Antioxidants and cardiovascular disease: Still a topic of interest

Cardiovascular disease constitutes a major public health concern in industrialised nations. Over recent decades, a large body of evidence has accumulated indicating that free radicals play a critical role in cellular processes implicated in atherosclerosis. Herein, we present a mechanism of oxidative stress, focusing mainly on the development of an oxidised low density lipoprotein, and the results of a clinical trial of antioxidant therapy and epidemiological studies on the relationships between nutrient antioxidants, such as vitamin E, vitamin C, β-carotene, coenzyme Q, flavonoids and L-arginine, and coronary events. These studies indicated that a diet high in antioxidants is associated with a reduced risk of cardiovascular disease, but did not confirm a strong causality link. With regard to vitamin E, observational studies suggested that the daily use of at least 400 International Units of vitamin E is associated with beneficial effects on coronary events. However, it is apparently too early to define the clinical benefits of vitamin E for cardiovascular disease. From the results of several randomised interventional trials, it appears that no single antioxidant given to subjects at high doses has substantial benefits, and the question of whether nutrient antioxidants truly protect against cardiovascular disease remains open. This article provides an overview of the epidemiological and clinical studies related to antioxidants and cardiovascular disease.     

Epidemiologic studies of antioxidants and cancer in humans.

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

Vitamin E dietary supplementation significantly affects multiple risk factors for cardiovascular disease in baboons

BACKGROUND: Oxidative stress is a widely accepted risk factor for cardiovascular disease (CVD), but the CVD benefit of dietary antioxidants, such as vitamin E, is controversial. OBJECTIVE: Therefore, we have investigated, in the baboon model, the effects of dietary vitamin E supplementation on risk factors for CVD. DESIGN: Pedigreed baboons (n = 251) were fed 2 atherogenic diets, high in fat and cholesterol, that differed in vitamin E concentrations. After 7 wk on each diet, blood samples were taken, and a panel of CVD risk factor traits (ie, indicators of lipoprotein metabolism and oxidative stress) were measured. RESULTS: Vitamin E supplementation caused significantly higher total antioxidant status (TAS) and lower oxidized LDL as expected. In addition, vitamin E caused 2 paradoxical effects on HDL metabolism: higher apolipoprotein A-I (apo A-I) concentrations and lower HDL sizes. We calculated a difference (Delta) variable for each trait as the value on the high-vitamin E diet minus that on the low-vitamin E diet and determined that several HDL concentration Delta variables were significantly correlated with Delta TAS, but only one, Delta apo A-I, was independently correlated. Genetic analyses showed that 2 Delta variables, Delta paraoxonase and Delta HDL(2), were significantly heritable, but that neither Delta TAS nor Delta apo A-I were heritable. CONCLUSIONS: Thus, our data show that dietary vitamin E improves TAS and LDL quality. They also show 2 apparently paradoxical effects on HDL metabolism: lower HDL(2), which is mediated by genes, and higher apo A-I, which is not. These effects have contrasting associations with CVD risk and may help account for the mixed results from clinical trials of dietary vitamin E.     

Effect of carrot intake on cholesterol metabolism and on antioxidant status in cholesterol-fed rat

BACKGROUND: Vegetables are major dietary sources of fibers and antioxidants such as carotenoids, polyphenols and vitamin C which contribute to explain their protective effects against cardiovascular diseases. AIM OF THE STUDY: We investigated in the rat the effects of a 3-week supplementation of the diet with carrot (15% dry matter) on lipid metabolism and antioxidant status. RESULTS: A significant decrease of cholesterol level in liver (-44%; P= 0.0007) was observed together with a reduction of the level of liver triglycerides (-40%; P= 0.0005). Fecal total steroids excretion increased by 30% upon feeding the carrot diet as compared to the control. The secretion of bile acids was maintained, whereas the cholesterol apparent absorption was reduced in rats fed carrot diet. Carrot consumption also improved the antioxidant status. It significantly decreased the urinary excretion of thiobarbituric acid reactive substances (TBARS), reduced the TBARS levels in heart, increased the vitamin E plasmatic level and tended to increase the ferric reducing ability of plasma (FRAP) as compared to the controls. The carrot diet provided carotenoid antioxidants: 5.1 mg beta-carotene, 1.6 mg alpha-carotene and 0.25mg lutein per 100 g diet. No carotenoids were found in plasma whereas the three carotenoids were detected in the plasma of the rats fed the carrot diet at 125, 41, 43 nmol/L respective concentrations. beta-Carotene was also detected in liver and heart. CONCLUSION: Carrot consumption modifies cholesterol absorption and bile acids excretion and increases antioxidant status and these effects could be interesting for cardiovascular protection.     

Dietary vitamin A may be a cardiovascular risk factor in a Saudi population

Traditional risk factors do not appear to explain fully the variation in the incidence of the cardiovascular diseases (CVD). Epidemiological studies have not been entirely consistent with regard to the relationship between antioxidant vitamin intake and CVD and there appears to be little data on this relationship in non-Caucasian populations. This study aimed to investigate the dietary intake of vitamin A, C, and vitamin E, and carotenoids, serum concentrations of vitamin E and A and indices of lipid peroxidation were measured in male Saudi patients with established CVD and age-matched controls. We assessed the dietary intakes of vitamins A, C, and E and carotenoids, by a food frequency questionnaire. Serum vitamins A and E concentrations were measured by HPLC, in 130 Saudi male subjects with established CVD, and 130 age-matched controls. We also determined serum lipid profiles (total cholesterol, triglycerides, HDL-C, LDL-C), lipoprotein (a), oxidized LDL, and serum lipid peroxide concentrations. Diabetes mellitus (P<0.0001), a positive smoking habit (P<0.0001) and hypertension (P<0.05) were more prevalent among CVD patients. Levels of dietary vitamin E and A were also significantly higher among cases. In conditional logistic regression analysis, the most significant characteristics differentiating CVD patients from controls were diabetes mellitus (Odds ratio 2.49, CI 1.42-4.37, P<0.001), total fat intake (Odds ratio 1.02, CI 1.01-1.03, P<0.01), serum vitamin A (Odds ratio 0.72, CI 0.53-0.99, P<0.05), and the vitamin A/total fat intake ratio (Odds ratio 1.04, CI 1.01-1.06, P<0.01). In a Saudi population, smoking habit and hypertension were significantly more common among patients with CVD. Multivariate analysis showed that dietary total fat and vitamin A and the presence of diabetes mellitus were independent coronary risk factors. This is the first report of a potentially deleterious effect of dietary vitamin A in a non-Caucasian population. However it is possible that unidentified residual confounding factors may account for this finding.     

Diet and asthma: nutrition implications from prevention to treatment

Asthma is characterized by lung airway inflammation initiated and perpetuated by an inappropriate immune response, increased airway responsiveness, and variable airflow obstruction. In Western countries there has been a marked increase in asthma prevalence such that it has become a public health concern. It has been hypothesized that the increase may be due to changing antioxidant intake, increasing dietary ratio of n-6:n-3 polyunsaturated fatty acids (PUFA), and vitamin D deficiency (and supplementation). Observational studies have reported associations between asthma and dietary antioxidants (vitamin E, vitamin C, carotenoids, selenium, polyphenols, and fruit), PUFA, and vitamin D. However, supplementing the diets of adults with asthma with antioxidants and n-3 PUFA has minimal, if any, clinical benefit. Currently there is insufficient evidence to support the use of nutrient supplements to complement conventional treatment; however, results of ongoing studies are awaited, and additional research is required, particularly in children. Interest in the potential of dietary intervention during pregnancy to reduce the likelihood of childhood asthma has increased. A small number of cohort studies have highlighted associations between childhood asthma and reduced maternal intake of some nutrients (vitamin E, vitamin D, selenium, zinc, and PUFA) during pregnancy. Although vitamin D intervention studies during pregnancy are ongoing and two intervention studies suggest that dietary PUFA manipulation during pregnancy may be advantageous, further trials are needed to establish if modification of maternal nutrient intake during pregnancy can be used as a healthy, low cost, public health measure to reduce the prevalence of childhood asthma.     

Beta-carotene and other carotenoids as antioxidants.

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

β-Carotene and Other Carotenoids as Antioxidants

Carotenoids are natural pigments which are synthesized by plants and are responsible for the bright colors of various fruits and vegetables. There are several dozen carotenoids in the foods that we eat, and most of these carotenoids have antioxidant activity. β-carotene has been best studied since, in most countries it is the most common carotenoid in fruits and vegetables. However, in the U.S., lycopene from tomatoes now is consumed in approximately the same amount as β-carotene. Antioxidants (including carotenoids) have been studied for their ability to prevent chronic disease. β-carotene and others carotenoids have antioxidant properties in vitro and in animal models. Mixtures of carotenoids or associations with others antioxidants (e.g. vitamin E) can increase their activity against free radicals. The use of animals models for studying carotenoids is limited since most of the animals do not absorb or metabolize carotenoids similarly to humans.

Epidemiologic studies have shown an inverse relationship between presence of various cancers and dietary carotenoids or blood carotenoid levels. However, three out of four intervention trials using high dose β-carotene supplements did not show protective effects against cancer or cardiovascular disease. Rather, the high risk population (smokers and asbestos workers) in these intervention trials showed an increase in cancer and angina cases. It appears that carotenoids (including β-carotene) can promote health when taken at dietary levels, but may have adverse effects when taken in high dose by subjects who smoke or who have been exposed to asbestos. It will be the task of ongoing and future studies to define the populations that can benefit from carotenoids and to define the proper doses, lengths of treatment, and whether mixtures, rather than single carotenoids (e.g. β-carotene) are more advantageous.     

Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials

BACKGROUND: Laboratory and observational studies suggest that antioxidant and B vitamin supplementation may prevent atherosclerosis. Although trials have not shown a benefit of these supplements on clinical cardiovascular events, it is unknown whether they affect the progression of atherosclerosis as measured by imaging techniques. OBJECTIVE: The objective was to perform a meta-analysis of randomized controlled trials of the effect of vitamin-mineral supplementation on atherosclerosis progression. DESIGN: We searched the MEDLINE, EMBASE, and CENTRAL databases for relevant studies. No language restrictions were applied. We separately analyzed trials using antioxidants (vitamins E and C, beta-carotene, or selenium) and trials using B vitamins (folate, vitamin B-6, or vitamin B-12). The progression of atherosclerosis was evaluated by B-mode ultrasound, intravascular ultrasound, or angiography. Effect sizes were calculated for the difference in slope of atherosclerosis progression between participants assigned to supplements and those assigned to the control group. RESULTS: In trials not involving percutaneous transluminal coronary angioplasty, the pooled effect size was -0.06 (95% CI: -0.20, 0.09; 7 trials) for antioxidants and -0.93 (95% CI: -2.11, 0.26; 4 trials) for B vitamins. In trials involving percutaneous transluminal coronary angioplasty, the pooled relative risk of restenosis was 0.82 (95% CI: 0.54, 1.26; 3 trials) for antioxidants and 0.84 (95% CI: 0.34, 2.07; 2 trials) for B vitamins. CONCLUSION: Our meta-analysis showed no evidence of a protective effect of antioxidant or B vitamin supplements on the progression of atherosclerosis, thus providing a mechanistic explanation for their lack of effect on clinical cardiovascular events.     

Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts

BACKGROUND: Epidemiologic studies have suggested a lower risk of coronary heart disease (CHD) at higher intakes of fruit, vegetables, and whole grain. Whether this association is due to antioxidant vitamins or some other factors remains unclear. OBJECTIVE: We studied the relation between the intake of antioxidant vitamins and CHD risk. DESIGN: A cohort study pooling 9 prospective studies that included information on intakes of vitamin E, carotenoids, and vitamin C and that met specific criteria was carried out. During a 10-y follow-up, 4647 major incident CHD events occurred in 293 172 subjects who were free of CHD at baseline. RESULTS: Dietary intake of antioxidant vitamins was only weakly related to a reduced CHD risk after adjustment for potential nondietary and dietary confounding factors. Compared with subjects in the lowest dietary intake quintiles for vitamins E and C, those in the highest intake quintiles had relative risks of CHD incidence of 0.84 (95% CI: 0.71, 1.00; P=0.17) and 1.23 (1.04, 1.45; P=0.07), respectively, and the relative risks for subjects in the highest intake quintiles for the various carotenoids varied from 0.90 to 0.99. Subjects with higher supplemental vitamin C intake had a lower CHD incidence. Compared with subjects who did not take supplemental vitamin C, those who took >700 mg supplemental vitamin C/d had a relative risk of CHD incidence of 0.75 (0.60, 0.93; P for trend <0.001). Supplemental vitamin E intake was not significantly related to reduced CHD risk. CONCLUSIONS: The results suggest a reduced incidence of major CHD events at high supplemental vitamin C intakes. The risk reductions at high vitamin E or carotenoid intakes appear small.     

Does vitamin E supplementation prevent cardiovascular events?

In recent years, vitamin E has been investigated as a cardioprotective agent. Experimental studies have identified potential mechanisms by which vitamin E may inhibit the development of atherosclerosis, and observational studies of individuals without coronary disease suggest that vitamin E intake may prevent future cardiovascular events. Secondary prevention trials to date have demonstrated little benefit from vitamin E supplementation. It remains possible, however, that supplementation may be useful among certain high-risk groups, including those with nutritional deficiencies. Limited data from completed primary prevention trials also indicate minimal cardioprotection from vitamin E, but large-scale trials now in progress may yet show benefit. Results from ongoing trials will contribute powerfully to the totality of evidence on which to formulate both appropriate clinical recommendations for individual patients and a rational public health policy for the population as a whole. At this time, there is insufficient evidence for issuing a public health recommendation to use vitamin E supplements to prevent cardiovascular disease (CVD). Rather, increased intake of fruits, vegetables, and other antioxidant-rich foods should be promoted as part of a healthy diet because they provide nutritional benefits beyond any potential antioxidant effect. Moreover, even if found to reduce CVD risk, vitamin supplement use should be considered an adjunct, not an alternative, to established cardioprotective measures, such as smoking abstention, avoidance of obesity, adequate physical activity, and control of high blood pressure and hyperlipidemia.     

The antioxidants--vitamin C,vitamin E, selenium, and carotenoids

This is the second in a series of articles reviewing the recent revisions of the Recommended Dietary Allowances (RDA) and the resulting Dietary Reference Intakes (DRI). In April of 2000, the Food and Nutrition Board of the National Academy of Sciences released Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. The central premise of the report did not perpetuate the prevailing popular thought that large doses of antioxidants will prevent chronic diseases. Instead the panel concluded that at this time, insufficient scientific evidence exists to sustain claims that ingesting megadoses of dietary antioxidants can prevent certain chronic illnesses such as cardiovascular disease or cancer. In some instances recommended nutrient levels were reduced from the previous report in 1989; e.g., for the first time upper tolerable levels of ingestion (UL) were established to prevent the harmful effects of over consumption of essential nutrients, such as vitamin C, vitamin E, and selenium. Although dietary recommendations do exist for vitamin A, the panel did not set recommendations for beta-carotene or the other carotenoids due to lack of sufficient research to support recommended intakes or upper tolerable levels of intake. However, the panel advises the public to avoid intakes of provitamin A compounds, such as the numerous carotenoids, beyond the levels required to prevent vitamin A deficiency. Changes were also made with regard to estimating the amount of provitamin A carotenoids required to make a unit of retinal. The revised estimate suggests a twofold higher conversion rate than previously believed. Although this comprehensive report on the dietary reference intakes for vitamin C, vitamin E, selenium, and the carotenoids did not decisively confirm the role of antioxidants for the prevention of chronic diseases in humans, many research studies have generated new data to support this concept. Additional research is needed to define the attributes of antioxidants as studies progress from in vitro and animal studies to human nutrition.     

Differential effect of dietary antioxidant classes (carotenoids, polyphenols, vitamins C and E) on lutein absorption

Lutein is assumed to protect the human retina from blue light and oxidative stress and diminish the incidence of age-related macular degeneration. This antioxidant is commonly ingested with other dietary antioxidants. The aim of the present study was to assess whether the main dietary antioxidants, i.e. carotenoids, polyphenols and vitamins C and E, affect lutein absorption. We measured the effect of adding a mixture of antioxidants (500 mg vitamin C, 67 mg (100 IU) vitamin E and 1 g polyphenols) to a lutein-containing meal (18 mg) on the postprandial lutein response in the chylomicron-rich fraction in eight healthy men. Lutein response was weakest (-23 %; P=0 x 07) after ingestion of the meal containing antioxidants (21 x 9 (sem 4 x 6) v. 28 x 4 (sem 7 x 2) nmol x h/l). To assess the effect of each class of antioxidants and potential interactions, we subsequently evaluated the effect of various combinations of antioxidants on lutein uptake by human intestinal Caco-2 TC-7 cells. A full factorial design showed that both a mixture of polyphenols (gallic acid, caffeic acid, (+)-catechin and naringenin) and a mixture of carotenoids (lycopene plus beta-carotene) significantly (P<0 x 05) impaired lutein uptake by (-10 to-30 %), while vitamins C and E had no significant effect. Subsequent experiments showed that the aglycone flavanone naringenin was the only polyphenol responsible for the effect of the polyphenol mixture, and that the carotenoid effect was not carotenoid species-dependent. Taken together, the present results suggest that lutein absorption is not markedly affected by physiological concentrations of vitamins C and E but can be impaired by carotenoids and naringenin     

Dietary antioxidants and lung cancer risk: a case-control study in Uruguay.

To examine the protective role of dietary antioxidants (carotenoids, vitamin C, vitamin E, glutathione, and flavonoids) in lung cancer risk, a case-control study involving 541 cases of lung cancer and 540 hospitalized controls was carried out in Uruguay. The relevant variables were energy adjusted using the residuals method and then categorized in quartiles. Adjusted odds ratios (ORs) for antioxidants were calculated through unconditional logistic regression. With the exception of lycopene and vitamin C, the remaining antioxidants were associated with significant reductions in risk of lung cancer. Of particular interest was the inverse association between dietary glutathione and lung cancer [OR of quartile with highest intake compared with lowest quartile = 0.42, 95% confidence interval (CI) = 0.27-0.63]. Also, carotenoids and vitamin E were associated with significant reductions in risk of lung cancer (OR = 0.43, 95% CI = 0.29-0.64 for total carotenoids and OR = 0.50, 95% CI = 0.39-0.85 for vitamin E). A joint effect for high vs. low intakes of beta-carotene and glutathione was associated with a significant reduction in risk (OR = 0.32, 95% CI = 0.22-0.46). It could be concluded that dietary antioxidants are associated with a significant protective effect in lung carcinogenesis and that the inverse association for glutathione persisted after controlling for total vegetables and fruits.     

Health effect of vegetable-based diet: lettuce consumption improves cholesterol metabolism and antioxidant status in the rat

BACKGROUND & AIMS: It is often assumed that fruits and vegetables contribute to protect against degenerative pathologies such as cardiovascular diseases. Besides epidemiological observations, scientific evidences for their mechanism of action are scarce. In the present study, we investigated the mean term and post-prandial effects of lettuce ingestion on lipid metabolism and antioxidant protection in the rat. RESULTS: Feeding rats a 20% lettuce diet for 3 weeks resulted in a decrease cholesterol LDL/HDL ratio and a marked decrease of liver cholesterol levels (-41%). Concurrently, fecal total steroid excretion increased (+44%) and apparent absorption of dietary cholesterol was significantly depressed (-37%) by the lettuce diet. Lettuce diet also displayed an improvement of vitamin E/TG ratio in plasma and limited lipid peroxidation in heart as evidenced by TBARS. In post-prandial experiment, lettuce intake significantly increased both ascorbic acid and alpha-tocopherol plasma levels which contribute to improve plasma antioxidant capacity within 2 h of consumption. Other lipid-soluble antioxidants (lutein and vitamin E) may also improve the plasma antioxidant capacity. CONCLUSION: Lettuce consumption increases the total cholesterol end-products excretion and improves antioxidant status due to the richness in antioxidants (vitamins C, E and carotenoids). In our model, lettuce clearly shows a beneficial effect on lipid metabolism and on tissue oxidation. Therefore regular consumption of lettuce should contribute to improve protection against cardiovascular diseases.     

Recent changes in concepts of antioxidant treatment

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

Both alpha- and beta-carotene, but not tocopherols and vitamin C, are inversely related to 15-year cardiovascular mortality in Dutch elderly men

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.     

Nutritional, dietary and postprandial oxidative stress

Nutritional, or dietary oxidative stress denotes a disturbance of the redox state resulting from excess oxidative load or from inadequate nutrient supply favoring prooxidant reactions. Low intake or impaired availability of dietary antioxidants including vitamins E and C, carotenoids, polyphenols, and other micronutrients (e.g., selenium) weakens the antioxidant network. Postprandial oxidative stress, as a subform of nutritional oxidative stress, ensues from sustained postprandial hyperlipidemia and/or hyperglycemia and is associated with a higher risk for atherosclerosis, diabetes, and obesity. In Western societies, a significant part of the day is spent in the postprandial state. Unsaturated fatty acids incorporated into LDL and oxidized LDL are an atherogenic factor. Lipid hydroperoxides present in the diet are absorbed, contributing to the prooxidant load. In hyperlipidemic and hyperglycemic subjects, endothelium-dependent vasodilation is impaired in the postprandial state, making postprandial oxidative stress an important factor modulating cardiovascular risk. Postprandial oxidative stress is attenuated when dietary antioxidants are supplied together with a meal rich in oxidized or oxidizable lipids. Ingestion of dietary polyphenols, e.g., from wine, cocoa, or tea, improves endothelial dysfunction and lowers the susceptibility of LDL lipids to oxidation. Polyphenols affect endothelial function not solely as antioxidants but also as modulatory signaling molecules.     

Können Antioxidanzien Atherosklerose verhindern?

In vitro studies have shown that antioxidants (e. g. beta-carotene, vitamin C and vitamin E) can interfere with some pathomechanisms of atherosclerosis and therefore might have a protective effect. From the investigated antioxidants vitamin E showed the best effect. Some animal and epidemiological studies confirmed such a protective effect in vivo especially after administration of high doses of vitamin E. However, most of the placebo-controlled studies for primary or secondary prevention failed to show a protective effect even after administration of high doses. In addition, other studies demonstrated a risk for adverse effects due to antioxidant supplementation (beta-carotene and vitamin E). Our review summarises the principle of antioxidant supplementation and a number of relevant epidemiological and clinical studies for prevention of atherosclerosis. The obtained results suggest that supplementation of antioxidants cannot be recommended for the normal population.     

Oxidative stress and cognitive impairment in the elderly

Cognitive impairment is a major component of age-related dementing diseases and it has been suggested that it could share the same pathological pathways with neurodegenerative processes and cerebrovascular lesions. The free radical theory of aging could be one of these pathways. Observational studies of relationships between cognitive impairment and antioxidant status are based on the evaluation of dietary intake or on the levels of carotenoids, selenium and vitamins A, C and E in plasma. More convincing results were obtained on vitamin C and carotenoids. Despite some limitations, the comparison between results obtained in various populations is becoming increasingly informative and these studies argue for a protective effect of antioxidants on cognitive performance.