthase Kinases; Humans; Mutation; Neoplasms

Aspirin and other NSAIDs are showing promise in the chemoprevention of colorectal cancer. Ongoing trials will eventually provide still lacking information about the optimum dose and treatment duration. NSAIDs may also help to lower the risk of cancer in other organs such as the oesophagus, and possibly breast, stomach, and lung. The chemoprevention by NSAIDs should be seen not as the sole method of prevention, but as an additional tool which will be accompanied by other approaches such as stopping smoking, limiting alcohol consumption, and eating more fruits and vegetables. The chemoprevention by NSAIDs needs also to be balanced against the risks of toxicity (particularly in the stomach) and the other beneficial effects such as prevention of cardiovascular morbidity and mortality. Some of the NSAID induced gastric ulceration and bleeding will most likely be avoided by adopting the use of cyclooxygenase-2 (COX-2) selective NSAIDs, which will selectively inhibit COX-2 while sparing COX-1.

Topics: Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; beta Carotene; Case-Control Studies; Child; Cohort Studies; Colorectal Neoplasms; Cricetinae; Cyclooxygenase Inhibitors; Esophageal Neoplasms; Humans; Neoplasms; Pancreatic Neoplasms; Prospective Studies; Prostaglandin Antagonists; Prostaglandins; Randomized Controlled Trials as Topic; Skin Neoplasms; Stomach Neoplasms; Time Factors

The three beta-carotene intervention trials: the Beta Carotene and Retinol Efficacy Trial (CARET), Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC), and Physician's Health Study (PHS) have all pointed to a lack of effect of synthetic beta-carotene in decreasing cardiovascular disease or cancer risk in well-nourished populations. The potential contribution of beta-carotene supplementation to increased risk of lung cancer in smokers has been raised as a significant concern. The safety of synthetic beta-carotene supplements and the role of isomeric forms of beta-carotene (synthetic all-trans versus "natural" cis-trans isomeric mixtures), in addition to the importance of the protective role of other carotenoids like lycopene and lutein, have become topics of debate in the scientific and medical communities. This review addresses the biochemistry and physiology of the cis versus trans isomers of beta-carotene as well as relevant studies comparing the absorption and storage of the synthetic versus natural forms of beta-carotene. In addition, the risk of potential pro-oxidant effects of synthetic beta-carotene supplementation in intervention trials is evaluated.

Topics: Absorption; beta Carotene; Drug Interactions; Humans; Isomerism; Neoplasms; Structure-Activity Relationship

The importance attributed to dietary change as a means of helping to achieve the major goals of the UK's public health policy as articulated in the Health of the Nation White paper (Department of Health, 1992) is less apparent in the most recent strategy document (Department of Health, 1999). Greater emphasis is given to amelioration of the socio-economic circumstances that are believed to contribute to inequalities in health. Better understanding of the elements of foods and diets which help protect health together with better evidence of effective dietary interventions are essential if the opportunities to use diet to reduce the burden of non-communicable diseases are to be realised. This is likely to need new research strategies that take advantage of emerging information from genomics and proteomics to produce evidence of safety, efficacy and applicability. Ethical exploitation of the rapid growth in interest in 'functional foods' by the food industry will require a level of investment in biomedical research unusual in the past.

Topics: Adult; beta Carotene; Cardiovascular Diseases; Diet; Female; Folic Acid; Food, Fortified; Health Policy; Humans; Male; Middle Aged; Neoplasms; Obesity; Pregnancy; Randomized Controlled Trials as Topic; Socioeconomic Factors; United Kingdom; Vitamins

This paper (and an extensive supplementary report) considers how far cancer/risk factor associations based on epidemiology have been confirmed by evidence from 226 studies involving interventions other than smoking. Many are small, uncontrolled, of unrepresentative populations, concern cancer markers not cancer, and may involve combinations of agents. Many agents suspected of causing cancer are untested by intervention trials. For seven of 16 agents tested (fibre, folic acid, low-fat diet, riboflavin, zinc, vitamin Bs, and vitamin D), the evidence is clearly inadequate to confirm or deny the epidemiology, while the evidence relating to calcium only concerns biomarkers. For other agents, the evidence relating to cancer itself is weak. In studies where cancer is the endpoint, only three effects have been replicated: (a) selenium supplementation and decreased liver cancer incidence, (b) treatment by the retinoid etretinate and reduced bladder tumours in susceptible individuals, and (c) beta-carotene supplementation and increased lung cancer incidence. Studies involving pre-cancerous conditions as the endpoint, which have a number of practical advantages, more frequently report benefits of intervention. Thus, oral pre-cancerous lesions can certainly be reduced by beta-carotene, vitamin A, and other retinoids, and possibly by vitamin E. It also seems that retinoids can reduce pre-cancerous cervix, skin and lung lesions, that vitamin C and the NSAID sulindac can reduce colonic polyps, and that sunscreens can reduce solar keratoses. Our findings clearly show that the great majority of causal relationships suggested by epidemiology have not been validated by intervention trials. This may be partly due to lack of suitable studies of adequate size or duration, or to using single dietary compounds as agents that are by themselves not responsible for the epidemiologically-observed associations between diet and cancer. However, this lack of validation must cause concern in view of the markedly conflicting evidence on beta-carotene and lung cancer between epidemiological and intervention studies. More intervention studies are needed, but in their absence, caution in interpreting epidemiological findings is warranted.

Topics: beta Carotene; Clinical Trials as Topic; Dietary Fiber; Dietary Supplements; Epidemiologic Methods; Etretinate; Humans; Liver Neoplasms; Lung Neoplasms; Neoplasms; Reproducibility of Results; Selenium; Urinary Bladder Neoplasms

Topics: beta Carotene; Diet; Humans; Immunity; Neoplasms

Carotenoids are natural pigments which are synthesized by plants and are responsible for the bright colors of various fruits and vegetables. There are several dozen carotenoids in the foods that we eat, and most of these carotenoids have antioxidant activity. Beta-carotene has been best studied since, in most countries it is the most common carotenoid in fruits and vegetables. However, in the U.S., lycopene from tomatoes now is consumed in approximately the same amount as beta-carotene. Antioxidants (including carotenoids) have been studied for their ability to prevent chronic disease. Beta-carotene and others carotenoids have antioxidant properties in vitro and in animal models. Mixtures of carotenoids or associations with others antioxidants (e.g. vitamin E) can increase their activity against free radicals. The use of animals models for studying carotenoids is limited since most of the animals do not absorb or metabolize carotenoids similarly to humans. Epidemiologic studies have shown an inverse relationship between presence of various cancers and dietary carotenoids or blood carotenoid levels. However, three out of four intervention trials using high dose beta-carotene supplements did not show protective effects against cancer or cardiovascular disease. Rather, the high risk population (smokers and asbestos workers) in these intervention trials showed an increase in cancer and angina cases. It appears that carotenoids (including beta-carotene) can promote health when taken at dietary levels, but may have adverse effects when taken in high dose by subjects who smoke or who have been exposed to asbestos. It will be the task of ongoing and future studies to define the populations that can benefit from carotenoids and to define the proper doses, lengths of treatment, and whether mixtures, rather than single carotenoids (e.g. beta-carotene) are more advantageous.

Topics: Animals; Antioxidants; beta Carotene; Biological Availability; Carotenoids; Clinical Trials as Topic; Fruit; Heart Diseases; Humans; Neoplasms; Vegetables

Oxidative damage to biological structures has been implicated in the pathophysiology of cardiovascular disease and cancer, the 2 most common causes of death in developed countries. This has stimulated interest in the possible role of natural antioxidant vitamins in preventing the development of these diseases. Epidemiological studies have offered support for the notion that high blood concentrations or dietary intake of antioxidant vitamins may have a protective effect. On the basis of these findings and powerful marketing strategies, many healthy members of the population are now voluntarily consuming antioxidant supplements. A number of long term, prospective, randomised, placebo-controlled trials examining the protective effect of antioxidant supplements have now been completed. Their results have been generally disappointing and have provided little evidence of efficacy. Of greater concern, they have unexpectedly raised concerns that antioxidants, notably betacarotene, might increase the rate of development of cancers in high risk individuals. For this reason regular consumption of antioxidant vitamins supplements cannot yet be advocated as a healthy lifestyle trait.

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Clinical Trials as Topic; Dietary Supplements; Humans; Neoplasms; Vitamins

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

Folate is an important cofactor in the transfer of one-carbon moieties and plays a key role in DNA synthesis, repair, and methylation. The role of folate has greatly evolved from the prevention of macrocytic anemia to the prevention of cardiovascular disease and neural tube defects. More recently, epidemiologic, animal, and clinical evidence suggests that folate may also play a role in cancer prevention. Two recently published large, prospective epidemiologic studies suggest that maintaining adequate levels of serum folate or moderately increasing folate intakes from dietary sources and vitamin supplements can significantly reduce the risk of pancreatic and breast cancer, respectively. This protective effect of folate appears to be operative in subjects at risk for developing these cancers, namely, male smokers for pancreatic cancer and women regularly consuming a moderate amount of alcohol for breast cancer. Because the expanding role of folate nutrition in cancer prevention has major public health implications, research is required to clearly elucidate the effect of folate on carcinogenesis.

Topics: Adolescent; Adult; Alcohol Drinking; Animals; beta Carotene; Breast Neoplasms; Case-Control Studies; Female; Folic Acid; Follow-Up Studies; Hematinics; Humans; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Mice; Middle Aged; Neoplasms; Odds Ratio; Pancreatic Neoplasms; Postmenopause; Premenopause; Prospective Studies; Randomized Controlled Trials as Topic; Rats; Risk; Risk Factors; Smoking; Time Factors; Vitamins

Many epidemiological studies have shown an association between diets rich in carotenoids and a reduced incidence of many forms of cancer, and it has been suggested that the antioxidant properties of these compounds are a causative factor. Attention has focused on the potential role of one specific carotenoid, beta-carotene, in preventing cancer, and numerous publications have described in vitro experiments and animal studies which suggest that not only can this carotenoid protect against the development of cancer, but also several other chronic diseases. Since the immune system plays a major role in cancer prevention, it has been suggested that beta-carotene may enhance immune cell function. Several human trials, using dietary beta-carotene supplementation with a wide range of intakes, have been undertaken to address this hypothesis. The general conclusion of these studies is that this compound can enhance cell-mediated immune responses, particularly in the elderly. The present article will review some of these human studies and, hopefully, complement the reviews of other authors associated with the present symposium, some of whom will also describe work in this area. Potential mechanisms for the effects of carotenoids on immune function will also be reviewed. Finally, possible reasons for the failure of three major prospective studies to demonstrate a beneficial effect of beta-carotene supplementation on lung cancer risk will be discussed.

Topics: Antioxidants; beta Carotene; Carotenoids; Humans; Immunity; Lymphocytes; Monocytes; Neoplasms; Oxidative Stress

Increased intake of fruits and vegetables seems to be one of the simplest means of decreasing the risk for cancer. Cancer-preventive effects of fruits and vegetables have been observed in epidemiological studies, which could not, however, distinguish the effects of the various ingredients. Antioxidant defence has been proposed as a mechanism of chemoprevention, although inconclusive results have been obtained. The results of randomized intervention trials have shown that beta-carotene supplements are of limited value and may even be deleterious. Vitamins are a good marker of the ingestion of fruits and vegetables, and vitamin E (alpha-tocopherol) is a lipid-soluble antioxidant which can scavenge free radicals. It has no significant effect on the risk for lung cancer of long-term smokers in an intervention trial, but it decreased both the incidence of and mortality from prostate cancer; however, there was a 50% increase in the occurrence of cerebral haemorrhage among the men given vitamin E. Aspirin and aspirin-like drugs appear to decrease the risk for intestinal tumours; the mechanism of action appears to involve diminishing prostaglandin production due to inhibition of cyclooxygenases. Dietary fibre has been linked to a reduced risk for colorectal cancer in many observational studies, but opposite findings were reported recently. In order to resolve these paradoxes, we need to understand better the underlying biology, develop mechanistic hypotheses and test them in clinical trials in humans. Until that time, we should confine any premature enthusiasm for chemopreventive micronutrient supplementation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; beta Carotene; Cyclooxygenase Inhibitors; Humans; Micronutrients; Neoplasms; Protective Agents; Reactive Oxygen Species

Topics: beta Carotene; Female; Fruit; Heart Diseases; Humans; Male; Neoplasms; Nutrition Policy; United States; Vegetables

Topics: beta Carotene; Carotenoids; Coronary Disease; Humans; Immunity; Male; Neoplasms

Epidemiological studies suggest that cancer risk is related to dietary intake of carotenoid-rich fruit and vegetables. Whether or not carotenoids are the active component has yet to be definitively proven, although some of these studies have shown that after elimination of obvious factors, such as fibre content, these foods still possess anticancer properties. On the other hand, two large intervention studies have shown that beta-carotene supplementation increases the risk of lung cancer in smokers. However, high doses of beta-carotene were used in these studies. Experimental work on animals and cells has shown that treatment with carotenoids can inhibit the development of cancer. Such studies have revealed a variety of mechanisms, in addition to antioxidant and conversion to vitamin A, including up-regulation of gap junctional communication, induction of detoxifying enzymes and inhibition of proliferation. Studies on tumour cells indicate that carotenoids can interfere with the growth of transformed cells, suggesting that they may be effective in the treatment of some cancers.

Topics: beta Carotene; Carotenoids; Diet; Female; Humans; Male; Neoplasms

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; beta Carotene; Carotenoids; Diet; Free Radical Scavengers; Humans; Lipid Peroxidation; Lipoproteins, LDL; Neoplasms

The basis for primary prevention of cancer is well-established, because significant causes of cancer are known. However, apart from reducing cigarette smoking, few easily applicable measures to decrease cancer incidence are available. Recently, there has been much interest in chemoprevention in cancer control, with several international bodies, including the International Union Against Cancer (UICC) and the European Union (EU), making important contributions. The results and relevance of these studies are discussed. Many of the problems associated with evaluating cancer prevention strategies generally apply particularly to chemoprevention, and these issues also are addressed.

Topics: Age Distribution; Anticarcinogenic Agents; beta Carotene; Colorectal Neoplasms; Europe; Female; Finland; Humans; Incidence; Lung Neoplasms; Male; Mortality; Neoplasms; Registries; Selenium; Stomach Neoplasms; Vitamin A; Vitamin E

This report reviews published epidemiologic research on the associations of vitamin and mineral supplementation with cancer risk. Although the literature on nutrition and cancer is vast, few reports to date have addressed supplemental nutrients directly (seven clinical trials, 16 cohort, and 36 case-control studies). These studies offer insight into effects of nutrients that are distinguishable from effects of other biologically active compounds in foods. Randomized clinical trials have not shown significant protective effects of beta-carotene, but have found protective effects of: alpha-tocopherol against prostate cancer; mixtures of retinol/zinc and beta-carotene/alpha-tocopherol/selenium against stomach cancer; and selenium against total, lung, and prostate cancers. Cohort studies provide little evidence that vitamin supplements are associated with cancer. Case-control studies have reported an inverse association between bladder cancer and vitamin C; oral/pharyngeal cancer and several supplemental vitamins; and several cancers and vitamin E. A randomized clinical trial, a cohort study, and a case-control study have all found inverse associations between colon cancer and vitamin E. Overall, there is modest evidence for protective effects of nutrients from supplements against several cancers. Future studies of supplement use and cancer appear warranted; however, methodologic problems that impair ability to assess supplement use and statistical modeling of the relation between cancer risk and supplement use need attention.

Topics: beta Carotene; Case-Control Studies; Cohort Studies; Dietary Supplements; Humans; Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Trace Elements; Vitamin E; Vitamins

The clinical development of cancer chemoprevention agents is similar to that of cytotoxic agents. On the basis of promising preclinical studies, agents with potential efficacy are introduced to the clinic as a phase I trial to study the dose-toxicity relationship of the agent and its human pharmacology. If doses projected to have biological activity have acceptable side effects, the agent proceeds to a phase II trial, which enrolls a larger number of participants and administers the agent for a longer time period (up to 5 years). Phase IIb trials test the effect of these agents on potential biomarkers of carcinogenesis to get some indication if the agent has activity. The phase II trial also pilots study design, mechanisms of recruitment, and adherence for future phase III trials. The phase III trial of a chemopreventive agent determines its effect on cancer incidence. Close attention is also paid to long-term side effects. The unique features of cancer prevention agents and their evaluation must be considered in this stepwise clinical evaluation. These features include (i) populations recruited to prevention trials are healthy; (ii) in this population there is a low tolerance for side effects; and (iii) the clinical end point of the trial, cancer, is statistically an uncommon event. The evaluation of beta-carotene and retinol as studied in the Carotene and Retinol Efficacy Trial (CARET) is used to illustrate this stepwise clinical development.

Topics: Anticarcinogenic Agents; beta Carotene; Chemoprevention; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cohort Studies; Humans; Neoplasms; Patient Selection; Smoking; Vitamin A

This symposium focused on the research which documents benefit and toxicity in beta-carotene supplementation. Reflecting on past and current studies, the panel of experts discussed: (1) the potential harm of a high intake of beta-carotene on selected populations, (2) biochemical antioxidant/prooxidant mechanisms of beta-carotene at the cellular level, (3) potential benefits of other carotenoids and antioxidants, and (4) future directions for research in beta-carotene and other antioxidants.

Topics: Animals; Antioxidants; beta Carotene; Carotenoids; Cell Line; Contraindications; Dietary Supplements; Epidemiologic Methods; Fatty Acids, Unsaturated; Fluorescent Dyes; Forecasting; Free Radicals; Humans; Lipid Peroxidation; Neoplasms; Oxidative Stress; Randomized Controlled Trials as Topic; Smoking; Structure-Activity Relationship

A growing body of literature exists regarding the effects of beta-carotene and other carotenoids on chronic diseases in humans. This article reviews and critically evaluates this literature and identifies areas for further research. This review is restricted to studies in humans, with a major emphasis on the most recent literature in the area of carotenoids and selected cancers. Effects of carotenoids on cardiovascular diseases, photosensitivity diseases, cataracts, and age-related macular degeneration are also discussed briefly. Numerous observational studies have found that people who ingest more carotenoids in their diets have a reduced risk of several chronic diseases. However, intervention trials of supplemental beta-carotene indicate that supplements are of little or no value in preventing cardiovascular disease and the major cancers occurring in well-nourished populations, and may actually increase, rather than reduce, lung cancer incidence in smokers. As a consequence of these findings, some of the ongoing trials of beta-carotene and disease prevention have been terminated or have dropped beta-carotene from their interventions. Researchers should now seek explanations for the apparently discordant findings of observational studies vs. intervention trials. The most pressing research issues include studies of interactions of carotenoids with themselves and with other phytochemicals and mechanistic studies of the actions of beta-carotene in lung carcinogenesis and cardiovascular disease. Paradoxically, the finding that lung carcinogenesis and cardiovascular disease can be enhanced by supplemental beta-carotene may ultimately lead to a clearer understanding of the role of diet in the etiology and prevention of these diseases. The conclusion that major public health benefits could be achieved by increasing consumption of carotenoid-rich fruits and vegetables still appears to stand; however, the pharmacological use of supplemental beta-carotene for the prevention of cardiovascular disease and lung cancer, particularly in smokers, can no longer be recommended.

Topics: beta Carotene; Cardiovascular Diseases; Carotenoids; Cataract; Humans; Macular Degeneration; Male; Neoplasms; Photosensitivity Disorders; Preventive Medicine

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 most effective means of avoiding the development of squamous cell carcinomas is the elimination of risk factors such as tobacco smoke and alcohol and of exposure to occupational and dietary carcinogens. In addition, chemoprevention by micronutrients such as beta-carotene may be promising. However, studies verifying such effects using cancer incidence or mortality as study endpoint are extremely costly of financial and manpower resources. Therefore, premalignant intermediate biomarkers such as histological lesions (dysplasias/leukoplakias/ polyps), genetic changes (DNA damage, mutations) or enzymatic changes (protein kinase C or ornithine decarboxylase activation) are increasingly being used as surrogate endpoints. Even though most preneoplastic biomarkers still need to be verified and shown to be linked to malignancy, their use in clusters may enhance their predictability. In human trials beta-carotene has reversed some lesions such as micronuclei, leukoplakias and dysplasias in the oral cavity, whereas other lesions, e.g. colorectal polyps (i.e. their recurrence after resection) have not been found to respond. But proliferation markers in the colon mucosa have been modified by beta-carotene. Preliminary findings are also available of a potential reduction of esophageal dysplasias in a high-risk Chinese population and of cervical dysplasias in a group of American women. The available beta-carotene data are sufficiently encouraging to justify continuation of trials using intermediate cancer markers.

Topics: beta Carotene; Biomarkers, Tumor; Carotenoids; Chemoprevention; Clinical Trials as Topic; Female; Humans; Male; Neoplasms

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: Anticarcinogenic Agents; beta Carotene; Chemoprevention; Double-Blind Method; Humans; Neoplasms; Placebos; Randomized Controlled Trials as Topic

Advances in diagnosis and treatment of cancer and cardiovascular disease as well as increased understanding of the mechanisms of the diseases have provided and will certainly continue to provide enormous benefit to affected individuals. At the same time, interventions that may prevent common cancers or atherosclerosis from developing in healthy people could, at least in theory, afford even greater benefits to society as a whole.

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Female; Humans; Male; Neoplasms; Randomized Controlled Trials as Topic

Topics: beta Carotene; Carotenoids; Fruit; Humans; Lung Neoplasms; Neoplasms; Smoking; Vegetables

OBJECTIVE AND CONCLUSIONS: This article gives an overview of observational and experimental epidemiological studies relating beta-carotene to risk of cancer and cardiovascular disease. Observational epidemiological studies have consistently shown that a diet rich in beta-carotene-rich fruits and vegetables or high blood levels of beta-carotene are associated with a reduced risk of cancer at a number of common sites, such as lung and stomach. For other cancer sites, such as prostate and breast, the observational evidence is not very consistent or absent altogether. For cardiovascular disease, observational studies are less numerous but do point to a protective effect of high beta-carotene intake. The associations from observational epidemiology may indeed be ascribed to beta-carotene, since a number of plausible preventive mechanisms have been demonstrated for cancer as well as cardiovascular disease. However, observational epidemiology cannot resolve the question whether other constituents from fruits and vegetables or other factors may explain the findings from the case-control and cohort studies. The results of intervention studies undertaken so far are disappointing and do not indicate a preventive potential for beta-carotene. Further intervention trials with longer follow-up may be needed to elucidate whether beta-carotene is protective against certain forms of cancer and against cardiovascular disease.

Topics: beta Carotene; Cardiovascular Diseases; Fruit; Humans; Neoplasms; Risk Factors; Vegetables

The hypothesis that antioxidant vitamins might reduce cardiovascular disease risk is based on a large body of both basic and human epidemiologic research. One of the most consistent findings in dietary research is that those who consume higher amounts of fruits and vegetables have lower rates of heart disease and stroke as well as cancer. Recent attention has focused on the antioxidant content of fruits and vegetables as a possible explanation for the apparent protective effects. Basic research provides a plausible mechanism by which antioxidants might reduce the risk of atherosclerosis. A large number of descriptive, case-control and cohort studies provide data suggesting that consumption of antioxidant vitamins is associated with reduced risks of cardiovascular disease. 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 cardiovascular disease but do not provide a definitive answer. Results from several large-scale randomized trials of antioxidant supplements are now available; however, results are not entirely consistent. The results of the major trials do not prove or disprove the value of antioxidant vitamins, nor do they incriminate them as harmful. They do, however, raise the possibility that some of the benefits from observational epidemiology may have been overestimated and that there may be some adverse effects. At this point randomized trial data are not yet sufficient to fully assess the risk-to-benefit ratios for antioxidant supplements. More reliable data should be forthcoming in the near future which will better define the role of antioxidants in the primary and secondary prevention of atherosclerotic disease as well as cancer.

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Humans; Neoplasms; Randomized Controlled Trials as Topic; Vitamins

Topics: Animals; Antioxidants; beta Carotene; Cardiovascular Diseases; Food, Formulated; Humans; Neoplasms; Reactive Oxygen Species

Cancer is currently regarded to be the phenotypic expression of an accumulation of heritable alterations in the regulators of cell growth and differentiation. Though detailed knowledge of the sequence and in vivo mechanistic effects of these alterations is rudimentary for most, if not all, cancers, their identification does offer the potential for classifying groups of individuals who are heterogeneous with respect to their cancer risks, into more nearly homogeneous subgroups. In this paper, we illustrate the value of using markers, which we define as any manifestation of cellular molecular diversity, to increase subgroup homogeneity. In the context of time-to-event data, we demonstrate for both somatic mutations (acquired p53 abnormalities in gastric mucosal cells) and inherited polymorphisms (polymorphisms in the phase 1 and 2 detoxifying enzymes) how knowledge regarding the population frequency of the marker the effect of the marker on the risk of cancer development, and/or the effect of the marker on response to therapy, can be used to plan and analyze such trials. Using as paradigms demographic features of the recently begun Shandong precancerous gastric lesion intervention trial, and the recently completed alpha-tocopherol beta-carotene (ATBC) lung cancer prevention study, we review the information, assumptions, and mathematical structure required for planning cancer prevention trials. We graphically demonstrate how informative markers make available strategies for selection, stratification, and optimal weighing, which, when properly implemented, increase the power of tests of effective cancer prevention agents.

Topics: Adult; Aged; beta Carotene; Biomarkers, Tumor; China; Clinical Trials as Topic; Cohort Studies; Finland; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Mutagenesis; Neoplasms; Polymorphism, Genetic; Research Design; Stomach Neoplasms; Vitamin E

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

In 1981 it was hypothesized that a high dietary intake of beta-carotene might reduce human cancer rates. Since then, several observational epidemiologic studies have addressed this topic. The results of both case-control and cohort studies show a remarkable consistency for the association of increased lung cancer risk with low amounts of dietary beta-carotene or low plasma beta-carotene concentrations. For stomach cancer, the evidence is also consistent, although the number of studies is more modest. For breast and prostate cancer, the studies indicate no consistent association of plasma or dietary beta-carotene and reduced cancer risk. For colorectal cancer, the effect will be moderate, if existent. For several other cancer sites, the numbers of cases in prospective studies are often small, implying that only strong associations can be detected. For some of these sites, results from retrospective studies are promising. The epidemiologic studies should be carefully interpreted because dietary habits may be misclassified and smoking may reduce plasma beta-carotene concentrations. Observational epidemiology cannot definitively resolve whether associations are indeed due to beta-carotene, or to other components of fruit and vegetables that are rich in beta-carotene. However, overall results are promising and several plausible cancer preventive mechanisms have been reported for beta-carotene. The ongoing human intervention studies will provide more answers regarding cancer prevention by beta-carotene but may need long follow-ups to be conclusive.

Topics: Antioxidants; beta Carotene; Carotenoids; Humans; Neoplasms

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 article reviews the current knowledge on the cancer-preventive potential of beta-carotene, a precursor of vitamin A, and plentiful in fruits and vegetables, which has been studied widely as a promising chemopreventive agent in reducing the risk of cancer in humans. Several retrospective and prospective epidemiological investigations have demonstrated that a diet rich in micronutrients such as vitamins, carotenoids and selenium, could prevent the arising, in 'high-risk' patients, of precancerous and neoplastic lesions of specific sites, particularly of the upper aerodigestive tract. Numerous in vitro expressions have been performed in order to verify the true role played by this agent on cell proliferation and differentiation; until now, findings have been very encouraging, uniformly showing the beta-carotene can affect carcinogenesis, particularly in early stages, through an antigenotoxic action. Antioxidant functions, immunomodulatory effects and control of intercellular messages via gap junctions are possible action mechanisms of the ability of beta-carotene to block the carcinogenetic process. In vivo animal studies partially confirm the results obtained in vitro showing that beta-carotene is able to reduce the induce cancer development; moreover, the association of the carotenoid with other microelements, such as vitamins E, C and glutathione often appears to be more effective than each agent used alone. From a clinical point of view, beta-carotene appears an 'ideal' agent to be used in chemoprevention trials in humans, although optimal doses and intake methods need to be better defined; its almost zero toxicity permits the long-term administration of the drug, a vital condition for its anti-cancer activity, with good patient compliance. Human intervention studies performed so far, both randomized and uncontrolled clinical trials, have showed positive findings in specific cancer sites such as oral cavity, head and neck and colon; less consistent or negative are results on skin, lung and oesophagus cancer. The ongoing studies will provide more answer on these issues. A definitive evaluation of the ability of beta-carotene to prevent cancer in human requires further controlled trials; studies on a larger spectrum of cancer sites and different stages of disease must be encouraged. In addition, further investigation on biomarkers related to cancer risk and cancer incidence are necessary, particularly focused on the measurements for genotoxic damage,

Topics: Animals; Antineoplastic Agents; beta Carotene; Carotenoids; Diet; Humans; Neoplasms; Neoplasms, Experimental; Risk Factors

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

Topics: Anticarcinogenic Agents; beta Carotene; Biomarkers, Tumor; Breast Neoplasms; Carotenoids; Clinical Trials as Topic; Female; Humans; Male; Minerals; Neoplasms; Selenium; Vitamin E; Vitamins

Evidence supports the potential role of beta-carotene in cancer prevention. Basic research has demonstrated that beta-carotene can trap organic free radicals and/or deactivate excited oxygen molecules which may have an anticancer effect by preventing tissue damage. Although observational epidemiologic studies are not entirely consistent, many show an inverse association between dietary intake or blood levels of beta-carotene and subsequent cancer risk. Two large-scale randomized trials of beta-carotene have been completed. A Finnish trial demonstrated no benefit of beta-carotene among middle-aged male smokers, with those assigned to this supplement in fact experiencing an increased risk of lung cancer. However, because of the long latency period for cancer, which may be a decade or more, the six-year duration of treatment in this trial may have been inadequate to detect an anticancer effect. A Chinese trial demonstrated a modest reduction in cancer mortality from a combined regimen of beta-carotene, vitamin E, and selenium. The effect of the individual agents could not be assessed, and because the trial was carried out among a nutritionally deficient population, its results may not have direct relevance to well-nourished individuals. Several additional large-scale trials of beta-carotene are ongoing. The Physicians' Health Study, which is testing beta-carotene among 22,071 US male physicians, will have an average duration of treatment of 12.5 years at its scheduled termination in late 1995. Data in women will be available from the Women's Health Study, which began in 1992, and will randomize approximately 40,000 US female health professionals.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anticarcinogenic Agents; Antioxidants; beta Carotene; Carotenoids; Female; Free Radical Scavengers; Humans; Male; Neoplasms; Randomized Controlled Trials as Topic; Risk Factors

Topics: Antineoplastic Agents; beta Carotene; Cardiovascular Diseases; Carotenoids; Cataract; Female; Free Radicals; Humans; Male; Neoplasms

Observational studies and randomized trials provide relevant and complementary information to a totality of evidence on which to base rational clinical decision making for patients and overall health policy for the general population. Observational studies are particularly useful for detecting moderate to large effects. The 15- to 20-fold greater risk of lung cancer among long term cigarette smokers was established by case-control and prospective cohort studies. The approximate 80% increased risk of coronary heart disease associated with current smoking also has been reliably demonstrated in observational studies. However, as the relative risk gets smaller, there is increasing concern that unmeasured or unknown confounding variables may account for all or part of any observed association. For these reasons, reliable inferences about interventions likely to confer small to moderate benefits will emerge only from randomized trials of sufficient sample size and duration of treatment and follow-up. Dietary variables have been postulated to account for as much as 35% of all human cancers. However, the hypothesized benefit of any specific dietary constituent, such as the antioxidant beta-carotene, is likely to be modest in size, on the order of a 20-30% reduction in risk. Therefore, although a large number of observational studies have demonstrated that individuals with higher dietary intakes or blood levels of beta-carotene have lower risks of cancer, only randomized trials can address this hypothesis definitively. Such trials, however, must be of sufficient duration to allow for the development of an anticancer effect. This may mean a decade or more based on the analogy with smoking cessation and decreased risks of lung cancer. Several ongoing large-scale trials are testing beta-carotene and other promising cancer chemoprevention agents, and their results will provide clear evidence on the balance of benefits and risks of these interventions.

Topics: beta Carotene; Carotenoids; Epidemiologic Methods; Humans; Neoplasms; Randomized Controlled Trials as Topic; Risk

In 1989, nearly 43% of deaths in the United States were due to some form of cardiovascular disease, and 23% were caused by cancer. Thus, two of every three people in this country die from either cardiovascular disease or cancer. Based on both experimental and epidemiological evidence, investigators believe that free radicals play a critical role in the development of both diseases. Low levels of antioxidants, which increases free radical activity, are clearly associated with an increased risk of these diseases. This link has led to the conclusion that use of antioxidant vitamin supplements to scavenge free radicals could potentially decrease the risks of cancer and cardiovascular disease. Results from numerous studies to date have been very promising, although a true protective or preventive causal relationship has not yet been established. Numerous primary and secondary intervention trials currently underway should more definitively assess the role of antioxidants in disease prevention. In the interim, many people feel the evidence is now strong enough to begin supplementation on their own. The pharmacist is in a position to advise patients on the safe and moderate use of antioxidants. The antioxidants discussed in this article are relatively non-toxic, with the exception of vitamin A. The possible benefits of vitamin A are better achieved with the use of beta-carotene. Megadose antioxidant supplementation does not appear to provide any additional benefit beyond what a more moderate supplement can provide and should therefore be discouraged. Taking a trace mineral with antioxidant potential is generally a waste of money, provided the patient is not initially deficient in the element.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antioxidants; Arthritis, Rheumatoid; beta Carotene; Cardiovascular Diseases; Carotenoids; Free Radicals; Humans; Neoplasms; Oxygen; Superoxides; Vitamin A; Vitamin E

Topics: Antioxidants; beta Carotene; Carotenoids; Clinical Trials as Topic; Diet; Female; Humans; Male; Neoplasms; Randomized Controlled Trials as Topic

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

Topics: Animals; Antioxidants; Artifacts; beta Carotene; Breast Neoplasms; Carotenoids; Case-Control Studies; Cohort Studies; Diet; Digestive System Neoplasms; Female; Genital Neoplasms, Female; Humans; Lung Neoplasms; Neoplasms; Neoplasms, Experimental; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Sampling Studies; Urogenital Neoplasms; Vitamin A; Vitamin E; Vitamins

Topics: beta Carotene; Carotenoids; Female; Humans; Male; Neoplasms; Retinoids; Tamoxifen

Topics: beta Carotene; Carotenoids; Clinical Trials as Topic; Diet; Esophageal Neoplasms; Fruit; Humans; Lung Neoplasms; Male; Neoplasms; Risk Factors; Stomach Neoplasms; Vegetables; Vitamins

Topics: Anticarcinogenic Agents; beta Carotene; Cardiovascular Diseases; Carotenoids; Cataract; Diet; Humans; Immune System; Neoplasms; Smoking; Vitamins

Carotenoid (CARs: beta-carotene BC and/or canthaxanthin CX) supplementation have been shown to be chemopreventive in animals, since 1980, against direct or indirect chemical carcinogenesis/photo-carcinogenesis of the skin, breast, stomach, salivary glands, colon-rectum, urinary bladder, and against transplanted tumors. This action could be either independent of or dependent on pro-vitamin A activity of BC. In vitro, both BC and CX proved to be antimutagenic and to have anti-malignant transformation properties in cell cultures. Preliminary interventions in humans with BC +/- CX prevented the onset of second primary tumors in lung, colon, urinary bladder, and head and neck. The powerful antioxidant properties of CARs, possibly associated with their retinoid potential, played a role in all the above observations, producing free-radical quenching and immunostimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antibody Formation; beta Carotene; Breast Diseases; Carotenoids; Humans; Lung Neoplasms; Neoplasms; Vitamin A

Cancer and cardiovascular disease are still the number one and two killer diseases in most developed countries. There is justified hope that beta-carotene will be proven efficacious in the prevention and/or delaying of the onset of these chronic diseases. Chronic disease prevention through better nutrition, judicious use of supplements and better lifestyles will assume added importance in the coming years as the proportion of the population over 65 years increases.

Topics: beta Carotene; Cardiovascular Diseases; Carotenoids; Humans; Neoplasms

Some 15 years ago there began to emerge a consensus among epidemiologists that diet might be responsible for 30-60% of cancers in the developed world, in the sense that it should be possible to reduce age-specific incidence rates by this amount by practicable dietary change. Within about 6 years it was also broadly agreed that the principal changes required to bring about this effect were a reduction in the consumption of fat; an increase in the consumption of fruit, green and yellow vegetables, dietary fiber, and some micronutrients; and possibly an improvement in the methods of food preservation. Very small effects, if any, were attributed to food additives and to the pollution of food by trace pesticides, which the public, who accepted much of the consensus advice, have increasingly regarded as important causes of risk. These past conclusions are reviewed in the light of increased knowledge of the etiology of cancer and the trends in its incidence. Contrary to common belief, the trends are broadly encouraging.

Topics: Age Factors; beta Carotene; Breast Neoplasms; Carotenoids; Colorectal Neoplasms; Dietary Fats; Dietary Fiber; Feeding Behavior; Humans; Incidence; Male; Neoplasms; Prostatic Neoplasms; Sex Factors

beta-Carotene protects against photooxidative dermatitis in porphyric humans and mice by quenching of photoactivated species. Other actions of beta-carotene in vivo are explained on the basis of its ability to scavenge free radicals in vitro. For example, in guinea pigs treated with CCl4, beta-carotene decreases pentane and ethane production. Epidemiological studies link low serum beta-carotene levels to elevated risk of lung and other cancers, and in intervention trials, beta-carotene diminishes preneoplastic lesions. However, the dose/response relationships are not well established, and antineoplastic mechanisms await clarification. Given a radical quenching mechanism, beta-carotene should block tumor promotion, but more typically the site of action is progression and an even later role in invasion has not been ruled out. Some antineoplastic actions of carotenoids (such as increased rejection of fibrosarcomas in mice) are attributed to immunoenhancement; others may reflect conversion to retinoids and subsequent gene regulation. Carotenoids other than beta-carotene may act at an earlier stage of carcinogenesis or be more effective as anticarcinogens at certain target sites. As scavengers of hydroxyl radicals, canthaxanthin and astaxanthin are more effective than beta-carotene. Canthaxanthin is sometimes more effective than beta-carotene in chemoprevention, but it is sometimes completely ineffective. Lycopene quenches singlet oxygen more than twice as effectively as beta-carotene. However, the antineoplastic actions of lycopene or astaxanthin remain untested. Explorations of the interactions of carotenoids with other nutrients are just beginning. Dietary fat increases absorption of carotene but decreases antineoplastic effectiveness. Research is hampered by technical problems, including the unavailability of rigorous controls, the instability of carotenoids, and the heterogeneous phase structure induced by hydrophobic compounds in aqueous media. Areas of current controversy and promising approaches for future research are identified.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Carotenoids; Free Radical Scavengers; Humans; Mutation; Neoplasms; Reactive Oxygen Species

Topics: beta Carotene; Carotenoids; Coronary Disease; Dietary Fats, Unsaturated; Humans; Malaysia; Neoplasms; Nutritional Physiological Phenomena; Palm Oil; Plant Oils

Case-control differences in prediagnostic serum levels of retinol, beta-carotene, vitamin E, and selenium are compared for 10 cancer sites in 10 study populations. For all four nutrients, the majority of results showed lower levels among persons who subsequently became cases than among controls. Low levels of beta-carotene were most likely to be associated with subsequent cancer, but there were marked differences by cancer site. The results indicate that it is unlikely that any of these serum micronutrients are associated with protection against carcinogenesis at all sites. A plea is made for greater emphasis on replication of results, for reporting findings for all sites no matter how small the number of cases may be, and for keeping constantly in mind the fact that observational associations are not necessarily causal in nature.

Topics: Antioxidants; beta Carotene; Carotenoids; Case-Control Studies; Female; Finland; Free Radicals; Humans; Japan; Male; Neoplasms; Selenium; Switzerland; United Kingdom; United States; Vitamin A; Vitamin E

Low intake of vegetables, fruits, and carotenoids is consistently associated with increased risk of lung cancer in both prospective and retrospective studies. In addition, low levels of beta-carotene in serum or plasma are consistently associated with the subsequent development of lung cancer. The simplest explanation is that beta-carotene is protective. Since retinol (preformed vitamin A) is not related in a similar manner to lung cancer risk, beta-carotene appears to function through a mechanism that does not require conversion into vitamin A. However, the importance of other carotenoids and other constituents of vegetables and fruit has not been adequately explored. Both prospective and retrospective studies suggest that vegetable and fruit intake may reduce the risk of cancers of the mouth, pharynx, larynx, esophagus, stomach, colon, rectum, bladder, and cervix. But because of fewer studies and less consistency among studies, the epidemiologic evidence is at present less persuasive than for lung cancer.

Topics: beta Carotene; Carotenoids; Case-Control Studies; Diet; Fruit; Humans; Neoplasms; Prospective Studies; Retrospective Studies; Risk Factors; Vegetables

Cancer chemoprevention research takes leads from epidemiologic and laboratory research and develops them through in vitro and in vivo preclinical research and initial human studies into randomized controlled clinical trials. At present, the chemoprevention program is sponsoring 21 human efficacy studies. These trials are testing the potential of agents (beta-carotene, folic acid, 13-cis retinoic acid, 4-hydroxyphenyl retinamide, vitamins C and E, and minerals) as inhibitors of a variety of cancers in humans (colon, lung, esophagus, cervix, bladder, and skin). Endpoints in these studies include overall incidence of cancer, incidence of specific cancers, rate of regression or progression of preneoplastic changes, and changes in cellular or biochemical parameters. Study participants include volunteers from the general population; populations at high risk for cancer because of occupation, lifestyle, or place of residence; persons with previously treated cancers; and persons with preneoplastic lesions. Study designs include single agent randomization, combination of agents and complete factorial designs.

Topics: Animals; Antioxidants; beta Carotene; Carotenoids; Clinical Trials as Topic; Disease Models, Animal; Humans; Lung Neoplasms; Neoplasms; Neoplasms, Experimental; Randomized Controlled Trials as Topic; Vitamin A

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

Cancer chemoprevention with beta-carotene (BC), canthaxanthin (CX) and retinol-BC is reported with respect to skin, breast, gastric, colon carcinogeneses induced by benzo(a)pyrene (BP) with or without ultra violet radiation (UV-A, UV-B), dimethylbenzathracene (DMBA) +/- UVB, P-UVA, N-methyl-N'-N-nitro-nitrosoguanidine (MNNG), dimethylhydrazine (DMH), and with respect to transplanted tumours. When animals were loaded with carotenoid supplementation one month before the carcinogenic induction (continued throughout the experiment), cancer prevention was observed up to 60-100%. The absence of provitamin A-activity in CX shows the carotenoid antioxidant property. Fifteen patients given BC + CX to prevent recurrences after radical removal of the primary neoplasia in organs like lung, breast, colon, urinary bladder, head and neck were studied in 1980-89. A longer than expected disease-free interval was preliminarily found. Supplementation of BC +/- retinol was also reported to prevent and treat oral leucoplakia. Supplementation and intermittent retinol administration was also tested in benign cyclical mastalgia with clear cut side effect free therapeutic results.

Topics: Animals; Antioxidants; beta Carotene; Breast; Canthaxanthin; Carotenoids; Drug Synergism; Humans; In Vitro Techniques; Neoplasms; Pain; Vitamin A

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

Topics: beta Carotene; Biomarkers; Carotenoids; Clinical Trials as Topic; Folic Acid; Health Planning; Humans; Neoplasms; Nutritional Physiological Phenomena; Vitamin A

A growing body of literature supports a possible role for beta-carotene in the prevention of human cancer. The most scientifically rigorous method for testing the hypothesis that beta-carotene has chemopreventive properties is with intervention trials, several of which are ongoing or soon to be initiated. Connecticut will be actively involved in three of these trials. This article reviews and critically evaluates the evidence supporting a role for beta-carotene in the prevention of human cancer, including animal studies, cell culture studies, epidemiologic studies, and intervention trials, and concludes with a brief description of chemoprevention research involving beta-carotene in Connecticut.

Topics: Animals; beta Carotene; Carotenoids; Diet; Humans; Neoplasms; Neoplasms, Experimental; Prospective Studies; Retrospective Studies

Topics: Animals; beta Carotene; Carotenoids; Diet; Follow-Up Studies; Humans; Neoplasms; Patient Compliance; Randomized Controlled Trials as Topic; Research Design; Vitamins

Topics: Animals; beta Carotene; Carotenoids; Gastrointestinal Neoplasms; Humans; Neoplasms; Nutritional Status; Vitamin A

Evidence from epidemiological dietary studies does not demonstrate an association between retinol intake and the risk of cancer in developed countries. There is, however, an inverse association between beta-carotene intake and the risk of cancer. Evidence from prospective biochemical epidemiological studies demonstrates that low serum retinol is associated with a high risk of cancer but only within about the first three years, indicating that it is probably a metabolic consequence of cancer. A low serum beta-carotene level is also associated with a high risk of cancer, but here the association persists for many years before the diagnosis of cancer, indicating that it probably also precedes its development. The dietary and serum studies are therefore consistent in showing a long-term inverse association between beta-carotene and the risk of cancer. This may be due to beta-carotene affecting the risk directly, or may reflect an indirect association with some other component of vegetables or with a non-vegetable component of diet that is itself related indirectly to vegetable consumption. Whatever the explanation, the association represents an interesting epidemiological clue to the relationship between diet and cancer.

Topics: beta Carotene; Carotenoids; Diet; Humans; Neoplasms; Prospective Studies; Retrospective Studies; Vitamin A

A current area of emphasis in cancer research is the determination of whether cancer can be prevented through the use of naturally occurring chemopreventive agents such as beta-carotene. A major area of concern in the design of long-term, large-scale population studies to ascertain the efficacy of such chemopreventive agents lies in the paucity of biological data on the activity of these agents in man. The studies described in this paper were performed to determine whether a series of short-term markers could be used in chemopreventive trials as indicators of the possible success of a chemopreventive regime. Three such markers are described. The first involves the measurement of genotoxic damage in the target tissues of carcinogen-exposed individuals by using the micronucleus test on exfoliated cells. This end point has been successfully used to demonstrate a reduction in carcinogen damage (micronuclei production) in the oral cavity of individuals in population groups at elevated risk for oral cancer (tobacco and betel quid users in the Philippines, snuff users in the Northwest Territories). The second marker involves the determination of DNA adducts in exfoliated cells of carcinogen-exposed individuals by the use of DNA postlabelling procedure. The final marker discussed involves a chemical determination of the levels of a chemopreventive agent in target tissues of individuals receiving a supplement in the diet. In this case, the example described is beta-carotene in exfoliated cells of carcinogen-exposed individuals. These three markers may be combined to determine whether a chemopreventive agent reaches a target tissue, affects DNA adduct formation, and prevents genotoxic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; beta Carotene; Carcinogens; Carotenoids; Cell Nucleus; DNA; Humans; Neoplasms; Precancerous Conditions; Retinoids

Topics: beta Carotene; Carotenoids; Clinical Trials as Topic; Diet; Dietary Fats; Dietary Fiber; Health Education; Humans; Life Style; National Institutes of Health (U.S.); Neoplasms; Prospective Studies; Research Design; Retinoids; Risk; Selenium; United States; Vitamins

This paper describes the development of the use of carotenoid pigments in the treatment of light-sensitive skin diseases. It also discusses the animal and human studies involved in determining whether carotenoids have any anti-cancer activity. The possible mechanisms of carotenoid photoprotective and anti-cancer actions are briefly discussed.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adolescent; Adult; Animals; Bacteria; Bacterial Physiological Phenomena; beta Carotene; Canthaxanthin; Carotenoids; Child; Child, Preschool; Diet; Humans; Infant; Light; Neoplasms; Neoplasms, Experimental; Photochemistry; Photosensitivity Disorders; Porphyrias; Protoporphyrins; Skin Diseases; Skin Neoplasms; Sunburn; Sunlight; Ultraviolet Rays

Topics: Animals; beta Carotene; Carotenoids; Clinical Trials as Topic; Humans; Neoplasms; Random Allocation; Retinoids

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

The discovery of some 40 specific factors that have caused cancer in humans has demonstrated conclusively that many fatal cancers are capable of being prevented. These known factors are responsible for less than half all fatal cancers in all countries and much less in most; but there is good evidence, derived from the variation in the incidence of cancer in different communities, in different countries, and at different times that in many countries it may be possible to prevent 80% of all cancers or even more. The practical problems facing each country are different. Not only are the types of cancer different that need most urgently to be prevented, but so are the social and economic conditions that permit or constrain the introduction of preventive measures. Well-understood measures are summarized and the prospects for others that are less established or as yet untried are discussed, including the use of low-tar cigarettes, dietary modification, and anti-viral vaccines.

Topics: Aflatoxins; Asbestos; beta Carotene; Carcinogens, Environmental; Carotenoids; Diet; Dietary Fiber; Hepatitis B; Humans; Iatrogenic Disease; Meat; Neoplasms; Neoplasms, Radiation-Induced; Nitrates; Occupational Diseases; Polycyclic Compounds; Selenium; Sexual Behavior; Smoking Prevention; Socioeconomic Factors; Vitamin A

Vitamin A, an unsaturated 20 carbon cyclic alcohol, subserves a number of important physiological functions. However, the biochemical basis of these roles is not well understood. The main sources of retinol are liver, egg yolk and milk fat. Several carotenoids show vitamin A activity. The conversion of beta-carotene to retinol is affected by copper-containing dioxygenase and zinc-containing retinene reductase. The efficiency of conversion varies in different species. The latter is defined in units as the daily dose required to produce a weight gain of 3 g/week in young rats between the 4th and 8th week. Retinol is unstable on exposure to light or heat, particularly in the presence of heavy metal ions and water. Much recent work has focused on the absorption, metabolism and excretion of vitamin A. It is now recognized that plasma vitamin A levels do not reflect the nutritional status except in severe hypo- and hypervitaminosis A. Also, many dietary factors may influence vitamin A metabolism. These basic and applied aspects of vitamin A are reviewed.

Topics: Absorption; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Artiodactyla; beta Carotene; Biological Availability; Biological Transport; Bone Development; Carotenoids; Chemical Phenomena; Chemistry; Drug Stability; Epithelium; Female; Fish Oils; Growth; Humans; Infections; Intestinal Absorption; Intracranial Pressure; Liver; Male; Neoplasms; Nutritional Requirements; Oxidation-Reduction; Reproduction; Silage; Structure-Activity Relationship; Tretinoin; Vision, Ocular; Vitamin A

Topics: Animals; Antineoplastic Agents; beta Carotene; Butylhydroxybutylnitrosamine; Carcinoma in Situ; Carcinoma, Papillary; Carotenoids; Cell Differentiation; Dose-Response Relationship, Drug; Epithelium; Fenretinide; Humans; Isotretinoin; Neoplasms; Neoplasms, Experimental; Tretinoin; Urinary Bladder Neoplasms; Vitamin A

In order to reduce the lipoprotein-related risk of coronary heart disease, nutritional recommendations have been formulated for use by communities prone to atherosclerosis and its complications. As such recommendations are potentially of widespread application they require careful scrutiny to assess possible risks as well as benefits. Epidemiological, clinical and experimental data concerning relationships between these nutrients and non-cardiovascular diseases are reviewed with emphasis on cancer mortality. Changes in intake of fats, including polyunsaturated fat, of cholesterol, carbohydrate, fibre, sodium and beta-carotene are discussed, and evidence of a relationship between serum cholesterol concentration and cancer is examined. These considerations offer reasonable reassurance as to the safety of recent dietary recommendations for the reduction of coronary heart disease.

Topics: beta Carotene; Carotenoids; Cholesterol, Dietary; Coronary Disease; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dose-Response Relationship, Drug; Fatty Acids, Unsaturated; Humans; Life Style; Lipids; Longitudinal Studies; Neoplasms; Risk

Both the provitamin beta-carotene and natural vitamin A and its derivatives (the retinoids) are being proposed as potential chemopreventive agents. The biochemistry and pharmacology of vitamin A suggest a number of mechanisms whereby carcinogenesis can be affected. Epidemiologic studies have consistently demonstrated an increased relative risk of cancer for people with low vitamin A intake or low-to-normal serum retinol values. Chemoprevention trials in humans are only now beginning. In the interim, daily consumption of vitamin-A-containing foods may be a "prescription" worth following.

Topics: beta Carotene; Carotenoids; Diet; Humans; Neoplasms; Prospective Studies; Retrospective Studies; Risk; Vitamin A

Retinol, the most biologically active form of vitamin A, might influence cancer-related biological pathways. However, results from observational studies of serum retinol and cancer risk have been mixed. We prospectively examined serum retinol and risk of overall and site-specific cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,104 men), conducted in 1985-1993, with follow-up through 2012. Serum retinol concentration was measured using reverse-phase high-performance liquid chromatography. Cox proportional hazards models estimated the association between baseline serum retinol quintile and overall and site-specific cancer risk in 10,789 cases. After multivariable adjustment, higher serum retinol was not associated with overall cancer risk (highest vs. lowest quintile: hazard ratio (HR) = 0.97, 95% confidence interval (CI): 0.91, 1.03; P for trend = 0.43). Higher retinol concentrations were, however, associated with increased risk of prostate cancer (highest vs. lowest quintile: HR = 1.28, 95% CI: 1.13, 1.45; P for trend < 0.0001) and lower risk of both liver and lung cancers (highest vs. lowest quintile: for liver, HR = 0.62, 95% CI: 0.42, 0.91; P for trend = 0.004; and for lung, HR = 0.80, 95% CI: 0.72, 0.88; P for trend < 0.0001). No associations with other cancers were observed. Understanding the mechanisms that underlie these associations might provide insight into the role of vitamin A in cancer etiology.

Topics: Aged; Alcohol Drinking; alpha-Tocopherol; beta Carotene; Body Weights and Measures; Cholesterol, HDL; Chromatography, High Pressure Liquid; Diet; Dietary Supplements; Double-Blind Method; Exercise; Finland; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Prostatic Neoplasms; Residence Characteristics; Smoking; Socioeconomic Factors

Several recent studies have suggested an increased cancer risk among patients with heart failure (HF). However, these studies are constrained by limited size and follow-up, lack of comprehensive data on other health attributes, and adjudicated cancer outcomes.. This study sought to determine whether HF is associated with cancer incidence and cancer-specific mortality.. The study assembled a cohort from the Physicians' Health Studies I and II, 2 randomized controlled trials of aspirin and vitamin supplements conducted from 1982 to 1995 and from 1997 to 2011, respectively, that included annual health evaluations and determination of cancer and HF diagnoses. In the primary analysis, the study excluded participants with cancer or HF at baseline and performed multivariable-adjusted Cox models to determine the relationship between HF and cancer, modeling HF as a time-varying exposure. In a complementary analysis, the study used the landmark method and identified cancer-free participants at 70 years of age, distinguishing between those with and without HF, and likewise performed Cox regression. Sensitivity analyses were performed at 65, 75, and 80 years of age.. Among 28,341 Physicians' Health Study participants, 1,420 developed HF. A total of 7,363 cancers developed during a median follow-up time of 19.9 years (25th to 75th percentile: 11.0 to 26.8 years). HF was not associated with cancer incidence in crude (hazard ratio: 0.92; 95% confidence interval: 0.80 to 1.08) or multivariable-adjusted analysis (hazard ratio: 1.05; 95% confidence interval: 0.86 to 1.29). No association was found between HF and site-specific cancer incidence or cancer-specific mortality after multivariable adjustment. Results were similar when using the landmark method at all landmark ages.. HF is not associated with an increased risk of cancer among male physicians.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; beta Carotene; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Forecasting; Heart Failure; Humans; Incidence; Male; Middle Aged; Neoplasms; Prognosis; Provitamins; Retrospective Studies; Risk Assessment; Risk Factors; Survival Rate; United States

Chocolate consumption has been shown to protect against various cardiovascular end points; however, little is known about the association between chocolate consumption and incident atrial fibrillation (AF). Therefore, we prospectively examined the association between chocolate consumption and incident AF in a cohort of 18,819 US male physicians. Chocolate consumption was ascertained from 1999 to 2002 through a self-administered food frequency questionnaire. Incident AF was ascertained through yearly follow-up questionnaires. Cox regression was used to estimate relative risks of AF. The average age at baseline was 66 years (±9.1). During a mean follow-up of 9.0 years (±3.0), 2,092 cases of AF occurred. Using <1 per month of chocolate consumption as the reference group, multivariable adjusted hazard ratios (95% confidence interval) for AF were 1.04 (0.93 to 1.18), 1.10 (0.96 to 1.25), 1.14 (0.99 to 1.31), and 1.05 (0.89 to 1.25) for chocolate intake of 1 to 3 per month and 1, 2 to 4, and ≥5 per week (p for trend 0.25), respectively. In a secondary analysis, there was no evidence of effect modification by adiposity (p interaction = 0.71) or age (p interaction = 0.26). In conclusion, our data did not support an association between chocolate consumption and risk of AF in US male physicians.

Topics: Aged; Aspirin; Atrial Fibrillation; beta Carotene; Cacao; Cohort Studies; Diet; Humans; Incidence; Male; Middle Aged; Neoplasms; Physicians; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; Sex Factors; Surveys and Questionnaires; Vitamins

Vitamin E inhibits lipid peroxidation in cell membranes, prevents oxidative damage to DNA by scavenging free radicals, and reduces carcinogen production. No study to our knowledge, however, has examined the association between genetic variants and response to long-term vitamin E supplementation. We conducted a genome-wide association study (GWAS) of common variants associated with circulating α-tocopherol concentrations following 3 y of controlled supplementation. The study population included 2112 middle-aged, male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort who received a trial supplementation of α-tocopherol (50 mg/d) and had fasting serum α-tocopherol concentrations measured after 3 y. Serum concentrations were log-transformed for statistical analysis and general linear models adjusted for age, BMI, serum total cholesterol, and cancer case status. Associations with serum response to α-tocopherol supplementation achieved genome-wide significance for 2 single nucleotide polymorphisms (SNP): rs964184 on 11q23.3 (P = 2.6 × 10(-12)) and rs2108622 on 19pter-p13.11 (P = 2.2 × 10(-7)), and approached genome-wide significance for one SNP, rs7834588 on 8q12.3 (P = 6.2 × 10(-7)). Combined, these SNP explain 3.4% of the residual variance in serum α-tocopherol concentrations during controlled vitamin E supplementation. A GWAS has identified 3 genetic variants at different loci that appear associated with serum concentrations after vitamin E supplementation in men. Identifying genetic variants that influence serum nutrient biochemical status (e.g., α-tocopherol) under supplementation conditions improves our understanding of the biological determinants of these nutritional exposures and their associations with cancer etiology.

Topics: Aged; alpha-Tocopherol; beta Carotene; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Neoplasms; Phenotype; Polymorphism, Single Nucleotide; Vitamins

To assess the association between dietary acrylamide intake and the risk of cancer among male smokers.. The study consisted of 27,111 male smokers, aged 50-69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire and a questionnaire on general background characteristics (including smoking habits) at baseline. Incident cases of cancer were identified through the national Finnish Cancer Registry.. During an average 10.2 year follow-up, 1,703 lung cancers, 799 prostate cancers, 365 urothelial cancers, 316 colorectal cancers, 224 stomach cancers, 192 pancreatic cancers, 184 renal cell cancers, and 175 lymphomas were diagnosed. Dietary acrylamide intake was positively associated with the risk of lung cancer; relative risk (RR) in the highest versus the lowest quintile in the multivariable-adjusted model was 1.18 ((95% confidence interval (CI) 1.01-1.38, p for trend 0.11). Other cancers were not associated with acrylamide intake.. High acrylamide intake is associated with increased risk of lung cancer but not with other cancers in male smokers.

Topics: Acrylamide; Aged; alpha-Tocopherol; beta Carotene; Diet; Dietary Supplements; Double-Blind Method; Eating; Finland; Follow-Up Studies; Food Contamination; Humans; Male; Middle Aged; Neoplasms; Placebos; Risk; Smoking

Interest in the dietary glycaemic index (GI) and glycaemic load (GL) as risk factors for chronic diseases has grown in recent years but findings have been controversial. We describe the compilation of the GI database for the cohort studies within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the main characteristics associating with diet GI and GL. The ATBC Study enrolled 29 133 male smokers aged 50-69 years who filled in a dietary history questionnaire upon study entry. The dietary data included 1097 foods, of which 195 foods with no or a negligible amount of available carbohydrates were assigned a GI of zero. Based on preset methodological criteria for published GI studies, the GI value of a similar food was available for 130 foods, and the GI of related food was assigned to 360 foods. The GI values of these foods served in the GI calculation of 412 composite foods. The median diet GI among the ATBC Study participants was 67.3 (interquartile range 64.8-70.0), and the median diet GL was 175 (interquartile range 158-192). The intakes of carbohydrates, protein and fat decreased, and the intake of fibre increased, with increasing GI. The GL showed a positive correlation with intakes of carbohydrates and dietary fibre and a negative correlation with intakes of protein and fat. The GI studies available that fulfilled the minimum methodological requirements cover a sufficient amount of foods to form a meaningful GI database for epidemiological study. This, however, requires the availability of GI values for relevant local carbohydrate-containing foods.

Topics: Aged; alpha-Tocopherol; beta Carotene; Blood Glucose; Databases, Factual; Dietary Fiber; Double-Blind Method; Energy Intake; Finland; Food Analysis; Glycemic Index; Humans; Male; Middle Aged; Motor Activity; Neoplasms

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

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

To test whether beta carotene supplementation affects the incidence of age-related maculopathy (ARM) in a large-scale randomized trial.. Randomized, double-masked, placebo-controlled trial among 22 071 apparently healthy US male physicians aged 40 to 84 years. Participants were randomly assigned to receive beta carotene (50 mg every other day) or placebo. Main Outcome Measure Incident ARM responsible for a reduction in best-corrected visual acuity to 20/30 or worse.. After 12 years of treatment and follow-up, there were 162 cases of ARM in the beta carotene group vs 170 cases in the placebo group (relative risk [RR], 0.96; 95% confidence interval [CI], 0.78-1.20). The results were similar for the secondary end points of ARM with or without vision loss (275 vs 274 cases; RR, 1.01; 95% CI, 0.86-1.20) and advanced ARM (63 vs 66 cases; RR, 0.97; 95% CI, 0.69-1.37).. These randomized data relative to 12 years of treatment among a large population of apparently healthy men indicate that beta carotene supplementation has no beneficial or harmful effect on the incidence of ARM. Long-term supplemental use of beta carotene neither decreases nor increases the risk of ARM.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; beta Carotene; Cardiovascular Diseases; Double-Blind Method; Humans; Incidence; Macular Degeneration; Male; Middle Aged; Neoplasms; Physicians; United States; Visual Acuity; Vitamins

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

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

We evaluated the accuracy and time to reporting of cancer diagnoses obtained through the Finnish Cancer Registry (FCR) for the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study in 1985-1997. In the ATBC Study suspect neoplasms were centrally reviewed through medical records and pathology specimens. The FCR data were compared against the reviewed data for 3600 cancers of eight sites. For most sites, 95% of the cases were reported to the FCR within 0.9 years with longer delays for lung and pancreatic cancers. Ninety-six percent of all FCR cases received the same primary site diagnosis in the ATBC review, and in 1.4% no malignancy was found. Conversely, 97% of cancers ascertained in the ATBC review had the same primary site in the FCR and 0.8% were unknown to the Registry. The accuracy of the FCR data is high but the delay in case notification should be considered in epidemiological studies.

Topics: beta Carotene; Cohort Studies; Finland; Follow-Up Studies; Humans; Medical Records; Neoplasms; Registries; Reproducibility of Results; Risk Factors; Time Factors; Vitamin E

In a nested case-control study of 513 women with cancer; 130 with cardiovascular disease and equal numbers of controls, we found no effect of randomised beta-carotene on risk of cancer or cardiovascular disease within any quartile of baseline plasma beta-carotene, nor was there a trend across quartiles (P for trend 0.15 and 0.62, respectively).

Topics: Aged; Antioxidants; beta Carotene; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Incidence; Middle Aged; Neoplasms; Women's Health

Pancreatic cancer is among the most fatal cancers worldwide and one for which few preventable risk factors have been established. Gastric carriage of Helicobacter pylori, particularly cytotoxin-associated gene-A-positive (CagA+) strains, is known to be a risk factor for peptic ulcer disease and gastric cancer and may have a similar etiologic relationship with pancreatic cancer.. We investigated the association of H. pylori carriage and exocrine pancreatic cancer in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29 133 male Finnish smokers aged 50-69 years at baseline. Case subjects (n = 121) were matched on date of baseline serum collection, study center, age, trial intervention, and completion of the dietary questionnaire to 226 control subjects who were alive at the time the matching case subject was diagnosed and who remained free of cancer, during up to 10 years of follow-up. Levels of immunoglobulin G antibodies to H. pylori whole-cell and CagA+ antigens from stored baseline serum were measured by enzyme-linked immunosorbent assay. Smoking-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression. Statistical tests were two-sided.. Seroprevalence of H. pylori was 82% and 73% among case and control subjects, respectively. Compared with seronegative subjects, those with H. pylori or CagA+ strains were at statistically significantly elevated risk of pancreatic cancer (OR = 1.87 [95% CI = 1.05 to 3.34]; OR = 2.01 [95% CI = 1.09 to 3.70], respectively).. Our findings support a possible role for H. pylori carriage in the development of exocrine pancreatic cancer.

Topics: Aged; Alcohol Drinking; Antibodies, Bacterial; Anticarcinogenic Agents; beta Carotene; Coffee; Cohort Studies; Double-Blind Method; Energy Intake; Finland; Follow-Up Studies; Helicobacter pylori; Humans; Male; Middle Aged; Neoplasms; Pancreatic Neoplasms; Reference Values; Risk Factors; Smoking; Time Factors; Vitamin E

To examine the development of age-related maculopathy (ARM) in a large-scale trial of low-dose aspirin treatment.. The Physicians' Health Study I was a randomized, double-masked, placebo-controlled trial of low-dose aspirin (325 mg every other day) and beta carotene (50 mg every other day) in the prevention of cardiovascular disease and cancer conducted among 22 071 US male physicians aged 40 to 84 years in 1982. A total of 21 216 participants did not report ARM at baseline, were followed up for at least 7 years, and are included in this analysis.. Total ARM, defined as a self-report confirmed by medical record evidence of an initial diagnosis subsequent to randomization, and ARM with vision loss, defined as total ARM but with vision loss to 20/30 or worse attributable to ARM.. Early termination of the randomized aspirin component of the Physicians' Health Study I, after an average of 60.2 months of treatment and follow-up due to a statistically extreme 44% reduced risk of first myocardial infarction, resulted in a far lower number of incident cases of ARM during the aspirin treatment period than would have accrued without early termination. Thus, during an average of 60.2 months of follow-up, a total of 117 cases of ARM were confirmed, including 57 cases responsible for vision loss to 20/30 or worse. There were 51 cases of ARM in the aspirin group and 66 in the placebo group (relative risk, 0.77; 95% confidence interval, 0.54-1.11). For ARM with vision loss, there were 25 cases in the aspirin group and 32 in the placebo group (relative risk, 0.78; 95% confidence interval, 0.46-1.32).. These randomized trial data tend to exclude any large beneficial effect of 5 years of low-dose aspirin treatment on ARM. However, a smaller, but potentially important, beneficial effect cannot be ruled out and would require testing in randomized trials of adequate size and duration.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Cardiovascular Diseases; Double-Blind Method; Follow-Up Studies; Humans; Macular Degeneration; Male; Middle Aged; Neoplasms; Physicians; Platelet Aggregation Inhibitors; Risk Factors; United States

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

An inverse association between moderate alcohol consumption and coronary heart disease (CHD) has been observed in several epidemiological studies. To assess whether a similar association exists among diabetics, we examined the relation between light to moderate alcohol consumption and CHD in men with and without diabetes mellitus in a prospective cohort study.. A total of 87 938 US physicians (2790 with diagnosed diabetes mellitus) who were invited to participate in the Physicians' Health Study and were free of myocardial infarction, stroke, cancer, or liver disease at baseline were followed for an average of 5.5 years for death with CHD as the underlying cause. During 480 876 person-years of follow-up, 850 deaths caused by CHD were documented: 717 deaths among nondiabetic men and 133 deaths among diabetic men. Among men without diabetes at baseline, the relative risk estimates for those reporting rarely/never, monthly, weekly, and daily alcohol consumption were 1.00 (referent), 1.02, 0. 82, and 0.61 (95% CI 0.49 to 0.78; P for trend <0.0001) after adjustment for age, aspirin use, smoking, physical activity, body mass index, and history of angina, hypertension, and high cholesterol. Among men with diabetes at baseline, the relative risk estimates were 1.00 (referent), 1.11, 0.67, and 0.42 (95% CI 0.23 to 0.77; P for trend=0.0019).. These results suggest that light to moderate alcohol consumption is associated with similar risk reductions in CHD among diabetic and nondiabetic men.

Topics: Alcohol Drinking; Aspirin; beta Carotene; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus; Double-Blind Method; Humans; Hypercholesterolemia; Hypertension; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Neoplasms; Physicians; Platelet Aggregation Inhibitors; Risk Factors

The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics.. Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models.. 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9-1.0); prostate (RR = 1.0, 95% CI = 0.9-1.1); colon (RR = 0.9, 95% CI = 0.7-1.2); or lung (RR = 0.9, 95% CI = 0.7-1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7-1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8-1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7-1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6-1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3-0.8).. The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Body Mass Index; Cardiovascular Diseases; Colonic Neoplasms; Double-Blind Method; Humans; Incidence; Life Style; Lung Neoplasms; Male; Middle Aged; Neoplasms; Physicians; Prostatic Neoplasms; Risk Factors; United States

In observational studies, individuals with high intakes of fruits and vegetables containing beta-carotene experience lower risks of developing cancer. However, the few randomized trials of beta-carotene supplementation show no overall benefits; some even suggest harm. This trial was designed to test the effects of beta-carotene supplementation in women.. The Women's Health Study is a randomized, double-blind, placebo-controlled trial originally testing aspirin, vitamin E, and beta-carotene in the prevention of cancer and cardiovascular disease among 39 876 women aged 45 years or older. The beta-carotene component was terminated early after a median treatment duration of 2.1 years (range = 0.00-2. 72 years). Statistical tests were two-sided.. Among women randomly assigned to receive beta-carotene (50 mg on alternate days; n = 19 939) or placebo (n =19 937), there were no statistically significant differences in incidence of cancer, cardiovascular disease, or total mortality after a median of 4.1 years (2.1 years' treatment plus another 2.0 years' follow-up). There were 378 cancers in the beta-carotene group and 369 cancers in the placebo group (relative risk [RR] = 1.03; 95% confidence interval [CI] = 0.89-1. 18). There were no statistically significant differences for any site-specific cancer or during years 1 and 2 combined and years 3 and up combined. For cardiovascular disease, there were no statistically significant differences for myocardial infarction (42 in the beta-carotene group versus 50 in the placebo group), stroke (61 versus 43), deaths from cardiovascular causes (14 versus 12), or the combined end point of these three events (116 versus 102; among women with more than one event, only the first was counted). Deaths from any cause were similar in the two groups (59 versus 55). Among smokers at baseline (13% of all women), there were no statistically significant differences in overall incidence of cancer (RR = 1.11; 95% CI = 0.78-1.58) or cardiovascular disease (RR = 1.01; 95% CI = 0. 62-1.63).. Among apparently healthy women, there was no benefit or harm from beta-carotene supplementation for a limited period on the incidence of cancer and of cardiovascular disease.

Topics: Aged; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Female; Health Personnel; Humans; Incidence; Middle Aged; Neoplasms; Risk; United States; Women's Health

5alpha-Reductase type 2, the predominant prostatic isozyme of this protein, converts testosterone to dihydrotestosterone. It has been hypothesized that individuals with greater 5alpha-reductase activity are at increased risk for prostate cancer (CaP). A single nucleotide polymorphism of the 5alpha-reductase type 2 gene (SRD5A2) gives rise to a substitution of leucine (leu) for valine (val) at codon 89 (V89L), the presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect of this polymorphism on the risk of prostate cancer in a prospective, nested, case-control design within the Physicians' Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasma AAG levels available, there was no significant association between AAG levels and V89L genotype. We also detected no significant association between risk for CaP and genotype [odds ratio: val/val = 1.0 (reference), leu/val = 0.96 (95% confidence interval, 0.76-1.20), and leu/ leu = 0.84 (95% confidence interval, 0.57-1.24)]. These data do not support a moderate to large effect of the SRD5A2 V89L polymorphism on plasma AAG levels or CaP risk in this predominantly Caucasian cohort, although a small effect cannot be completely excluded.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Anticarcinogenic Agents; Aspirin; beta Carotene; Boston; Double-Blind Method; Heart Diseases; Humans; Isoenzymes; Leucine; Male; Middle Aged; Neoplasms; Polymorphism, Genetic; Prostatic Neoplasms; Risk Factors; Valine; White People

The number of bleomycin-induced chromosomal breaks in cultured peripheral blood lymphocytes has been proposed as a measure of the sensitivity of an individual to carcinogens. Although "mutagen sensitivity" (clastogenicity) may be a useful biomarker for the identification of individuals at high risk for DNA damage, there is some uncertainty whether the results of this assay can be modified by environmental factors, such as diet. We designed an intervention study to determine whether micronutrient supplementation with beta-carotene and alpha-tocopherol influenced the mutagenicity score among 22 healthy volunteers. This intervention study followed a double-blind, randomized, cross-over design. Chromatid breaks ranged from 0.30 to 2.30 per cell and were uncorrelated with plasma beta-carotene (r = -0.07; P = 0.50) and a-tocopherol (r = -0.01; P = 0.92) levels, after accounting for the time of the measurement. The average number of breaks per cell was similar (P for difference in means = 0.90) among subjects during periods of vitamin supplementation (mean = 0.87 breaks per cell) and placebo (mean = 0.86 breaks per cell), averaged over groups and after adjustment for baseline breaks. Substantial within-person variation may indicate some imprecision in the mutagen sensitivity assessment. Our results suggest that mutagen sensitivity is not affected by plasma levels of beta-carotene or alpha-tocopherol. Although mutagen sensitivity does not appear to be modified by changes in plasma levels of two common antioxidant vitamins, it may be useful for the identification of high-risk individuals for participation in large intervention studies with cancer outcomes.

Topics: Adult; beta Carotene; Bleomycin; Chromosome Breakage; Cross-Over Studies; Diet; Female; Humans; Lymphocytes; Male; Mutagenicity Tests; Mutagens; Neoplasms; Predictive Value of Tests; 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

Antioxidants protect the body against cellular oxidative damage and thus some of the adverse effects induced by cisplatin and other cytostatic drugs.. The effect of cisplatin-combination chemotherapy on concentrations of plasma antioxidants was studied in 36 cancer patients, including osteosarcoma and testicular carcinoma patients.. Eight to 15 days after the start of each cytostatic drug infusion concentrations of various plasma antioxidants were measured and compared to pretreatment values: vitamin C and E, uric acid and ceruloplasmin levels fell significantly (P < 0.01-0.005) and returned to baseline levels before the start of the next chemotherapy cycle. Levels of the antioxidants bilirubin albumin and the ratio vitamin E/cholesterol + triglycerides measured three weeks after the start of chemotherapy significantly decreased compared to pretreatment levels and remained low thereafter (P < 0.001-0.002). Dietary intake of antioxidants and anthropometric measurements, evaluated in 14 patients did not change during the whole treatment period.. Cisplatin-combination chemotherapy induces a fall in plasma antioxidant levels, that may reflect a failure of the antioxidant defense mechanism against oxidative damage induced by commonly used anticancer drugs. This probably results from consumption of antioxidants caused by chemotherapy induced-oxidative stress as well as renal loss of water-soluble, small molecular weight antioxidants such as uric acid.

Topics: Adolescent; Adult; Aged; Anthropometry; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; beta Carotene; Ceruloplasmin; Cisplatin; Copper; Diet; Female; Glomerular Filtration Rate; Hearing Loss, Sensorineural; Humans; Kidney; Male; Middle Aged; Neoplasms; Oxidative Stress; Vitamins

Moderate alcohol consumption decreases the risk of coronary heart disease, but its relation to peripheral arterial disease (PAD) is uncertain.. In the Physicians' Health Study, a randomized trial of the use of aspirin and beta-carotene in 22071 apparently healthy men, we documented 433 incident cases of PAD during 11 years of follow-up. After we controlled for age and treatment assignment, daily drinkers (> or = 7 drinks per week) had a relative risk (RR) of PAD of 0.92 (95% confidence interval, 0.72 to 1.17) compared with the reference group (< 1 drink per week). After additional control for smoking, however, the RR was 0.68 (0.52 to 0.89). Further control for exercise, diabetes mellitus, and parental history of myocardial infarction revealed an RR of 0.74 (0.57 to 0.97).. Moderate alcohol consumption appears to decrease the risk of PAD in apparently healthy men.

Topics: Adult; Alcohol Drinking; Arteries; Aspirin; beta Carotene; Cardiovascular Diseases; Double-Blind Method; Humans; Incidence; Male; Middle Aged; Neoplasms; Physicians; Prospective Studies; Risk Factors; United States; Vascular Diseases

We examined the primary preventive effect of vitamin E (alpha-tocopherol) and beta-carotene supplementation on intermittent claudication. The subjects--participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study--were male smokers aged 50 to 69 years who were randomly assigned to receive 50 mg of alpha-tocopherol daily, 20 mg of beta-carotene daily, both, or placebo. At baseline, there were 26 289 men with no history or symptoms of intermittent claudication. The Rose questionnaire on intermittent claudication was administered annually to discover incident cases. We observed 2704 cases of first occurrence of typical intermittent claudication during a median follow-up time of 4.0 years. Compared with placebo, the adjusted relative risk for typical intermittent claudication among those who received alpha-tocopherol only was 1.11 (95% confidence interval, 1.00-1.24); among those who received alpha-tocopherol and beta-carotene, 1.02 (0.91-1.13); and among those who received beta-carotene only, 1.02 (0.92-1.14). When we compared the alpha-tocopherol-supplemented subjects with those who received no alpha-tocopherol, the adjusted relative risk for typical intermittent claudication was 1.05 (0.98-1.14), and for beta-carotene-supplemented subjects compared with those who did not receive beta-carotene, the relative risk was 0.96 (0.89-1.04). In conclusion, no primary preventive effect on intermittent claudication was observed among middle-aged male smokers who were supplemented with alpha-tocopherol, beta-carotene, or both.

Topics: Antioxidants; beta Carotene; Diabetes Complications; Humans; Intermittent Claudication; Male; Middle Aged; Neoplasms; Vitamin E

Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease, and earlier basic research suggested plausible mechanisms. Because large randomized trials of long duration were necessary to test this hypothesis directly, we conducted a trial of beta carotene supplementation.. In a randomized, double-blind, placebo-controlled trial of beta carotene (50 mg on alternate days), we enrolled 22,071 male physicians, 40 to 84 years of age, in the United States; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982. By December 31, 1995, the scheduled end of the study, fewer than 1 percent had been lost to follow-up, and compliance was 78 percent in the group that received beta carotene.. Among 11,036 physicians randomly assigned to receive beta carotene and 11,035 assigned to receive placebo, there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease, or in overall mortality. In the beta carotene group, 1273 men had any malignant neoplasm (except nonmelanoma skin cancer), as compared with 1293 in the placebo group (relative risk, 0.98; 95 percent confidence interval, 0.91 to 1.06). There were also no significant differences in the number of cases of lung cancer (82 in the beta carotene group vs. 88 in the placebo group); the number of deaths from cancer (386 vs. 380), deaths from any cause (979 vs. 968), or deaths from cardiovascular disease (338 vs. 313); the number of men with myocardial infarction (468 vs. 489); the number with stroke (367 vs. 382); or the number with any one of the previous three end points (967 vs. 972). Among current and former smokers, there were also no significant early or late differences in any of these end points.. In this trial among healthy men, 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms, cardiovascular disease, or death from all causes.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Cardiovascular Diseases; Carotenoids; Double-Blind Method; Humans; Incidence; Male; Middle Aged; Mortality; Neoplasms; Proportional Hazards Models; Risk

Topics: Asbestos; beta Carotene; Carotenoids; Food, Fortified; Humans; Male; Neoplasms; Smoking; Vitamin A

Topics: Adolescent; Adult; Antioxidants; beta Carotene; Cross-Over Studies; Diet; Double-Blind Method; Humans; In Vitro Techniques; Male; Middle Aged; Monocytes; Neoplasms; Tumor Necrosis Factor-alpha

Even though dietary fiber has been hypothesized to reduce the risk of coronary heart disease, few large epidemiological studies have examined this relation with good methodology.. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was a randomized, double-blind, placebo-controlled trial with daily supplementation of alpha-tocopherol and/or beta-carotene. Of the participants, 21930 smoking men aged 50 to 69 years who were free of diagnosed cardiovascular disease and had completed a validated dietary questionnaire at baseline were followed for 6.1 years. We monitored the incidence of major coronary events (a combination of first nonfatal myocardial infarction and coronary heart disease death; n = 1399) and mortality from coronary heart disease (n = 635). Both entities had a significant inverse association with dietary fiber, but the association was stronger for coronary death. For men in the highest quintile of total dietary fiber intake (median, 34.8 g/d), the relative risk for coronary death was 0.69 (95% confidence interval, 0.54 to 0.88; P < .001 for trend) compared with men in the lowest quintile of intake (median, 16.1 g/d). With an adjustment for known cardiovascular risk factors, intake of saturated fatty acids, beta-carotene, vitamin C, and vitamin E did not materially change the result. Water-soluble fiber was slightly more strongly associated with reduced coronary death than water-insoluble fiber, and cereal fiber also had a stronger association than vegetable or fruit fiber.. These findings suggest that independent of other risk factors, greater intake of foods rich in fiber can substantially reduce the risk of coronary heart disease, and particularly coronary death, in middle-aged, smoking men.

Topics: Aged; beta Carotene; Cohort Studies; Coronary Disease; Dietary Fiber; Double-Blind Method; Humans; Male; Middle Aged; Neoplasms; Risk Factors; Smoking; Vitamin E

The Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study was a placebo-controlled, randomized intervention trial testing the hypothesis that beta-carotene and alpha-tocopherol (vitamin E) supplements prevent lung and other cancers. The study is predicated on a substantial body of evidence supporting a role in cancer prevention for these micronutrients. Based on the 2 x 2 factorial study design, 29,133 eligible male cigarette smokers aged 50-69 y were randomly assigned to receive beta-carotene (20 mg), alpha-tocopherol (50 mg), beta-carotene and alpha-tocopherol, or placebo daily for 5-8 y. Capsule compliance was high (median = 99%). beta-Carotene treatment did not result in a decrease in cancer at any of the major sites but rather in an increase at several sites, most notably lung, prostate, and stomach (number of cases 474 compared with 402, 138 compared with 112, and 70 compared with 56, respectively). The vitamin E group had fewer incident cancers of the prostate and colorectum compared with the group not receiving vitamin E (number of cases 99 compared with 151 and 68 compared with 81, respectively), but more cancers of the stomach (70 compared with 56). In contrast to these intervention-based findings for beta-carotene and vitamin E supplements, we observed lower lung cancer rates in men with higher amounts of both serum and dietary beta-carotene and vitamin E at baseline.

Topics: Aged; Antioxidants; beta Carotene; Carotenoids; Humans; Incidence; Male; Middle Aged; Neoplasms; Smoking; 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

To examine whether body mass index is an independent predictor of cataract. (Body mass index is a standardized measure defined as weight in kilograms divided by the square of the height in meters.). Prospective cohort study, with 5 years of follow-up.. A total of 17,764 US male physicians participating in the Physicians' Health Study, aged 40 to 84 years, who were free of cataract, myocardial infarction, stroke, and cancer at baseline and reported complete information about body mass index and other cataract risk factors.. Incident cataract, defined as a self-report, confirmed by medical record review, first diagnosed after randomization, age-related in origin, and responsible for a decrease in best corrected visual acuity to 20/30 or worse.. Incident cataract occurred during follow-up in 370 participants. In proportional hazards models that adjusted for potential confounding variables, body mass index had a strong, graded relationship with risk of cataract. Relative to those with body mass index less than 22, relative risks (95% confidence intervals) associated with body mass index of 22 to less than 25, 25 to less than 27.8, and 27.8 or more were 1.54 (1.04 to 2.27), 1.46 (0.98 to 2.20), and 2.10 (1.35 to 3.25), respectively. Relative to any given level of body mass index, a 2-unit higher level predicted a 12% increase in risk of cataract (95% confidence interval, 5% to 19%). Higher body mass index was especially strongly related to risk of posterior subcapsular and nuclear sclerotic cataracts and was also significantly related to risk of cataract extraction.. In a prospective cohort study of apparently healthy men, higher body mass index, a potentially modifiable risk factor, was a determinant of cataract. The leanest men had the lowest rates, consistent with experimental evidence that restriction of energy intake slows development of cataract. Although precise mechanisms are unclear, the effect of body mass index on cataractogenesis is apparently independent of other risk factors, including age, smoking, and diagnosed diabetes.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Body Constitution; Body Mass Index; Cardiovascular Diseases; Carotenoids; Cataract; Cohort Studies; Double-Blind Method; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Prospective Studies; Risk Factors; United States

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

Case-control differences in prediagnostic serum levels of retinol, beta-carotene, vitamin E, and selenium are compared for 10 cancer sites in 10 study populations. For all four nutrients, the majority of results showed lower levels among persons who subsequently became cases than among controls. Low levels of beta-carotene were most likely to be associated with subsequent cancer, but there were marked differences by cancer site. The results indicate that it is unlikely that any of these serum micronutrients are associated with protection against carcinogenesis at all sites. A plea is made for greater emphasis on replication of results, for reporting findings for all sites no matter how small the number of cases may be, and for keeping constantly in mind the fact that observational associations are not necessarily causal in nature.

Topics: Antioxidants; beta Carotene; Carotenoids; Case-Control Studies; Female; Finland; Free Radicals; Humans; Japan; Male; Neoplasms; Selenium; Switzerland; United Kingdom; United States; Vitamin A; Vitamin E

The Physicians' Health Study is a randomized, double-blind, placebo-controlled prevention trial of 22,071 US physicians, using a factorial design to evaluate the role of aspirin in the prevention of cardiovascular mortality and beta carotene in the reduction of cancer incidence. After approximately 5 years of follow-up, the aspirin component was terminated, 3 years ahead of schedule. Several factors were considered in the decision to terminate, including a cardiovascular mortality rate markedly lower than expected in both aspirin and placebo subjects, precluding the evaluation of the primary aspirin hypothesis, and a highly significant (P < .00001) and impressive (44%) reduction in the risk of first myocardial infarction in the aspirin group. Issues in the decision to terminate are described in this report.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Double-Blind Method; Humans; Male; Middle Aged; Neoplasms; Physicians

Topics: beta Carotene; Carotenoids; Dose-Response Relationship, Drug; Humans; Leukoplakia, Oral; Neoplasms; Tretinoin

Doses of beta-carotene for cancer-prevention trials have been chosen based on epidemiologic data. Mechanisms of the putative antineoplastic effects by beta-carotene are unknown but may involve modulation of the immune system. We measured plasma carotenoid concentrations and selected immunologic indices at baseline and at 2 and 4 wk in 50 healthy humans (5 groups of 10 each) ingesting 0, 15, 45, 180, or 300 mg beta-carotene/d for 1 mo in this randomized placebo-controlled, open-label, parallel study. Plasma beta-carotene concentrations were markedly increased by 2 wk and were correlated with dose. Beta-carotene concentrations plateaued between 2 and 4 wk except for the 300-mg group. Thus, we developed a dose-concentration curve to optimize beta-carotene-dose selection to achieve target plasma concentrations. We were unable to identify any effects of beta-carotene ingestion on the immunologic indices studied, but modest increases in high-density-lipoprotein cholesterol were observed in all beta-carotene-treated groups.

Topics: Adult; beta Carotene; Carotenoids; Female; Humans; Immunity; Leukocyte Count; Lipoproteins; Lutein; Lycopene; Lymphocyte Activation; Male; Middle Aged; Neoplasms; Vitamin A; Vitamin E

Topics: beta Carotene; Biomarkers; Carotenoids; Clinical Trials as Topic; Folic Acid; Health Planning; Humans; Neoplasms; Nutritional Physiological Phenomena; Vitamin A

Topics: beta Carotene; Carotenoids; Drug Evaluation; Humans; Isotretinoin; Neoplasm Recurrence, Local; Neoplasms; Neoplasms, Multiple Primary; Randomized Controlled Trials as Topic

Topics: Adult; Aged; Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Cerebrovascular Disorders; Clinical Trials as Topic; Double-Blind Method; Humans; Male; Middle Aged; Myocardial Infarction; Neoplasms; Random Allocation

Topics: beta Carotene; Carotenoids; Clinical Trials as Topic; Diet; Dietary Fats; Dietary Fiber; Health Education; Humans; Life Style; National Institutes of Health (U.S.); Neoplasms; Prospective Studies; Research Design; Retinoids; Risk; Selenium; United States; Vitamins

Topics: Animals; beta Carotene; Carotenoids; Clinical Trials as Topic; Humans; Neoplasms; Random Allocation; Retinoids

Topics: beta Carotene; Carotenoids; Clinical Trials as Topic; Humans; Neoplasms; Vitamins

The Physicians' Health Study is a randomized, placebo-controlled, double-blind clinical trial underway in the United States to assess the effects of aspirin (325 mg q.o.d.) on total cardiovascular mortality, and of beta-carotene (50 mg q.o.d.) on cancer incidence. The participants are 22,071 U.S. male physicians between the ages of 40-84 years. The design of the study is 2 x 2 factorial, which enables us to address two important research questions simultaneously. The trial is conducted entirely by mail, which involves sending calendar packs of drugs and questionnaires on health status and compliance, initially at six-month then at annual intervals. Compliance and follow-up rates to date are excellent. The large size of the trial, its simple design, and the use of highly motivated, dedicated, and health-conscious physicians should allow us to perform definitive tests of whether low-dose aspirin consumption reduces total cardiovascular mortality and beta-carotene decreases cancer incidence in a healthy population.

Topics: Adult; Aged; Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Humans; Male; Middle Aged; Neoplasms; Physicians; Random Allocation; Research Design; Time Factors

Topics: beta Carotene; Carotenoids; Clinical Trials as Topic; Diet; Female; Humans; Male; National Institutes of Health (U.S.); Neoplasms; Nutritional Physiological Phenomena; Research; Retinoids; United States

Cancer cachexia is a metabolic disease affecting multiple organs and characterized by loss adipose and muscle tissues. Metabolic dysregulated of adipose tissue has a crucial role in cancer cachexia. β-Carotene (BC) is stored in adipose tissues and increases muscle mass and differentiation. However, its regulatory effects on adipose tissues in cancer cachexia have not been investigated yet. In this study, we found that BC supplementations could inhibit several cancer cachexia-related changes, including decreased carcass-tumor (carcass weight after tumor removal), adipose weights, and muscle weights in CT26-induced cancer cachexia mice. Moreover, BC supplementations suppressed cancer cachexia-induced lipolysis, fat browning, hepatic gluconeogenesis, and systemic inflammation. Altered diversity and composition of gut microbiota in cancer cachexia were restored by the BC supplementations. BC treatments could reverse the down-regulated adipogenesis and dysregulated mitochondrial respiration and glycolysis in adipocytes and colon cancer organoid co-culture systems. Taken together, these results suggest that BC can be a potential therapeutic strategy for cancer cachexia.

Topics: Adipose Tissue; Animals; beta Carotene; Cachexia; Colonic Neoplasms; Gastrointestinal Microbiome; Mice; Muscle, Skeletal; Neoplasms

Type 2 diabetes (T2D) is a complex chronic disease with substantial phenotypic heterogeneity affecting millions of individuals. Yet, its relevant metabolites and etiological pathways are not fully understood. The aim of this study is to assess a broad spectrum of metabolites related to T2D in a large population-based cohort. We conducted a metabolomic analysis of 4,281 male participants within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The serum metabolomic analysis was performed using an LC-MS/GC-MS platform. Associations between 1,413 metabolites and T2D were examined using linear regression, controlling for important baseline risk factors. Standardized β-coefficients and standard errors (SEs) were computed to estimate the difference in metabolite concentrations. We identified 74 metabolites that were significantly associated with T2D based on the Bonferroni-corrected threshold (

Topics: alpha-Tocopherol; beta Carotene; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fatty Acids; Galactose; Humans; Male; Mannose; Metabolomics; Neoplasms

Certain popular supplements, notably beta carotene and vitamin E, may even cause harm.

Topics: beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Minerals; Neoplasms; Vitamin A; Vitamin E; Vitamin K; Vitamins

US Preventive Services Task Force; Mangione CM, Barry MJ, et al.

Topics: Adult; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Minerals; Neoplasms; Practice Guidelines as Topic; Vitamin E; Vitamins

Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied, but there is a lack of effective strategies and drugs for the treatment of tumor metastases. Here, we describe a functional product based on a combination of compounds, which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases, improving anti-cancer treatment, and enhancing immunity and antioxidant capacity. Our designed combination, named MVBL, consists of four inexpensive compounds: L-selenium-methylselenocysteine (MSC), D-‍α‍-tocopheryl succinic acid (VES), β‍-carotene (β‍-Ca), and L-lysine (Lys).. The effects of MVBL on cell viability, cell cycle, cell apoptosis, cell migration, cell invasion, reactive oxygen species (ROS), and paclitaxel (PTX)-combined treatment were studied in vitro. The inhibition of tumor metastasis, antioxidation, and immune enhancement capacity of MVBL were determined in vivo.. MVBL exhibited higher toxicity to tumor cells than to normal cells. It did not significantly affect the cell cycle of cancer cells, but increased their apoptosis. Wound healing, adhesion, and transwell assays showed that MVBL significantly inhibited tumor cell migration, adhesion, and invasion. MVBL sensitized MDA-MB-231 breast cancer cells to PTX, indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs. In mice, experimental data showed that MVBL inhibited tumor metastasis, prolonged their survival time, and enhanced their antioxidant capacity and immune function.. This study revealed the roles of MVBL in improving immunity and antioxidation, preventing tumor growth, and inhibiting metastasis in vitro and in vivo. MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.

Topics: alpha-Tocopherol; Animals; Antioxidants; Apoptosis; beta Carotene; Cell Line, Tumor; Cell Proliferation; Lysine; Mice; Neoplasms; Paclitaxel; Quality of Life; Succinates

Topics: beta Carotene; Biological Availability; Carotenoids; Lutein; Lycopene; Neoplasms

Vitamins are among the most frequently used supplements (48% of US adults). However, little is known about contributions of genetic variation to their efficacy and safety. Multiple pathways link catechol-O-methyltransferase (COMT) to the vitamin E supplement, alpha-tocopherol, and cancer.. Here we determined if COMT exerted pharmacogenetic effects on cancer prevention in two randomized trials of alpha-tocopherol supplementation. Pharmacogenetic effects of common COMT rs4680 (val158met), which encodes a nonsynonymous valine-to-methionine substitution, were examined in the trial plus a 10-year post-trial follow-up (overall) period of The Women's Genome Health Study (WGHS, N = 23 294), a 10-year alpha-tocopherol and aspirin trial with 10 years post-trial follow-up. Results were validated in a case/control (N = 2396/2235) subset of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC, N = 29 133). The primary outcome was total cancers. Rates of cancer types prevalent in women (colorectal, breast, lung, uterine, and lymphoma/leukemia) were also examined. All statistical tests were two-sided.. Random-effects meta-analysis of rs4680 genotype strata, in WGHS and ATBC overall periods, revealed differential alpha-tocopherol effects compared with placebo: met/met (hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.80 to 0.97; P = .01), val/met (HR = 0.99; 95% CI = 0.92 to 1.06; P = .74), and val/val (HR = 1.18; 95% CI = 1.06 to 1.31; P = .002) with a statistically significant COMT by alpha-tocopherol interaction (Pinteraction <.001). Timing of effects differed, with stronger effects in WGHS trial and ATBC post-trial.. Pharmacogenetic analysis of COMT and cancer prevention in two large randomized trials revealed statistically significant COMT by alpha-tocopherol interaction, such that alpha-tocopherol was beneficial among rs4680 met-allele (28.0%), but not val-allele (22.8%) homozygotes. These effects indicate the need for additional studies of genetic variation as a determinant of the benefits and possible harms of over-the-counter supplements, like alpha-tocopherol, used for health promotion.

Topics: Alleles; alpha-Tocopherol; beta Carotene; Catechol O-Methyltransferase; Dietary Supplements; Female; Genetic Association Studies; Genotype; Humans; Male; Neoplasms; Pharmacogenomic Testing; Randomized Controlled Trials as Topic

Finite mixture of Gaussian distributions provide a flexible semiparametric methodology for density estimation when the continuous variables under investigation have no boundaries. However, in practical applications, variables may be partially bounded (e.g., taking nonnegative values) or completely bounded (e.g., taking values in the unit interval). In this case, the standard Gaussian finite mixture model assigns nonzero densities to any possible values, even to those outside the ranges where the variables are defined, hence resulting in potentially severe bias. In this paper, we propose a transformation-based approach for Gaussian mixture modeling in case of bounded variables. The basic idea is to carry out density estimation not on the original data but on appropriately transformed data. Then, the density for the original data can be obtained by a change of variables. Both the transformation parameters and the parameters of the Gaussian mixture are jointly estimated by the expectation-maximization (EM) algorithm. The methodology for partially and completely bounded data is illustrated using both simulated data and real data applications.

Topics: beta Carotene; Biometry; Data Analysis; Environmental Monitoring; Humans; Models, Statistical; Neoplasms; Normal Distribution; Racial Groups; Risk; Schools; Vitamin A

Tobacco use, hypertension, hyperglycemia, overweight, and inactivity are leading causes of overall and cardiovascular disease (CVD) mortality worldwide, yet the relevant metabolic alterations responsible are largely unknown. We conducted a serum metabolomic analysis of 620 men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985-2013). During 28 years of follow-up, there were 435 deaths (197 CVD and 107 cancer). The analysis included 406 known metabolites measured with ultra-high-performance liquid chromatography/mass spectrometry-gas chromatography/mass spectrometry. We used Cox regression to estimate mortality hazard ratios for a 1-standard-deviation difference in metabolite signals. The strongest associations with overall mortality were N-acetylvaline (hazard ratio (HR) = 1.28; P < 4.1 × 10-5, below Bonferroni statistical threshold) and dimethylglycine, 7-methylguanine, C-glycosyltryptophan, taurocholate, and N-acetyltryptophan (1.23 ≤ HR ≤ 1.32; 5 × 10-5 ≤ P ≤ 1 × 10-4). C-Glycosyltryptophan, 7-methylguanine, and 4-androsten-3β,17β-diol disulfate were statistically significantly associated with CVD mortality (1.49 ≤ HR ≤ 1.62, P < 4.1 × 10-5). No metabolite was associated with cancer mortality, at a false discovery rate of <0.1. Individuals with a 1-standard-deviation higher metabolite risk score had increased all-cause and CVD mortality in the test set (HR = 1.4, P = 0.05; HR = 1.8, P = 0.003, respectively). The several serum metabolites and their composite risk score independently associated with all-cause and CVD mortality may provide potential leads regarding the molecular basis of mortality.

Topics: alpha-Tocopherol; beta Carotene; Cardiovascular Diseases; Cause of Death; Chromatography, Liquid; Dietary Supplements; Finland; Humans; Male; Metabolomics; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Tandem Mass Spectrometry

Although the health effects of beta carotene have been studied extensively, a systematic examination of serum concentrations and long-term mortality, including cardiovascular disease mortality, has not been reported.. Explore whether serum beta carotene is associated with overall and cause-specific mortality and to elucidate the strength and dose-response of the association.. We conducted a prospective serological analysis of 29 103 men in the ATBC study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention). During 31 years of follow-up, 23 796 deaths occurred, including deaths because of cardiovascular disease (9869), cancer (7692), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2700). Serum beta carotene was assayed using high-performance liquid chromatography. Adjusting for major risk factors measured, men with higher serum beta carotene had significantly lower all-cause mortality (hazard ratios=0.81, 0.71, 0.69, and 0.64 for quintile 2 (Q2)-Q5 versus Q1, respectively; P. This study provides evidence that higher beta carotene biochemical status is associated with lower overall, cardiovascular disease, heart disease, stroke, cancer, and other causes of mortality. The dose-response associations over a 30-year period were not attenuated by adjustment for other important risk factors and support greater fruit and vegetable consumption as a means to increase beta carotene status and promote longevity.

Topics: Aged; beta Carotene; Cardiovascular Diseases; Diabetes Mellitus; Finland; Humans; Male; Middle Aged; Mortality; Neoplasms; Respiratory Tract Diseases; Wounds and Injuries

Premna resinosa (Hochst.) Schauer (Lamiaceae) is used in many places to treat bronchitis, respiratory illness and convulsions of the rib cage.. This study evaluates the anticancer, antimicrobial and antioxidant activities of P. resinosa, and isolates some responsible constituents.. The methanol extract of P. resinosa aerial parts and its fractions (n-hexane, dichloromethane, ethyl acetate and n-butanol) were tested. Antimicrobial activity was tested using microdilution method against three Gram-positive and four Gram-negative bacteria. The tested concentrations ranged from 4000 to 7.8 μg/mL and MIC values were determined after 24 h incubation. Anticancer activity was evaluated against three human cancer cell lines (Daoy, HepG2 and SK-MEL28) using MTT assay. Antioxidant activity was investigated by DPPH scavenging method and β-carotene-linoleic acid assay.. The greatest antimicrobial activity was exhibited by n-hexane fraction (MIC 10 μg/mL) against Staphylococcus aureus, Enterococcus faecalis, and Shigella flexneri. The n-hexane fraction induced the greatest cytotoxic activity against Daoy, HepG2, and SK-MEL28 cell lines with IC. Our results indicate that P. resinosa is a source for antimicrobial and cytotoxic compounds. However, further work is required to isolate other active principles and to determine the mechanism of action.

Topics: Anti-Bacterial Agents; Antineoplastic Agents, Phytogenic; Antioxidants; beta Carotene; Biphenyl Compounds; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Gram-Negative Bacteria; Gram-Positive Bacteria; Hep G2 Cells; Humans; Inhibitory Concentration 50; Lamiaceae; Microbial Sensitivity Tests; Neoplasms; Phytotherapy; Picrates; Plant Components, Aerial; Plant Extracts; Plants, Medicinal; Saudi Arabia; Solvents

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

The issue of multidrug resistance (MDR) cancer is one of the major barriers to successful chemotherapy treatment. The ATP-binding cassette (ABC) efflux transporters play an important role in the chemotherapeutic failure. Several generations of ABC efflux transporter inhibitors have been developed, however, none of them could provide better clinical outcome due to systemic toxicities and significant drug-drug interactions. Therefore, the present study focused on identifying the effect of the natural carotenoid on ABC transporters and may provide a safer choice to defeat MDR cancer.. The aim of the present study was to evaluate the inhibitory potency of β-carotene on the ABC efflux transporters, as well as the reversal effect of β-carotene toward MDR cancers. The underlying molecular mechanisms and inhibitory kinetics of β-carotene on the major ABC efflux transporter, P-glycoprotein, were further investigated.. The human P-gp (ABCB1/Flp-In(TM)-293), MRP1 (ABCC1/Flp-In(TM)-293) and BCRP (ABCG2/Flp-In(TM)-293) stable expression cells were established by using the Flp-In(TM) system. The cytotoxicity of β-carotene was evaluated by MTT assay in the established cell lines, sensitive cancer cell lines (HeLaS3 and NCI-H460) and resistant cancer cell lines (KB-vin and NCI-H460/MX20). Surface protein detection assay and eFluxx-ID Green Dye assay were applied for confirmation of surface expression and function of the transporters. The transporter inhibition potency of β-carotene was evaluated by calcein-AM uptake assay and mitoxantrone accumulation assay. Further interaction kinetics between β-carotene and P-gp were analyzed by rhodamine123 and doxorubicin efflux assay. The influence of β-carotene on ATPase activity was evaluated by Pgp-Glo(TM) Assay System.. Among the tested ABC efflux transporters, β-carotene significantly inhibited human P-gp efflux function without altering ABCB1 mRNA expression. Furthermore, β-carotene stimulated both P-gp basal ATPase activity and the verapamil-stimulated P-gp ATPase activity. In addition, β-carotene exerted partially inhibitory effect on BCRP efflux function. The combination of β-carotene and chemotherapeutic agents significantly potentiated their cytotoxicity in both cell stably expressed human P-gp (ABCB1/Flp-In(TM)-293) and MDR cancer cells (KB-vin and NCI-H460/MX20).. The present study indicated that β-carotene may be considered as a chemo-sensitizer and regarded as an adjuvant therapy in MDR cancer treatment.

Topics: Adenosine Triphosphatases; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; beta Carotene; Cell Line, Tumor; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Neoplasms; Verapamil

Typically, multiplexing high nanoparticle uptake, imaging, and therapy requires careful integration of three different functions of a multiscale molecular-particle assembly. Here, we present a simpler approach to multiplexing by utilizing one component of the system for multiple functions. Specifically, we successfully synthesized and characterized colloidal carotene carbon nanoparticle (C(3)-NP), in which a single functional molecule served a threefold purpose. First, the presence of carotene moieties promoted the passage of the particle through the cell membrane and into the cells. Second, the ligand acted as a potent detrimental moiety for cancer cells and, finally, the ligands produced optical contrast for robust microscopic detection in complex cellular environments. In comparative tests, C(3)-NP were found to provide effective intracellular delivery that enables both robust detection at cellular and tissue level and presents significant therapeutic potential without altering the mechanism of intracellular action of β-carotene. Surface coating of C(3) with phospholipid was used to generate C(3)-Lipocoat nanoparticles with further improved function and biocompatibility, paving the path to eventual in vivo studies.

Topics: beta Carotene; Biological Transport; Carbon; Cell Membrane; Coated Materials, Biocompatible; Colloids; Humans; Microscopy; Nanoparticles; Neoplasms; Optical Rotation; Phospholipids

Vitamin D has been discussed in the context of cardiovascular disease, cancer, bone health and other outcomes. Epidemiological studies have reported on the importance of vitamin D in cancer prevention and treatment. The discovery of vitamin D-associated metabolites through agnostic metabolomics analyses offers a new approach for elucidating disease aetiology and health-related pathway identification.. Baseline serum 25-hydroxy-vitamin D [25(OH)D] and 940 serum metabolites were measured in 392 men from eight nested cancer case-control studies in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers (aged 50-69 years). The metabolomic profiling was conducted using mass spectrometry. We used linear regression to estimate the standardized beta-coefficient as the effect metric for the associations between metabolites and 25(OH)D levels.. A majority of the metabolites associated with 25(OH)D were of lipid origin, including 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) [beta-estimate 0.38 per 1 standard deviation (SD) increment], stearoyl-arachidonoyl-glycerophosphoethanolamine (GPPE) (-0.38 per SD) and two essential fatty acids: eicosapentaenoate (EPA; 0.17 per SD) and docosahexaenoate (DHA; 0.13 per SD). Each of these lipid metabolites was associated with 25(OH)D at the principal components corrected P-value of 3.09 × 10

Topics: Aged; alpha-Tocopherol; Amino Acids; beta Carotene; Case-Control Studies; Dietary Supplements; Fatty Acids; Finland; Furans; Humans; Linear Models; Male; Mass Spectrometry; Metabolomics; Middle Aged; Multivariate Analysis; Neoplasms; Propionates; Randomized Controlled Trials as Topic; Risk Factors; Smoking; Vitamin D

Dietary supplements (DS) may influence cancer prognosis. Their use in cancer patients has been described in the United States, but data are largely lacking in Europe and notably in France. The present study's objectives were (1) to assess DS use and its sociodemographic, lifestyle, and dietary correlates in a large sample of French cancer survivors; (2) to evaluate the involvement of physicians in such DS use; and (3) to assess the extent of potentially harmful practices. Data were collected by self-administered web-based questionnaires among participants of the NutriNet-Santé cohort. Data on DS use was available for 1081 cancer survivors. DS users were compared to non-users with unconditional logistic regressions. DS use was reported by 62% of women and 29% of men. Vitamins D, B6, C and Mg were the most frequently consumed nutrients. 14% of cancer survivors initiated DS use after diagnosis. For 35% of the DS consumed, subjects did not inform their attending physician. DS use was associated with a healthier lifestyle (normal weight, never smoking and better diet) and substantially contributed to nutrient intake. 18% of DS users had potentially harmful DS use practices, such as the simultaneous use of vitamin E and anticoagulant/antiplatelet agents, the use of β-carotene and smoking or the use of phyto-oestrogens in hormone-dependent cancer patients. The present study suggests that DS use is widespread among cancer survivors, a large amount of that use is performed without any medical supervision and a substantial proportion of that use involves potentially harmful practices. Physicians should be encouraged to more routinely discuss DS use with their cancer patients.

Topics: Adolescent; Adult; Aged; beta Carotene; Cohort Studies; Diet; Dietary Supplements; Female; France; Humans; Life Style; Logistic Models; Male; Middle Aged; Neoplasms; Prognosis; Surveys and Questionnaires; Survivors; Vitamin E; Young Adult

Topics: Aspirin; beta Carotene; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Health Promotion; Humans; Minnesota; Myocardial Infarction; Neoplasms; Self Medication; Stroke

In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study among 29,133 Finnish male smokers aged 50-69 years, daily α-tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas β-carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the postintervention effects of α-tocopherol and β-carotene, 25,563 men were followed 18 years for cancer incidence and all causes of mortality through national registers. Neither supplement had significant effects on post-trial cancer incidence. Relative risk (RR) for lung cancer (n = 2,881) was 1.04 (95% confidence interval [CI], 0.96-1.11) among β-carotene recipients compared with nonrecipients. For prostate cancer (n = 2,321), RR was 0.97 (95% CI, 0.89-1.05) among α-tocopherol recipients compared with nonrecipients with the preventive effect of α-tocopherol continuing ∼8 years postintervention. Body mass index significantly modified the effect of α-tocopherol on prostate cancer (p for interaction = 0.01) RR 1.00 (95% CI, 0.88-1.14) in normal-weight men, 0.87 (95% CI, 0.77-0.98) in overweight men, and 1.25 (95% CI, 1.01-1.55) in obese men. The post-trial relative mortality (based on 16,686 deaths) was 1.02 (95% CI, 0.98-1.05) for α-tocopherol recipients compared with nonrecipients and 1.02 (95% CI, 0.99-1.05) for β-carotene recipients compared with nonrecipients. α-Tocopherol decreased post-trial prostate cancer mortality (RR, 0.84; 95% CI, 0.70-0.99), whereas β-carotene increased it (RR, 1.20; 95% CI, 1.01-1.42). In conclusion, supplementation with α-tocopherol and β-carotene appeared to have no late effects on cancer incidence. The preventive effect of moderate-dose α-tocopherol on prostate cancer continued several years post-trial and resulted in lower prostate cancer mortality.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Clinical Trials as Topic; Dietary Supplements; Female; Finland; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms

Update of the 2003 U.S. Preventive Services Task Force (USPSTF) recommendation on vitamin supplementation to prevent cardiovascular disease and cancer.. The USPSTF reviewed the evidence on the efficacy of multivitamin or mineral supplements in the general adult population for the prevention of cardiovascular disease and cancer.. This recommendation applies to healthy adults without special nutritional needs (typically aged 50 years or older). It does not apply to children, women who are pregnant or may become pregnant, or persons who are chronically ill or hospitalized or have a known nutritional deficiency.. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of multivitamins for the prevention of cardiovascular disease or cancer. (I statement). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of single- or paired-nutrient supplements (except β-carotene and vitamin E) for the prevention of cardiovascular disease or cancer. (I statement). The USPSTF recommends against β-carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer. (D recommendation).

Topics: Adult; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Middle Aged; Minerals; Neoplasms; Primary Prevention; Research; Risk Assessment; Vitamin E; Vitamins

Topics: Adult; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Minerals; Neoplasms; Primary Prevention; Risk Assessment; Vitamin E; Vitamins

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

The hallmarks of cancer described by Hanahan and Weinberg are properties that cancer cells must possess for successful transformation. It is believed that each of these hallmarks is independently driven. Although elongation of telomeres is thought to be the prime function of reactivated telomerase reverse transcriptase, this activity does not account for all its effects, such as increasing cell proliferation, resistance to apoptosis, and invasion. Recent studies suggest that the telomerase subunit telomerase reverse transcriptase (TERT) has novel molecular functions including transcriptional regulation and metabolic reprogramming. We summarize these functions and discuss how they could directly regulate the various hallmarks of cancer. Finally, we suggest that therapeutics targeting noncanonical telomerase functions may work better than those that target its role in telomere extension.

Topics: Animals; beta Carotene; Humans; Neoplasms; NF-kappa B; Signal Transduction; Telomerase

Alpinia pahangensis, a wild ginger distributed in the lowlands of Pahang, Malaysia, is used by the locals to treat flatulence. In this study, the antioxidant and cytotoxic activities of the crude aqueous methanol and fractionated extracts of Alpinia pahangensis against five different cancer and one normal cell lines were investigated. The total phenolic content of each extract and its fractions were also quantified. This is the first report on the antioxidant and cytotoxic activities of Alpinia pahangensis extract.. In the current study, the crude methanol and fractionated extract of the rhizomes of Alpinia pahangensis were investigated for their antioxidant activity using four different assays namely, the DPPH scavenging activity, superoxide anion scavenging, β-carotene bleaching and reducing power assays whilst their phenolic contents were measured by the Folin-Ciocalteu's method.In vitro neutral red cytotoxicity assay was employed to evaluate the cytotoxic activity against five different cancer cell lines, colon cancer (HCT 116 and HT-29), cervical cancer (Ca Ski), breast cancer (MCF7) and lung cancer (A549) cell lines, and one normal cell line (MRC-5). The extract that showed high cytotoxic activity was further investigated for its chemical constituents by GC-MS (gas chromatography-mass spectrometry) analysis.. The ethyl acetate fraction showed the strongest DPPH radical scavenging (0.35 ± 0.094 mg/ml) and SOD activities (51.77 ± 4.9%) whilst the methanol extract showed the highest reducing power and also the strongest antioxidant activity in the β-carotene bleaching assays in comparison to other fractions. The highest phenolic content was found in the ethyl acetate fraction, followed by the crude methanol extract, hexane and water fractions. The results showed a positive correlation between total phenolic content with DPPH radical scavenging capacities and SOD activities. The hexane fraction showed potent cytotoxic effect against KB, Ca Ski and HCT 116 cell lines with IC₅₀ of 5.8 ± 0.1 and 9.1 ± 2.0 ug/ml, respectively. The major components of hexane fraction analysed by GC-MS analysis were mostly methyl esters.. The current study suggests that the methanol extract and ethyl acetate fraction of A. pahangensis is a potential source of natural antioxidant for protective as well as prevention of life-threatening diseases. The hexane fraction of A. pahangensis may have the potential to be developed into therapeutic option for treating cancer.

Topics: Alpinia; Analysis of Variance; Antioxidants; beta Carotene; Biphenyl Compounds; Cell Line, Tumor; Cell Survival; Gas Chromatography-Mass Spectrometry; HCT116 Cells; HT29 Cells; Humans; MCF-7 Cells; Neoplasms; Neutral Red; Oxidation-Reduction; Phenols; Picrates; Plant Extracts; Rhizome; Superoxides

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

Intake of marine-based n-3 fatty acids (EPA, docosapentaenoic acid and DHA) is recommended to prevent CHD. Stearidonic acid (SDA), a plant-based n-3 fatty acid, is a precursor of EPA and may be more readily converted to EPA than a-linolenic acid (ALA). While transgenic soyabeans might supply SDA at low cost, it is unclear whether SDA is associated with CHD risk. Furthermore, associations of other n-3 fatty acids with CHD risk remain inconsistent. The present ancillary study examined the association of erythrocyte SDA as well as other n-3 fatty acids with the risk of CHD. In a prospective nested case-control study of the Physicians' Health Study, we randomly selected 1000 pairs of incident CHD with matching controls. Erythrocyte fatty acids were measured using GC. We used conditional logistic regression to estimate relative risks. Mean age was 68·7 (SD 8·7) years. In a multivariable model controlling for matching factors and established CHD risk factors, OR for CHD for each standard deviation increase of log-SDA was 1·03 (95% CI 0·90, 1·18). Corresponding values for log-ALA and log-marine n-3 fatty acids were 1·04 (95% CI 0·94, 1·16) and 0·97 (95% CI 0·88, 1·07), respectively. In conclusion, the present data did not show an association among erythrocyte SDA, ALA or marine n-3 fatty acids and the risk of CHD in male physicians.

Topics: Aged; Aging; Aspirin; beta Carotene; Case-Control Studies; Coronary Disease; Double-Blind Method; Erythrocytes; Fatty Acids, Omega-3; Humans; Macular Degeneration; Male; Middle Aged; Neoplasms; Risk Factors; Vitamins

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

Reactive oxygen species, along with reactive nitrogen species, may play an important role in the pathogenesis and progress of many diseases, including cancer, diabetes and sickle cell disease. It has been postulated that hydroxyurea, one of the main treatments in sickle cell disease, achieves its activity partly also through its antioxidant properties. A series of hydroxyurea derivatives of L- and D-amino acid amides and cycloalkyl-N-aryl-hydroxamic acids was synthesized and investigated for their radical scavenging activity, chelating properties and antioxidant activity. All the compounds showed exceptional antiradical activities. For example, free radical scavenging activities of investigated hydroxyureas were higher than the activity of standard antioxidant, butylated hydroxyanisole (BHA). Moreover, most of the investigated hydroxamic acids were stronger Fe²⁺ ion chelators than quercetin. In addition, the investigated compounds, especially hydroxamic acids, were proven to be excellent antioxidants. They were as effective as BHA in inhibiting β-carotene-linoleic acid coupled oxidation. It is reasonable to assume that the antioxidant activity of the investigated compounds could contribute to their previously proven biological properties as cytostatic and antiviral agents.

Topics: Anemia, Sickle Cell; beta Carotene; Biphenyl Compounds; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Free Radical Scavengers; Humans; Hydroxamic Acids; Hydroxyurea; Iron; Iron Chelating Agents; Linoleic Acid; Magnetic Resonance Spectroscopy; Neoplasms; Oxidation-Reduction; Picrates; Reactive Oxygen Species; Spectrophotometry, Infrared

The authors performed a matched case-control study (1982-2007) nested in a prospective cohort of 22,071 US men to determine the prevalence of chronic diseases of aging in those with newly diagnosed cancer. They matched one control by age to each of 5,622 men who developed cancer over the 25 years of follow-up, as of the date of cancer diagnosis. A modified Charlson score was calculated that reflected comorbidities prior to the matching date, and the authors used conditional logistic regression to determine the odds ratios of various diseases. No substantial differences were found between the scores of cases and controls overall, by cancer subtype, or by age at diagnosis. Overall, men who developed cancer were less likely to have had hypercholesterolemia (odds ratio (OR) = 0.79, 95% confidence interval (CI): 0.72, 0.87) or coronary artery disease (OR = 0.85, 95% CI: 0.77, 0.96). Compared with controls, men with cancers for which there is routine screening had fewer diseases, whereas those with smoking-related cancers had more. Prostate cancer was inversely associated with both coronary artery disease (OR = 0.72, 95% CI: 0.62, 0.84) and diabetes (OR = 0.72, 95% CI: 0.58, 0.89). Overall, men who developed cancer had no more comorbidity or frequent history of chronic disease than their age-matched controls.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; beta Carotene; Cardiovascular Diseases; Case-Control Studies; Chronic Disease; Comorbidity; Drug Administration Schedule; Health Status; Humans; Male; Middle Aged; Neoplasms; Prevalence; Risk Factors; Smoking

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

Topics: beta Carotene; Calcium; Clinical Trials as Topic; Folic Acid; Food-Drug Interactions; Humans; Micronutrients; Neoplasms; Research Design; Selenium; Trace Elements; Treatment Failure; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamins

Topics: alpha-Tocopherol; Antioxidants; beta Carotene; Clinical Trials as Topic; Humans; Neoplasms

To evaluate the association between type 2 diabetes and newly reported Parkinson's disease.. Our study included 21,841 participants in the Physicians' Health Study, a cohort of U.S. male physicians. Diabetes and Parkinson's disease were self-reported via questionnaire. We used time-varying Cox regression to calculate adjusted relative risk (RR) for Parkinson's disease.. Over 23 years, 556 individuals with Parkinson's disease were identified. Subjects with diabetes had an increased Parkinson's disease risk (multivariable-adjusted RR 1.34 [95% CI 1.01-1.77]). The association remained significant after exclusion of those with known vascular disease. The diagnosis of diabetes was clustered around the diagnosis of Parkinson's disease and was more apparent among men with short diabetes duration and those without complications from diabetes.. Results of this large prospective study in men do not suggest that diabetes is a preceding risk factor for Parkinson's disease. Whether the positive association may be explained by ascertainment bias or a common underlying biological mechanism remains to be established.

Topics: Adult; Aged; Aspirin; beta Carotene; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Parkinson Disease; Patient Selection; Physicians; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors

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

Typically locus specific genotype data do not contain information regarding the gametic phase of haplotypes, especially when an individual is heterozygous at more than one locus among a large number of linked polymorphic loci. Thus, studying disease-haplotype association using unphased genotype data is essentially a problem of handling a missing covariate in a case-control design. There are several methods for estimating a disease-haplotype association parameter in a matched case-control study. Here we propose a conditional likelihood approach for inference regarding the disease-haplotype association using unphased genotype data arising from a matched case-control study design. The proposed method relies on a logistic disease risk model and a Hardy-Weinberg equilibrium (HWE) among the control population only. We develop an expectation and conditional maximization (ECM) algorithm for jointly estimating the haplotype frequency and the disease-haplotype association parameter(s). We apply the proposed method to analyze the data from the Alpha-Tocopherol, Beta-Carotene Cancer prevention study, and a matched case-control study of breast cancer patients conducted in Israel. The performance of the proposed method is evaluated via simulation studies.

Topics: Algorithms; alpha-Tocopherol; Anticarcinogenic Agents; beta Carotene; Biostatistics; Breast Neoplasms; Case-Control Studies; Female; Genotype; Haplotypes; Humans; Likelihood Functions; Logistic Models; Male; Neoplasms

Relative risks for lung and bladder cancers by smoking intensity level off at more than 15-20 cigarettes per day. A three-parameter excess relative risk model in pack-years and intensity quantified this leveling (Lubin et al., Am J Epidemiol 2007;166:479-89). Above 15-20 cigarettes per day was an "inverse exposure rate" effect whereby, for equal pack-years, the excess relative risk/pack-year decreased with increasing intensity; that is, smoking at a lower intensity for a longer duration was more deleterious than smoking at a higher intensity for a shorter duration. After adjustment for pack-years, intensity effects were quantitatively homogeneous across multiple case-control studies of lung, bladder, oral cavity, pancreas, and esophagus cancers. The authors extended those analyses to examine intensity patterns for incident bladder, esophagus, kidney, larynx, liver, lung, oropharynx, and pancreas cancers by using data from a single prospective cohort in Finland, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, with follow-up from enrollment, which occurred between 1985 and 1988, through April 2004. At more than 10 cigarettes per day, they found an inverse exposure rate pattern for each cancer site. After adjustment for pack-years, intensity effects were quantitatively homogeneous across the diverse cancer sites and homogeneous with intensity effects from the prior analysis of multiple studies. Consistency of intensity patterns suggested a general phenomenon and may provide clues to the molecular basis of smoking-related cancer risk.

Topics: Aged; alpha-Tocopherol; beta Carotene; Feeding Behavior; Finland; Health Surveys; Humans; Male; Middle Aged; Models, Statistical; Neoplasms; Nutritional Status; Prospective Studies; Risk; Risk Assessment; Risk Factors; Smoking; Surveys and Questionnaires; Time Factors

To quantify measurement error in the estimation of family diet intakes using 7-day household food inventories and to investigate the effect of measurement-error adjustment on diet-disease associations.. Historical cohort study in 16 districts in England and Scotland, between 1937 and 1939.. 4999 children from 1352 families in the Carnegie Survey of Diet and Health. 86.6% of these children were traced as adults and form the Boyd Orr cohort. The reproducibility analysis was based on 195 families with two assessments of family diet recorded 3-15 months apart.. Intraclass correlation coefficients (ICCs) were calculated for a variety of nutrients and food groups. Diet-cancer associations reported previously in the Boyd Orr cohort were reassessed using two methods: (a) the ICC and (b) the regression calibration.. The ICCs for the dietary intakes ranged from 0.44 (beta carotene) to 0.85 (milk and milk products). The crude fully adjusted hazard ratio (HR) for cancer mortality per 1 MJ/day increase in energy intake was 1.15 (95% CI 1.06 to 1.24). After adjustment using the ICC for energy (0.80) the HR (95% CI) increased to 1.19 (1.08 to 1.31), and the estimate from regression calibration was 1.14 (0.98 to 1.32). The crude fully adjusted odds ratio (OR) for cancer incidence per 40 g/day increase in fruit intake was 0.84 (95% CI 0.73 to 0.97). After adjustment using the fruit ICC (0.78) it became 0.81 (0.67 to 0.96) and the OR derived from regression calibration was 0.81 (0.59 to 1.10).. The diet-disease relationships for the dietary intakes with low measurement error were robust to adjustment for measurement error.

Topics: Animals; beta Carotene; Cohort Studies; Diet; Diet Surveys; Energy Intake; England; Family Health; Fruit; Humans; Milk; Neoplasms; Odds Ratio; Proportional Hazards Models; Reproducibility of Results; Scotland; Vegetables

Topics: beta Carotene; Cardiovascular Diseases; Diet; Humans; Neoplasms; Vitamin E

In this communication, we report the efficacy of beta-carotene towards differentiation and apoptosis of leukemia cells. Dose (20 microM) and time dependence (12 h) tests of beta- carotene showed a higher magnitude of decrease (significance p < 0.05) in cell numbers and cell viability in HL-60 cells than U937 cells but not normal cell like Peripheral blood mononuclear cell (PBMC). Microscopical observation of beta-carotene treated cells showed a distinct pattern of morphological abnormalities with inclusion of apoptotic bodies in both leukemia cell lines. When cells were treated with 20 microM of beta-carotene, total genomic DNA showed a fragmentation pattern and this pattern was clear in HL-60 than U937 cells. Both the cell lines, on treatment with beta- carotene, showed a clear shift in G(1) phase of the cell cycle. In addition the study also revealed anti-oxidant properties of beta-carotene since there was reduction in relative fluorescent when treated than the control at lower concentration. Collectively this study shows the dual phenomenon of apoptosis and differentiation of leukemia cells on treatment with beta-carotene.

Topics: Anticarcinogenic Agents; Apoptosis; beta Carotene; Cell Cycle; Cell Differentiation; Cell Proliferation; DNA Fragmentation; Flow Cytometry; G1 Phase; HL-60 Cells; Humans; Leukemia; Neoplasms; Reactive Oxygen Species; U937 Cells

Some research findings based on observational epidemiology are contradicted by randomized trials, but may nevertheless still be supported in some scientific circles.. To evaluate the change over time in the content of citations for 2 highly cited epidemiological studies that proposed major cardiovascular benefits associated with vitamin E in 1993; and to understand how these benefits continued being defended in the literature, despite strong contradicting evidence from large randomized clinical trials (RCTs). To examine the generalizability of these findings, we also examined the extent of persistence of supporting citations for the highly cited and contradicted protective effects of beta-carotene on cancer and of estrogen on Alzheimer disease.. For vitamin E, we sampled articles published in 1997, 2001, and 2005 (before, early, and late after publication of refuting evidence) that referenced the highly cited epidemiological studies and separately sampled articles published in 2005 and referencing the major contradicting RCT (HOPE trial). We also sampled articles published in 2006 that referenced highly cited articles proposing benefits associated with beta-carotene for cancer (published in 1981 and contradicted long ago by RCTs in 1994-1996) and estrogen for Alzheimer disease (published in 1996 and contradicted recently by RCTs in 2004).. The stance of the citing articles was rated as favorable, equivocal, and unfavorable to the intervention. We also recorded the range of counterarguments raised to defend effectiveness against contradicting evidence.. For the 2 vitamin E epidemiological studies, even in 2005, 50% of citing articles remained favorable. A favorable stance was independently less likely in more recent articles, specifically in articles that also cited the HOPE trial (odds ratio for 2001, 0.05 [95% confidence interval, 0.01-0.19; P < .001] and the odds ratio for 2005, 0.06 [95% confidence interval, 0.02-0.24; P < .001], as compared with 1997), and in general/internal medicine vs specialty journals. Among articles citing the HOPE trial in 2005, 41.4% were unfavorable. In 2006, 62.5% of articles referencing the highly cited article that had proposed beta-carotene and 61.7% of those referencing the highly cited article on estrogen effectiveness were still favorable; 100% and 96%, respectively, of the citations appeared in specialty journals; and citations were significantly less favorable (P = .001 and P = .009, respectively) when the major contradicting trials were also mentioned. Counterarguments defending vitamin E or estrogen included diverse selection and information biases and genuine differences across studies in participants, interventions, cointerventions, and outcomes. Favorable citations to beta-carotene, long after evidence contradicted its effectiveness, did not consider the contradicting evidence.. Claims from highly cited observational studies persist and continue to be supported in the medical literature despite strong contradictory evidence from randomized trials.

Topics: Alzheimer Disease; beta Carotene; Epidemiologic Studies; Estrogens; Evidence-Based Medicine; Humans; Neoplasms; Observation; Publication Bias; Randomized Controlled Trials as Topic; Vitamin E; Vitamins

Topics: beta Carotene; Female; Humans; Neoplasms; Smoking; Smoking Cessation

Topics: Animals; Apoptosis; beta Carotene; Caspase 2; Enzyme Activation; Humans; Neoplasms; Reactive Oxygen Species; Signal Transduction

Topics: Animals; Antioxidants; beta Carotene; Carotenoids; Diet; DNA Damage; Humans; Neoplasms; Oxidative Stress

Pectin was dissolved in deionized distilled water (2%, vol/vol) and irradiated at 20 kGy using a Co-60 gamma ray irradiator. The resulting solution was dialyzed and lyophilized. The samples were separated into three groups to estimate their antioxidant and cancer cell proliferation effects: non-irradiated (0 kGy), irradiated (20 kGy), and dialyzed (20 kGy-F, mol wt <10,000) samples. Antioxidant properties of each treatment was tested by a beta-carotene-linoleic acid bleaching assay and electron donating ability and compared for antioxidant index, which indicated that the activity was higher in the order of 20 kGy-F > 20 kGy > 0 kGy. Spleen cell survival effect of the irradiated pectin (20 kGy) and dialyzed (20 kGy-F) samples was higher than the non-irradiated control (0 kGy). The pectins inhibited growth of the cancer cell in the order of 20 kGy- F > 20 kGy > 0 kGy. The Ames test revealed that none of the fractions was mutagenic, and there was no indication of a dose-dependent response for any of the samples. These results suggest that a functional pectin oligosaccharide can be produced by irradiation for the food industry without any chemical treatment.

Topics: Antioxidants; beta Carotene; Biphenyl Compounds; Cell Division; Cell Line, Tumor; Citrus; Free Radical Scavengers; Fruit; Gamma Rays; Humans; Linoleic Acid; Mutagenicity Tests; Neoplasms; Oligosaccharides; Oxidation-Reduction; Pectins; Picrates

Colonization with Helicobacter pylori is a risk factor for gastric adenocarcinoma, but the magnitude of this association and its relationship to anatomic location of the cancer, duration of follow-up, age at diagnosis, histologic subtype, and H. pylori strain differences are less clear. We conducted a prospective nested case-control study of H. pylori serology to address these questions.. Case and control subjects were selected from the 29,133 50- to 69-year-old males recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. At baseline, detailed demographic data and a serum sample were collected. From 1985 to 1999, 243 incident cases of gastric adenocarcinoma were diagnosed in cohort members. Serum samples from 234 case subjects (173 with noncardia gastric cancers and 61 with gastric cardia cancers) and 234 age-matched control subjects were assayed for antibodies against H. pylori whole-cell and CagA antigens. We fit conditional logistic regression models to estimate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of H. pylori seropositivity, defined as seropositivity to either whole-cell or CagA antigens, with noncardia gastric and gastric cardia cancers. All statistical tests were two-sided.. H. pylori seropositivity was strongly associated with the risk of noncardia gastric cancer (adjusted OR = 7.9, 95% CI = 3.0 to 20.9) but was inversely associated with the risk of gastric cardia cancer (adjusted OR = 0.31, 95% CI = 0.11 to 0.89). H. pylori seropositivity rates did not vary statistically significantly by length of follow-up, age at diagnosis, or histologic subtype. A calculation of rates showed that the absolute risks of noncardia gastric and cardia gastric adenocarcinomas in the H. pylori-positive participants of this cohort would be 63 and 12 per 100,000 person-years, respectively, whereas corresponding rates in H. pylori-negative participants would be 8 and 37 per 100,000 person-years, respectively.. H. pylori is a strong risk factor for noncardia gastric cancer but is inversely associated with the risk of gastric cardia cancer. These findings bolster the hypothesis that decreasing H. pylori prevalence during the past century may have contributed to lower rates of noncardia cancer and higher rates of cardia cancer in Western countries.

Topics: Adenocarcinoma; Aged; alpha-Tocopherol; Antigens, Bacterial; Antioxidants; Bacterial Proteins; beta Carotene; Cardia; Case-Control Studies; Developed Countries; Dietary Supplements; Finland; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Neoplasms; Odds Ratio; Prevalence; Primary Prevention; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Seroepidemiologic Studies; Stomach Neoplasms; Time Factors

An important question being raised by nutritionists today is whether available scientific data support an important role for polyphenols in the prevention of pathologic conditions that represent an important public health burden, such as cardiovascular diseases, cancers, and osteoporosis. More broadly, when can we consider scientific knowledge sufficient to allow specific public health implications and recommendations? The history of the relationship between beta-carotene and cancer illustrates the complexity of the research process leading to the demonstration of a causal relationship between nutritional factors and the prevention of disease. The beta-carotene story, which has developed in the past 30 y, is particularly significant and illustrative because of apparent controversies that are far from resolved. This is an extremely interesting example from which many lessons can be learned. For beta-carotene, we need to collect sufficient information from experimental, clinical, and epidemiologic research before we support any specific public health recommendations. The same principles must be applied to recommendations regarding polyphenols (in particular, which polyphenols, at which doses, to achieve which benefits for which populations). If these questions are not answered, then we run the risk of needing to renounce recommendations regarding polyphenols in the future, damaging the credibility of nutritional recommendations for public health.

Topics: Animals; Antioxidants; beta Carotene; Flavonoids; History, 20th Century; History, 21st Century; Humans; Neoplasms; Phenols; Polyphenols

Expression of connexin 43 (Cx43) is correlated with reduced indexes of neoplasia and is upregulated by cancer-preventive retinoids and carotenoids in nontransformed human and murine fibroblasts and keratinocytes. The molecular mechanism of upregulation, however, is poorly understood. Three retinoic acid receptor (RAR) antagonists (Ro 41-5253, BMS453, and BMS493) were capable of suppressing retinoid-induced Cx43 protein expression in 10T1/2 cells. However, Ro 41-5253 did not suppress protein expression by the non-provitamin A carotenoids astaxanthin or lycopene. In contrast, Cx43 induction by astaxanthin but not by a RAR-specific retinoid was inhibited by GW9662, an antagonist of peroxisome proliferator activated receptor-gamma activation. Simultaneous treatment with the maximally effective concentration of a retinoid and with beta-carotene or the non-provitamin A carotenoid astaxanthin resulted in supraadditive upregulation of Cx43 expression, again indicating separate mechanisms of gene regulation by these two cancer preventive agents.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Benzoates; beta Carotene; Carotenoids; Cell Line; Connexin 43; Gene Expression Regulation, Neoplastic; Humans; Mice; Neoplasms; PPAR gamma; Receptors, Retinoic Acid; Retinoids; Up-Regulation; Xanthophylls

Topics: Adult; beta Carotene; Carcinogens; Carotenoids; Female; France; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Primary Prevention; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Research Design; Smoking; United States

Intervention studies have demonstrated that, in smokers, beta-carotene supplements had a deleterious effect on risk of lung cancer and may have a deleterious effect on digestive cancers as well. We investigated a potential interaction between beta-carotene intake and smoking on the risk of tobacco-related cancers in women.. A total of 59,910 women from the French Etude Epidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective investigation were studied from 1994. After a median follow-up of 7.4 years, 700 women had developed cancers known to be associated with smoking. Diet, supplement use, and smoking status at baseline were assessed by self-report. beta-carotene intake was classified into four groups: first (low intake), second, and third tertiles of dietary intake, and use of supplements (high intake). Unadjusted and multivariable Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (CIs) for cancer risk. All statistical tests were two-sided.. Among never smokers, multivariable hazard ratios of all smoking-related cancers were 0.72 (95% CI = 0.57 to 0.92), 0.80 (95% CI = 0.64 to 1.01), and 0.44 (95% CI = 0.18 to 1.07) for the second and third tertiles of dietary intake, and high beta-carotene intake, respectively, compared with low intake (Ptrend = .03). Among ever smokers, multivariable hazard ratios were 1.43 (95% CI = 1.05 to 1.96), 1.20 (95% CI = 0.86 to 1.67), and 2.14 (95% CI = 1.16 to 3.97) for the second and third tertiles of dietary intake, and high beta-carotene intake, respectively, compared with low intake (Ptrend = .09). Tests for interaction between beta-carotene intake and smoking were statistically significant (Ptrend =.017). In this population, the absolute rates over 10 years in those with low and high beta-carotene intake were 181.8 and 81.7 cases per 10,000 women in never smokers and 174.0 and 368.3 cases per 10,000 women in ever smokers.. beta-carotene intake was inversely associated with risk of tobacco-related cancers among nonsmokers with a statistically significant dose-dependent relationship, whereas high beta-carotene intake was directly associated with risk among smokers.

Topics: Adult; Antioxidants; beta Carotene; Carcinogens; Dietary Supplements; Feeding Behavior; Female; Follow-Up Studies; France; Humans; Lung Neoplasms; Middle Aged; Multivariate Analysis; Neoplasms; Odds Ratio; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Smoking

Only a few observational studies have related plasma carotene and alpha-tocopherol to mortality in elderly subjects.. The objective was to study the association of plasma carotene (alpha-and beta-carotene) and alpha-tocopherol with all-cause and cause-specific mortality in elderly subjects who participated in a European prospective study.. Plasma concentrations of carotene and alpha-tocopherol were measured in 1168 elderly men and women. After a follow-up period of 10 y, 388 persons had died. The association between plasma antioxidants and mortality was analyzed by using Cox proportional hazard models. To put our results in context, we performed a meta-analysis of 5 studies on plasma antioxidants and all-cause mortality in elderly populations.. Plasma carotene concentrations were associated with a lower mortality risk [adjusted rate ratio (RR) for an increment of 0.39 micromol/L: 0.79; 95% CI: 0.70, 0.89]. This lower mortality risk was observed for both cancer (RR: 0.59; 95% CI: 0.44, 0.79) and cardiovascular disease (RR: 0.83; 95% CI: 0.70, 1.00). The lower risk of cardiovascular death was confined to those with a body mass index (in kg/m2) <25 (RR: 0.67; 95% CI: 0.49, 0.94). Plasma concentrations of alpha-tocopherol were not associated with all-cause or cause-specific mortality. The results for both plasma antioxidants and all-cause mortality were confirmed by the meta-analysis.. This prospective study suggests that high plasma concentrations of carotene are associated both with lower mortality from all causes and with cancer in the elderly. For cardiovascular mortality, the inverse association was confined to elderly with body mass indexes <25.

Topics: Aged; Aging; alpha-Tocopherol; Antioxidants; beta Carotene; Body Mass Index; Cardiovascular Diseases; Carotenoids; Cause of Death; Cohort Studies; Confidence Intervals; Europe; Female; Follow-Up Studies; Health Status; Humans; Life Style; Male; Meta-Analysis as Topic; Neoplasms; Nutritional Status; Odds Ratio; Proportional Hazards Models; Prospective Studies

Overweight and obesity are well-established risk factors for cardiovascular disease and decline in kidney function in individuals with existing chronic kidney disease (CKD). Conversely, their association with the development of CKD is less clear.. We evaluated the association between body mass index (BMI) and risk for CKD in a cohort of 11,104 initially healthy men who participated in the Physicians' Health Study and provided a blood sample after 14 years. BMI was calculated from self-reported weight and height. We estimated glomerular filtration rate (GFR) by using the abbreviated equation from the Modification of Diet in Renal Disease Study and defined CKD as GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2).. After an average 14-year follow-up, 1,377 participants (12.4%) had a GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). Higher baseline BMI was associated consistently with increased risk for CKD. Compared with participants in the lowest BMI quintile (<22.7 kg/m2), those in the highest quintile (>26.6 kg/m2) had an odds ratio (OR) of 1.45 (95% confidence interval [CI], 1.19 to 1.76; P trend <0.001) after adjusting for potential confounders. We found similar associations by using different categories of BMI. Compared with men who remained within a +/-5% range of their baseline BMI, those who reported a BMI increase greater than 10% had a significant increase in risk for CKD (OR, 1.27; 95% CI, 1.06 to 1.53).. In this large cohort of initially healthy men, BMI was associated significantly with increased risk for CKD after 14 years. Strategies to decrease CKD risk might include prevention of overweight and obesity.

Topics: Adult; Aspirin; beta Carotene; Body Mass Index; Cardiovascular Diseases; Chronic Disease; Cohort Studies; Diabetes Complications; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypercholesterolemia; Hypertension; Kidney Diseases; Male; Middle Aged; Neoplasms; Obesity; Overweight; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Smoking; United States

To study the effect of intermediates of the tricarboxylic acid (TCA) cycle on the production of zeaxanthin from Flavobacterium multivorum in order to optimize production of this xanthophyll carotenoid.. The concentration of selected TCA cycle intermediates (malic acid, isocitric acid and alpha-ketoglutarate) was optimized in shake flask culture, using a statistical two-level, three-variable factorial approach. The carotenoid production profile was also studied in the optimized medium at various growth phases. Optimized medium resulted in a sixfold increase in volumetric production of zeaxanthin (10.65 +/- 0.63 microg ml-1) using malic acid (6.02 mm), isocitric acid (6.20 mm) and alpha-ketoglutarate (0.02 mm). The majority of zeaxanthin was produced in the late logarithmic growth phase whereas a substantial amount of beta-cryptoxanthin and beta-carotene were observed in the early logarithmic phase.. This study demonstrates improvement of zeaxanthin production from F. multivorum which might aid in the commercialization of zeaxanthin production from this microbe.

Topics: beta Carotene; Bioreactors; Chromatography, High Pressure Liquid; Citric Acid Cycle; Culture Media; Dietary Supplements; Flavobacterium; Humans; Isocitrates; Ketoglutaric Acids; Macular Degeneration; Malates; Neoplasms; Xanthophylls; Zeaxanthins

Fruit and vegetable intake is inversely associated with cancer risk in many epidemiological studies. Accurate assessment of consumption of these foods is difficult, and biomarkers of intake would overcome several drawbacks of currently used dietary assessment methods. Therefore, we investigated the relation between plasma carotenoids and usual vegetable and fruit intake.. Plasma carotenoid concentrations were measured and vegetable, fruit and juice consumption was assessed by a food frequency questionnaire (FFQ) in a random sample of 591 Dutch men and women aged 20-59 y from the MORGEN-project, one of the contributions to the European Prospective Investigation into Cancer and Nutrition (EPIC)-study.. In this sample of the general Dutch population, in both genders, relative to the other carotenoids, plasma beta-cryptoxanthin was the best indicator for fruit intake, and for the sum of vegetable, fruit and juice intake, while lutein concentrations best reflected intake of vegetables, although quartiles of intake were not consistently separated. Since levels of lycopene were not associated with any of the main food groups examined, associations with total carotenoids improved when excluding lycopene, and monotonously increasing plasma levels were seen for intakes of vegetables, of fruits, and of the sum of vegetables, fruits and juices. Several vegetable types and orange/grapefruit juice were associated with plasma levels of one of the carotenoids.. Plasma carotenoids were only crude indicators of vegetable and fruit intake as assessed by a FFQ; beta-cryptoxanthin for fruit intake and lutein for vegetable intake. None of the plasma carotenoids could distinguish all four quartiles of vegetables, fruit and/or juice intake.

Topics: Adult; beta Carotene; Beverages; Biomarkers; Carotenoids; Cryptoxanthins; Diet; Female; Fruit; Humans; Lutein; Lycopene; Male; Middle Aged; Neoplasms; Netherlands; Prospective Studies; Surveys and Questionnaires; Vegetables; Xanthophylls

Both randomized and observational studies commonly examine composite end points, but the literature on model development and criticism in this setting is limited.. We examined approaches for evaluating heterogeneity in the effects of risk factors for different components of the end point, and determining the impact of heterogeneity on the ability to predict the composite end point. A specific example considered the composite cardiovascular disease end point in the Physicians' Health Study that occurred in 1,542 (myocardial infarction, n = 716; stroke, n = 557; cardiovascular death, n = 269) of 16,688 participants with complete information on baseline covariates. The strategy compared alternative polytomous logistic regression models assuming different effects of risk factors on components of the end point and a comparable logistic model assuming common effects.. Likelihood ratio tests identified heterogeneity in the effects of age, alcohol consumption, and diabetes across components of the outcome, but comparability in the effects of other risk factors. However, a model assuming uniform effects explained over 90% of the log-likelihood change in the best polytomous model, and the two models also performed similarly based on a comparison of ROC curves.. The overall strategy may be helpful for evaluating the validity of a composite end point analysis and identifying heterogeneity in risk factors.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aspirin; beta Carotene; Cardiovascular Diseases; Health Surveys; Humans; Likelihood Functions; Male; Middle Aged; Models, Statistical; Neoplasms; Risk Assessment

Topics: Adult; Antioxidants; beta Carotene; Cardiovascular Diseases; Evidence-Based Medicine; Female; Humans; Neoplasms; Smoking; Vitamins

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

Smoking is an established risk factor for ischemic stroke and subarachnoid hemorrhage (SAH), but the impact of smoking on intracerebral hemorrhage (ICH) is less clear.. Prospective cohort study among 22,022 US male physicians participating in the Physicians' Health Study. Incidence of stroke was measured by self-report and confirmed by medical record review. We used Cox proportional-hazards models to evaluate the association of smoking with risk of total hemorrhagic stroke, ICH, and SAH. We categorized smoking into 4 groups: never, past, or current smokers of <20 or of >or=20 cigarettes per day.. During 17.8 years of follow-up, 108 ICHs and 31 SAHs occurred. Never smokers and past smokers had equal rates of ICH and SAH. Current smokers of <20 cigarettes per day had multivariable-adjusted relative risks of 1.65 (95% CI, 0.61 to 4.50) for total hemorrhagic stroke, 1.60 (95% CI, 0.50 to 5.07) for ICH, and 1.75 (95% CI, 0.24 to 13.09) for SAH when compared with never smokers. Current smokers of >or=20 cigarettes had relative risks of 2.36 (95% CI, 1.38 to 4.02) for total hemorrhagic stroke, 2.06 (95% CI, 1.08 to 3.96) for ICH, and 3.22 (95% CI, 1.26 to 8.18) for SAH when compared with never smokers.. This prospective study suggests an increased risk of total hemorrhagic stroke, ICH, and SAH in current cigarette smokers with a graded increase in risk that depended on how many cigarettes were smoked. The effect of smoking on ICH is of about the same magnitude as the effect of smoking on ischemic stroke. Our results add to the multiple health benefits that can be accrued by abstaining from cigarette smoking.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Alcohol Drinking; Aspirin; beta Carotene; Body Mass Index; Brain Ischemia; Cardiovascular Diseases; Cerebral Arteries; Cerebral Hemorrhage; Cohort Studies; Comorbidity; Confounding Factors, Epidemiologic; Diabetes Mellitus; Exercise; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertension; Incidence; Male; Medical Records; Middle Aged; Multivariate Analysis; Neoplasms; Physicians; Proportional Hazards Models; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Smoking; Stroke; Subarachnoid Hemorrhage; United States

Topics: Alcohol Drinking; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; beta Carotene; Cardiovascular Diseases; Cohort Studies; Exercise; Humans; Neoplasms; Physicians; Randomized Controlled Trials as Topic; Risk Factors; Smoking; United States

In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, alpha-tocopherol supplementation decreased prostate cancer incidence, whereas beta-carotene increased the risk of lung cancer and total mortality. Postintervention follow-up provides information regarding duration of the intervention effects and may reveal potential late effects of these antioxidants.. To analyze postintervention effects of alpha-tocopherol and beta-carotene on cancer incidence and total and cause-specific mortality.. Postintervention follow-up assessment of cancer incidence and cause-specific mortality (6 years [May 1, 1993-April 30, 1999]) and total mortality (8 years [May 1, 1993-April 30, 2001]) of 25 563 men. In the ATBC Study, 29 133 male smokers aged 50 to 69 years received alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5 to 8 years. End point information was obtained from the Finnish Cancer Registry and the Register of Causes of Death. Cancer cases were confirmed through medical record review.. Site-specific cancer incidence and total and cause-specific mortality and calendar time-specific risk for lung cancer incidence and total mortality.. Overall posttrial relative risk (RR) for lung cancer incidence (n = 1037) was 1.06 (95% confidence interval [CI], 0.94-1.20) among recipients of beta-carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving alpha-tocopherol compared with nonrecipients. No late preventive effects on other cancers were observed for either supplement. There were 7261 individuals who died by April 30, 2001, during the posttrial follow-up period; the RR was 1.01 (95% CI, 0.96-1.05) for alpha-tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for beta-carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for beta-carotene recipients was no longer evident 4 to 6 years after ending the intervention and was primarily due to cardiovascular diseases.. The beneficial and adverse effects of supplemental alpha-tocopherol and beta-carotene disappeared during postintervention follow-up. The preventive effects of alpha-tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid beta-carotene supplementation.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Cause of Death; Dietary Supplements; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Risk; Smoking

In this study, we examined possible mechanisms of caspase activation during carotenoid-induced apoptosis in tumor cells. We found that beta-Carotene induces apoptosis by the activation of caspase-3 in human leukemia (HL-60), colon adenocarcinoma (HT-29) as well as melanoma (SK-MEL-2) cell lines. This activation is dose dependent and follows that of caspase-8 and caspase-9. Although caspase-8 cleavage is an early event, reaching its maximum activation at 3 h, caspase-9 reaches its maximum activation only at 6 h. The addition of IETD-CHO, a caspase-8-specific inhibitor, completely prevents beta-Carotene-induced apoptosis, whereas only a partial prevention was observed in the presence of LEHD-CHO, a caspase-9-specific inhibitor. beta-Carotene activates caspase-9 via cytochrome c release from mitochondria and loss of mitochondrial membrane potential (Dym). Concomitantly, a dose-dependent decrease in the antiapoptotic protein Bcl-2 and a dose-dependent increase in the cleaved form of BID (t-BID) are observed. Moreover, NF-kB activation is involved in beta-Carotene-induced caspase cascade. These results support a pharmacological role for beta-Carotene as a candidate antitumor agent and show a possible sequence of molecular events by which this molecule may induce apoptosis in tumor cells.

Topics: Adenocarcinoma; Apoptosis; beta Carotene; BH3 Interacting Domain Death Agonist Protein; Carrier Proteins; Caspase 3; Caspase 8; Caspase 9; Caspases; Colonic Neoplasms; Cytochromes c; Enzyme Activation; Enzyme Inhibitors; HL-60 Cells; Humans; Melanoma; Membrane Potentials; Mitochondria; Neoplasms; NF-kappa B; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured

Carotenoids are widely used as important micronutrients in food. Furthermore, carotenoid supplementation has been used in the treatment of diseases associated with oxidative stress. However, in some clinical studies harmful effects have been observed, for example, a higher incidence of lung cancer in individuals exposed to extraordinary oxidative stress. The causal mechanisms are still unclear. Carotenoid cleavage products (CCPs), including highly reactive aldehydes and epoxides, are formed during oxidative attacks in the course of antioxidative action. Here, we tested the hypothesis that CCPs may increase oxidative stress by impairing mitochondrial function. We found that CCPs strongly inhibit state 3 respiration of isolated rat liver mitochondria even at concentrations between 0.5 and 20 microM. This was true for retinal, beta-ionone, and mixtures of cleavage products, which were generated in the presence of hypochlorite to mimic their formation in inflammatory regions. The inhibition of mitochondrial respiration was accompanied by a reduction in protein sulfhydryl content, decreasing glutathione levels and redox state, and elevated accumulation of malondialdehyde. Changes in mitochondrial membrane potential favor functional deterioration of the adenine nucleotide translocator. The findings may reflect a basic mechanism of increasing the risk of cancer induced by CCPs.

Topics: Animals; beta Carotene; Carcinogens; Cell Respiration; Dose-Response Relationship, Drug; Glutathione; Kinetics; Malondialdehyde; Mitochondria; Models, Biological; Neoplasms; Norisoprenoids; Oxidative Phosphorylation; Oxidative Stress; Rats; Retinaldehyde; Risk Factors; Terpenes

Clinical triallists are often reluctant to alter the protocol or the design of an ongoing study in part because of concern that changes may affect the integrity of the study. This paper encourages considering changes in long-term clinical trials when the medical environment changes or when the accruing data from the trial lead to questioning the assumptions underlying the original design. One must make such changes in a way that will not cast doubt on the integrity of the trial. An important aspect of the design is choice of sample size. Methodology for sample size recalculation has matured over the decade. Several techniques are now available for the usual types of endpoints - continuous, discrete and time-to-failure - as well as for longitudinal analysis. Published papers describe the choices of variance at the time of recalculation, approaches to estimation and testing at the end of the study, and the time of recalculation. In a study with a sponsor, a Data Safety Monitoring Board (DSMB) and an Executive Committee, one or more of these three groups is responsible for recommending increases in sample size when the accruing data indicate that the assumed variance underestimated the true variance. Sometimes a statistician independent of all three bodies performs the relevant calculations and sends the recommendation to the sponsor. This paper argues that the DSMB should not generally be the responsible body because knowledge of treatment effect can place it in an uncomfortable position.

Topics: Aspirin; beta Carotene; Clinical Trials Data Monitoring Committees; Coronary Artery Disease; Data Interpretation, Statistical; Game Theory; Humans; Hypolipidemic Agents; Longitudinal Studies; Neoplasms; Randomized Controlled Trials as Topic; Research Design; Sample Size; Treatment Outcome

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

The results of epidemiologic studies have consistently shown associations between dietary intake or plasma carotenoid status and incidence of cancers and cardiovascular and eye diseases.. The aim was to assess whether vegetable-borne carotenoids (lycopene, lutein, and beta-carotene) compete for intestinal absorption and whether this affects the plasma status of carotenoids in the medium term (ie, after 3 wk).. During 3-wk periods separated by 3-wk washout periods, 20 women were supplemented with either 96 g tomato purée/d (14.98 mg lycopene + 1.50 mg beta-carotene), 92 g cooked chopped spinach/d (11.93 mg lutein + 7.96 mg beta-carotene), 96 g tomato purée/d + 92 g chopped spinach/d, 96 g tomato purée/d + 2 lutein pills (12 mg lutein), or 92 g chopped spinach/d + 1 lycopene pill (15 mg lycopene). Plasma carotenoids were measured before and after each supplementation period. The subjects also participated in postprandial experiments in which they ingested meals containing double amounts of the supplements described above. Carotenoids were measured in chylomicrons to assess the interaction of carotenoids on absorption.. Adding a second carotenoid to a meal that provided a first carotenoid diminished the chylomicron response to the first carotenoid. However, cosupplementation with a second carotenoid of a diet supplemented with a first carotenoid did not diminish the medium-term plasma response to the first carotenoid.. Consumption of carotenoids from different vegetable sources does not diminish plasma carotenoid concentrations in the medium term, despite the finding in postprandial testing of competitive inhibitory interactions among different carotenoids.

Topics: Adult; beta Carotene; Biological Availability; Cardiovascular Diseases; Carotenoids; Chylomicrons; Eye Diseases; Female; Humans; Intestinal Absorption; Lutein; Lycopene; Neoplasms; Nutritional Status; Postprandial Period; Seroepidemiologic Studies; Vegetables

Topics: Antioxidants; beta Carotene; Free Radical Scavengers; Fruit; Humans; Lung Neoplasms; Neoplasms; Smoking; Vegetables

Topics: Animals; Animals, Laboratory; beta Carotene; Carcinogens; Disease Models, Animal; Ferrets; Liver Neoplasms; Lung Neoplasms; Marmota; Mice; Mutation; Neoplasms; Phenotype; Sciuridae; Skin Neoplasms; Zebrafish

Topics: beta Carotene; Humans; Neoplasms; Randomized Controlled Trials as Topic; Vitamin E

Topics: Anticarcinogenic Agents; beta Carotene; Breast Neoplasms; Clinical Trials as Topic; Female; Humans; Lung Neoplasms; Neoplasms; Tamoxifen; Treatment Outcome; Uterine Cervical Neoplasms

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

Topics: Antioxidants; beta Carotene; Diet; Evidence-Based Medicine; Fruit; Humans; Neoplasms; Research Design; Vegetables

Serum CD44 (s-CD44) concentrations were measured in sera taken from 49 individuals who were diagnosed with non-Hodgkin's lymphoma 0.9 to 7.2 years after taking the blood sample, and from 49 controls matched for age. The serum samples had been collected in conjunction of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, which evaluated the influence of vitamin supplementation on cancer prevention. S-CD44 was measured using chemiluminescence enzyme immunoassay. S-CD44 concentrations of the cases were significantly elevated before the diagnosis of lymphoma when compared to the serum levels found in the controls (median, 447 ng/mL; range, 108-780 ng/mL vs. median, 364 ng/mL; range, 53-660 ng/mL; p=0.012). Individuals who were later diagnosed with high grade lymphoma according to the Kiel classification (n=21) had significantly higher values than the controls 0.9-4.0 years before the diagnosis, but such a difference could not be detected if serum samples had been taken more than 4 years before the diagnosis. The s-CD44 levels were not significantly elevated among individuals who were later diagnosed with low grade malignant non-Hodgkin's lymphoma (n=25) as compared to their controls. The prediagnostic s-CD44 levels in cases and controls overlapped markedly, and a value higher than the highest value found among the controls (660 ng/mL) was found only in 5 (10%) samples taken from individuals who were later diagnosed with lymphoma. We conclude that serum CD44 may be elevated a few years preceding the diagnosis of non-Hodgkin's lymphoma, but the levels overlap markedly with those found in individuals without lymphoma.

Topics: Aged; alpha-Tocopherol; Anticarcinogenic Agents; beta Carotene; Biomarkers, Tumor; Cohort Studies; Humans; Hyaluronan Receptors; Immunoenzyme Techniques; Luminescent Measurements; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms; Predictive Value of Tests; Smoking; Solubility; Time Factors

Seven labdane-type diterpenoids from the stem bark of Thuja standishii (Gord.) Carr. (Cupressaceae) and their analogues showed strong inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among these compounds, 15,16-bisnor-13-oxolabda-8(17), 11E-dien-19-oic acid was revealed to have the strongest inhibitory effect on the EBV-EA activation, being stronger than that of beta-carotene which has been intensively studied in cancer prevention using animal models. 15,16-bisnor-13-Oxolabda-8(17), 11E-dien-19-oic acid was also found to exhibit the excellent anti-tumor promoting activity in two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene and TPA.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antigens, Viral; beta Carotene; Carboxylic Acids; Carcinogens; Diterpenes; Female; Humans; Mice; Mice, Inbred ICR; Naphthalenes; Nasopharyngeal Neoplasms; Neoplasms; Papilloma; Plant Extracts; Plant Stems; Skin Neoplasms; Tetradecanoylphorbol Acetate; Trees

Topics: Antioxidants; beta Carotene; Diet; Fruit; Humans; Neoplasms; Smoking; Vegetables

Topics: Anticarcinogenic Agents; beta Carotene; Health Behavior; Humans; Neoplasms

Topics: beta Carotene; Case-Control Studies; Confounding Factors, Epidemiologic; Humans; Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Treatment Failure; United States

Topics: Anticarcinogenic Agents; beta Carotene; China; Clinical Trials as Topic; Dietary Supplements; Humans; Neoplasms; Nutritional Status; Research Design; Vitamins

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

Topics: Anticarcinogenic Agents; beta Carotene; Chemoprevention; Diet; Humans; Imidazoles; Neoplasms; Risk Factors; Vitamin A

Topics: Anticarcinogenic Agents; beta Carotene; Chemoprevention; Diet; Enzyme Inhibitors; Humans; Mutagens; Neoplasms; Risk Factors; Vitamin A; Xenobiotics

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 A and beta-carotene and the risk in adults of atherosclerosis, coronary heart disease, amd certain cancers. This interim final 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 interim final rule is effective immediately upon publication.

Topics: Adult; Arteriosclerosis; beta Carotene; Coronary Disease; Drug Approval; Food Labeling; Humans; Neoplasms; Risk Factors; United States; United States Food and Drug Administration; Vitamin A

The results of the ATBC study, the first large intervention trial of antioxidants, were intriguing. While the possibility that beta-carotene may in some circumstances enhance carcinogenesis has now been confirmed in another large trial, the mechanisms of action remain obscure.

Topics: Aged; beta Carotene; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Smoking; Vitamin E

Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc, and selenium, and cholesterol and related proteins for 170 children with newly diagnosed malignancy were measured at diagnosis and 6 months after initiation of treatment, and compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited between 1986 and 1989. At diagnosis, age- and sex-adjusted serum concentrations of retinol, beta-carotene, zinc, and alpha-tocopherol were significantly inversely associated with cancer. No significant decreases in mean values were observed at 6 month, except for the alpha-tocopherol-to-cholesterol ratio in patients with bone tumors and serum zinc in bone tumors and central nervous system malignancies. An increase during the period of treatment was found for retinol and selenium in leukemia patients. beta-carotene was maintained at the initial concentrations determined prior to therapy. These findings provide further information about micronutrient requirements in children with cancer.

Topics: Adolescent; Antioxidants; beta Carotene; Bone Neoplasms; C-Reactive Protein; Case-Control Studies; Central Nervous System Neoplasms; Child; Child, Preschool; Cholesterol; Chromatography, High Pressure Liquid; Female; Follow-Up Studies; Humans; Immunoglobulins; Infant; Leukemia; Male; Micronutrients; Neoplasms; Pilot Projects; Selenium; Serum Albumin; Vitamin A; Vitamin E; Zinc

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: beta Carotene; Clinical Trials as Topic; Humans; Neoplasms; Vitamins

Serum vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and selenium, and related proteins for 157 children with newly diagnosed and histologically proven malignancy were compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years of age and recruited in 1986-1989. Age and sex-adjusted serum concentrations of beta-carotene and alpha-tocopherol were significantly inversely associated with cancer. No significant association with cancer was observed for serum values of selenium. Although low levels of antioxidants might in part be involved through a causality link, the reported decreased peripheral nutrient levels are considered rather as an impairment of the body's defence system, occurring during the cancer-related metabolic and nutritional disturbances and inflammation processes. The cancer cases group was followed-up and examined 6 months after diagnosis. Among the 157 subjects, 24 had died and 133 were reported to be alive. No substantial difference for any antioxidant or chemistry variable at onset was observed as a function of clinical outcome and health status.

Topics: Adolescent; Antioxidants; beta Carotene; Child; Child, Preschool; Female; Humans; Infant; Male; Neoplasms; Nutritional Status; Prognosis; Reference Values; Selenium; Vitamin A; Vitamin E; Zinc

Topics: beta Carotene; Clinical Trials as Topic; Diet; Dietary Supplements; Neoplasms; Risk Factors; Trace Elements; Vitamins

Topics: Anticarcinogenic Agents; Asbestos; beta Carotene; Carotenoids; Controlled Clinical Trials as Topic; Heart Diseases; Humans; Lung Neoplasms; Neoplasms; Smoking

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Carotenoids; Female; Humans; Male; Neoplasms; Vitamin E

Topics: Aged; Anticarcinogenic Agents; Antioxidants; beta Carotene; Double-Blind Method; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Vitamin E

Topics: Antioxidants; beta Carotene; Carotenoids; Humans; Neoplasms; Stereoisomerism

Topics: Antioxidants; beta Carotene; Breast Neoplasms; Carotenoids; Female; Fruit; Humans; Neoplasms; Vegetables

Topics: Antineoplastic Agents; Antioxidants; beta Carotene; Cardiovascular Agents; Cardiovascular Diseases; Carotenoids; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Neoplasms; Vitamin E

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: beta Carotene; Carcinogens; Cell Transformation, Neoplastic; Chemoprevention; Environmental Exposure; Humans; Imidazoles; Mutagens; Neoplasms; Neoplasms, Unknown Primary; Precancerous Conditions; Primary Prevention; Quinoxalines; Risk Factors

Previous studies indicated that serum beta-carotene levels were low among smokers and drinkers. However these findings may result from the strong relationship between smoking and drinking.. Data were collected from 1902 males randomly selected from participants of a cohort study. The effects of smoking on serum beta-carotene levels were assessed according to drinking status (non-drinker, ex-drinker and current drinker), and those of drinking were assessed according to smoking status (ex-smoker and current smoker) using general linear model including other factors (age, intake of green-yellow vegetables, intake of carrot or pumpkin, body mass index serum cholesterol levels.). An inverse dose-response relationship between daily consumption of alcohol and beta-carotene levels was observed regardless of smoking status, and also between number of cigarettes smoked per day and beta-carotene levels regardless of drinking status.. These results suggest that cigarette smoking and alcohol drinking reduce beta-carotene levels independently.

Topics: Adult; Alcoholism; beta Carotene; Cohort Studies; Cross-Sectional Studies; Diet Surveys; Humans; Japan; Linear Models; Male; Middle Aged; Neoplasms; Population Surveillance; Risk Factors; Smoking; Surveys and Questionnaires

Topics: Antineoplastic Agents; beta Carotene; Carotenoids; Humans; Neoplasms

It has been asserted that clinical trials hold the answer to questions about the role of nutrients in preventing chronic diseases. This is not the case. Clinical trials give us rigorous answers to restricted questions. Rarely can more than one or two substances be tested, usually at a single dose. Subjects usually have to be persons with precancerous conditions or an extremely high risk of the disease in question. Rarely can any diseases other than the most common ones be studied. Most important, clinical trials test the efficacy of an agent that is administered for a limited time, beginning fairly late in life. Few trials will tell us anything about whether dietary amounts of nutrients might contribute to prevention of long-term chronic diseases. They also tell us nothing about whether agents at high doses might reduce disease risk if taken throughout the lifetime. Furthermore, they tell us nothing about other antioxidants, other combinations, or other doses. Clinical trials were developed for therapeutic situations to determine which treatment was better for curing a specific disease. However, the questions about prevention that are of interest may involve persons with no unusual risk of disease, lifetimes of exposure, enormously complex interactions among nutrients, and the effects of these nutrients on hundreds of often uncommon disease conditions. Clinical trials simply cannot answer these questions. Only a solid examination of the laboratory and epidemiologic evidence can approximate the answers to most of the questions of interest.

Topics: beta Carotene; Carotenoids; Chronic Disease; Clinical Trials as Topic; Humans; Neoplasms

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

Numerous epidemiological studies have demonstrated that consuming large quantities of fruits and vegetables reduces the risk for several types of human cancers. Carotenoids are abundant in fruits and vegetables and have been extensively studied as cancer preventive agents. A proposed mechanism of action for the protective effect of carotenoids against cancer is based on their antioxidant capability. Recently, we have isolated and characterized 14 new carotenoids, including seven metabolites from the extracts of human serum/plasma. This brings the total number of identified blood carotenoids to 21. Lutein and lycopene, abundant in most fruits and vegetables as well as human serum, have been shown to possess strong antioxidant capability. Among the metabolites of lutein, four results from oxidation and two from non-enzymatic dehydration. The metabolite of lycopene has been identified as 5,6-dihydroxy-5,6-dihydrolycopene, which apparently results from oxidation of lycopene to an intermediate, lycopene epoxide. This intermediate may undergo metabolic reduction to form the lycopene metabolite. Although in vivo oxidation of lutein to its metabolites has been demonstrated based on data obtained from two human studies, in vivo oxidation of lycopene to its metabolite has not yet been established. Recent preliminary studies involving healthy subjects ingesting purified lutein and zeaxanthin (a dietary dihydroxycarotenoid isomeric to lutein) are presented. We propose a possible antioxidant mechanism of action for lutein and lycopene that leads to formation of the oxidation products of these promising chemopreventive agents.

Topics: Anticarcinogenic Agents; beta Carotene; Carotenoids; Food Analysis; Fruit; Humans; Lutein; Lycopene; Neoplasms; Oxidation-Reduction; Vegetables; Xanthophylls; Zeaxanthins

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

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Carotenoids; Clinical Trials as Topic; Humans; Lung Neoplasms; Neoplasms; Smoking

Topics: beta Carotene; Carotenoids; Clinical Trials as Topic; Humans; Lung Neoplasms; Neoplasms; Oxygen; Photochemistry; Singlet Oxygen; Stomach Neoplasms

Topics: Aged; beta Carotene; Carotenoids; Controlled Clinical Trials as Topic; Counseling; Diet; Drug Combinations; Fruit; Humans; Male; Middle Aged; Neoplasms; Placebos; Vegetables; Vitamin E

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

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: beta Carotene; Carotenoids; Cerebrovascular Disorders; Free Radicals; Humans; Neoplasms; Nutritional Requirements

Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and selenium for 418 children with newly diagnosed malignancy were compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited in 1986-1989. Age- and sex-adjusted serum concentrations of retinol, beta-carotene and alpha-tocopherol were significantly inversely associated with cancer. In similar models, the odds ratio (OR) comparing the highest with the lowest quintile was 2.06 (95% confidence interval [CI] 1.40-3.02) for retinol, 3.87 (95% CI: 2.54-5.90) for beta-carotene, 2.15 (95% CI: 1.48-3.10) for alpha-tocopherol, 1.29 (95% CI: 0.75-2.23) for selenium, and 1.94 (95% CI: 1.17-2.23) for zinc. The cancer sites that were associated with serum beta-carotene were, in general, leukaemia, lymphoma, central nervous system, bone and renal tumours. Moreover, leukaemia was associated with low mean serum levels of retinol, selenium and zinc. Subjects with lymphoma, bone and renal tumours also had lower mean retinol and alpha-tocopherol levels than controls. Brain tumour patients had low vitamin E levels. Low serum values of antioxidant vitamins were associated with childhood neoplasm occurrence. Some site-specific effect was reported. Low peripheral nutrient levels are not considered as cancer promoters but rather as an impairment of the body's defence mechanism occurring during the cancer-related metabolic and nutritional disturbances and inflammation processes.

Topics: Adjuvants, Immunologic; Adolescent; beta Carotene; Carotenoids; Case-Control Studies; Child; Child, Preschool; Cholesterol; Chromatography, High Pressure Liquid; Female; France; Humans; Infant; Male; Neoplasms; Regression Analysis; Risk Factors; Selenium; Vitamin A; Vitamin E; Zinc

Topics: Adult; beta Carotene; Cardiovascular Diseases; Carotenoids; China; Chronic Disease; Deficiency Diseases; Diet; Humans; Neoplasms; Selenium; Vitamin E

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

Topics: Anticarcinogenic Agents; beta Carotene; Carotenoids; Diet; Humans; Neoplasms

To examine the association between cigarette smoking and the incidence of cataract.. The design was a prospective cohort study using data from the Physicians' Health Study, a randomized trial of aspirin and beta carotene among 22,071 US male physicians aged 40 to 84 years that began in 1982. This analysis includes the 17,824 physicians who did not report cataract at baseline and did provide complete risk factor information. Based on information reported at baseline, 10% were current smokers, 39% were past smokers, and 51% were never smokers.. An incident cataract was defined as a self-report confirmed by medical record review to have been first diagnosed after randomization, age-related in origin, and responsible for a decrease in best corrected visual acuity to 20/30 or worse.. During 60 months of follow-up, 557 incident cataracts among 371 participants were confirmed. Compared with never smokers, current smokers of 20 or more cigarettes per day had a statistically significant increase in the risk of cataract (relative risk [RR], 2.16; 95% confidence interval [Cl], 1.46 to 3.20; P less than .001). Similar results were obtained after simultaneously controlling for other potential cataract risk factors in a logistic regression model (RR, 2.05; 95% Cl, 1.38 to 3.05; P less than .001). Among the 557 eyes with cataract, nuclear sclerotic changes were present in 442 while posterior subcapsular changes were present in 204. After controlling for other potential cataract risk factors, current smokers of 20 or more cigarettes per day had statistically significant increases in nuclear sclerosis (RR, 2.24; 95% Cl, 1.47 to 3.41; P less than .001) and posterior subcapsular (RR, 3.17; 95% Cl, 1.81 to 5.53; P less than .001) cataract. Past smokers had an elevated risk of posterior subcapsular (RR, 1.44; 95% Cl, 0.97 to 2.13; P = .07) but not nuclear sclerosis cataract. For current smokers of fewer than 20 cigarettes per day, no increased risks were observed of total, nuclear sclerosis, or posterior subcapsular cataract.. These data provide support for the hypothesis that cigarette smoking increases the risk of developing both nuclear sclerosis and posterior subcapsular cataract.

Topics: Adult; Aged; Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Cataract; Follow-Up Studies; Humans; Incidence; Logistic Models; Male; Middle Aged; Neoplasms; Physicians; Prospective Studies; Risk Factors; Smoking

Topics: Animals; beta Carotene; Carotenoids; Humans; Neoplasms; Vitamin E

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Heart Diseases; Humans; Male; Neoplasms

Increased intake of vegetables, fruits, and carotenoids and elevated blood levels of beta-carotene are consistently associated with reduced risk of lung cancer in epidemiologic studies. Epidemiologic research also suggests that carotenoids may reduce the risk of other cancers, although the evidence is less extensive and consistent. The simplest explanation is that beta-carotene is protective. However, the possible roles of other carotenoids, other constituents of vegetables and fruits, and associated dietary patterns have not been adequately explored. To evaluate these alternative hypotheses, we are undertaking three lines of research. (a) With dietary data from the 1987 National Health Interview Survey and the 1982-1984 Epidemiologic Follow-up of the first National Health and Nutrition Examination Study, we have determined which food groups and nutrients are highly correlated with vegetable and fruit intake. (b) We have developed and characterized a liquid chromatography method for optimal recovery and resolution of the common carotenoids in blood, specifically lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene. (c) In a population-based case-control study of lung cancer in white men in New Jersey, we are assessing whether estimates of the intake of the individual carotenoids might produce stronger inverse associations than estimates of provitamin A carotenoids based on current food composition tables.

Topics: beta Carotene; Carotenoids; Case-Control Studies; Chromatography, Liquid; Diet Surveys; Energy Intake; Fruit; Humans; Lung Neoplasms; Neoplasms; Prospective Studies; Retrospective Studies; Stomach Neoplasms; Vegetables

Topics: Aging; beta Carotene; Carotenoids; Education; Environmental Pollution; Humans; Neoplasms; United States; United States Environmental Protection Agency; United States Food and Drug Administration

The associations between serum alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and selenium levels and the subsequent occurrence of different cancers of low incidence were investigated in a nested case-control study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. During follow-up from the baseline in 1968-1972 to the end of 1977, a total of 115 cancers of the lip, oral cavity, pharynx, larynx, esophagus, liver, gallbladder, kidney, urinary bladder, brain, and skin were reported to the nationwide Finnish Cancer Registry. Alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and selenium concentrations were determined from stored serum samples collected from these cancer cases and matched controls at baseline. Several sites indicated an elevated risk of cancer at low levels of the serum variables, although only a few of these associations were statistically significant. Only melanoma patients had significantly lower serum alpha-tocopherol and beta-carotene levels than corresponding controls. Since the numbers of cancer cases were small, no firm conclusions can be drawn from these results until they have been confirmed in studies based on larger cohorts or on pooled data from several small samples.

Topics: Adult; Aged; beta Carotene; Carotenoids; Cohort Studies; Female; Finland; Humans; Incidence; Male; Mass Screening; Middle Aged; Neoplasms; Retinol-Binding Proteins; Selenium; Vitamin A; Vitamin E

In the Physicians' Health Study, a randomized, placebo-controlled, double-blind trial of aspirin in the reduction of cardiovascular mortality and beta-carotene in decreasing cancer incidence, 33,223 subjects were eligible and willing to enter the trial. Instead of randomizing this group immediately, all participants received identical calendar packs that contained active aspirin and beta-carotene placebo. Following an 18-week run-in, only 22,071 subjects who remained eligible and willing and had taken at least 2/3 of their pills were randomized. We estimated the effect of the run-in as follows: pill taking compliance increased 20-41 per cent; sample size decreased 34 per cent; duration of follow-up decreased 7 per cent which resulted in a 7 per cent decrease in the expected event rate for the placebo group. To estimate these changes, we made assumptions about compliance and outcome risk for those excluded by the run-in. Our conclusion, however, about the net effect of the run-in on the power of the study remains constant across variations in a number of those assumptions. The power with the run-in, with 22,071 good compliers was typically higher, and never more than negligibly lower, than the power without the run-in, with 33,223 good and poor compliers. In addition, savings from enrolling 11,152 fewer subjects in the trial resulted from the use of the run-in.

Topics: Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Data Interpretation, Statistical; Double-Blind Method; Humans; Neoplasms; Patient Compliance; Randomized Controlled Trials as Topic; Research Design; Surveys and Questionnaires

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

Topics: Animals; beta Carotene; Carotenoids; Cell Physiological Phenomena; Cells; Humans; Isotretinoin; Neoplasms; Vitamin A

A unique case-control study design including family members of cases and controls was used to assess the association between serum beta-carotene and cancer. The cases (n = 389) were incident cancer cases diagnosed between 1981 and 1984 in Wellington, New Zealand, and the controls (n = 391) were hospital patients without cancer. Both cases and controls were on a home diet at the time beta-carotene levels were measured. Since findings concerning patients who have already been diagnosed with cancer may reflect changes that occurred subsequent to development of cancer, family members of cancer patients (n = 618) and control patients (n = 675) were included, giving a total of 2,073 study participants. Low levels of beta-carotene were observed for individuals with a number of cancers, including cancers of the lung stomach, esophagus, small intestine, cervix, and uterus. Low levels of beta-carotene were also found in the relatives of these cancer patients. These differences persisted after stratification by current cigarette smoking. The strongest findings were those for lung cancer. Excluding adenocarcinoma, lung cancer patients had average serum beta-carotene levels of 40.2 micrograms/dl, 25.9 micrograms/dl lower than those of controls, adjusted for age, sex, and length of sample storage (p less than 0.01). Family members of the lung cancer patients also had lower values than family members of control patients, with an adjusted difference of 10.8 micrograms/dl (p less than 0.01). Odds ratio estimates for lung cancer by quartiles of beta-carotene residuals ranged from 3.6 (90% confidence interval (CI) 1.1-12.2) for the second-highest quartile to 6.6 (90% CI 1.9-23.0) for the lowest quartile (test for trend, p less than 0.001). Patients with cancers of the breast, colon, prostate, and skin did not have lower levels of serum beta-carotene than expected. Family members of individuals with these cancers also did not have lower levels of serum beta-carotene. The cancer sites that were associated with serum beta-carotene are, in general, sites for which smoking is a strong risk factor, and the sites that were not associated with beta-carotene do not have smoking as a risk factor.

Topics: Adenocarcinoma; Adult; beta Carotene; Carotenoids; Case-Control Studies; Family; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; New Zealand; Smoking

In a one year-study, 9 healthy human donors were being supplemented with beta-carotene (BC) plus canthaxanthin (CX), to determine the effect of carotenoids on chromosomal damage (micronuclei) induced in the donors' lymphocyte cell cultures by exposure to bleomycin (BLM), an antineoplastic drug that has been shown to produce chromosomal aberrations through the production of free radicals. The first four months monitoring data, including determination of carotenoid blood levels, are here reported. These data show that carotenoid supplementation significantly decrease (up to 50%) the formation of micronuclei induced by BLM in human lymphocyte cell cultures. This decrease is in correlation with carotenoid blood levels.

Topics: Adult; beta Carotene; Bleomycin; Canthaxanthin; Carotenoids; Chromosome Aberrations; Female; Humans; Lymphocytes; Male; Neoplasms

Topics: beta Carotene; Carotenoids; Diet; Humans; Neoplasms

From 1968 to 1977, the association between the level of vitamin A in serum and the subsequent incidence of cancer was examined in a longitudinal study of 36,265 persons initially aged 15-99 years in 25 population groups in Finland. During a mean follow-up of 8 years, 766 cancers were diagnosed. Serum retinol, retinol-binding protein, and beta-carotene levels were measured from frozen serum samples (stored at -20 degrees C) drawn from these persons before the start of follow-up and from 1,419 controls matched for sex, age, and place of residence who did not develop cancer during follow-up. The mean level of serum retinol among the cancer cases was 645 micrograms/liter for men and 587 micrograms/liter for women. The corresponding levels in the controls were 3.3% and 2.8% higher. There was an inverse gradient between serum retinol level and the occurrence of cancer among men. This association was, however, mainly concentrated in the first 2 years of follow-up. The mean level of serum beta-carotene was 72.3 micrograms/liter among male cases and 119.5 micrograms/liter among female cases. The corresponding levels of the controls were 14.0% and 5.5% higher. The differences were particularly clear with regard to lung cancer. These findings suggest that the association between retinol and cancer may be due to preclinical cancer and that there may be an association between beta-carotene and cancer.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta Carotene; Blood Pressure; Carotenoids; Female; Finland; Humans; Longitudinal Studies; Male; Mass Screening; Middle Aged; Neoplasms; Parity; Registries; Risk Factors; Sex Factors; Smoking; Vitamin A; Vitamin E

Topics: beta Carotene; Carotenoids; Diet; Humans; Leukoplakia, Oral; Neoplasms; Tretinoin

Topics: Adult; beta Carotene; Carotenoids; Cholesterol; Female; Humans; Lutein; Male; Neoplasms; Risk Factors

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

Topics: beta Carotene; Carotenoids; Diet; Humans; Neoplasms

Topics: beta Carotene; Canthaxanthin; Carotenoids; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neoplasms

The serum levels of the cholesterol derivative 1-keto-24-methyl-25-hydroxycholecalciferol found in patients with cancer varies after surgical, chemical or radiotherapy treatments. The serum level associated with the vitamin profile has a predictive value for evaluating progress of the disease and therapeutic efficacy. The detection, identification and assay of a vitamin D3 derivative, 1-keto-24-methyl-25-hydroxycholecalciferol, named carcinomedin by us, in the serum of cancer patients was described in prior work. Also, the assay of carcinomedin, combined with those of serum levels of vitamin A, beta-carotene and alpha-tocopherol indicated a statistically significant correlation between these parameters and the localization of the primary neoplastic mass. In spite of the probable connection between carcinomedin and the presence of a neoplastic mass, several questions remain unanswered. In particular, it may be asked if the stage and progression of the tumor, surgical, chemotherapeutic or radiotherapeutic treatments may be related with any type of change in the serum levels of carcinomedin and fat soluble vitamins? To verify and respond to these questions, patients with various cancers (stomach, esophagus, breast, ovaries, uterus, etc.) were followed for three years. Clinical data were compared to analytical data supplied by assays of carcinomedin and the fat soluble vitamins.

Topics: Adult; Aged; beta Carotene; Biomarkers, Tumor; Calcitriol; Carotenoids; Female; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Vitamin A; Vitamin E

Topics: beta Carotene; Carotenoids; Humans; Neoplasms; Risk Factors; Vitamin A

In the BUPA Study, a prospective study of 22,000 men attending a screening centre in London, serum samples were collected and stored. The concentration of beta-carotene was measured in the stored serum samples from 271 men who were subsequently notified as having cancer and from 533 unaffected controls, matched for age, smoking history and duration of storage of the serum samples. The mean beta-carotene level of the cancer subjects was significantly lower than that of their matched controls (198 and 221 micrograms l-1 respectively, P = 0.007). The difference was apparent in subjects from whom blood was collected several years before the diagnosis of the cancer, indicating that the low beta-carotene levels in the cancer subjects were unlikely to have been simply a consequence of pre-clinical disease. Men in the top two quintiles of serum beta-carotene had only about 60% of the risk of developing cancer compared with men in the bottom quintile. The study was not large enough to be able to indicate with confidence the sites of cancer for which the inverse association between serum beta-carotene and risk of cancer applied, though the association was strongest for lung cancer. The association may be due to beta-carotene affecting the risk directly or it may reflect an indirect association of cancer risk with some other component of vegetables or with a nonvegetable component of diet that is itself related to vegetable consumption.

Topics: Adult; beta Carotene; Blood Preservation; Carotenoids; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Smoking; Time Factors

Many investigations suggested relations between fat soluble vitamin levels in blood and incidence of cancer. These studies are concerning both therapeutical efficiency of vitamins intake, seric levels and cancer risk, and the supposed correlation between blood fat soluble vitamin levels and the cancer localization. The purpose of the present study was to investigate whether the alterations of fat soluble vitamin levels (A-vitamin, beta-carotene and alpha-tocopherol) were correlated not only to carcinogenic processes but also to the localizations of their developments. In a former article, we have found that an abnormal ketone derivative of D3 vitamin (1-keto-24-methyl-25-hydroxycholecalciferol) or carcinomedin was present in the serum of all cancer patients and absent in that of healthy control subjects. Serum levels of the four above substances were determined in 1068 subjects suffering from differently localized cancers and in 880 healthy subjects. A statistical multidimensional analysis of data led a separate five groups of cancer types (p less than 0.001). Within each group alterations of vitamin spectra, compared to controls, were identical; between groups they were significantly different. These groups were: anal and intestinal cancer; pancreatic, hepatic, oesophageal and gastric cancer; laryngeal and lung cancer; uro-genital and breast cancer; brain cancer. All these groups are statistically different from the reference one (p less than 0.001). This grouping roughly corresponds to the embryologic origin of affected organs. This suggests that carcinogenesis may alter fat soluble vitamin metabolism, specifically in various forms of cancer, or these alterations of vitamin metabolism are in some way involved in the carcinogenic process.

Topics: Adult; beta Carotene; Breast Neoplasms; Calcitriol; Carotenoids; Digestive System Neoplasms; Female; Humans; Intestinal Neoplasms; Laryngeal Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasms; Nervous System Neoplasms; Urogenital Neoplasms; Vitamin A; Vitamin E

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

A cohort of 10,473 residents of Leisure World, Laguna Hills, CA, who were initially free of cancer were followed from 1981 to 1986. A health survey questionnaire completed by all cohort members included usual frequencies of consumption of certain food items, including vegetables, fruits, dairy products, liver, and cereal, as well as specific information on brand and formulation of vitamin supplements containing vitamins A, C, or E. Pathologic diagnosis of incident cancer was confirmed in 643 persons (56 lung, 110 colon, 59 bladder, 93 prostate, 123 female breast, and 202 cancers of other sites). Our study found little indication that increased intake of vitamin A or beta-carotene from the diet or supplements protects against the development of cancer overall. Dietary vitamin A intake was highly associated with smoking status; 25% of current smokers were in the highest third of dietary vitamin A consumption versus 32% of past smokers and 36% of never-smokers. In males who never smoked there was some indication that cancer rates decreased with increasing vitamin A intake, but the results were not statistically significant.

Topics: beta Carotene; Carotenoids; Diet; Female; Humans; Lung Neoplasms; Male; Neoplasms; Prospective Studies; Risk; Smoking; Vitamin A

Assay of serum levels of retinol, retinyl palmitate, alpha-carotene, and beta-carotene to assess nutritional status, to trials of retinol and/or beta-carotene to assess nutritional status, to monitor compliance with medication schedules, and to conduct toxicity surveillance. The optimal assay method for clinical trial use represents a balance between analytical power and speed/simplicity. Three such methods were evaluated by means of shared samples between two laboratories. Each method required less than 15 minutes per assay and detected all of the analytes of interest. Careful evaluation of calibration materials and procedures permitted different laboratories using different methods to produce results with an interlaboratory variability smaller than the within-laboratory variability for each separate method. Typical precisions for the analytes in serum samples are: retinol, 0.06 relative standard deviation (RSD; standard deviation divided by mean value); retinyl palmitate, 0.08 RSD; alpha-carotene, 0.15 RSD; and beta-carotene, 0.11 RSD. Application of these methods to several hundred samples indicated that retinyl palmitate and beta-carotene levels were indicative of administered retinol and beta-carotene, whereas retinol itself was not. Population variability in pretreatment serum levels of these micronutrients expressed as RSD (retinol, 0.24; alpha-carotene, 1.11; and beta-carotene, 0.98) far exceeded the analytical imprecision in these determinations, confirming that the present assays could meet the needs of current clinical intervention trials.

Topics: beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Diterpenes; Humans; Individuality; Neoplasms; Retinyl Esters; Vitamin A

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

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

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; DNA; Furocoumarins; Humans; Neoplasms; Skin; Ultraviolet Rays; Vegetables

Topics: Abnormalities, Drug-Induced; Animals; beta Carotene; Carotenoids; Cattle; Diet; Female; Fruit; Humans; Milk; Neoplasms; Pregnancy; Retinoids; Risk; Vegetables; Vitamin A

Topics: beta Carotene; Carotenoids; Female; Humans; Male; Neoplasms; Risk; Thailand; Vitamin A

Topics: beta Carotene; Carotenoids; Humans; Neoplasms; Vitamin A; Vitamin E

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

Serum specimens were obtained from over 6800 men of Japanese ancestry in Hawaii from 1971 to 1975. Since then, the following numbers of newly diagnosed cancer cases have been identified: 81 colon, 74 lung, 70 stomach, 32 rectum, and 27 urinary bladder. The stored sera of the cases and 302 controls were tested to determine their beta-carotene, vitamin A, and vitamin E levels. There was no association of either vitamin A or E with any of the cancers. For serum beta-carotene, there was a significant association only with lung cancer (20.0 micrograms/dl in cases versus 29.0 in controls, P less than 0.005). The lung cancer odds ratio for men in the lowest quintile of beta-carotene was 3.4 relative to men in the highest quintile. These findings suggest that a low serum beta-carotene level is a predictor of increased lung cancer risk in men.

Topics: beta Carotene; Carotenoids; Hawaii; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Neoplasms; Risk; Vitamin A; Vitamin E; Vitamins

Topics: beta Carotene; Cancer Care Facilities; Carotenoids; England; Hospitals, Special; Humans; Neoplasms

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

Some epidemiological studies have suggested an inverse relation between serum cholesterol concentration and mortality from cancer. Two hypotheses that might explain such a relation were investigated. To assay potentially deleterious effects of hypocholesterolaemia on cell membranes the lipid content and fluidity of blood mononuclear cells were measured in healthy male volunteers with a wide range of serum cholesterol concentration (3.2-10.0 mmol/l (124-387 mg/100 ml)). Fluidity, unesterified cholesterol content, and the ratio of cholesterol to phospholipid were unrelated to serum cholesterol and to low density lipoprotein cholesterol concentrations. Similar measurements were made on fibroblasts and mononuclear cells incubated with a range of concentrations of low density lipoprotein; fluidity was altered only at extremely low concentrations, suggesting that changes in cell membranes are unlikely to occur at serum cholesterol concentrations attainable by dietary or drug treatment of hyperlipidaemia. In the same population direct relations were confirmed between low density lipoprotein concentration and plasma concentrations of retinol and beta carotene. This is compatible with the suggestion that an association between low cholesterol concentration and cancer may be secondary to a relation between low retinoid concentrations and cancer.

Topics: Adult; beta Carotene; Carotenoids; Cells, Cultured; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Fibroblasts; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Lymphocytes; Male; Middle Aged; Neoplasms; Phospholipids; Viscosity; Vitamin A

Faced with limited resources, the United States must set priorities for research to identify preventable causes of cancer. A quantitative approach to priority setting, based on principles of decision analysis and cost-effectiveness analysis, can offer guidance in this process. An illustrative application of such a model suggests that the National Institutes of Health-supported clinical trial of dietary beta-carotene offers a greater expected reduction in cancer mortality per research dollar than carcinogen bioassays of high-volume industrial chemicals such as p-dichlorobenzene. National research priorities should reflect the relative cost-effectiveness of such investments.

Topics: Animals; beta Carotene; Biological Assay; Carcinogens; Carotenoids; Chlorobenzenes; Cost-Benefit Analysis; Costs and Cost Analysis; Humans; Neoplasms; Policy Making; United States

Topics: beta Carotene; Carotenoids; Diet; Humans; Neoplasms

Topics: beta Carotene; Carotenoids; Cholesterol; Humans; Neoplasms; Vitamin E

Topics: Aged; Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Humans; Male; Middle Aged; Neoplasms; Random Allocation