beta-carotene and Cardiovascular-Diseases

β-carotene is widely available in plant-based foods, while the efficacy of β-carotene supplementation on cardiovascular disease (CVD) risk remains controversial. Hence, we performed a systematic review and meta-analysis on randomized controlled trials to investigate the associations between β-carotene supplementation and CVD risk as well as mortality. We conducted literature searches across eight databases and screened the publications from January 1900 to March 2022 on the topic of β-carotene treatments and cardiovascular outcomes. There were 10 trials and 16 reports included in the meta-analysis with a total of 182,788 individuals enrolled in the study. Results from the random-effects models indicated that β-carotene supplementation slightly increased overall cardiovascular incidence (RR: 1.04; 95% CI: 1.00, 1.08) and was constantly associated with increased cardiovascular mortality (RR: 1.12; 95% CI: 1.04, 1.19). Subgroup analyses suggested that, when β-carotene treatments were given singly, a higher risk of cardiovascular outcomes was observed (RR: 1.06; 95% CI: 1.01, 1.12). In addition, cigarettes smoking was shown to be a risk behavior associated with increased cardiovascular incidence and mortality in the β-carotene intervention group. In sum, the evidence of this study demonstrated that β-carotene supplementation had no beneficial effects on CVD incidence and potential harmful effects on CVD mortality. Further studies on understanding the efficacy of multivitamin supplementation in nutrient-deficient or sub-optimal populations are important for developing the tolerable upper intake level for β-carotene of different age and sex groups.

Topics: beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Randomized Controlled Trials as Topic; Vitamins

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

This review is aimed to provide a comprehensive overview of the physicochemical properties and extraction processes of red palm oil, its nutritional properties and applications in food. Crude palm oil is firstly extracted from the fruit mesocarp and processed into red palm oil using pre-treatment of crude palm oil, with deacidification steps, and deodorization via short-path distillation. These processes help to retain β-carotene and vitamin E in red palm oil. Palmitic, stearic and myristic acids are the saturated fatty acids in red palm oil, while the unsaturated fatty acids are oleic, linoleic and linolenic acids. It is reported to overcome vitamin A deficiency, promote heart health and have anti-cancer properties.

Topics: Antineoplastic Agents, Phytogenic; beta Carotene; Cardiovascular Diseases; Chemical Phenomena; Fatty Acids; Fatty Acids, Unsaturated; Food Handling; Humans; Liquid-Liquid Extraction; Nutritive Value; Palm Oil; Vitamin A Deficiency; Vitamin E

The present review aimed to quantify the association of dietary intake and circulating concentration of major dietary antioxidants with risk of total CVD mortality.. Systematic review and meta-analysis.. Systematic search in PubMed and Scopus, up to October 2017.ParticipantsProspective observational studies reporting risk estimates of CVD mortality across three or more categories of dietary intakes and/or circulating concentrations of vitamin C, vitamin E and β-carotene were included. A random-effects meta-analysis was conducted.. A total of fifteen prospective cohort studies and three prospective evaluations within interventional studies (320 548 participants and 16 974 cases) were analysed. The relative risks of CVD mortality for the highest v. the lowest category of antioxidant intakes were as follows: vitamin C, 0·79 (95 % CI 0·68, 0·89; I 2=46 %, n 10); vitamin E, 0·91 (95 % CI 0·79, 1·03; I 2=51 %, n 8); β-carotene, 0·89 (95 % CI 0·73, 1·05; I 2=34 %, n 4). The relative risks for circulating concentrations were: vitamin C, 0·60 (95 % CI 0·42, 0·78; I 2=65 %, n 6); α-tocopherol, 0·82 (95 % CI 0·76, 0·88; I 2=0 %, n 5); β-carotene, 0·68 (95 % CI 0·52, 0·83; I 2=50 %, n 6). Dose-response meta-analyses demonstrated that the circulating biomarkers of antioxidants were more strongly associated with risk of CVD mortality than dietary intakes.. The present meta-analysis demonstrates that higher vitamin C intake and higher circulating concentrations of vitamin C, vitamin E and β-carotene are associated with a lower risk of CVD mortality.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Cardiovascular Diseases; Diet; Eating; Female; Humans; Male; Middle Aged; Nutritional Status; Observational Studies as Topic; Prospective Studies; Risk; Risk Factors; 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

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

Atherosclerosis, the hardening of arteries under oxidative stress is related to oxidative changes of low density lipoproteins (LDL). The antioxidants prevent the formation of oxidized LDL during atherogenesis. Perhaps more than one mechanism is involved in the atherosclerosis disease where LDL is oxidized in all the cells of arterial wall during the development of this disease. The oxidation of LDL produces lipid peroxidation products such as isoprostans from arachidonic, eicosapentaenoic and docosahexaenoic acids, oxysterols from cholesterol, hydroxyl fatty acids, lipid peroxides and aldehydes. The lipid peroxidation bioassay can serve as a marker for the risk of cardiovascular. An in vivo test of levels of oxidative lipid damage is an early prediction of development of cardiovascular disease (CVD). Serum paraoxonase (PON) activity is correlated to severity of the coronary artery disease. The antioxidants level in the serum and serum paraoxonase activity provides information for the risk of CVD. The antioxidant enzyme superoxide dismutase is responsible for dismutation of superoxide, a free radical chain initiator. The subcellular changes in the equilibrium in favor of free radicals can cause increase in the oxidative stress which leads to cardiomyopathy, heart attack or cardiac dysfunction. The oxidative damage and defense of heart disease has been reported where dietary antioxidants protect the free radical damage to DNA, proteins and lipids. The ascorbic acid, vitamin C is an effective antioxidant and high vitamin E intake can reduce the risk of coronary heart disease (CHD) by inhibition of atherogenic forms of oxidized LDL. The vitamin A and beta-carotene protect lipid peroxidation and provitamin-A activity. It has been recently suggested that the protection of oxidative damage and related CVD is best served by antioxidants found in the fruits and vegetables. The oxidative damage and antioxidant protection of CVD have been described here.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Diet; Free Radicals; Humans; Lipid Peroxidation; Lipid Peroxides; Lipoproteins, LDL; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase

Antioxidant vitamin (vitamin E, beta-carotene, and vitamin C) are widely used for preventing major cardiovascular outcomes. However, the effect of antioxidant vitamin on cardiovascular events remains unclear.. We searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the proceedings of major conferences for relevant literature. Eligible studies were randomized controlled trials that reported on the effects of antioxidant vitamin on cardiovascular outcomes as compared to placebo. Outcomes analyzed were major cardiovascular events, myocardial infarction, stroke, cardiac death, total death, and any possible adverse events. We used the I(2) statistic to measure heterogeneity between trials and calculated risk estimates for cardiovascular outcomes with random-effect meta-analysis. Independent extraction was performed by two reviewers and consensus was reached. Of 293 identified studies, we included 15 trials reporting data on 188209 participants. These studies reported 12749 major cardiovascular events, 6699 myocardial infarction, 3749 strokes, 14122 total death, and 5980 cardiac deaths. Overall, antioxidant vitamin supplementation as compared to placebo had no effect on major cardiovascular events (RR, 1.00; 95%CI, 0.96-1.03), myocardial infarction (RR, 0.98; 95%CI, 0.92-1.04), stroke (RR, 0.99; 95%CI, 0.93-1.05), total death (RR, 1.03; 95%CI, 0.98-1.07), cardiac death (RR, 1.02; 95%CI, 0.97-1.07), revascularization (RR, 1.00; 95%CI, 0.95-1.05), total CHD (RR, 0.96; 95%CI, 0.87-1.05), angina (RR, 0.98; 95%CI, 0.90-1.07), and congestive heart failure (RR, 1.07; 95%CI, 0.96 to 1.19).. Antioxidant vitamin supplementation has no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, total death, and cardiac death.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Odds Ratio; Publication Bias; Randomized Controlled Trials as Topic; Risk; Vitamin E; Vitamins

Cardiovascular disease related to atherosclerosis represents nowadays the largest cause of morbidity and mortality in developed countries. Due to inflammatory nature of atherosclerosis, several studies had been conducted in order to search for substances with anti-inflammatory activity on arterial walls, able to exert beneficial roles on health. Researches investigated the role of dietary carotenoids supplementation on cardiovascular disease, due to their free radicals scavenger properties and their skills in improving low-density lipoprotein cholesterol resistance to oxidation. Nevertheless, literature data are conflicting: although some studies found a positive relationship between carotenoids supplementation and cardiovascular risk reduction, others did not find any positive effects or even prooxidant actions. This paper aimed at defining the role of carotenoids supplementation on cardiovascular risk profile by reviewing literature data, paying attention to those carotenoids more present in our diet (β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein, zeaxanthin, and astaxanthin).

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Atherosclerosis; beta Carotene; Cardiovascular Diseases; Carotenoids; Cholesterol, LDL; Clinical Trials as Topic; Cryptoxanthins; Diet; Free Radical Scavengers; Humans; Lutein; Lycopene; Oxygen; Risk; Xanthophylls; Zeaxanthins

Cardiovascular disease represents an unparalleled proportion of the global burden of disease and will remain the main cause of mortality for the near future. Fortunately, most premature cardiovascular deaths are preventable. Therefore, prevention becomes vital and diet has shown beneficial effects to protect from CVD (CVD). Fruits and vegetables are dietary sources of natural antioxidants and it is generally accepted that antioxidants in these foods are key in explaining the inverse association between fruits and vegetables intake and the risk of developing a cardiovascular event or having elevated levels of cardiovascular risk factors. Available evidence supports the central role of oxidative stress in the atherosclerosis process and the correlation between increased oxidative stress and vascular disease. Theoretically, antioxidants in fruits and vegetables are important in inhibiting oxidative mechanisms that lead to various degenerative diseases including CVD. However, results from many interventional trials using antioxidants given as supplements have not been concordant with previous positive findings from observational epidemiologic cohort studies. The present manuscript gives a brief overview of the relationship between natural antioxidants (specially vitamin C, vitamin E and beta-carotene) intake and the risk of CVD.

Topics: Aged; Antioxidants; beta Carotene; Cardiovascular Diseases; Cohort Studies; Diet; Dietary Supplements; Female; Fruit; Humans; Male; Meta-Analysis as Topic; Middle Aged; Oxidation-Reduction; Oxidative Stress; Randomized Controlled Trials as Topic; Risk Factors; Vegetables; Vitamin E; Vitamins

Carotenoids are naturally occurring organic pigments that are believed to have therapeutic benefit in treating cardiovascular disease (CVD) because of their antioxidant properties. However, prospective randomized trials have failed to demonstrate a consistent benefit for the carotenoid beta-carotene in patients at risk for CVD. The basis for this apparent paradox is not well understood but may be attributed to the distinct antioxidant properties of various carotenoids resulting from their structure-dependent physicochemical interactions with biologic membranes. To test this hypothesis, we measured the effects of astaxanthin, zeaxanthin, lutein, beta-carotene, and lycopene on lipid peroxidation using model membranes enriched with polyunsaturated fatty acids. The correlative effects of these compounds on membrane structure were determined using small-angle x-ray diffraction approaches. The nonpolar carotenoids, lycopene and beta-carotene, disordered the membrane bilayer and stimulated membrane lipid peroxidation (>85% increase in lipid hydroperoxide levels), whereas astaxanthin (a polar carotenoid) preserved membrane structure and exhibited significant antioxidant activity (>40% decrease in lipid hydroperoxide levels). These results suggest that the antioxidant potential of carotenoids is dependent on their distinct membrane lipid interactions. This relation of structure and function may explain the differences in biologic activity reported for various carotenoids, with important therapeutic implications.

Topics: beta Carotene; Cardiovascular Diseases; Carotenoids; Endothelium, Vascular; Humans; Lipid Peroxidation; Lutein; Lycopene; Oxidative Stress; Xanthophylls; Zeaxanthins

Topics: Animals; beta Carotene; Cardiovascular Diseases; Folic Acid; Humans; Vitamin E

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

Results from experimental and epidemiologic studies suggest an influence of oxidative stress on development and progression of atherosclerosis in man. Prospective endpoint studies failed to support this hypothesis. The current literature is summarized in this review.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Antioxidants; Arteriosclerosis; Ascorbic Acid; Aspirin; beta Carotene; Cardiovascular Diseases; Controlled Clinical Trials as Topic; Double-Blind Method; Female; Follow-Up Studies; Free Radicals; Humans; Male; Nutritional Physiological Phenomena; Oxidative Stress; Placebos; Platelet Aggregation Inhibitors; Primary Prevention; Prospective Studies; Ramipril; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Tocopherols; Vitamins

Topics: Arteriosclerosis; beta Carotene; Biomarkers; Blood Chemical Analysis; Cardiovascular Diseases; Cataract; Humans; Hyperthyroidism; Liver Diseases; Lung Neoplasms; Pancreatic Diseases; Smoking; Specimen Handling; Stress, Physiological

Topics: Adult; Aged; alpha-Tocopherol; Antioxidants; Aspirin; beta Carotene; Cardiovascular Diseases; Coronary Disease; Dietary Supplements; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Vitamins

Oxidised LDL is thought to play an important part in the pathogenesis of atherosclerosis. Observational studies have associated alpha tocopherol (vitamin E), beta carotene, or both, with reductions in cardiovascular events, but not clinical trials. We did a meta-analysis to assess the effect of these compounds on long-term cardiovascular mortality and morbidity.. We analysed seven randomised trials of vitamin E treatment and, separately, eight of beta carotene treatment; all trials included 1000 or more patients. The dose range for vitamin E was 50-800 IU, and for beta carotene was 15-50 mg. Follow-up ranged from 1.4 to 12.0 years.. The vitamin E trials involved a total of 81788 patients and the beta carotene trials 138113 in the all-cause mortality analyses. Vitamin E did not provide benefit in mortality compared with control treatment (11.3 vs 11.1%, odds ratio 1.02 [95% CI 0.98-1.06] p=0.42) or significantly decrease risk of cardiovascular death (6.0 vs 6.0%, p=0.86) or cerebrovascular accident (3.6 vs 3.5%, p=0.31). Beta carotene led to a small but significant increase in all-cause mortality (7.4 vs 7.0%, 1.07 [1.02-1.11] p=0.003) and with a slight increase in cardiovascular death (3.4 vs 3.1%, 1.1 [1.03-1.17] p=0.003). No significant heterogeneity was noted for any analysis.. The lack of a salutary effect was seen consistently for various doses of vitamins in diverse populations. Our results, combined with the lack of mechanistic data for efficacy of vitamin E, do not support the routine use of vitamin E.

Topics: alpha-Tocopherol; Antioxidants; beta Carotene; Cardiovascular Diseases; Cause of Death; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Risk Factors

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

It is logical that the requirement for antioxidant nutrients depends on a person's exposure to endogenous and exogenous reactive oxygen species. Since cigarette smoking results in an increased cumulative exposure to reactive oxygen species from both sources, it would seem cigarette smokers would have an increased requirement for antioxidant nutrients. Logic dictates that a diet high in antioxidant-rich foods such as fruits, vegetables, and spices would be both protective and a prudent preventive strategy for smokers. This review examines available evidence of fruit and vegetable intake, and supplementation of antioxidant compounds by smokers in an attempt to make more appropriate nutritional recommendations to this population.

Topics: Antioxidants; beta Carotene; Biomarkers; Cardiovascular Diseases; Cohort Studies; Dietary Supplements; Feeding Behavior; Food-Drug Interactions; Fruit; Humans; Lung Neoplasms; Oxidative Stress; Randomized Controlled Trials as Topic; Smoking; Vegetables; Vitamin A

People who consume a diet rich in fruit and vegetables have lower risks of cancer, cardiovascular disease and all-cause mortality. Many prospective cohort studies have reported inverse associations between dietary intake or blood levels of beta-carotene and risks of cancer. Several large-scale trials were set up to assess whether beta-carotene supplementation might reduce the risk of cancer. Subsequently, evidence emerged from basic research which indicated that oxidative modification of low-density lipoprotein cholesterol increases its atherogenicity. The evidence from basic research, and epidemiological evidence for a possible protective effect of antioxidant vitamins for cardiovascular disease was strongest for vitamin E. More recently, further trials were set up to examine if supplementation with anti-oxidant vitamins might also reduce the risk of cardiovascular disease. This review summarises the available randomised evidence from published trials of beta-carotene supplementation involving 70,000 people from 3 large-scale trials in healthy populations and on vitamin E supplementation involving 29,000 patients at high-risk of cardiovascular disease from 5 large-scale trials. The results of these trials have been disappointing and failed to confirm any protective effect of these vitamins for either cancer or for cardiovascular disease.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Carotenoids; Cholesterol, LDL; Humans; Lycopene; Oxidative Stress; Randomized Controlled Trials as Topic; Risk Assessment; Vitamin E; Vitamins

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Carotenoids; Coenzymes; Free Radicals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins, LDL; Lycopene; Oxidative Stress; Primary Prevention; Risk Factors; Ubiquinone; Vitamin E

Naturally occurring antioxidants such as vitamin E, beta-carotene, and vitamin C can inhibit the oxidative modification of low density lipoproteins. This action could positively influence the atherosclerotic process and, as a consequence, the progression of coronary heart disease. A wealth of experimental studies provide a sound biological rationale for the mechanisms of action of antioxidants, whereas epidemiologic studies strongly sustain the "antioxidant hypothesis." To date, however, clinical trials with beta-carotene supplements have been disappointing, and their use as a preventive intervention for cancer and coronary heart disease should be discouraged. Only scanty data from clinical trials are available for vitamin C. As to vitamin E, discrepant results have been obtained by the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study with a low-dose vitamin E supplementation (50 mg/d) and the Cambridge Heart Antioxidant Study (400-800 mg/d). The results of the GISSI-Prevenzione (300 mg/d) and HOPE (400 mg/d) trials suggest the absence of relevant clinical effects of vitamin E on the risk of cardiovascular events. Currently ongoing are several large-scale clinical trials that will help in clarifying the role of vitamin E in association with other antioxidants in the prevention of atherosclerotic coronary disease.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Clinical Trials as Topic; Female; Humans; Lipid Peroxidation; Male; MEDLINE; Randomized Controlled Trials as Topic; Vitamin E; Vitamins

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

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

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Flavonoids; Humans; Probucol; Vitamin E

Observational studies have shown an inverse relationship between consumption of fruits and vegetables high in beta-carotene, vitamins C and E, and ischemic heart disease (IHD) and stroke. In large observational studies, beta- carotene reduced the risk of IHD events in men, particularly in smokers. In contrast, four large randomized trials did not reveal a reduction in cardiovascular events with beta-carotene use, and may, in fact, increase IHD and total mortality in male smokers. There have been only a few large observational studies and one randomized trial with vitamin C, which have shown no beneficial or deleterious impact of this vitamin on cardiovascular events. Most large observational studies have shown an inverse relationship between vitamin E and IHD. However, a meta-analysis of the four randomized trials done in Europe and America involving a total of 51,000 participants allocated to vitamin E or placebo for 1.4 to 6 years, did not demonstrate a reduction in cardiovascular and IHD mortality and nonfatal myocardial infarction. Currently, there are no data to support the use of these vitamins to reduce the risk of cardiovascular events. Trials are in progress to determine whether a longer duration of administration of vitamin E or the association of vitamin E with cofactors may reduce cardiovascular events.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Endothelium, Vascular; Humans; Male; Myocardial Ischemia; Randomized Controlled Trials as Topic; Vitamin E

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

The faith that an oxidizing of LDL is necessary for he foam cell formation is basically for the so called oxidative hypothesis of atherosclerosis. The role of LDL-oxidation for the atherosclerotic plaque formation, as well as its association with inflammatory processes in the vascular wall, are well established. The important conclusion of this hypothesis is the possible role of the antioxidants attenuating atherosclerotic mechanisms. The advances in studying the principal antioxidant vitamins E, C and beta-carotene effects, revealed a great part of their molecular mechanisms, which are not necessarily antioxidative. The important aspects of the cooperative antioxidant action are revealed too, including the so called tocopherol-mediated peroxidation, suggesting the need for the co-antioxidants for effective antioxidant defense. In the recent years many vitamin antioxidant supplementations are used. The epidemiological results of such supplementation do not always reveal the same beneficial effects as expected theoretically or based on the observations made with a diet rich in fruits and vegetables. The present paper generalizes the thought concerning the impact of oxidized LDL in atherosclerosis, as well as mechanisms of action and pharmacokinetiks of the most widely used antioxidant vitamins--E, C and beta-carotene, and the perspectives of their usage in cardiovascular prophylaxy bazed upon the recent experience in antioxidant vitamin supplementation.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Dietary Supplements; Humans; Lipoproteins, LDL; Oxidative Stress; Vitamin E

Topics: beta Carotene; Cardiovascular Diseases; Humans; Meta-Analysis as Topic; Risk Factors; Statistics as Topic

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Diet; Drug Therapy, Combination; Humans; Risk Factors; Vitamin E

Naturally occurring antioxidants like vitamin E, beta-carotene, and vitamin C can inhibit the oxidative modification of low-density lipoproteins. This action could positively influence the atherosclerotic process and, as a consequence, the progression of coronary heart disease. A wealth of experimental studies provide a sound biological rationale for the mechanisms of action of antioxidants, whereas epidemiological studies strongly sustain the 'antioxidant hypothesis'. To data, however, clinical trials with beta-carotene supplements have been disappointing and their use as a preventive intervention for cancer and coronary heart disease should be discouraged. Only scant data from clinical trials are available for vitamin C. As for vitamin E, discrepant results have been obtained by the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study with a low-dose vitamin E supplementation (50 mg daily) and the Cambridge Heart Antioxidant Study (400-800 mg daily). Currently ongoing are several large-scale clinical trials that will help in clarifying the role of vitamin E in the prevention of atherosclerotic coronary disease.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Humans; Lipoproteins, LDL; Randomized Controlled Trials as Topic; Vitamin E

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; Cardiovascular Diseases; Female; Humans; Male; Randomized Controlled Trials as Topic; Vitamin E

Considerable interest has risen in the idea that oxidative stress is instrumental in the etiology of numerous human diseases. Oxidative stress can arise through the increased production of reactive oxygen species (ROS) and/or because of a deficiency of antioxidant defenses. Antioxidant deficiencies can develop as a result of decreased antioxidant intake (such as vitamins C and E), synthesis of enzymes (such as superoxide dismutase and glutathione peroxidase) or increased antioxidant utilization. Insufficient antioxidant enzyme synthesis may in turn be due to decreased micronutrient availability (such as selenium, magnese, copper and zinc). Of those diseases linked with oxidative stress, cardiovascular disease provides the strongest evidence for the protective role of antioxidants. A high consumption of fruit and vegetables, which are good sources of antioxidants, is associated with a lower coronary risk. More specifically, there is evidence of a reduced coronary risk in populations with high blood levels of the antioxidant nutrients, vitamins C and E. Evidence is also accumulating that diabetes, and microvascular complications associated with diabetes, involve oxidative stress and have compromised antioxidant status. In addition, patients who develop acute respiratory distress syndrome (ARDS) also exhibit clear evidence of oxidative stress. Definitive proof for active oxygen formation and oxidative cell damage being causative rather than a result of other underlying these pathologies remains elusive; however, evidence is sufficiently compelling to suggest that antioxidants are potential therapeutic agents in the above conditions.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Diabetes Mellitus; Humans; Oxidative Stress; Respiratory Distress Syndrome; Vitamin E

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Humans; Nutritional Requirements; Randomized Controlled Trials as Topic; Vitamin A; Vitamins

Topics: Animals; Antioxidants; beta Carotene; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Vitamin E

To review prospective epidemiological studies and randomized clinical trials regarding the role of antioxidant vitamins (vitamins E and C and beta-carotene) in the prevention of cardiovascular diseases.. Computerized (MEDLINE and Science Citation Index) and manual searches on the role of antioxidant vitamins in cardiovascular disease management.. Only prospective epidemiological studies and double-blind, controlled, randomized clinical trials, including at least 100 participants and providing sufficient data to allow quantitative estimation of the effects of vitamin intake were included. Retrospective epidemiological evaluations and other retrospective studies were excluded. Geographic correlation studies of population-based intake of antioxidants and cardiovascular disease rates were also excluded due to the potential large impact of confounders in cross-sectional analyses.. Relative risk was evaluated for all prospective epidemiological studies. Relative risk reductions were evaluated for clinical trials. The Mantel-Haenszel method was used to estimate the relative risk reduction in clinical trials when not calculated in the original publication. A formal meta-analysis was not performed because very significant differences among study populations, type (supplemental versus dietary) and dosage of antioxidant vitamins, duration of follow-up and overall study design exist for both epidemiological investigations and clinical trials, and the pooling of study results could be misleading.. Prospective epidemiological investigations suggest a reduction in cardiovascular risk associated with increased intake of antioxidant vitamins, particularly vitamin E. Randomized clinical trials remain inconclusive with regard to the role of vitamin E in cardiovascular protection. The large, randomized clinical trials of beta-carotene in primary prevention show no effect and potential for harm associated with the use of beta-carotene. There are inconclusive and insufficient epidemiological and clinical trial data with regard to the role of vitamin C in cardiovascular protection. Overall, it is recommended that wide-spread use of antioxidant vitamins in cardiovascular protection should not be instituted and should await the results of further ongoing clinical trials.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Clinical Trials as Topic; Epidemiologic Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin E; Vitamins

This review summarizes the scientific evidence for a possible role of antioxidants in the prevention of coronary heart disease (CHD). Dietary antioxidants include vitamin E, vitamin C and beta-carotene, whereas selenium is an integral part of the antioxidant enzyme glutathione peroxidase. Experimental studies suggest that the oxidation of low-density lipoproteins (LDL) in the vessel wall plays an important role in the development of atherosclerotic lesions. The resistance of LDL to oxidation is increased by antioxidant supplementation, at least in vitro. Epidemiological studies have not demonstrated unequivocally that a high intake of antioxidants leads to a decreased risk of CHD. Studies on dietary intake and serum levels of antioxidants do point in the direction of a preventive effect of antioxidants, whereas the results of intervention studies are less conclusive. Beta-carotene supplementation is not associated with any decrease in CHD; high doses of vitamin E may be beneficial, but results from large trials are to be awaited. General preventive measures based on antioxidant supplementation are not yet justifiable.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Coronary Disease; Diet; Female; Free Radicals; Humans; Lipoproteins, LDL; Male; Oxidation-Reduction; Prospective Studies; Risk Factors; Selenium; Vitamin E

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

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

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

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

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

To review prospective epidemiologic studies and randomized trials regarding the role of antioxidant vitamins (vitamins E and C and beta-carotene) in the prevention of cardiovascular disease, with emphasis on differences in results obtained by these two types of studies.. Computerized and manual searches of the literature on antioxidant vitamins and cardiovascular disease.. Prospective epidemiologic studies and randomized trials that included 100 or more participants and provided quantified estimates of antioxidant vitamin intake.. Comparisons of relative risk reductions (RRR) across observational studies and randomized trials, including assessment of dose-response relations.. All three large epidemiologic cohort studies of vitamin E noted that high-level vitamin E intake or supplementation was associated with a significant reduction in cardiovascular disease (RRR range, 31% to 65%), as measured by various fatal and nonfatal cardiovascular end points. To obtain these reductions, vitamin E supplementation must last at least 2 years. Less consistent reductions were seen in studies of beta-carotene (RRR range, -2% to 46%) and vitamin C (RRR range, -25% to 51%). Considerable biases in observational studies, such as different health behaviors of persons using antioxidants, may account for the observed benefit. By contrast, none of the completed randomized trials showed any clear reduction in cardiovascular disease with vitamin E, vitamin C, or beta-carotene supplementation. The trials were not specifically designed to assess cardiovascular disease, did not provide data on nonfatal cardiovascular end points, may have had insufficient treatment durations, and used suboptimal vitamin E doses. The completed trials were of adequate size to indicate that the true therapeutic benefit of vitamin E and other antioxidants in reducing fatal cardiovascular disease (a survival benefit as long as 5 years) is probably more modest than the epidemiologic data suggest.. The epidemiologic data suggest that antioxidant vitamins reduce cardiovascular disease, with the clearest effect for vitamin E; however, completed randomized trials do not support this finding. Much of this controversy should be resolved by the ongoing large-scale and long-term randomized trials designed specifically to evaluate effects on cardiovascular disease.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Carotenoids; Epidemiologic Methods; Humans; Randomized Controlled Trials as Topic; Vitamin E

The tremendous chemical potential of the highly conjugated double bonds in carotenoids has driven research into their protective role in cardiovascular disease development. Prevention of low-density-lipoprotein oxidation and reduction of oxidative stress at the plaque formation are popular hypotheses underlying this research. Many epidemiologic studies have examined relations between beta-carotene exposure and cardiovascular disease risk. These studies used different measures to determine carotenoid exposure: semiquantitative food-frequency questionnaires, carotenoid concentrations in serum taken before the onset of disease and analyzed after diagnosis, and carotenoid concentrations in adipose tissue. Although the epidemiologic evidence is consistent with a protective association between beta-carotene and cardiovascular disease, findings from the first single intervention trial conducted in a large free-living population cast doubts on the utility of beta-carotene for all high-risk populations. Beta-Carotene may only represent a marker of dietary behavior conductive to lower risk of cardiovascular disease. Research on other carotenoids is needed.

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Carotenoids; Ethanol; Humans; Smoking

The hypothesis that antioxidant vitamins might decrease the risk of cardiovascular disease (CVD) is a promising area of research. At present, however, it is far from certain whether antioxidant vitamins confer protection against CVD. Evidence for the antioxidant vitamin-cardiovascular disease hypothesis has accumulated from several lines of research. Laboratory research has identified biochemical properties of antioxidant vitamins that could explain their possible role in inhibiting and delaying coronary atherosclerosis. Epidemiologic studies have provided support for the hypothesis by showing that people who consume high amounts of antioxidant vitamins through diet or supplements, or those with high concentrations of these nutrients in their blood, tend to have lower risks of CVD. In the case of the former, however, laboratory findings may not have relevance to free-living humans. Observational epidemiologic studies cannot exclude the possibility that people who consume antioxidant-rich diets or who take vitamin supplements also share other lifestyle or dietary practices that actually account for their lower disease rates. Because of these uncertainties, the only way to determine reliably whether antioxidants play any role in reducing the risk of CVD is to conduct large-scale, randomized trials of these agents, in which adequate doses of antioxidant vitamins are tested for a sufficient duration to allow for any benefits to emerge. Several large-scale trials are now ongoing in both primary and secondary prevention. The results of these trials over the next several years should provide reliable evidence for this promising, but as yet unproven, hypothesis.

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

Topics: Antioxidants; Arteriosclerosis; Autoantigens; beta Carotene; Cardiovascular Diseases; Carotenoids; Coronary Artery Disease; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Vitamin E

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

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: Adult; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Cardiovascular Diseases; Carotenoids; Cohort Studies; Diet; Female; Humans; Male; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic

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

In spite of the significant decline in cardiovascular disease (CVD) mortality over the past several decades, CVD remains the leading cause of death in the United States. Although age-specific CVD rates are higher in men than women, CVD is nonetheless the leading cause of death for both sexes, and is responsible for approximately one-third of all fatalities in women as well as men. Antioxidant vitamins are a promising area of current research in the prevention of CVD. The postulated mechanism for such an effect derives from basic research demonstrating the ability of antioxidants to inhibit the oxidation of low-density lipoprotein cholesterol. Epidemiologic studies that have explored the antioxidant vitamin hypothesis include descriptive and cross-sectional studies, analytic investigations using case-control and prospective cohort study designs, as well as several small randomized clinical trials. Findings from these studies are not totally consistent, but generally support the hypothesis that antioxidant vitamins reduce the risk of CVD. Overall, there are fewer data in women than men. Large-scale randomized trials are now ongoing that will provide reliable evidence on this question. The ongoing Physicians' Health Study of over 22,000 men is testing beta-carotene, while the recently begun Women's Health Study of 40,000 women will test, utilizing a factorial design, beta-carotene as well as vitamin E. A trial has also recently been funded to test beta-carotene, vitamin E and vitamin C in secondary prevention among a high-risk population of 8,000 women with prior CVD events.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Animals; Antioxidants; beta Carotene; Cardiovascular Diseases; Carotenoids; Diet; Female; Humans; Male; Middle Aged; Selenium; Vitamins

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

Topics: Antioxidants; Arteriosclerosis; beta Carotene; Cardiovascular Diseases; Carotenoids; Humans; In Vitro Techniques; Lipoproteins, LDL; Oxidation-Reduction; Risk Factors

In vitro, ex vivo and animal studies suggest palm-based tocotrienols and carotenes enhance vascular function, but limited data in humans exists. The aim was to examine the effects of palm-tocotrienols (TRF- 80) and palm-carotene (CC-60) supplementation on vascular function and cardiovascular disease (CVD) risk factors in adults at increased risk of impaired vascular function.. Plasma α- and β-carotene and α-, δ- and γ-tocotrienol concentrations increased in CC-60 and TRF-80 groups, respectively, compared to placebo (mean ± SE difference in total plasma carotene change between CC-60 and placebo: 1.5 ± 0.13 μg/ml, p < 0.0001; total plasma tocotrienol change between TRF-80 and placebo: 0.36 ± 0.05 μg/ml, p < 0.0001). Neither FMD (treatment x time effect for CC-60 vs. placebo, p = 0.71; TRF-80 vs. placebo, p = 0.80) nor any other vascular function and CVD outcomes were affected by treatments.. CC-60 and TRF-80 supplementation increased bioavailability of palm-based carotenes and tocotrienols but had no effects, superior or detrimental, on vascular function or CVD risk factors.

Topics: Adolescent; Adult; Aged; beta Carotene; Blood Glucose; Brachial Artery; Cardiovascular Diseases; Carotenoids; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Insulin; Male; Middle Aged; Oxidative Stress; Palm Oil; Risk Factors; Tocotrienols; Young Adult

Assessment of compliance with dietary interventions is necessary to understand the observed magnitude of the health effects of the diet per se. To avoid reporting bias, different dietary biomarkers (DBs) could be used instead of self-reported data. However, few studies investigated a combination of DBs to assess compliance and its influence on cardiometabolic risk factors. The objectives of this study were to use a combination of DBs to assess compliance and to investigate how a healthy Nordic diet (ND) influences cardiometabolic risk factors in participants with high apparent compliance compared with the whole study population. From a recently conducted isocaloric randomized trial, SYSDIET (Systems Biology in Controlled Dietary Interventions and Cohort Studies), in 166 individuals with metabolic syndrome, several DBs were assessed to reflect different key components of the ND: canola oil (serum phospholipid α-linolenic acid), fatty fish [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], vegetables (plasma β-carotene), and whole grains (plasma alkylresorcinols). High-fat dairy intake (expectedly low in the ND) was reflected by serum pentadecanoic acid. All participants with biomarker data (n = 154) were included in the analyses. Biomarkers were combined by using a biomarker rank score (DB score) and principal component analysis (PCA). The DB score was then used to assess compliance. During the intervention, median concentrations of alkylresorcinols, α-linolenic acid, EPA, and DHA were >25% higher in the ND individuals than in the controls (P < 0.05), whereas median concentrations of pentadecanoic acid were 14% higher in controls (P < 0.05). Median DB score was 57% higher in the ND than in controls (P < 0.001) during the intervention, and participants were ranked similarly by DB score and PCA score. Overall, estimates of group difference in cardiometabolic effects generally appeared to be greater among compliant participants than in the whole study population (e.g., estimates of treatment effects on blood pressure and lipoproteins were ∼1.5- to 2-fold greater in the most compliant participants), suggesting that poor compliance attenuated the dietary effects. With adequate consideration of their limitations, DB combinations (e.g., DB score) could be useful for assessing compliance in intervention studies investigating cardiometabolic effects of healthy dietary patterns. The study was registered at clinicaltrials.gov as NCT00992641.

Topics: alpha-Linolenic Acid; Apolipoproteins; beta Carotene; Biomarkers; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Cholesterol; Diet; Docosahexaenoic Acids; Edible Grain; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Monounsaturated; Feeding Behavior; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Patient Compliance; Phospholipids; Rapeseed Oil; Triglycerides; Vegetables

Recent studies suggest increased cancer risk in patients with type 2 diabetes mellitus (T2DM) compared with healthy individuals. The present study aims to assess whether T2DM is associated with increased genome instability and whether a healthy diet with natural foods can improve genome stability in peripheral blood lymphocytes (PBLs). Seventy-six diabetic and 21 non-diabetic individuals were randomly assigned to either an 'intervention' or an 'information only' group. All participants received information about the beneficial effects of a healthy diet, while subjects of the intervention group received additionally 300g of vegetables and 25ml of plant oil rich in polyunsaturated fatty acids per day for 8 weeks. Chromosomal damage was assessed using the cytokinesis-block micronucleus (MN) cytome assay. Levels of chromosomal damage did not differ between diabetic and non-diabetic individuals. However, diabetic individuals with MN frequency above the high 50th percentile had significantly higher levels of fasting plasma glucose, glycosylated haemoglobin and were at higher risk for cardiovascular disease (CVD), assessed by the Framingham general cardiovascular risk score. Non-diabetic individuals with MN frequency above the 50th percentile had significantly lower vitamin B12 levels. The intervention with vegetables and plant oil led to significant increases in folate, γ-tocopherol, α- and β-carotene while vitamin B12 was significantly reduced. Levels of chromosomal damage were not altered, only apoptosis was slightly increased. The results suggest interactions between glycaemic control, CVD risk and genome stability in individuals with T2DM. However, a healthy diet does not improve genome damage in PBLs.

Topics: Aged; Anthropometry; beta Carotene; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Carotenoids; Chromosome Aberrations; Diabetes Mellitus, Type 2; DNA Damage; Fatty Acids, Unsaturated; Female; Folic Acid; gamma-Tocopherol; Genome, Human; Genomic Instability; Glycated Hemoglobin; Humans; Lymphocytes; Male; Micronucleus Tests; Middle Aged; Plant Oils; Risk Factors; Vegetables; Vitamin B 12

Cardiovascular risk factors such as elevated levels of asymmetric dimethylarginine (ADMA)/C-reactive protein (CRP) and homocysteine are potentially related to essential micronutrients such as certain B vitamins and antioxidant vitamins. The aim of the present study was to investigate whether supplementation with moderate doses of B vitamins and/or antioxidants could alter either ADMA and/or CRP concentrations in middle-aged, apparently healthy men with mildly elevated homocysteine levels.. A randomised, double-blind, factorial design, intervention study was carried out on 132 men with mildly elevated homocysteine levels, allocated to four groups (a) B vitamins alone--1 mg folic acid, 7.2 mg pyridoxine, 0.02 mg cyanocobalamin daily, (b) antioxidants alone--150 mg ascorbic acid, 67 mg vitamin E, 9 mg β-carotene daily, (c) B vitamins with antioxidant vitamins, or (d) placebo. A total of 101 men completed the study to 8 weeks.. When the percentage of baseline ADMA and CRP was examined at 8 weeks, no statistically significant differences were observed between the four groups (p = 0.21 and p = 0.90, respectively). Similar non-significant results were observed when analysis was stratified based on baseline CRP levels (<1.0 mg/L, p = 0.10; ≥1.0 mg/L, p = 0.64) and smoking status (all p ≥ 0.05).. Supplementation with moderate doses of B vitamins and/or antioxidants did not alter either ADMA or CRP concentrations in these middle-aged, apparently healthy men with mildly elevated homocysteine levels.

Topics: Adult; Antioxidants; Arginine; Ascorbic Acid; beta Carotene; Biomarkers; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Dietary Supplements; Double-Blind Method; Homocysteine; Humans; Male; Middle Aged; Protective Agents; Triglycerides; Vitamin B Complex; Vitamin E

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

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

Cardiovascular factors are associated with cognitive decline. Antioxidants may be beneficial.. The Women's Antioxidant Cardiovascular Study was a trial of vitamin E (402 mg every other day), beta carotene (50 mg every other day), and vitamin C (500 mg daily) for the secondary prevention of cardiovascular disease. From 1995 to 1996, women > or =40 years of age with cardiovascular disease or > or =3 coronary risk factors were randomized. From 1998 to 1999, a cognitive function substudy was initiated among 2824 participants > or =65 years of age. With 5 cognitive tests, cognition was assessed by telephone 4 times over 5.4 years. The primary outcome was a global composite score averaging all scores; repeated-measures analyses were used to examine cognitive change over time. Vitamin E supplementation and beta carotene supplementation were not associated with slower rates of cognitive change (mean difference in change for vitamin E versus placebo, -0.01; 95% confidence interval, -0.05 to 0.04; P=0.78; for beta carotene, 0.03; 95% confidence interval, -0.02 to 0.07; P=0.28). Although vitamin C supplementation was associated with better performance at the last assessment (mean difference, 0.13; 95% confidence interval, 0.06 to 0.20; P=0.0005), it was not associated with cognitive change over time (mean difference in change, 0.02; 95% confidence interval, -0.03 to 0.07; P=0.39). Vitamin C was more protective against cognitive change among those with new cardiovascular events during the trial (P for interaction=0.009).. Antioxidant supplementation did not slow cognitive change among women with preexisting cardiovascular disease or cardiovascular disease risk factors. A possible late effect of vitamin C or beta carotene among those with low dietary intake on cognition warrants further study.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cognition Disorders; Female; Follow-Up Studies; Humans; Memory Disorders; Middle Aged; Neuroprotective Agents; Neuropsychological Tests; Oxidative Stress; Risk Factors; Single-Blind Method; Treatment Failure; Vitamin E

Homocysteinemia may play an etiologic role in the pathogenesis of type 2 diabetes by promoting oxidative stress, systemic inflammation, and endothelial dysfunction. We investigated whether homocysteine-lowering treatment by B vitamin supplementation prevents the risk of type 2 diabetes.. The Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a randomized, double-blind, placebo-controlled trial of 5,442 female health professionals aged > or = 40 years with a history of cardiovascular disease (CVD) or three or more CVD risk factors, included 4,252 women free of diabetes at baseline. Participants were randomly assigned to either an active treatment group (daily intake of a combination pill of 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12) or to the placebo group.. During a median follow-up of 7.3 years, 504 women had an incident diagnosis of type 2 diabetes. Overall, there was no significant difference between the active treatment group and the placebo group in diabetes risk (relative risk 0.94 [95% CI 0.79-1.11]; P = 0.46), despite significant lowering of homocysteine levels. Also, there was no evidence for effect modifications by baseline intakes of dietary folate, vitamin B6, and vitamin B12. In a sensitivity analysis, the null result remained for women compliant with their study pills (0.92 [0.76-1.10]; P = 0.36).. Lowering homocysteine levels by daily supplementation with folic acid and vitamins B6 and B12 did not reduce the risk of developing type 2 diabetes among women at high risk for CVD.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Middle Aged; Placebos; Proportional Hazards Models; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin E

Vitamin C, vitamin E, and beta-carotene are major antioxidants and as such may protect against the development of type 2 diabetes via reduction of oxidative stress.. The purpose of this study was to investigate the long-term effects of supplementation with vitamin C, vitamin E, and beta-carotene for primary prevention of type 2 diabetes.. In the Women's Antioxidant Cardiovascular Study, a randomized trial that occurred between 1995 and 2005, 8171 female health professionals aged > or =40 y with either a history of cardiovascular disease (CVD) or > or =3 CVD risk factors were randomly assigned to receive vitamin C (ascorbic acid, 500 mg every day), vitamin E (RRR-alpha-tocopherol acetate, 600 IU every other day), beta-carotene (50 mg every other day), or their respective placebos.. During a median follow-up of 9.2 y, a total of 895 incident cases occurred among 6574 women who were free of diabetes at baseline. There was a trend toward a modest reduction in diabetes risk in women assigned to receive vitamin C compared with those assigned to receive placebo [relative risk (RR): 0.89; 95% CI: 0.78, 1.02; P = 0.09], whereas a trend for a slight elevation in diabetes risk was observed for vitamin E treatment (RR: 1.13; 95% CI: 0.99, 1.29; P = 0.07). However, neither of these effects reached statistical significance. No significant effect was observed for beta-carotene treatment (RR: 0.97; 95% CI: 0.85, 1.11; P = 0.68).. Our randomized trial data showed no significant overall effects of vitamin C, vitamin E, and beta-carotene on risk of developing type 2 diabetes in women at high risk of CVD. This trial was registered at clinicaltrials.gov as NCT00000541.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Follow-Up Studies; Humans; Incidence; Middle Aged; Odds Ratio; Oxidative Stress; Primary Prevention; Risk Assessment; Risk Factors; United States; Vitamin E

As evidence of the involvement of inflammation and oxidative damage in pathogenesis of age-related chronic diseases is growing, epidemiologists need to develop measures of both conditions to study their relationships in human populations. One way of searching for appropriate biomarkers is to examine correlations between different inflammatory markers and oxidative indices. We examined cross-sectional correlations between two inflammatory markers, serum C-reactive protein (CRP) and interleukin (IL)-6, and three oxidative indices, plasma levels of alpha-tocopherol and beta-carotene, and urinary levels of 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoP), in 60 individuals at high risk of cardiovascular disease. Correlations between the biomarkers were examined graphically and using the Pearson correlation coefficient. No correlation was found between plasma levels of alpha-tocopherol and either of the inflammatory markers. Plasma beta-carotene inversely correlated with IL-6 (r = -0.46, p=0.0002) and CRP (r = -0.41, p = 0.001). Although urinary F2-IsoP did not correlate with IL-6, this biomarker positively correlated with CRP (r = 0.31, p = 0.002). As only urinary F2-IsoP levels have been validated against known oxidative assaults, their positive association with CRP levels is interpreted as evidence of an interconnection between low-level inflammation and oxidative status. Urinary levels of F2-IsoP and serum levels of CRP represent appropriate biomarkers for future studies of inflammation and oxidative status in humans.

Topics: Aged; alpha-Tocopherol; beta Carotene; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Dinoprost; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Oxidative Stress; Risk

High blood pressure (BP) has been associated with a decrease in kidney function. However, it remains unclear which BP measure best predicts impaired kidney function.. We compared systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP) in predicting risk of chronic kidney disease (CKD). We prospectively followed 8093 male participants in the Physicians' Health Study, without a known history of kidney disease at baseline, who provided BP values on the baseline and 24-month questionnaires, and for whom we had creatinine measures after 14 years of follow-up. Reported BP was averaged from both questionnaires. The main outcome was CKD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2). We used multivariable-adjusted logistic regression to evaluate the association between BP measures and CKD and compared models using the likelihood ratio test.. After 14 years of follow-up, 1039 men (12.8%) had CKD. An increase of 10 mmHg had corresponding multivariable-adjusted odds ratios (95% confidence intervals) of 1.11 (1.03-1.19) for SBP, 1.11 (1.00-1.23) for MAP, 1.14 (1.05-1.25) for PP and 1.05 (0.93-1.17) for DBP. SBP and PP were the strongest predictors of chronic kidney function, with equal predictive abilities. Combining BP measures did not add significantly to the prediction.. Increases in SBP, PP and MAP were significantly associated with CKD. SBP may be the most clinically useful predictor of CKD, since no further calculations are required.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Chronic Disease; Confidence Intervals; Creatinine; Disease Progression; Drug Therapy, Combination; Follow-Up Studies; Humans; Kidney Diseases; Male; Massachusetts; Middle Aged; Odds Ratio; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Vitamins

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

High dietary intakes of tomato products are often associated with a reduced risk of CVD, but the atheroprotective mechanisms have not been established. This study was conducted to investigate the effects of increased dietary intake of tomato products on plasma lipids and LDL oxidation. The diet intervention included a baseline period, a 3-week low tomato diet (no tomato products allowed) and a 3-week high tomato diet (400 ml tomato juice and 30 mg tomato ketchup daily). Twenty-one healthy study subjects participated in the study. Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet. The changes in total and LDL cholesterol concentrations correlated significantly with the changes in serum lycopene (r 0.56, P = 0.009; r 0.60, P = 0.004, total and LDL, respectively), beta-carotene (r 0.58, P = 0.005; r 0.70, P < 0.001) and gamma-carotene concentrations (r 0.64, P = 0.002; r 0.64, P = 0.002). The level of circulating LDL to resist formation of oxidized phospholipids increased 13 % (P = 0.02) in response to the high tomato diet. In conclusion, a high dietary intake of tomato products had atheroprotective effects, it significantly reduced LDL cholesterol levels, and increased LDL resistance to oxidation in healthy normocholesterolaemic adults. These atheroprotective features associated with changes in serum lycopene, beta-carotene and gamma-carotene levels.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Beverages; Cardiovascular Diseases; Carotenoids; Cholesterol; Cholesterol, LDL; Diet; Female; Humans; Lipids; Lycopene; Male; Middle Aged; Oxidation-Reduction; Solanum lycopersicum; Vitamin E

To determine how change in BMI over 8 years is associated with risk of subsequent cardiovascular disease (CVD) among middle aged men.. Prospective cohort study among 13,230 healthy men (aged 51.6+/-8.7 years) in the Physicians' Health Study. BMI was collected at baseline in 1982 and after 8 years, at which time follow-up began. Subsequent CVD events were collected and confirmed through March 31, 2005. Cox proportional hazards models evaluated BMI at 8 years and risk of CVD, 8-year change in BMI and risk of CVD, and whether change in BMI added prognostic information after the consideration of BMI at 8 years.. 1308 major CVD events occurred over 13.5 years. A higher BMI at year 8 was associated with an increased risk of CVD. Compared to a stable BMI (+/-0.5 kg/m(2)), a 0.5-2.0 kg/m(2) increase had a multivariable-adjusted RR of 1.00 (0.86-1.16). A >/=2.0 kg/m(2) increase had a multivariable-adjusted RR of 1.39 (1.16-1.68), however further adjustment for BMI reduced the RR to 1.00 (0.81-1.23). A decrease in BMI had a multivariable RR of 1.23 (1.07-1.42) which was unaffected by adjustment for BMI at 8 years.. A higher BMI and a rising BMI were both associated with an increased risk of CVD, however an increasing BMI did not add prognostic information once current BMI was considered. In contrast, a declining BMI was associated with an increased risk of CVD independent of current BMI.

Topics: Adult; Aspirin; beta Carotene; Body Mass Index; Cardiovascular Diseases; Cause of Death; Cohort Studies; Double-Blind Method; Follow-Up Studies; Health Status Indicators; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Physicians; Prognosis; Proportional Hazards Models; Prospective Studies; Survival Analysis; Weight Loss

An exonic polymorphism (Y402H) in the complement factor H (CFH) gene, which locates within the binding sites for heparin and C-reactive protein, has recently been described and hypothesized to play an important role in atherothrombosis.. We, therefore, evaluated the CFH genetic variant Y402H amongst 685 Caucasian individuals who subsequently developed arterial or venous thrombotic event (incident myocardial infarction (MI), ischaemic stroke, or venous thromboembolism) and amongst 685 age- and smoking-matched Caucasian individuals who remained free of reported vascular disease during follow-up (controls) within the Physicians' Health Study cohort.. Genotype distribution for the polymorphism tested was in Hardy-Weinberg equilibrium in the control group. In contrast to expected results, we found no association of Y402H polymorphism with risk of atherothrombosis (adjusted: myocardial infarction, OR=1.09, 95%CI 0.88-1.36, p=0.43; ischaemic stroke, OR=1.11, 95%CI 0.81-1.54, p=0.52; venous thromboembolism, OR=1.41, 95%CI 0.88-2.24, p=0.15), nor with baseline plasma C-reactive protein levels [median (interquartile range) mg/L: YY, 1.39 (0.70-2.60); YH, 1.10 (0.57-2.16); HH, 1.00 (0.48-1.79); p=0.14].. In this large, prospective cohort of apparently healthy Caucasian men, we found no association of the complement factor H Y402H gene polymorphism with risk of incident thromboembolic events, nor with baseline levels of C-reactive protein.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Brain Ischemia; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Complement Factor H; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prospective Studies; Risk Factors; Stroke; Venous Thrombosis; Vitamins; White People

We have investigated the effect of modest supplementation with alpha-tocopherol (100 mg/day), beta-carotene (6 mg/day), vitamin C (100 mg/day) and selenium (50 microg/day) on oxidative stress and chromosomal damage, and the influence of methylenetetrahydrofolate reductase (MTHFR) genotype on these end-points. Subjects were two groups of middle-aged men differing in cardiovascular risk; 46 survivors of myocardial infarction before age 50 and 60 healthy controls. They were randomly divided into equal groups to receive antioxidants or placebo for 12 weeks. Twenty-eight patients and 58 controls completed the intervention. Micronucleus levels in peripheral lymphocytes and changes seen after intervention were studied in relation to the MTHFR C677T genotype, basal homocysteine and plasma folate levels. Ferric reducing ability of plasma and concentration of malondialdehyde were measured to assess the antioxidant effect of supplementation. There was no association of micronuclei with folate, homocysteine or malondialdehyde levels before supplementation. Micronucleus frequencies and plasma folate levels did not vary significantly with MTHFR genotype. Homocysteine levels in subjects with the TT variant genotype were significantly higher compared with CT or CC (P = 0.001), especially in subjects with low folate (P = 0.012). In the placebo control group an increase in micronuclei (P = 0.04) was detected at the end of the intervention period. This effect was not seen in the supplemented group. In antioxidant-supplemented myocardial infarction survivors we found an increase in the ferric reducing ability of plasma (P < 0.001) and a decrease in malondialdehyde (P = 0.001). Micronucleus frequency showed a decrease, strongest in subjects with normal folate levels (P = 0.015). In subjects with low folate levels, a high correlation was found between micronuclei after supplementation and homocysteine, both before (r = 0.979, P = 0.002) and after supplementation (r = 0.922, P = 0.009). Thus, folate deficiency may amplify the effect of other risk factors such as elevated homocysteine levels or variant MTHFR genotype, as well as influencing the ability of antioxidant supplementation to protect against genetic damage.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Dietary Supplements; DNA Damage; Folic Acid; Folic Acid Deficiency; Genotype; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Micronucleus Tests; Middle Aged; Myocardial Infarction; Oxidative Stress; Selenium

The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the incidence of lung cancer, other cancers, and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group.. After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided.. With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males.. The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.

Topics: Adult; Aged; Anticarcinogenic Agents; beta Carotene; Carcinogens; Cardiovascular Diseases; Confidence Intervals; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Sex Factors; United States

Excessive consumption of energy and fat increases the risk for obesity. Snacks containing sucrose polyesters (SPE) as a dietary fat replacer are on the market in the United States. SPE products have been shown to lower concentrations of serum carotenoids in short-term studies. Experimental studies on the longer-term effects on health of decreased carotenoid concentrations are lacking. A 1-y randomized, double-blind, placebo-controlled parallel trial was performed. Subjects (n = 380) with a habitual low or high fruit and vegetable intake were assigned to the treatments (0, 7, 10 or 17 g/d SPE). SPE was given in the form of spreads, chips or both. The groups were compared for serum carotenoids, vitamins and markers of oxidative damage, eye health, cardiovascular health and immune status. After 1 y, serum lipid-adjusted carotenoids showed the largest decrease in the SPE chips and spread group (17 g/d) compared with the control group [alpha-carotene 33%; beta-carotene 31%, lycopene 24%, beta-cryptoxanthin 18%, lutein 18% (all P < 0.001) and zeaxanthin 13% (P < 0.05)]. Consumption of SPE spread (10 g/d SPE) decreased carotenoid concentrations by 11-29% (all P < 0.05). SPE chips (7 g/d SPE) decreased zeaxanthin (11%), beta-carotene (12%) and alpha-carotene (21%; all P < 0.05). Serum lipid adjusted alpha-tocopherol decreased significantly by 6-8% (all P < 0.001) in all SPE groups. No negative effects were observed on markers of oxidation, eye health, cardiovascular health or immune status. This study shows that decreases in serum carotenoid concentrations do not affect possible markers of disease risk.

Topics: Adolescent; Adult; Aged; alpha-Tocopherol; beta Carotene; Body Weight; Cardiovascular Diseases; Carotenoids; Dietary Fats, Unsaturated; Double-Blind Method; Endothelium, Vascular; Eye Diseases; Fatty Acids; Female; Health Status; Humans; Immunity; Lipid Peroxidation; Lipids; Macula Lutea; Male; Middle Aged; Patient Compliance; Placebos; Risk Factors; Sucrose; Xanthophylls; Zeaxanthins

Older persons are at risk of both poor nutrition and increased oxidative stress. Plasma ascorbate concentrations fall with increasing age, and concentrations of other antioxidants may also be reduced.. The goal was to examine the association between antioxidants and mortality in older persons.. We randomly selected persons aged 75-84 y from the lists of 51 British family practitioners taking part in a randomized trial of assessment of older persons. A total of 1214 participants provided a blood sample and were interviewed about their usual diet with the use of a food-frequency questionnaire. Statistical analyses were based on deaths after a median of 4.4 y of follow-up, and hazard ratios were estimated for quintiles of dietary or blood antioxidants.. We found strong inverse trends for blood ascorbate concentrations with all-cause and cardiovascular disease mortality, which were only marginally reduced after adjustment for confounders or supplement use. Those in the lowest fifth (< 17 micromol/L) had the highest mortality, whereas those in the highest fifth (> 66 micromol/L) had a mortality risk nearly half that (hazard ratio = 0.54; 95% CI: 0.34, 0.84). Similar results were found after the exclusion of those subjects with cardiovascular disease or cancer at baseline (hazard ratio = 0.51; 0.28, 0.93). In fully adjusted models, there was no evidence for an influence of alpha-tocopherol, beta-carotene, or retinol on total mortality. Dietary antioxidants measured by the food-frequency questionnaire were not associated with all-cause or cardiovascular disease mortality.. Low blood vitamin C concentrations in the older British population are strongly predictive of mortality.

Topics: Aged; Aged, 80 and over; Aging; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Diet; Diet Records; Dietary Supplements; Female; Humans; Male; Mortality; Nutrition Assessment; Nutritional Physiological Phenomena; Proportional Hazards Models; Risk Factors; Surveys and Questionnaires; Vitamin A; Vitamins

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

The oxidative modification of LDL is considered to play a central role in the pathogenesis of atherosclerosis and coronary heart disease (CHD). Paraoxonase (PON1) protects LDL from oxidation and may therefore retard the development of atherosclerosis. The PON1-192 polymorphism is associated with diminished PON1 concentrations and an increased risk for CHD in RR-allele subjects.. To investigate the effect of tomato juice consumption on PON1 activity and other parameters related to oxidative stress in healthy elderly subjects. Furthermore, the PON1-192 genotype has been determined in the volunteers in order to see whether possible treatment effects are related to the PON1-192 polymorphism.. Fifty elderly subjects were randomly assigned to control (mineral water) or intervention group (tomato juice). Subjects of the tomato juice group consumed daily 330 mL tomato juice for 8 weeks. Antioxidant status was measured as LDL oxidation, plasma malondialdehyde, ferric reducing ability of plasma (FRAP) and PON1 activity. The PON1-192 polymorphism was determined by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). Plasma carotenoids were analyzed by HPLC.. Tomato juice consumption reduced LDL-oxidation and improved antioxidant status in R-allele carriers, but not in the QQ genotype group. PON1 activity increased irrespective of the genotype in both, control and intervention group.. The changes in antioxidant status after tomato juice consumption seem to depend on the PON1-192 genotype. Healthy elderly, carrying the R-allele, could specifically reduce their higher cardiovascular risk by changing dietary habits.

Topics: Aged; Antioxidants; Aryldialkylphosphatase; beta Carotene; Beverages; Cardiovascular Diseases; Carotenoids; Chromatography, High Pressure Liquid; Esterases; Female; Gene Frequency; Genotype; Heterozygote; Homozygote; Humans; Lipid Peroxidation; Longitudinal Studies; Lycopene; Male; Middle Aged; Oxidation-Reduction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Solanum lycopersicum

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

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

Reports have suggested relationships of body weight with age-related maculopathy (ARM), particularly its nonneovascular (dry) forms, but results are inconsistent and prospective data are scarce.. To examine prospectively relationships of body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) with visually significant dry and neovascular ARM during an average of 14.5 years of follow-up.. Incident ARM was assessed by medical record confirmation of self-reported ARM among the 21 121 men participating in the Physicians' Health Study who (1) were followed up for at least 7 years, (2) were free of visually significant ARM at baseline, and (3) had information on BMI and cigarette smoking. We used proportional hazards regression models to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for visually significant dry ARM (256 cases) and neovascular ARM (84 cases) within 4 categories of BMI: lean (< 22.0), normal (22.0-24.9), overweight (25.0-29.9), and obese (> or = 30.0).. Adjusting for age, randomized aspirin and beta carotene assignments, and cigarette smoking, the incidence for visually significant dry ARM was lowest in men with a normal BMI. Compared with these men, the RRs (95% CIs) were as follows: 1.43 (1.01-2.04) for lean, 1.24 (0.93-1.66) for overweight, and 2.15 (1.35-3.45) for obese men. Although there was no significant relationship of BMI with the diagnosis of neovascular ARM, due to the small number of cases these analyses could not rule out an important relationship.. Obesity is a risk factor for visually significant ARM in men, in particular for dry ARM. However, the relationship of BMI with dry ARM appears to be J-shaped, and the leanest individuals also appear to be at increased risk.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Body Mass Index; Cardiovascular Diseases; Double-Blind Method; Follow-Up Studies; Humans; Incidence; Macular Degeneration; Male; Massachusetts; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors

Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. We studied simvastatin-niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of HDL.. In a three-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels and normal LDL cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, vitamins, simvastatin-niacin plus antioxidants; or placebos. The end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization).. The mean levels of LDL and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by -42 percent and +26 percent, respectively) in the simvastatin-niacin group. The protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants. The average stenosis progressed by 3.9 percent with placebos, 1.8 percent with antioxidants (P=0.16 for the comparison with the placebo group), and 0.7 percent with simvastatin-niacin plus antioxidants (P=0.004) and regressed by 0.4 percent with simvastatin-niacin alone (P<0.001). The frequency of the clinical end point was 24 percent with placebos; 3 percent with simvastatin-niacin alone; 21 percent in the antioxidant-therapy group; and 14 percent in the simvastatin-niacin-plus-antioxidants group.. Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels. The use of antioxidant vitamins in this setting must be questioned.

Topics: alpha-Tocopherol; Antioxidants; Apolipoproteins; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Coronary Angiography; Coronary Disease; Coronary Stenosis; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Lipids; Male; Middle Aged; Niacin; Selenium; Simvastatin; Vitamin E

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

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

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

The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. This study was designed when the CARET intervention was halted to evaluate the effects of long-term supplementation with beta-carotene and retinol on serum triglyceride and cholesterol levels, in an attempt to explore possible explanations for the CARET result.. Serum triglyceride levels, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were determined in a subgroup of 52 CARET participants. Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment who were then serially followed for 10 months after trial termination.. Triglyceride, and total, HDL and LDL cholesterol levels were similar in the two groups at baseline. After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group, but no difference in total, HDL, or LDL cholesterol levels. After stopping the intervention there was a decrease in triglyceride levels in the active intervention group, and no change in the other parameters.. Based on a small convenience sample, CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention, and a decrease in serum triglyceride levels after the intervention was discontinued. No significant changes in total or HDL cholesterol were noted. These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group.

Topics: beta Carotene; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Chromatography, High Pressure Liquid; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Survival Rate; Treatment Outcome; Triglycerides; Vitamin A

Several prospective studies have demonstrated a direct association between C-reactive protein (CRP) levels and the risks of developing cardiovascular disease. Few studies, however, have explored the interrelations between CRP levels and other risk factors for cardiovascular disease. We evaluated the relation of CRP with several cardiovascular risk factors in a cross-sectional survey of 1,172 apparently healthy men. There were significant positive associations between CRP levels and age, number of cigarettes smoked per day, body mass index, systolic and diastolic blood pressure, total cholesterol, triglycerides, lipoprotein(a), apolipoprotein B, tissue-type plasminogen activator antigen, D-dimers, total homocysteine, and fibrinogen (all p values <0.05). Significant inverse associations were observed for exercise frequency, high-density lipoprotein cholesterol, and apolipoprotein A-I and A-II (all p values <0.02). In multivariate analysis, age, smoking status, and serum levels of tissue-type plasminogen activator antigen, fibrinogen, lipoprotein(a), and total homocysteine were independent correlates of CRP levels. Finally, in an analysis controlled either for all the independent correlates or for several usual risk factors, we observed progressive increases in levels of CRP with increasing prevalence of risk factors (p for trend <0.001 for independent correlates and <0.01 for usual risk factors). In conclusion, in a large cohort of apparently healthy men, CRP levels were associated with several cardiovascular risk factors. These data are compatible with the hypothesis that CRP levels may be a marker for preclinical cardiovascular disease.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Double-Blind Method; Humans; Lipids; Male; Middle Aged; Reference Values; Risk Factors

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

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

The objective of this study was to examine whether definite hypertension and borderline isolated systolic hypertension predict subsequent cardiovascular disease and mortality.. This was a prospective cohort study with a mean follow-up of 11.7 years. The subjects were a group of 18,682 apparently healthy US men, aged 40 to 84 years, participating in the Physicians' Health Study, a randomized trial of low-dose aspirin and beta-carotene. The main outcome measures were total cardiovascular disease, myocardial infarction, stroke, cardiovascular death, and all-cause mortality. Hypertension was associated with substantially increased risks of total cardiovascular disease (relative risk [RR] 1.92; 95% confidence interval [CI], 1.70 to 2.18), myocardial infarction (RR,1.78; 95% CI, 1.49 to 2.13), stroke (RR, 2.19; 95% CI, 1.78 to 2.69), and cardiovascular death (RR, 2.10; 95% CI, 1.68 to 2.63). Borderline isolated systolic hypertension was associated with significantly increased risks of cardiovascular disease (RR, 1.32; 95% CI, 1.09 to 1.59), stroke (RR, 1.42; 95% CI, 1.04 to 1.93), and cardiovascular death (RR, 1.56; 95% CI, 1.13 to 2.15), as well as a possible but non-significant increased risk of myocardial infarction (RR, 1.26; 95% CI, 0.95 to 1.67). Hypertension and borderline isolated systolic hypertension were associated with significantly increased risks of 41% and 22%, respectively, for all-cause mortality.. Hypertension as well as borderline isolated systolic hypertension are associated with elevated risks of cardiovascular diseases, especially stroke and cardiovascular death. Hypertension is associated with an increased risk of myocardial infarction, and borderline isolated systolic hypertension predicts a possible but more modest increase in risk. These data add to the existing evidence that hypertension is a major cardiovascular risk factor and extend the findings to borderline isolated systolic hypertension.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Aspirin; beta Carotene; Cardiovascular Diseases; Cerebrovascular Disorders; Cohort Studies; Confidence Intervals; Factor Analysis, Statistical; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Physicians; Platelet Aggregation Inhibitors; Prevalence; Prospective Studies; Risk Factors; Systole; Time Factors; United States

Evidence from observational epidemiologic studies has indicated that antioxidants consumed through the diet or as dietary supplements lower the risk of developing atherosclerotic cardiovascular disease. Evidence suggesting that the major mechanism for the protective effect of antioxidants is mediated through decreased oxidation of lipids, particularly low-density lipoprotein (LDL) cholesterol is accumulating. Other evidence, however, suggests that antioxidants may influence traditional modifiable cardiovascular risk factors such as the blood pressure and serum lipids favorably. The purpose of this study was to determine the effect of antioxidant vitamin supplementation on modifiable risk factors for atherosclerotic cardiovascular disease.. A randomized, placebo-controlled, clinical trial of antioxidant vitamin supplementation, conducted at a single community-based clinical research center.. We assigned 297 retired teachers who were members of the Maryland Retired Teachers Association randomly to 2-4 months of dietary supplementation with placebo or combined antioxidant vitamin capsules providing 400 IU/day vitamin E, 500 mg/day vitamin C, and 6 mg/day beta-carotene. The outcome measures were the blood pressure, fasting serum total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, and fasting glucose.. After 2-4 months of supplementation the combined antioxidant supplement had had no significant effect on the systolic and diastolic blood pressures, fasting serum lipids (total cholesterol, high-density lipoprotein cholesterol, and LDL cholesterol) and fasting glucose, with unadjusted and adjusted analyses.. Data from this trial suggest that the protective effect from antioxidant vitamin supplementation, if there is one, likely results from mechanisms other than modification of traditionally modifiable cardiovascular risk factors.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Double-Blind Method; Female; Humans; Lipids; Male; Middle Aged; Pilot Projects; Risk Factors; Time Factors; 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

Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders.. We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo.. A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years.. After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

Topics: Aged; Antioxidants; Asbestos; beta Carotene; Cardiovascular Diseases; Carotenoids; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Mortality; Occupational Exposure; Risk; Smoking; Vitamin A

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

A high intake of beta-carotene has been associated with a decreased risk for cardiovascular disease. To evaluate whether beta-carotene may exert a protective effect through an impact on haemostasis a randomized, placebo-controlled trial was conducted in male smokers (n = 149) using 20 mg/day beta-carotene for 14 weeks. For comparisons, haemostatic indicators were also evaluated in a group of non-smokers (n = 54). Smokers compared with non-smokers had higher fibrinogen (3.5 vs. 3.1 mg/ml, P < 0.01), higher tissue-type plasminogen activator antigen (t-PA; 8.03 vs. 6.60 ng/ml, P < 0.05), lower levels of soluble fibrin (3.40 vs. 5.16 micrograms/ml, P < 0.01) and slightly higher plasma levels of total degradation products of fibrin and fibrinogen (TDP; 47.0 vs. 41.3 ng/ml, P = 0.21). Within the group of smokers, there were no initial differences in the four haemostatic indicators between the placebo (n = 77) and beta-carotene (n = 72) groups, and in both groups there was virtually no change in the indicators during the 14 weeks treatment. It is concluded that the different haemostatic profile in smokers may partly explain their increased risk for cardiovascular disease. beta-Carotene has no influence on the measured haemostatic indicators, and cardiovascular protection for beta-carotene via a beneficial effect on haemostasis seems improbable.

Topics: Adult; Antioxidants; beta Carotene; Cardiovascular Diseases; Carotenoids; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemostasis; Humans; Male; Middle Aged; Smoking; Tissue Plasminogen Activator; Vitamins

To evaluate, in a prospective design, whether migraine is an independent risk factor for subsequent stroke.. Evaluated as part of the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in the primary prevention of cardiovascular disease and cancer begun in 1982. The aspirin component of the study was terminated in 1988, with average follow-up of 60.2 months.. Conducted by mail among male physicians throughout the United States.. A total of 22,071 US male physicians aged 40 to 84 years in 1982 with no prior history of cancer or cardiovascular diseases who were enrolled in the Physicians' Health Study.. Participants were randomized to receive 325 mg of aspirin or aspirin placebo every other day and to receive 50 mg of beta-carotene or placebo on alternate days.. The primary outcomes of the Physicians' Health Study were cardiovascular disease and cancer. Because stroke was a main outcome, this provided the opportunity to evaluate the association between migraine headaches and stroke.. Physicians reporting migraine (n = 1479) had significantly increased risks of subsequent total stroke and ischemic stroke compared with those not reporting migraine. After adjustment for age, aspirin and beta-carotene treatment assignment, and a number of cardiovascular risk factors, the relative risks were 1.84 (95% confidence interval, 1.06 to 3.20) for total stroke and 2.00 (95% confidence interval, 1.10 to 3.64) for ischemic stroke. There were too few hemorrhagic strokes in the study to evaluate this end point. No associations were seen between ordinary nonmigraine headache and subsequent stroke or between migraine and subsequent myocardial infarction or cardiovascular death.. These data raise the possibility that vascular events associated with migraine may also have causative importance in stroke but require confirmation in other studies specifically designed to evaluate this question.

Topics: Adult; Aged; Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Cerebrovascular Disorders; Double-Blind Method; Health Surveys; Humans; Middle Aged; Migraine Disorders; Physicians; Placebos; Prospective Studies; Risk Factors

The evidence for a potential benefit of antioxidant vitamins in the prevention and therapy of atherosclerotic disease is derived from laboratory, clinical, and observational epidemiologic studies but remains inconclusive. Data from randomized clinical trials are sparse, particularly for women. Therefore, it is both timely and important to conduct large-scale primary and secondary prevention trials of antioxidants and cardiovascular disease (CVD). The Women's Antioxidant and Cardiovascular Study (WACS) is a randomized, double-blind, placebo-controlled secondary prevention trial of the balance of benefits and risks of antioxidant vitamins (vitamins E and C, and beta-carotene) among 8000 women with preexisting CVD. This secondary prevention trial will be conducted as a companion to the recently started Women's Health Study, a primary prevention trial of vitamin E and beta-carotene, as well as aspirin. In the WACS, US female health professionals aged 40 years and older with a history of myocardial infarction, angina pectoris, coronary revascularization, stroke, transient cerebral ischemia, carotid endarterectomy, or peripheral artery surgery will be randomly assigned, utilizing a 2 x 2 x 2 factorial design, to receive vitamin E, vitamin C, beta-carotene, and/or placebo. Cardiovascular end points include nonfatal myocardial infarction, nonfatal stroke, coronary revascularization procedures, and total CVD mortality. The present article describes the rationale, design, and methods of the trial.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Carotenoids; Double-Blind Method; Female; Humans; Middle Aged; Research Design; Risk Factors; United States; Vitamin E

In recent years, increasing attention has focused on the need for more research to be conducted in women on health issues directly relevant to women. No one would disagree that the need for such studies is both crucial and timely. However, while the need for more research in women is urgent, the planning and conduct of such studies must always be driven by good science. Specifically, investigations in women may have unique and important scientific and logistic problems which must be recognized and addressed. However, if the trials are well designed and conducted, they will provide a sound and reliable body of data upon which to base rational clinical decision making and public health recommendations for women from women. These general issues are discussed in the context of a particular trial, the Women's Health Study, a randomized trial of the risks and benefits of low-dose aspirin, beta-carotene and vitamin E in the primary prevention of cardiovascular disease and cancer among healthy women.

Topics: Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Female; Humans; Middle Aged; Primary Prevention; Randomized Controlled Trials as Topic; Research Design; 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

To evaluate the efficacy of low-dose aspirin in the primary prevention of myocardial infarction among patients with chronic stable angina.. A randomized, double-blind, trial.. The study included 333 men with baseline chronic stable angina but with no previous history of myocardial infarction, stroke, or transient ischemic attack who were enrolled in the Physicians' Health Study, a trial of aspirin among 22,071 male physicians.. Patients were randomly assigned to receive alternate-day aspirin therapy (325 mg) or placebo and were followed for an average of 60.2 months for the occurrence of myocardial infarction, stroke, or cardiovascular death.. During follow-up, 27 patients had confirmed myocardial infarctions; 7 were among the 178 patients with chronic stable angina who received aspirin therapy and 20 were among the 155 patients who received placebo (relative risk, 0.30; 95% CI, 0.14 to 0.63; P = 0.003). While simultaneously controlling for other cardiovascular risk factors in a proportional hazards model, an overall 87% risk reduction was calculated (relative risk, 0.13; CI, 0.04 to 0.42; P less than 0.001). For the subgroup of patients with chronic stable angina but no previous coronary bypass surgery or coronary angioplasty, an almost identical reduction in the risk for myocardial infarction was found (relative risk, 0.14; CI, 0.04 to 0.56; P = 0.006). Of 13 strokes, 11 occurred in the aspirin group and 2 in the placebo group (relative risk, 5.4; CI, 1.3 to 22.1; P = 0.02). No stroke was fatal, but 4 produced some long-term impairment of function. One stroke, in the aspirin group, was hemorrhagic.. Our data indicated that alternate-day aspirin therapy greatly reduced the risk for first myocardial infarction among patients with chronic stable angina, a group of patients at high risk for cardiovascular death (P less than 0.001). Although our results for stroke were based on small numbers, they suggested an apparent increase in frequency of stroke with aspirin therapy; this finding requires confirmation in randomized trials of adequate sample size.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Cerebrovascular Disorders; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Middle Aged; Myocardial Infarction; Risk; Statistics 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

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: Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Clinical Trials as Topic; Double-Blind Method; Humans; Lung Neoplasms; Prospective Studies

The causal association between circulating β-carotene concentrations and cardiovascular disease (CVD) remains controversial. We conducted a Mendelian randomization study to explore the effects of β-carotene on various cardiovascular diseases, including myocardial infarction, atrial fibrillation, heart failure, and stroke. Three single nucleotide polymorphisms (SNPs) associated with the β-carotene levels were obtained by searching published data and used as instrumental variables. Genetic association estimates for 4 CVDs (including myocardial infarction, atrial fibrillation, heart failure, and stroke) in the primary analysis, blood pressure and serum lipids (high-density lipoprotein [HDL] cholesterol, LDL cholesterol, and triglycerides) in the secondary analysis were obtained from large-scale genome-wide association studies (GWASs). We applied inverse variance-weighted as the primary analysis method, and 3 others were used to verify as sensitivity analysis. Genetically predicted circulating β-carotene levels (natural log-transformed, µg/L) were positively associated with myocardial infarction (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.18, P = .011) after Bonferroni correction. No evidence supported the causal effect of β-carotene on atrial fibrillation (OR 1.02, 95% CI 0.96-1.09, P = .464), heart failure (OR 1.07, 95% CI 0.97-1.19, P = .187), stroke (OR 1.03, 95% CI 0.93-1.15, P = .540), blood pressure (P > .372) and serum lipids (P > .239). Sensitivity analysis produced consistent results. This study provides evidence for a causal relationship between circulating β-carotene and myocardial infarction. These findings have important implications for understanding the role of β-carotene in CVD and may inform dietary recommendations and intervention strategies for preventing myocardial infarction.

Topics: Atrial Fibrillation; beta Carotene; Cardiovascular Diseases; Cholesterol, HDL; Genome-Wide Association Study; Heart Failure; Humans; Mendelian Randomization Analysis; Myocardial Infarction; Polymorphism, Single Nucleotide; Stroke; Triglycerides

Although carotenoids have been suggested to exhibit antioxidant properties, some experimental studies reported that β-carotene may show pro-oxidant effects under certain conditions. Current evidence regarding the cardiovascular effects of carotenoids among patients with type 2 diabetes (T2D) is scarce. This study aimed to prospectively examine the associations of individual serum carotenoid concentrations with cardiovascular mortality among adults with T2D.. This analysis included 3,107 individuals with T2D from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2001-2006. Cardiovascular mortality was ascertained by linkage to National Death Index records through 31 December 2015. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs.. During an average of 14 years of follow-up, 441 cardiovascular deaths occurred. After multivariate adjustment including lifestyles, dietary factors, glucose control, and other major carotenoids, higher serum β-carotene concentrations were significantly associated with an elevated risk of cardiovascular mortality in a dose-response manner. When extreme quartiles of β-carotene were compared, the multivariable-adjusted HR was 2.47 (95% CI 1.62, 3.76) for cardiovascular mortality (Ptrend = 0.002); and per one-unit increment in natural log-transformed serum β-carotene was associated with a 46% higher risk of cardiovascular mortality (P = 0.001). Other individual carotenoids (α-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin) were not significantly associated with the risk of cardiovascular mortality. Consistent results were observed when stratifying by age, sex, race, BMI, smoking status, diabetes duration, and glycated hemoglobin A1c levels.. Higher concentrations of serum β-carotene, but not other individual carotenoids, were significantly associated with an increased risk of cardiovascular mortality among individuals with T2D. Our findings, if replicated, underscore the need to estimate the optimal serum β-carotene concentrations in individuals with T2D.

Topics: Adult; beta Carotene; Cardiovascular Diseases; Carotenoids; Diabetes Mellitus, Type 2; Humans; Nutrition Surveys; Risk Factors

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

An effect of dietary carotenes on risk of cardiovascular disease (CVD) is uncertain. We aimed to investigate whether the association between dietary carotenes intake and risk of CVD mortality will persist after controlling for the intakes of potential cardioprotective dietary factors that correlate with dietary alpha- and/or beta-carotenes.. We followed up a total of 58,646 Japanese between 1988 and 1990 and 2009. We used a food frequency questionnaire (FFQ) to determine the dietary intakes of carotenes, and estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) of CVD mortality in relation to carotene intake by the proportional hazard regression developed by David Cox. During 965,970 person-years of follow-up (median 19.3 years), we identified 3388 total CVD deaths. After adjusting for demographic and lifestyle factors, dietary intakes of alpha-carotene were significantly associated with the reduced risk of mortality from coronary heart disease (CHD); adjusted HR (95% CI) in the highest versus lowest quintiles of intake was 0.75 (0.58-0.96; P-trend = 0.02) and dietary intakes of beta-carotene were significantly associated with the reduced risk of mortality from CVD, CHD, and other CVD; adjusted HRs (95% CIs) were 0.88 (0.79-0.98; P-trend = 0.04), 0.78 (0.61-0.99; P-trend = 0.01), and 0.81 (0.67-0.98; P-trend = 0.04), respectively. However, after further adjusting for the dietary intakes of potassium, calcium, vitamins C, E, or K, these associations disappeared.. -Dietary alpha- and beta-carotene intakes were not associated with risk of CVD mortality after controlling for intakes of other potential cardioprotective nutrients.

Topics: Aged; beta Carotene; Cardiovascular Diseases; Carotenoids; Cause of Death; Diet, Healthy; Female; Humans; Japan; Male; Middle Aged; Nutritive Value; Prognosis; Prospective Studies; Protective Factors; Risk Assessment; Risk Factors; Risk Reduction Behavior; Time Factors

Although the associations of antioxidant micronutrients, such as carotenoids and vitamins, with cardiovascular diseases (CVDs) have been studied extensively, blood concentrations of antioxidant micronutrients and heart rate variability (HRV), which has been proven to be an indicator of cardiac autonomic control, has not been reported. We aimed to explore whether blood concentrations of antioxidant micronutrients, including carotenoids and vitamins, are associated with elevated heart rate variability (HRV (beneficial change) in a cross-sectional analysis.. Data were obtained from the Midlife in the United States (MIDUS) study that includes a general adult population. A total of 1074 (aged 34-84) individuals were included. Multivariable analyses were performed to investigate the association between main blood carotenoids (total lutein, zeaxanthin, beta-cryptoxanthin, 13-cis-beta-carotene, alpha-carotene, all-trans-beta-carotene and total lycopene) and vitamins A (retinol) and E (gamma-tocopherol and alpha-tocopherol) and HRV after adjustments were made for lifestyle factors and age-related confounders.. Pearson correlation analyses showed that the increased levels of carotenoids and vitamins were positively correlated with higher HRV (all P < 0.05). After adjustments were made for age, gender, race, body mass index(BMI), ever-smoker, number of drinking years and exercise, blood alpha-carotene, all-trans-beta-carotene and total lycopene levels were independently associated with higher HRV in the linear regression model (all P < 0.05). Sensitivity analysis by adding "ever chronic respiratory diseases" as a covariate suggested that blood concentrations of these three carotenoids were still associated with higher low-frequency (LF)-HRV and high-frequency (HF)-HRV (all P < 0.05). Furthermore, stratified analyses suggested that the associations were affected by adding "heart disease" and "hypertension" as covariates.. We provide the first evidence that elevated blood concentrations of alpha-carotene, trans-beta-carotene and lycopene are associated with beneficial changes in HRV in the general population. Daily intake of fruit and vegetables may be beneficial to increase blood carotenoid status and further prevent autonomic dysfunction.

Topics: Adult; beta Carotene; Cardiovascular Diseases; Carotenoids; Cross-Sectional Studies; Heart Rate; Humans; Lycopene

Background: evidence indicates a role of vitamin A in the regulation of fat mass influencing obesity and cardiovascular diseases. Material and methods: a cross-sectional study in 200 women, paired by age and by the recommended dietary intake of vitamin A. Subjects were divided into four groups according to body mass index (BMI): 80 eutrophic (E), 40 overweight (OW), 40 class I obesity (OI) and 40 class II obesity (OII). Lipid and glycemic profiles were measured and oxidative stress was evaluated through serum concentrations of uric acid, glutathione peroxidase (GSH-Px), and thiobarbituric acid reactive substances (TBARS). Results: the cutoff points for deficiency of serum retinol and β-carotene levels were < 1.05 µmol/L and 40 µg/dL, respectively. For the recommended dietary intake of vitamin A it was 700 µg/day. Retinol and β-carotene deficiency was found in the E group at 5 % and 15 %, respectively, reaching 77.5 % and 82.5 % in the OII group. Conclusions: a correlation was observed between serum concentrations of retinol and β-carotene and glycemic, lipid, and markers of oxidative stress profiles in the groups studied. It was observed that OI and OII subjects who had retinol and β-carotene deficiency presented a risk that was 16 and 20.7 times greater, respectively, of having a diagnosis with DM2 as compared to E subjects with adequate concentrations of vitamin A. Increased demand of vitamin A may be related to increased BMI, body adiposity, and oxidative stress even when a recommended intake of vitamin A is reached.. Introducción: la evidencia indica un papel de la vitamina A en la regulación de la masa grasa que influye en la obesidad y las enfermedades cardiovasculares. Material y métodos: estudio transversal con 200 mujeres emparejadas por edad y por la ingesta dietética de vitamina A recomendada. Se dividieron en cuatro grupos según el índice de masa corporal (IMC): 80 eutróficas (E), 40 con sobrepeso (OW), 40 con obesidad de clase I (OI) y 40 con obesidad de clase II (OII). Se midieron los perfiles lipídicos y glucémicos y se evaluó el estrés oxidativo a través de las concentraciones séricas de ácido úrico, glutatión-peroxidasa (GSH-Px) y sustancias reactivas del ácido tiobarbitúrico (TBARS). Resultados: los puntos de corte para la deficiencia de las concentraciones séricas de retinol y caroteno fueron de 1,05 µmol/L y 40 g/dL, respectivamente. Para la ingesta dietética recomendada de vitamina A fue de 700 g/día. Se encontró deficiencia de retinol y caroteno en el grupo E, del 5 % y 15 %, respectivamente, alcanzando un 77,5 % y 82,5 % en el grupo OII. Conclusiones: se observó correlación entre las concentraciones séricas de retinol y caroteno y los perfiles glucémico, lipídico y de marcadores de perfiles de estrés oxidativo en los grupos estudiados. Se observó que los sujetos con OI y OII que tenían deficiencia de retinol y caroteno presentaban un riesgo 16 y 20,7 veces mayor, respectivamente, de ser diagnosticados de DM2 en comparación con los E con concentraciones adecuadas de vitamina A. El aumento de la demanda de vitamina A puede estar relacionado con el aumento del IMC, la adiposidad corporal y el estrés oxidativo, incluso cuando se alcanza la ingesta recomendada de vitamina A.

Topics: Adiposity; beta Carotene; Blood Glucose; Body Mass Index; Cardiometabolic Risk Factors; Cardiovascular Diseases; Cross-Sectional Studies; Female; Glutathione Peroxidase; Humans; Lipids; Middle Aged; Night Blindness; Obesity; Obesity, Morbid; Overweight; Oxidative Stress; Recommended Dietary Allowances; Risk Factors; Thiobarbituric Acid Reactive Substances; Uric Acid; Vitamin A; Vitamin A Deficiency; Vitamins

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

In vivo and in vitro evidence suggests that antioxidant vitamins and carotenoids may be key factors in the treatment and prevention of obesity and obesity-associated disorders. Hence, the objective of the present study was to determine the relationship between plasma lipid-soluble antioxidant vitamin and carotenoid levels and adiposity and cardio-metabolic risk markers in overweight and obese adolescents participating in a multidisciplinary weight loss programme.. A therapeutic programme was conducted with 103 adolescents aged 12-17 years old and diagnosed with overweight or obesity. Plasma concentrations of α-tocopherol, retinol, β-carotene and lycopene, anthropometric indicators of general and central adiposity, blood pressure and biochemical parameters were analysed at baseline and at 2 and 6 months of treatment.. Lipid-corrected retinol (P < 0.05), β-carotene (P = 0.001) and α-tocopherol (P < 0.001) plasma levels increased significantly, whereas lipid-corrected lycopene levels remained unaltered during the treatment. Anthropometric indicators of adiposity (P < 0.001), blood pressure (P < 0.01) and biochemical parameters (P < 0.05) decreased significantly, whereas fat free mass increased significantly (P < 0.001). These clinical and biochemical improvements were related to changes in plasma lipid-corrected antioxidant vitamin and carotenoid levels. The adolescents who experienced the greatest weight loss also showed the largest decrease in anthropometric indicators of adiposity and biochemical parameters and the highest increase in fat free mass. Weight loss in these adolescents was related to an increase in plasma levels of lipid-corrected α-tocopherol (P = 0.001), β-carotene (P = 0.034) and lycopene (P = 0.019).. Plasma lipid-soluble antioxidant vitamin and carotenoid levels are associated with reduced adiposity, greater weight loss and an improved cardio-metabolic profile in overweight and obese adolescents.

Topics: Adiposity; Adolescent; alpha-Tocopherol; Anthropometry; Antioxidants; Apolipoproteins; beta Carotene; Cardiovascular Diseases; Carotenoids; Child; Cholesterol; Cohort Studies; Diet; Female; Follow-Up Studies; Humans; Lycopene; Male; Metabolic Syndrome; Nutrition Assessment; Overweight; Pediatric Obesity; Risk Factors; Triglycerides; Vitamin A; Vitamins

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 interaction between genetics and diet may explain the present disagreement in the protective role of vitamin intake on cardiovascular disease. We cross-sectionally assessed the interaction of habitual dietary intake of β-carotene, vitamin C, folate, and vitamin E with single nucleotide polymorphisms (SNPs) on brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness.. Dietary intakes of β-carotene, vitamin C, folate, and vitamin E were quantified by a food frequency questionnaire in 3198 healthy men and women (≥ 40 years) from the Korea Multi-Rural communities Cohort study. baPWV was measured, and 19 SNPs were genotyped. The associations and interactions between dietary vitamin intake, SNP genotype, and baPWV were assessed using general linear models.. In both men and women, dietary intake of β-carotene, vitamin C, folate, or vitamin E and baPWV were not directly associated. Vitamin C, folate, and vitamin E intake had an interaction with rs4961 (ADD1) genotype on baPWV in men. rs4961 also interacted with folate intake on baPWV in women. In women, rs10817542 (ZNF618) and rs719856 (CD2AP) had an interaction with β-carotene and folate intake and rs5443 (GNB3) had an interaction with vitamin E intake on baPWV. In general, minor allele homozygotes with low vitamin intake had higher baPWV than other subgroups. Results were similar when supplement users were excluded.. Higher intake of dietary vitamin C, folate, and vitamin E may be related to high baPWV in healthy Korean men who are minor allele homozygotes of rs4961. In healthy Korean women, dietary folate, β-carotene, and vitamin E intake may affect baPWV differently according to rs4961, rs10817542, rs719856, or rs5443 genotype. Greater dietary intake of these nutrients may protect those that are genetically vulnerable to stiffening of the arteries.

Topics: Alleles; Ankle Brachial Index; Ascorbic Acid; beta Carotene; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Diet; Female; Folic Acid; Gene-Environment Interaction; Genotype; Humans; Male; Middle Aged; Nutrition Assessment; Polymorphism, Single Nucleotide; Republic of Korea; Risk Factors; Rural Population; Vascular Stiffness; Vitamin E

Lutein is a carotenoid with strong antioxidant properties. Previous studies in adults suggest a beneficial role of lutein on cardiometabolic health. However, it is unknown whether this relation also exists in children; therefore, we aimed to assess the relation between lutein intake at 13 months of age and cardiometabolic outcomes at the age of 6 years. We included 2044 Dutch children participating in a population-based prospective cohort study. Diet was measured at 13 months of age with an FFQ. Lutein intake was standardised for energy and β-carotene intake. Blood pressure, anthropometrics, serum lipids and insulin were measured at the age of 6 years. Dual-energy X-ray absorptiometry was performed to measure total and regional fat and lean mass. A continuous cardiometabolic risk factor score was created, including the components body fat percentage, blood pressure, insulin, HDL-cholesterol and TAG. Age- and sex-specific standard deviation scores were created for all outcomes. Multivariable linear regression was performed, including socio-demographic and lifestyle variables. Median (energy-standardised) lutein intake was 1317 mcg/d (95% range 87, 6069 mcg/d). There were no consistent associations between lutein intake at 13 months and anthropometrics and body composition measures at 6 years of age. In addition, lutein intake was not associated with a continuous cardiometabolic risk factor score, nor was it associated with any of the individual components of the cardiometabolic risk factor score. Results from this large population-based prospective cohort study do not support the hypothesis that lutein intake early in life has a beneficial role for later cardiometabolic health.

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Child Development; Cohort Studies; Diet; Energy Intake; Female; Hospitals, Pediatric; Humans; Infant; Infant Nutritional Physiological Phenomena; Longitudinal Studies; Lutein; Male; Metabolic Syndrome; Netherlands; Nutrition Surveys; Prospective Studies; Risk Factors

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

Hyperlipidemia and elevated circulating C-reactive protein (CRP) and total homocysteine (tHcy) concentrations are cardiovascular disease (CVD) risk factors. Previous studies indicated that higher serum carotenoid concentrations were inversely associated with some of these biomarkers. However, whether dietary carotenoid intake is inversely associated with these CVD risk biomarkers is not well known. We assessed the associations between individual dietary carotenoid intake and CVD risk biomarkers and tested whether the serum carotenoid concentrations explain (mediate) or influence the strength of (moderate) the associations, if any association exists. Dietary data collected from 2 24-h dietary recalls and serum measurements in adult men (n = 1312) and women (n = 1544) from the NHANES 2003-2006 were used. Regression models designed for survey analysis were used to examine the associations between individual dietary carotenoids and log-transformed blood cholesterol, CRP, and tHcy. The corresponding individual serum carotenoid concentration was considered as mediator (and moderator if applicable). After adjustment for covariates, significant inverse associations with LDL cholesterol were observed for dietary β-carotene (P < 0.05) and lutein + zeaxanthin (P < 0.001), and with tHcy for dietary β-carotene (P < 0.05), lycopene (P < 0.05), and total carotenoids (P < 0.05). Dietary lutein + zeaxanthin intake was also positively associated with HDL cholesterol concentrations (P < 0.01). Most of these associations were null after additional adjustment for corresponding serum carotenoid concentrations, indicating the complete mediation effects of serum carotenoids. Serum β-carotene significantly moderated the associations between dietary β-carotene and CRP (P-interaction < 0.05), and quartile 4 of dietary β-carotene was associated with lower CRP concentrations only among participants with serum β-carotene > 0.43 μmol/L. In this population-based cross-sectional study, serum carotenoids were mediators of dietary carotenoids and CVD risk biomarker associations. Serum β-carotene was also a moderator of the dietary β-carotene and CRP association. These findings may help in the design of future intervention studies on dietary carotenoids in the prevention of CVD.

Topics: Adult; beta Carotene; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Carotenoids; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Diet; Female; Homocysteine; Humans; Hypercholesterolemia; Hyperhomocysteinemia; Lutein; Lycopene; Male; Nutrition Surveys; Risk Factors; United States; Xanthophylls; Zeaxanthins

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

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

Assessment of cardiovascular disease (CVD) risk factors can predict clinical manifestations of atherosclerosis in adulthood. In this pilot study with hypercholesterolemic children and adolescents, we investigated the effects of a combination of plant sterols, fish oil and B vitamins on the levels of four independent risk factors for CVD; LDL-cholesterol, triacylglycerols, C-reactive protein and homocysteine.. Twenty five participants (mean age 16 y, BMI 23 kg/m2) received daily for a period of 16 weeks an emulsified preparation comprising plant sterols esters (1300 mg), fish oil (providing 1000 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) and vitamins B12 (50 μg), B6 (2.5 mg), folic acid (800 μg) and coenzyme Q10 (3 mg). Atherogenic and inflammatory risk factors, plasma lipophilic vitamins, provitamins and fatty acids were measured at baseline, week 8 and 16.. The serum total cholesterol, LDL- cholesterol, VLDL-cholesterol, subfractions LDL-2, IDL-1, IDL-2 and plasma homocysteine levels were significantly reduced at the end of the intervention period (p<0.05). The triacylglycerols levels decreased by 17.6%, but did not reach significance. No significant changes in high sensitivity C-reactive protein, HDL-cholesterol and apolipoprotein A-1 were observed during the study period. After standardisation for LDL cholesterol, there were no significant changes in the levels of plasma γ-tocopherol, β-carotene and retinol, except for reduction in α-tocopherol levels. The plasma levels of n-3 fatty acids increased significantly with the dietary supplementation (p<0.05).. Daily intake of a combination of plant sterols, fish oil and B vitamins may modulate the lipid profile of hypercholesterolemic children and adolescents.. Current Controlled Trials ISRCTN89549017.

Topics: Adolescent; Apolipoprotein A-I; beta Carotene; C-Reactive Protein; Cardiovascular Diseases; Child; Cholesterol, HDL; Cholesterol, LDL; Fatty Acids, Omega-3; Female; Fish Oils; gamma-Tocopherol; Humans; Hypercholesterolemia; Male; Phytosterols; Pilot Projects; Risk Factors; Triglycerides; Vitamin B Complex; Young Adult

Deficiencies of essential nutrients have been responsible for many epidemic outbreaks of deficiency diseases in the past. Large observational studies point at possible links between nutrition and chronic diseases. Low intake of antioxidant vitamins e. g. have been correlated to increased risk of cardiovascular diseases or cancer. The main results of these studies are indications that an intake below the recommendation could be one of the risk factors for chronic diseases. There was hardly any evidence that amounts above the RDA could be of additional benefit. Since observational studies cannot prove causality, the scientific community has been asking for placebo-controlled, randomized intervention trials (RCTs). Thus, the consequences of the epidemiological studies would have been to select volunteers whose baseline vitamin levels were below the recommended values. The hypothesis of the trial should be that correcting this risk factor up to RDA levels lowers the risk of a disease like CVD by 20 - 30 %. However, none of the RCTs of western countries was designed to correct a chronic marginal deficiency, but they rather tested whether an additional supplement on top of the recommended values would be beneficial in reducing a disease risk or its prognosis. It was, therefore, not surprising that the results were disappointing. As a matter of fact, the results confirmed the findings of the observational studies: chronic diseases are the product of several risk factors, among them most probably a chronic vitamin deficiency. Vitamin supplements could only correct the part of the overall risk that is due to the insufficient vitamin intake.

Topics: Antioxidants; Ascorbic Acid; Avitaminosis; beta Carotene; Cardiovascular Diseases; Chronic Disease; Dietary Supplements; Dose-Response Relationship, Drug; Female; Humans; Male; Nutrition Policy; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Vitamin E; Vitamins

Oxidative stress induced by reactive oxygen species plays an important role in the etiology of many diseases. Dietary phytochemical products, such as bioactive food components and marine carotenoids (asthaxantin, lutein, β-carotene, fucoxanthin), have shown an antioxidant effect in reducing oxidative markers stress. Scientific evidence supports the beneficial role of phytochemicals in the prevention of some chronic diseases. Many carotenoids with high antioxidant properties have shown a reduction in disease risk both in epidemiological studies and supplementation human trials. However, controlled clinical trials and dietary intervention studies using well-defined subjects population have not provided clear evidence of these substances in the prevention of diseases. The most important aspects of this special issue will cover the synthesis, biological activities, and clinical applications of marine carotenoids, with particular attention to recent evidence regarding anti-oxidant and anti-inflammatory properties in the prevention of cardiovascular disease.

Topics: Animals; beta Carotene; Cardiovascular Diseases; Carotenoids; Humans; Lutein; Oxidative Stress; Xanthophylls

We explored the characteristics of the vitamin status in 471 patients with cardiovascular diseases, according to sex, and BMI values. All patients underwent examination of the system Nutritest-IP: studying their actual meals at home, determined anthropometric measurement, body composition, using biochemical methods evaluated the state of the protein, lipid and carbohydrate metabolism, the functional state of liver and biliary tract, hemostasis, vitamin provision. The results suggest a lack of availability of patients with vitamins C and B group. The number of patients with deficient serum beta-carotene increased proportional to body mass index. The concentration of beta-carotene decreased and vitamin E - increased in blood serum proportionally to increase the degree of obesity. Thus the availability of vitamins in the blood serum depends from sex and body mass index values of the patients. These data suggest that the rate of supply of vitamins are reliable markers to assess the adequacy of the diet consumed by the content of vitamins in people with normal body weight. Appraisingly the content of beta-carotene and vitamin E in the serum of patients it should be taken into account that they have overweight or obese, and abnormality of lipid spectrum of blood serum.

Topics: Aged; Ascorbic Acid; beta Carotene; Body Mass Index; Cardiovascular Diseases; Diet; Female; Humans; Male; Meals; Middle Aged; Obesity; Riboflavin; Sex Factors; Vitamin B 6; Vitamin E; Vitamins

Topics: beta Carotene; Cardiovascular Diseases; Humans; Risk Factors; Skin Aging; Vitamins

Emerging evidence suggests a role of lycopene in the primary prevention of cardiovascular disease. This study aimed to investigate the association of serum lycopene concentration with brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness and markers of oxidative stress and inflammation.. healthy women (n=264, 31-75 yrs) were classified into tertiles according to serum lycopene concentration. Multivariate linear regression analyses were used to assess the relationship between serum lycopene and baPWV.. Subjects in middle tertile (T2) and upper tertile (T3) had lower baPWV (1263+/-23 and 1265+/-14 cm/s vs. 1338+/-21 cm/s; p=0.009) and lower oxidized LDL (oxLDL) (53+/-3 and 55+/-3 U/L vs. 66+/-3 U/L; p<0.001) than those in lower tertile (T1). Subjects in T3 showed higher LDL particle size (24.3+/-0.08 nm vs. 24.0+/-0.07 nm, p=0.005) and lower C-reactive protein (hs-CRP) (0.80+/-0.25mg/dL vs. 1.27+/-0.24 mg/dL, p=0.015), compared with those in T1. Logistic regression analysis showed that baPWV decreased with the increment of lycopene concentration; log baPWV decreased by 0.21 cm/s (95% CI -0.168;-0.045, p=0.001) per unit change in lycopene. After adjustment for age, BMI, smoking, drinking, menopause and blood pressure, the estimated effect was attenuated by 35%, but remained statistically significant [-0.13 cm/s (95% CI -0.112;-0.018, p=0.006)]. Further adjustment for beta-carotene, alpha-tocopherol, oxLDL, LDL particle size, and hs-CRP increased the strength of the association [beta=-0.221 (95% CI -0.215;-0.012, p=0.029)].. This study supports the presence of an independent inverse relationship between circulating lycopene and baPWV. Additionally, reduced oxidative modification of LDL may be one of mediators on the mechanisms how lycopene reduces arterial stiffness.

Topics: Adult; Aged; alpha-Tocopherol; Arteries; beta Carotene; Cardiovascular Diseases; Carotenoids; Female; Humans; Inflammation; Lipoproteins, LDL; Lycopene; Middle Aged; Oxidative Stress; Oxygen; Regression Analysis

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

The factors influencing total plasma homocysteine levels (tHcy) are of special interest in the attempt to reduce cardiovascular risk.. This investigation aimed to assess the independent effects of antioxidant vitamins on tHcy in elderly people.. Our cross-sectional analysis included data of 184 subjects (≥60 years) from the longitudinal study in an aging population in Giessen (GISELA), Germany. We examined the effects of plasma levels, intake and supplementation of vitamin C, vitamin E, and β-carotene on tHcy.. The mean tHcy was within the normal range in this population. Serum folate, the estimated glomerular filtration rate (eGFR), and plasma vitamin C showed a negative association with tHcy in simple regression analysis. In a subsequent multiple regression analysis, eGFR, serum folate, and plasma vitamin C were the relevant independent predictors of tHcy. Intake and supplementation of vitamin C, as well as plasma levels, intake and supplementation of vitamin E, and β-carotene were not associated with tHcy.. Vitamin C may be an independent predictor of tHcy in free-living elderly people and, therefore, should be considered in attempts to reduce tHcy.

Topics: Aged; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cross-Sectional Studies; Female; Folic Acid; Germany; Glomerular Filtration Rate; Homocysteine; Humans; Longitudinal Studies; Male; Vitamin E; Vitamins

to evaluate retinol and β-carotene serum levels and their relationship with risk factors for cardiovascular disease in individuals with morbid obesity, resident in Rio de Janeiro.. blood serum concentrations of retinol and β-carotene of 189 morbidly obese individuals were assessed. The metabolic syndrome was identified according to the criteria of the National Cholesterol Education Program (NCEP) and World Health Organization (WHO). Lipid profile, insulin resistance, basal insulin, glycemia, blood pressure, and anthropometry and their correlation with retinol and β-carotene serum levels were evaluated.. metabolic syndrome diagnosis was observed in 49.0% of the sample. Within this percentage the levels of β-carotene were significantly lower when body mass index increased. Serum retinol didn't show this behavior. Serum retinol inadequacy in patients with metabolic syndrome (61.3%), according to WHO criterion, was higher (15.8%) than when the whole sample was considered (12.7%). When metabolic syndrome was diagnosed by NCEP criterion, β-carotene inadequacy was higher (42.8%) when compared to the total sample (37.5%). There was a significant difference between average β-carotene values of patients with and without metabolic syndrome (p=0.048) according to the classification of the NCEP. Lower values were found in patients with metabolic syndrome.. considering the vitamin A contribution in antioxidant protection, especially when risk factors for cardiovascular disease are present, it is suggested that great attention be given to morbidly obese. This could aid in prevention and treatment of cardiovascular disease, which affects a significant part of the population.

Topics: Adult; Aged; Aging; beta Carotene; Body Mass Index; Brazil; Cardiovascular Diseases; Cholesterol, LDL; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Obesity, Morbid; Prevalence; Risk Factors; Severity of Illness Index; Urban Health; Vitamin A; Vitamin A Deficiency; Young Adult

Topics: Antihypertensive Agents; beta Carotene; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Down-Regulation; Elasticity; Female; Femoral Artery; Humans; Hypertension; Male; Middle Aged; Oxidative Stress; Pulsatile Flow; Regional Blood Flow; Risk Assessment; Risk Factors

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

The role of beta-carotene, alpha-tocopherol, and vitamin C in the prevention of cardiovascular diseases (CVD) is controversial. Prospective studies on gamma-tocopherol and carotenoids other than beta-carotene are sparse. We assessed relations between the intake of different carotenoids, alpha- and gamma-tocopherol, and vitamin C with 15-y CVD mortality in elderly men who participated in the Zutphen Elderly Study. Information on diet and potential confounding factors was collected in 1985, 1990, and 1995. In 1985, 559 men (mean age approximately 72 y) free of chronic diseases were included in the current analysis. After 15 y of follow-up, comprising 5744 person-years, 197 men had died from CVD. After adjustment for age, smoking, and other potential lifestyle and dietary confounders, relative risks (RR) (95% CI) of CVD death for a 1-SD increase in intake were 0.81 (0.66-0.99) for alpha-carotene and 0.80 (0.66-0.97) for beta-carotene. Carrots were the primary source of alpha- and beta-carotene and their consumption was related to a lower risk of death from CVD (adjusted RR, 0.83; 95% CI = 0.68-1.00). Intakes of carotenoids other than alpha- and beta-carotene were not associated with CVD mortality, nor were vitamin C and alpha- and gamma tocopherol. In conclusion, dietary intakes of alpha-carotene and beta-carotene are inversely associated with CVD mortality in elderly men. This study does not indicate an important role for other carotenoids, tocopherols, or vitamin C in lowering the risk of CVD death.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Carotenoids; Cohort Studies; Diet; Feeding Behavior; Humans; Male; Netherlands; Tocopherols

Individual plasma carotenoids have been associated with various chronic diseases but little is known about the relationship between total plasma carotenoids and risk factors for chronic diseases. In the Physicians' Health Study, we examined 492 men free of CVD and cancer for the relationship between total plasma carotenoids (the sum of alpha-carotene, beta-carotene, lycopene, zeaxanthin, lutein and beta-cryptoxanthin) and a wide variety of factors that predict chronic disease. Multivariate linear and logistic regression was performed to calculate parameter estimates (95% CI) and OR (95% CI) for total plasma carotenoids. In linear regression models, BMI, hypertension, alcohol intake and plasma levels of each lipid parameter and a-tocopherol significantly predicted levels of total plasma carotenoids. Upon adjustment for multiple chronic disease risk factors, the OR for levels of total plasma carotenoids greater than or equal to the median (> or=1.301 micromol/l) was statistically significant for current smoking (OR 0.21; 95% CI 0.06, 0.77), weekly alcohol ingestion (OR 2.30; 95% CI 1.06, 4.99), daily alcohol ingestion (OR 2.46; 95% CI 1.29, 4.67), each 100 mg/l increase in total cholesterol (OR 0.73; 95% CI 0.58, 0.91), LDL-cholesterol (OR 1.48; 95% CI 1.17, 1.89) and HDL-cholesterol (OR 1.58; 95% CI 1.26, 1.99), each 100 mg/ml increase in intercellular adhesion molecule-1 (OR 0.70; 95% CI 0.53, 0.93) and each 10 micromol/l increase in alpha-tocopherol (OR 1.33; 95% CI 1.12, 1.57), using logistic regression. Few lifestyle and clinical risk factors appear to be related to levels of total plasma carotenoids; however, levels of biomarkers such as plasma lipids and alpha-tocopherol may be strongly related.

Topics: Aged; Alcohol Drinking; alpha-Tocopherol; beta Carotene; Cardiovascular Diseases; Carotenoids; Cholesterol; Chronic Disease; Cross-Sectional Studies; Cryptoxanthins; Humans; Life Style; Logistic Models; Lutein; Lycopene; Male; Middle Aged; Risk; Risk Factors; Smoking; Vitamins; Xanthophylls; Zeaxanthins

To investigate the contribution of the total antioxidant capacity (TAC) of the diet to plasma concentrations of beta-carotene.. Cross-sectional study.. Department of Public Health and Department of Internal Medicine and Biomedical Sciences, University of Parma.. A total of 247 apparently healthy adult men (n=140) and women (n=107).. A medical history, a physical exam including height, weight, waist circumference and blood pressure measurements, a fasting blood draw, an oral glucose tolerance test and a 3-day food record.. We observe a negative trend across quartiles of plasma beta-carotene for most biological variables clustering in the insulin resistance syndrome, as well as for traditional and new risk factors for type II diabetes and cardiovascular disease (CVD), including C-reactive protein and gamma-glutamyltranspeptidase (P<0.05). Regarding dietary characteristics, energy-adjusted intake of fat, fiber, fruits, vegetables, beta-carotene, vitamin C, vitamin E and dietary TAC significantly increased with increasing plasma beta-carotene (P<0.05), whereas alcohol intake decreased (P=0.013). Adjusted geometric means (95% confidence interval) of plasma beta-carotene significantly increased across quartiles of dietary TAC, even when single dietary antioxidants were considered in the model (QI=0.087 mg/dl (0.073-0.102); QII=0.087 mg/dl (0.075-0.103); QIII=0.114 mg/dl (0.098-0.132) and QIV=0.110 mg/dl (0.093-0.130); P for linear trend=0.026). When the population was divided on the basis of alcohol consumption, this trend was also observed in subjects drinking <20 g alcohol/day (P=0.034), but not in those with higher alcohol intake (P=0.448).. Dietary TAC is an independent predictor of plasma beta-carotene, especially in moderate alcohol drinkers. This may explain, at least in part, the inverse relationship observed between plasma beta-carotene and risk of chronic diseases associated to high levels of oxidative stress (i.e., diabetes and CVD), as well as the failure of beta-carotene supplements alone in reducing such risk.

Topics: Alcohol Drinking; Antioxidants; beta Carotene; Cardiovascular Diseases; Cluster Analysis; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet; Female; Food Analysis; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Oxidation-Reduction; Oxidative Stress; Predictive Value of Tests; Risk Factors; Vitamins

Oxidative stress is associated with the development of several disorders including cardiovascular disease and cancer. Among conditions known to influence oxidative stress, the use of oral contraception (OC) in women has been a matter of ongoing discussion.. A total of 897 eligible and healthy volunteers were recruited from among the patients of 50 general practitioners participating in the ELAN study (Etude Liégeoise sur les ANtioxydants). A subsample consisting of 209 women aged 40-48 years was studied for a comprehensive oxidative stress status (OSS), including the analysis of antioxidants, trace elements and three markers of oxidative damage to lipids. Among 209 subsample, 49 (23%) were OC users (OCU), 119 (57%) non-contraception users (NCU) and 41 (20%) were intrauterine (hormonal and copper) devices users (IUD).. After adjustment for smoking, systolic and diastolic blood pressure and BMI (or waist circumference), a marked and significant increase in lipid peroxides was observed among OCU women when compared with NCU and IUD users. A cut-off value of 660 microM in lipid peroxides allowed the discrimination of OCU from the two other groups. In contrast, no difference was observed in the plasma concentration of both oxidized low-density lipoprotein (LDL) and their related antibodies. The increased level in lipid peroxides was strongly related to higher concentrations of copper (r < 0.84; P < 0.0001, cut-off value 1.2 mg/l). When compared with NCU and IUD users, plasma antioxidant defences were significantly altered in OCU women as shown by lower levels of beta-carotene (decrease of 39%; P < 0.01) and gamma-tocopherol (decrease by 22%; P < 0.01). In contrast, higher concentrations of selenium (increased by 11.8%; P < 0.01) were observed in OCU women. Blood concentrations of vitamin C, alpha-tocopherol and zinc were unaffected by OC use.. The intake of OC significantly increases the lipid peroxidation in women aged 40-48 years. This may represent a potential cardiovascular risk factor for these women.

Topics: Adult; Antioxidants; beta Carotene; Cardiovascular Diseases; Contraceptives, Oral; Copper; Female; gamma-Tocopherol; Humans; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Lipid Peroxidation; Lipid Peroxides; Lipoproteins, LDL; Middle Aged; Oxidative Stress; Risk Factors; Selenium

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

Some observational epidemiologic studies suggest that dietary and serum carotenoids are associated with reduced cardiovascular disease mortality.. Three thousand and sixty-one subjects (1,190 males and 1,871 females), aged 39 to 80 years, were recruited from residents of Hokkaido, Japan who had attended comprehensive health check-up programs from 1988 through 1995. Serum levels of alpha-carotene, beta-carotene, and lycopene were separately determined by high-performance liquid chromatography. Serum levels of total carotene consisted of the sum of alpha-carotene, beta-carotene, and lycopene levels. Each serum level of alpha-carotene, beta-carotene, lycopene, total carotene, triglyceride, and alanine transaminase (ALT) activity was transformed logarithmically. The hazard ratios of serum alpha- and beta-carotenes, lycopene, and total carotene values were estimated by the Cox proportional hazard model after adjusting for sex, age, and other potential confounding factors.. During the 11.9-year follow-up period, 80 deaths (49 males and 31 females) from cardiovascular disease, 40 deaths from heart disease, and 37 deaths from stroke were identified among the cohort subjects. High serum values of carotenoids such as alpha- and beta-carotenes, and lycopene were found to be significantly associated with low hazard ratios for cardiovascular disease mortality. However, a significant inverse association between high serum lycopene value and the risk for stroke mortality was not always observed.. High serum levels of total carotene, comprising alpha- and beta-carotenes and lycopene, may reduce the risk for cardiovascular disease mortality among the Japanese population.

Topics: Adult; Aged; Analysis of Variance; beta Carotene; Cardiovascular Diseases; Carotenoids; Chromatography, High Pressure Liquid; Female; Follow-Up Studies; Humans; Japan; Lycopene; Male; Middle Aged; Proportional Hazards Models

Topics: beta Carotene; Cardiovascular Diseases; Cataract; Humans; Lung Neoplasms; Lutein; Macular Degeneration; Radiodermatitis; Retinitis Pigmentosa; Xanthophylls; Zeaxanthins

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

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; Anticarcinogenic Agents; Antioxidants; beta Carotene; Carcinogens; Cardiovascular Diseases; Clinical Trials as Topic; Dietary Supplements; Disease Models, Animal; Female; Follow-Up Studies; Humans; Incidence; Lung; Lung Neoplasms; Male; Oxidants; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Smoking; United States

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

Topics: Adult; Aged; alpha-Tocopherol; beta Carotene; Cardiovascular Diseases; Cholesterol, Dietary; Dietary Supplements; Female; Health Surveys; Humans; Male; Middle Aged; Primary Prevention; Risk Factors; Treatment Outcome; United States

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

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Contraindications; Female; Humans; Male; Meta-Analysis as Topic; Treatment Outcome; Vitamin E; Vitamins

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Cardiovascular Diseases; Female; Humans; Male; Meta-Analysis as Topic; Middle Aged; Survival Rate; Treatment Outcome; Vitamin E

Increased levels of homocysteine (Hcy) and cysteine (Cys) are associated with risk of cardiovascular diseases (CVD). These thiol compounds can generate various free radicals and so cause endothelial dysfunction. Antioxidant vitamins are effective scavengers of reactive oxygen species (ROS) and prevent endothelial dysfunction. In this study, we investigated the plasma homocysteine, cysteine, vitamins E, C and A, and beta-carotene (BC) levels in cardiovascular patients to compare with controls. We also investigated whether there is a correlation between the plasma thiol compounds and antioxidant vitamins.. Blood samples were collected from 47 patients with cardiovascular disease (16 women and 31 men) and 21 healthy subjects (8 women and 13 men) in the overnight fasting state. Serum thiol compound and antioxidant vitamin levels were measured by high-pressure liquid chromatography (HPLC) methods.. The plasma homocysteine and cysteine levels were significantly higher in patients than those of controls. While vitamin C (VC), vitamin A (VA) and beta-carotene levels were significantly lower in patients than in controls, vitamin E (VE) levels did not change in both groups. There is a positive correlation between homocysteine and cysteine levels (r=0.622, p=0.000) in all study population. We found that the plasma level of homocysteine was significantly correlated in negative manner with vitamins E and A levels (r=-0.260, p=0.033 and r=-0.255, p=0.036, respectively) of all study population. Plasma cysteine levels were negatively correlated with only vitamin C levels (r=-0.320, p=0.008) in all study populations.. Our data suggest that Hcy and Cys are associated with cardiovascular disease and there is negative but weak correlation's between thiol compounds and antioxidant vitamins.

Topics: Antioxidants; beta Carotene; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Cysteine; Female; Homocysteine; Humans; Male; Middle Aged; Vitamins

Although subjects randomized into clinical trials tend to have different mortality experiences from those not randomized, few studies have examined how baseline characteristics may explain these differences. We used the recruitment experience of the Physicians' Health Study (PHS) to describe and compare subgroups of subjects ultimately randomized - or not - into the PHS. A total of 112528 male physicians ages 40-84 years responded to letters of invitation and baseline questionnaires sent to 261248 subjects. Baseline information was collected on eligibility criteria, plus lifestyle and clinical risk factors. Total, cardiovascular, cancer, and other mortality were determined through the National Death Index after a mean follow-up of 5.39 years. Respondents had 19 and 19% lower total and cardiovascular mortality rates than nonrespondents. Similarly, willing respondents were 19 and 16% less likely to die than unwilling respondents. However, much of this difference in mortality was explained by disease and lifestyle factors. Respondents who were eligible for the PHS had significantly lower age-adjusted relative risks (RRs) that were attenuated but remained substantially below 1 upon multivariate adjustment in models for total (RRs from 0.48 to 0.79), cardiovascular (from 0.40 to 0.85), and cancer mortality (from 0.55 to 0.87). Finally, a nearly halving in the age-adjusted risk of total and cause-specific mortality among men completing a run-in and randomized into PHS compared with those not randomized was nominally altered upon adding all covariates into multivariate models. In conclusion, a difference in mortality rates according to willingness to participate in a trial was explained by disease and lifestyle factors. In contrast, diseases and risk factors explain some, but not all, of the lower mortality rates of physicians based on eligibility status and their ability to complete a run-in phase.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Cardiovascular Diseases; Cause of Death; Humans; Life Style; Male; Middle Aged; Mortality; Multivariate Analysis; Patient Selection; Physicians; Randomized Controlled Trials as Topic; Risk

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

In this study, we clarified the status of the fat-soluble vitamins retinol and tocopherol, as well as beta-carotene, as antioxidants in the prevention of cardiovascular disease in middle-aged Vietnamese populations with different incomes. In order to measure simultaneously the serum concentrations of retinol, beta-carotene and tocopherol, we carried out high-performance liquid chromatography analysis with three separate detectors. The analytical method was modified, omitting the saponification process, and used a multi-evaporating system with dry ice. This allowed the analysis to proceed more rapidly, use a small amount of serum (40 microL) and be free of hexane contamination to the environment. The analyses reflected an adequate status of vitamin A (serum retinol = 20 microg/dL), but inadequate status of beta-carotene and vitamin E (serum beta-carotene <40 microg/dL; serum tocopherol < 600 microg/dL) in all three Vietnamese populations. As large numbers of Vietnamese subjects were observed with very low serum concentrations of beta-carotene and tocopherol, higher consumptions of green and yellow vegetables, fruits, vegetable oils and other foods rich in vitamin E are recommended for these Vietnamese populations.

Topics: Adult; Antioxidants; beta Carotene; Body Mass Index; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged; Reference Values; Social Class; Tocopherols; Vietnam; Vitamin A

Several large epidemiological studies have shown a correlation between elevated plasma carotenoid levels and decreased risk of cardiovascular disease (CVD). One proposed mechanism for the beneficial effect of carotenoids is through functional modulation of potentially atherogenic processes associated with the vascular endothelium. To test this, we incubated confluent human aortic endothelial cell (HAEC) cultures (passages 4-8) for 24 h with each of the five most prevalent carotenoids in human plasma, which are alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and lycopene, at an approximate concentration of 1 micromol/l. Carotenoids were solubilized in 0.7% (v/v) tetrahydrofuran and incorporated into FBS before adding to cell culture medium. Due to disparate solubilities in aqueous medium, final concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and lycopene were 1.7, 1.1, 0.7, 0.9, and 0.3 micromol/l and monolayers accumulated 647, 158, 7, 113, and 9 pmol/mg protein, respectively. Monolayers were then stimulated with IL-1beta (5 ng/ml) for 6 h with subsequent determination of cell surface expression of adhesion molecules as measured by an enzyme-linked immunosorbent assay (ELISA). To assess endothelial cell adhesion to monocytes, IL-1beta-stimulated monolayers were incubated for 10 min with 51Cr-labeled U937 monocytic cells and adhesion determined by isotope counting. Pre-incubation of HAEC with beta-carotene, lutein and lycopene significantly reduced VCAM-1 expression by 29, 28, and 13%, respectively. Pre-incubation with beta-carotene and lutein significantly reduced E-selectin expression by 38 and 34%, respectively. Pre-treatment with beta-carotene, lutein and lycopene significantly reduced the expression of ICAM-1 by 11, 14, and 18%, respectively. While other carotenoids were ineffective, lycopene attenuated both IL-1beta-stimulated and spontaneous HAEC adhesion to U937 monocytic cells by 20 and 25%, respectively. Thus, among the carotenoids, lycopene appears to be most effective in reducing both HAEC adhesion to monocytes and expression of adhesion molecules on the cell surface.

Topics: Anticarcinogenic Agents; Antioxidants; Aorta, Thoracic; beta Carotene; Cardiovascular Diseases; Carotenoids; Cell Adhesion; Cell Adhesion Molecules; Cryptoxanthins; Culture Media; E-Selectin; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Humans; Intercellular Adhesion Molecule-1; Interleukin-1; Lutein; Lycopene; Monocytes; U937 Cells; Vascular Cell Adhesion Molecule-1; Xanthophylls

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

One explanation for discrepant results between epidemiologic studies and randomized trials of beta-carotene and cardiovascular disease may be a failure to consider inflammation as a confounder. To evaluate the potential for such confounding, the authors relate the serum concentrations of five carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin) to levels of three inflammatory markers (C-reactive protein, fibrinogen, and white blood cell count) measured during the Third National Health and Nutrition Survey, 1988-1994. The analysis included 4,557 nonsmoking participants aged 25-55 years. Adjusted concentrations of all five carotenoids were significantly lower in those with C-reactive protein levels above 0.88 mg/dl (p = 0.001). There was a trend toward lower adjusted beta-cryptoxanthin concentrations with increasing level of fibrinogen (p value test for trend = 0.01), but other carotenoids were not related. Many of the carotenoid concentrations were lower among participants with high white blood cell counts. After log transformation, only adjusted mean beta-carotene levels were significantly lower in those with white blood cell counts above 7.85 x 10(9)/liter (p < 0.01). These cross-sectional data do not clarify the biologic relation between carotenoids and C-reactive protein but, to the extent that the carotenoids are associated with C-reactive protein levels, a carotenoid-heart disease association may be, in part, an inflammation-heart disease association.

Topics: Acute-Phase Proteins; Adult; beta Carotene; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Carotenoids; Cross-Sectional Studies; Effect Modifier, Epidemiologic; Female; Fibrinogen; Humans; Inflammation; Leukocyte Count; Male; Risk

To search for determinants of endothelial dysfunction in type 2 diabetes.. We performed a comprehensive analysis of cardiovascular risk markers and measured blood flow responses to endothelium-dependent (acetylcholine [ACh] and NG-monomethyl-L-arginine) and -independent (sodium nitroprusside [SNP]) vasoactive agents in 30 nonsmoking men with type 2 diabetes (age 51 +/- 1 years, BMI 27.8 +/- 0.4 kg/m2, HbA1c 7.4 +/- 0.3%) and 12 matched normal control men.. ACh-induced vasodilation was 37% lower in type 2 diabetic (6.1 +/- 0.5) than in normal subjects (9.7 +/- 1.5 ml.dl-1.min-1, P < 0.01), while flows during SNP were similar (9.1 +/- 0.6 vs. 9.9 +/- 1.3 ml.dl-1.min-1, NS). The ratio of endothelium-dependent vs. -independent flow (ACh:SNP ratio) was 31% lower in type 2 diabetic (0.70 +/- 0.05) than in normal subjects (1.10 +/- 0.18, P < 0.01). Total (2.2 +/- 0.4 vs. 1.3 +/- 0.2 mmol/l, P < 0.05), VLDL, and intermediate-density lipoprotein triglycerides were significantly higher, and the mean LDL particle diameter was significantly smaller in type 2 diabetic than in normal subjects. The lag times for LDL oxidation by Cu2+ in vitro were similar in patients with type 2 diabetes (183 +/- 7) and in normal subjects (183 +/- 9 min, NS). Measured and calculated (sum of concentration of individual antioxidants in serum) total peroxyl radical-trapping capacities (TRAPs) were comparable between the groups. In the patients with type 2 diabetes, LDL size was significantly correlated with endothelium-dependent vasodilation (r = 0.43, P < 0.05), serum triglycerides (r = -0.75, P < 0.001), and the lag time for LDL oxidation in vitro (r = 0.38, P < 0.05). HbA1c was inversely correlated with the lag time for LDL oxidation in vitro (r = -0.41, P < 0.05) and TRAP.. In summary, patients with type 2 diabetes exhibited impaired endothelium-dependent vasodilation in vivo, elevated serum triglycerides, decreased LDL size, and normal antioxidant capacity. Of these parameters, LDL size was significantly correlated with endothelial function.

Topics: Acetylcholine; Antioxidants; Apolipoproteins; beta Carotene; Blood Flow Velocity; Cardiovascular Diseases; Cholesterol; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2; Endothelium, Vascular; Humans; Lipoproteins; Lipoproteins, LDL; Male; Middle Aged; Nitroprusside; omega-N-Methylarginine; Reference Values; Risk Factors; Vasodilation; Vitamin A; Vitamin E

Topics: beta Carotene; Cardiovascular Diseases; Dietary Supplements; Environmental Exposure; Humans; Lung Diseases; Lung Neoplasms; Pneumonectomy; Pulmonary Emphysema; Risk Factors; Sleep Apnea Syndromes; Vitamin A

Antioxidants, in particular carotenoids, may influence the risk for cardiovascular disease. This study investigates the influence of oral contraceptives (OC) on the serum concentration of beta-carotene, which may in turn affect the risk of cardiovascular diseases due to its antioxidative impact.. Cross-sectional epidemiologic study. Examinations included a detailed questionnaire on medical history and lifestyle factors, a 7 day food record, and blood samples.. National health and nutrition survey among healthy people living in private homes in West Germany in 1987-1988.. Nonpregnant and nonlactating women aged 18-44 (n = 610).. Overall, the use of OC was negatively associated with serum beta-carotene concentration in bi- and multivariable analyses after adjustment for age, smoking, alcohol consumption, dietary intake of beta-carotene, use of vitamin supplements, body mass index, pregnancies, and serum concentrations of total triglyceride and cholesterol. A strong interaction between OC use and age on beta-carotene concentration was observed. While no relationship between OC use and serum beta-carotene was seen in the youngest age-group (18-24 y), there was a modest but significant negative association between OC use and beta-carotene levels among 25-34 y old women. The use of OC was associated with a strong decrease in beta-carotene levels among 35-44 y old women. The interaction between OC use and age could partly be explained by age dependent use of OC with higher estrogen content.. OC use seems to be strongly related to serum beta-carotene levels, particularly among women above the age of 35. Further studies are needed to clarify the underlying mechanisms of this association and its implications for health risks of OC use.. Beta-carotene, a provitamin with antioxidant effects, may substantially reduce the risk of coronary artery disease and acute myocardial infarction. A cross-sectional epidemiologic study involving 610 West German women 18-44 years of age indicates that oral contraceptive (OC) use has a negative impact on serum levels of beta-carotene. 195 respondents (32%) were current OC users, 322 (53%) were past users, and 91 (15%) had never used OCs. Median serum beta-carotene levels were significantly lower in current OC users (25.1 mcg/dl) than in past (32.5 mcg/dl) and never users (31.2 mcg/dl). The percentage of women with beta-carotene levels below the desirable value of 21.5 mcg/dl was significantly higher in the current OC use group (34%) than in the 2 other groups combined (21%), yielding an overall odds ratio (OR) of 1.9 (95% confidence interval, 1.3-2.8). The strength of the association between OC use and decreased beta-carotene increased with age (OR of 1.5 for women 18-24 years, 1.9 for those 25-34 years, and 3.4 for 35-44-year old women). In addition, the decrease of beta-carotene was larger for OCs containing 50 mcg of ethinyl estradiol than for low-dose formulations. Also observed were significant associations between serum beta-carotene levels and smoking, alcohol intake, body mass index, triglycerides, nutrient intake, and total cholesterol levels. Although further studies are required to identify the mechanisms underlying the OC-beta-carotene association and define its implications for women's health, OC users should be advised to consume vegetables rich in beta-carotene.

Topics: Adolescent; Adult; Age Distribution; Age Factors; Alcohol Drinking; beta Carotene; Body Mass Index; Cardiovascular Diseases; Cholesterol; Contraceptives, Oral; Cross-Sectional Studies; Female; Germany; Health Surveys; Humans; Life Style; Linear Models; Smoking; Triglycerides

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

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

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Cardiovascular Diseases; Contraindications; Humans; Leukoplakia, Oral; Lung Neoplasms; Male; Middle Aged; Randomized Controlled Trials as Topic; Vitamin A; Vitamin E

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Carotenoids; Humans; Vitamin E

Recent evidence suggests that oxidative damage may be involved in atherogenesis, and thus dietary antioxidants, such as beta-carotene, may reduce the risks of cardiovascular disease (CVD). We examined the association between consumption of carotene-containing fruits and vegetables and CVD mortality among 1299 elderly Massachusetts residents who provided dietary information as a part of the Massachusetts Health Care Panel Study. During a mean follow-up of 4.75 years, there were 161 deaths attributable to CVD, 48 of which were due to myocardial infarction. For total CVD death and fatal myocardial infarction, risks were lower among those residents in the highest quartile for consumption of carotene-containing fruits and vegetables as compared with those in the lowest. For death due to CVD, the relative risk (RR) was 0.54 (95% confidence interval (CI), 0.34 to 0.86; P for trend across quartiles, 0.004). For myocardial infarction the RR was 0.25 (95% CI, 0.09 to 0.67; P for trend, 0.002). These observational data are compatible with the hypothesis that increased dietary intake of carotenoids decreases the risks of CVD mortality; however, confounding cannot be ruled out. This hypothesis requires rigorous evaluation in randomized trials of sufficient size to detect reliably whether carotenoids confer small-to-moderate but clinically important protection against CVD.

Topics: Aged; Aged, 80 and over; Antioxidants; beta Carotene; Cardiovascular Diseases; Carotenoids; Cohort Studies; Diet; Eating; Female; Follow-Up Studies; Fruit; Humans; Male; Massachusetts; Multivariate Analysis; Myocardial Infarction; Prospective Studies; Risk Factors; Vegetables

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; beta Carotene; Cardiovascular Diseases; Carotenoids; Female; Humans; Lung Neoplasms; Male; Middle Aged; Vitamin E

Serum beta-carotene levels in patients with cardiovascular disease and control subjects were measured. The mean values for beta-carotene were found to be 82.2 +/- 3.5 micrograms/dl for the cases as a single group, 74.83 +/- 5.6 micrograms/dl in acute myocardial infarction (AMI) cases, 88.19 +/- 6.1 micrograms/dl in atherosclerotic cases, 85.11 +/- 6.1 micrograms/dl in others and 118.2 +/- 4.3 micrograms/dl in controls. beta-carotene levels in the cases were significantly lower than in the controls (P < 0.05). Serum beta-carotene levels in cases and controls were also compared to take account of age, sex and smoking status. Our data indicate that there are apparent associations between serum beta-carotene levels, sex and smoking status.

Topics: Adult; Age Factors; Aged; Arteriosclerosis; beta Carotene; Cardiovascular Diseases; Carotenoids; Female; Humans; Male; Middle Aged; Myocardial Infarction; Sex Characteristics; Smoking

Large-scale prospective studies of disease development often rely on self-reported data. To assess the accuracy of self-reports of cataract, we compared the self-reports with medical record data obtained from diagnosing ophthalmologists and optometrists for participants in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among 22,071 male U.S. physicians aged 40-84 years. A report of cataract, defined as a positive response to a question about whether cataract had ever been diagnosed in either eye and the date of diagnosis, was found to be a very good indicator of lens opacification but was not a good indicator of an incident, age-related opacity that reduced visual acuity. These results indicate that in large prospective studies of clinically significant cataract, where examination of all study participants is not feasible and self-reported data are used, additional documentation to supplement the self-reports should be obtained and strict diagnostic criteria applied to minimize the likely effects of misclassification.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Aspirin; beta Carotene; Cardiovascular Diseases; Carotenoids; Cataract; Double-Blind Method; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Physicians; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Reproducibility of Results; Retrospective Studies; Self Disclosure; United States; Visual Acuity

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

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

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

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