Influence of vitamin E and C supplementation on lipoprotein oxidation in patients with Alzheimer's disease.

Because increased oxidation is an important feature of Alzheimer's disease (AD) and low concentrations of antioxidant vitamins C and E have been observed in cerebrospinal fluid (CSF) of AD patients, supplementation with these antioxidants might delay the development of AD. Major targets for oxidation in brain are lipids and lipoproteins. We studied whether supplementation with antioxidative vitamins E and C can increase their concentrations not only in plasma but also in CSF, and as a consequence decrease the susceptibility of lipoproteins to in vitro oxidation. Two groups, each consisting of 10 patients with AD, were for 1 month supplemented daily with either a combination of 400 IU vitamin E and 1000 mg vitamin C, or 400 IU vitamin E alone. We found that supplementation with vitamin E and C significantly increased the concentrations of both vitamins in plasma and CSF. Importantly, the abnormally low concentrations of vitamin C were returned to normal level following treatment. As a consequence, susceptibility of CSF and plasma lipoproteins to in vitro oxidation was significantly decreased. In contrast, the supplementation with vitamin E alone significantly increased its CSF and plasma concentrations, but was unable to decrease the lipoprotein oxidizability. These findings document a superiority of a combined vitamin E + C supplementation over a vitamin E supplementation alone in AD and provide a biochemical basis for its use.     

Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials

Background

Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke.

Methods

A total of 17 trials (86 393 patients) comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions.

Results

B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12.

Conclusions

B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied.     

Can antioxidant vitamins materially reduce oxidative damage in humans?

Endogenous oxidative damage to proteins, lipids, and DNA is thought to be an important etiologic factor in aging and the development of chronic diseases such as cancer, atherosclerosis, and cataract formation. The pathology associated with these diseases is likely to occur only after the production of reactive oxygen species has exceeded the body's or cell's capacity to protect itself and effectively repair oxidative damage. Vitamin C, vitamin E, and beta-carotene, often referred to as "antioxidant vitamins," have been suggested to limit oxidative damage in humans, thereby lowering the risk of certain chronic diseases. However, epidemiological studies and clinical trials examining the efficacy of antioxidant vitamins, either individually or in combination, to affect disease outcome rarely address possible underlying mechanisms. Thus, in these studies it is often assumed that antioxidant vitamins act by lowering oxidative damage, but evidence in support of this contention is not provided. Therefore, in this review, we examine the scientific evidence that supplementation of humans with vitamin C, vitamin E, or beta-carotene lowers in vivo oxidative damage to lipids, proteins, or DNA based on the measurement of oxidative biomarkers, not disease outcome. With the only exception of supplemental vitamin E, and possibly vitamin C, being able to significantly lower lipid oxidative damage in both smokers and nonsmokers, the current evidence is insufficient to conclude that antioxidant vitamin supplementation materially reduces oxidative damage in humans.     

Update on the effects of vitamins A, C, and E and selenium on carcinogenesis

The effects of vitamins A, C, and E and of selenium on carcinogenesis are briefly summarized and updated. These vitamins and minerals were selected because they have been studied extensively in recent years with a variety of carcinogenesis models. The consumption of vitamin A and its precursors (carotenoids) has been negatively correlated with cancer at a number of sites, particularly the lung. Animal investigations on vitamin A involvement in carcinogenesis have generally been of three types: those assessing the effect of vitamin A deficiency, the effect of excess vitamin A, or the effect of supplementation with synthetic analogs of vitamin A. Vitamin A deficiency had no effect on salivary gland carcinogenesis, enhanced urinary bladder, lung, and liver carcinogenesis, and inhibited colon carcinogenesis. Excess of various forms of vitamin A enhanced or inhibited skin tumorigenesis, inhibited mammary carcinogenesis in rats (but not in mice), and carcinogenesis of the forestomach, liver, and urinary bladder (with one model, but not with another), or enhanced or did not influence lung carcinogenesis. Vitamin A analogs have enhanced or inhibited skin tumorigenesis, inhibited salivary gland, mammary, and urinary bladder carcinogenesis, enhanced tracheal and liver carcinogenesis, and either enhanced or inhibited pancreas carcinogenesis, depending upon the model employed. Although retinoids have been shown to inhibit carcinogenesis at many sites, numerous negative studies have been reported and some reports have indicated enhanced carcinogenesis. The most convincing evidence for the involvement of vitamin C in cancer prevention is the ability of ascorbic acid to prevent formation of nitrosamine and of other N-nitroso compounds. In addition vitamin C supplementation was shown to inhibit skin, nose, tracheal, lung, and kidney carcinogenesis, to either not influence or enhance skin, mammary gland, and colon carcinogenesis, and to enhance urinary bladder carcinogenesis, when given as sodium ascorbate, but not when given as ascorbic acid. Like vitamin C, vitamin E can inhibit nitrosation. Vitamin E was shown to inhibit skin, cheek pouch, and forestomach carcinogenesis, to enhance or inhibit colon carcinogenesis, and to have no effect on or to inhibit mammary gland carcinogenesis, depending upon the method of vitamin E administration or the level of dietary selenium or dietary fat. Selenium effects on carcinogenesis have been recently reviewed and the present discussion only updates this area by indicating that enhancement of carcinogenesis by dietary selenium supplements has been observed in the liver, pancreas, and skin.(ABSTRACT TRUNCATED AT 400 WORDS)     

A systematic review of the role of vitamin insufficiencies and supplementation in COPD

Background

Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD. The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms. Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy.

Methods

A systematic literature review was performed on the association of vitamins and COPD. The role of vitamin supplements in COPD was then evaluated.

Conclusions

The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function. High vitamin intake would probably reduce the annual decline of FEV1. There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function.     

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men.

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the "Antioxidant Supplementation in Atherosclerosis Prevention" (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of D-alpha-tocopheryl acetate daily), both vitamins (CellaVie), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F2-isoprostane concentration was lowered by 17.3% (95% CI 3.9-30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.     

Clinical trials testing cardiovascular benefits of antioxidant supplementation

Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. ASAP was a 6-year randomized trial to study the effect of supplementation with vitamin E plus slow-release vitamin C on carotid atherosclerotic progression in 520 hypercholesterolemic men and women aged 45-69 years. The supplementation reduced the progression of carotid atherosclerosis by 26% ( P =0.014), by 33% ( P =0.024) in men and 14% (not significant) in women. The effect was larger in subjects with low baseline vitamin C or atherosclerotic plaques. In the Harvard IVUS trial, the combined supplementation with vitamins E and C significantly inhibited the progression of coronary atherosclerosis in one year. These data confirm that the supplementation with a combination of vitamins E and C can retard atherosclerotic progression. The findings of completed trials testing the effect on cardiovascular events are less consistent. The major on-going clinical trials include the SU.VI.MAX, WHS, WACS and WAVE studies. These involve in total over 80,000 subjects, who are treated with antioxidative supplements for years. The results of these studies will become available during 2003-2006. They may provide the necessary additional information concerning the effect of antioxidants on cardiovascular events.     

Clinical Trials Testing Cardiovascular Benefits of Antioxidant Supplementation

Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. ASAP was a 6-year randomized trial to study the effect of supplementation with vitamin E plus slow-release vitamin C on carotid atherosclerotic progression in 520 hypercholesterolemic men and women aged 45-69 years. The supplementation reduced the progression of carotid atherosclerosis by 26% ( P =0.014), by 33% ( P =0.024) in men and 14% (not significant) in women. The effect was larger in subjects with low baseline vitamin C or atherosclerotic plaques. In the Harvard IVUS trial, the combined supplementation with vitamins E and C significantly inhibited the progression of coronary atherosclerosis in one year. These data confirm that the supplementation with a combination of vitamins E and C can retard atherosclerotic progression. The findings of completed trials testing the effect on cardiovascular events are less consistent. The major on-going clinical trials include the SU.VI.MAX, WHS, WACS and WAVE studies. These involve in total over 80,000 subjects, who are treated with antioxidative supplements for years. The results of these studies will become available during 2003-2006. They may provide the necessary additional information concerning the effect of antioxidants on cardiovascular events.     

Vitamin‐regulated cytokines and growth factors in the CNS and elsewhere

There is a growing awareness that natural vitamins (with the only exception of pantothenic acid) positively or negatively modulate the synthesis of some cytokines and growth factors in the CNS, and various mammalian cells and organs. As natural vitamins are micronutrients in the human diet, studying their effects can be considered a part of nutritional genomics or nutrigenomics. A given vitamin selectively modifies the synthesis of only a few cytokines and/or growth factors, although the same cytokine and/or growth factor may be regulated by more than one vitamin. These effects seem to be independent of the effects of vitamins as coenzymes and/or reducing agents, and seem to occur mainly at genomic and/or epigenetic level, and/or by modulating NF‐κB activity. Although most of the studies reviewed here have been based on cultured cell lines, but their findings have been confirmed by some key in vivo studies. The CNS seems to be particularly involved and is severely affected by most avitaminoses, especially in the case of vitamin B₁₂. However, the vitamin‐induced changes in cytokine and growth factor synthesis may initiate a cascade of events that can affect the function, differentiation, and morphology of the cells and/or structures not only in the CNS, but also elsewhere because most natural vitamins, cytokines, and growth factors cross the blood–brain barrier. As cytokines are essential to CNS‐immune and CNS‐hormone system communications, natural vitamins also interact with these circuits. Further studies of such vitamin‐mediated effects could lead to vitamins being used for the treatment of diseases which, although not true avitaminoses, involve an imbalance in cytokine and/or growth factor synthesis.     

Effects of immunostimulants on ranched southern bluefin tuna Thunnus maccoyii: immune response, health and performance

Ranched southern bluefin tuna Thunnus maccoyii were fed baitfishes supplemented with vitamins (predominantly E and C) or vitamins and immunostimulants, nucleotides and β-glucans, over 12 weeks after transfer and monitored for enhancement in immune response, health and performance through their 19 week grow-out period. Fish from two different tows were sampled separately at three different sampling points: at transfer to grow-out pontoons, at 8 weeks post-transfer and at harvest, 19 weeks post-transfer. Lysozyme activity was enhanced during vitamin supplementation compared to control fish. Performance (i.e. survival, condition index and crude fat), health (i.e. blood plasma variables including pH, osmolality, cortisol, lactate and glucose) and alternative complement activity were not commonly improved through diet supplementation. There were some tow-specific improvements in performance through vitamin supplementation including survival, selected parasite prevalence and intensity, and alternative complement activity. Immunostimulant supplementation also showed a tow-specific improvement in plasma cortisol level. Tow-specific responses may suggest that life history, previous health condition and husbandry can affect the success of vitamin and immunostimulant enhancement of immune response, health and performance of ranched T. maccoyii.     

The role of nutritional supplementation on the outcome of superovulation in cattle

Since the 1990s nutritional supplements including protein, fatty acids, vitamins, and minerals have been used to try and improve the superovulatory response of embryo donors in cattle. However, the accumulated information indicates that nutritional supplementation with protein, fatty acids, or minerals does not increase the number of viable embryos from superovulated cattle. Most of the evidence has shown that vitamin supplementation may increase the mean production of transferable embryos, but only in cows, as a detrimental effect on embryo viability has been reported in young heifers. Nevertheless, vitamin supplementation seems to be effective only when compared with control cows displaying a poor mean embryo production (i.e. less than four viable embryos), questioning the economical significance of such approach. Detrimental effects on embryo development have been reported in superovulated cattle supplemented with protein or fatty acids as well. New approaches to investigate the role of nutritional supplementation on superovulatory outcome in cattle are suggested in the present review. Overall, the available evidence indicates that nutritional supplementation strategies tested are not an effective approach to enhance the superovulatory outcome of well-fed cattle donors.     

Effect of One-Year Vitamin C- and E-Supplementation on Cerebrospinal Fluid Oxidation Parameters and Clinical Course in Alzheimer’s Disease

Antioxidant vitamins are being widely discussed as a therapeutic option in Alzheimer??s disease (AD). We recently found that supplementation with vitamin C and E over 1?month leads to an increase of their levels in cerebrospinal fluid (CSF) and a reduction of CSF lipid peroxidation. In the present study, we followed-up the biochemical and clinical effect of vitamin C and E supplementation in an open clinical trial over 1?year. Twelve AD patients stably taking a cholinesterase inhibitor were supplemented with vitamin C (1,000?mg/day) and E (400 I.U./day), while 11 patients taking cholinergic medication only served as a control group. Cognition was assessed at baseline, after 6 months and 12 months using the Mini-Mental State Examination; a more detailed testing of cognitive function was performed at baseline and after 12 months. From eight of the vitamin-supplemented patients, CSF was taken at baseline, after 1?month and after 1?year to measure the antioxidant effect of vitamin supplementation on CSF lipids using a recently established in vitro oxidation assay. CSF antioxidant vitamins were significantly increased after 1?month and 1?year of supplementation, while in vitro oxidation of CSF lipids was significantly reduced only after 1?year of the supplementation. The clinical course of AD did not significantly differ between the vitamin and the control group. We conclude that supplementation with vitamins E and C did not have a significant effect on the course of AD over 1?year despite of a limited antioxidant effect that could be observed in CSF.     

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F₂-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the “Antioxidant Supplementation in Atherosclerosis Prevention” (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of d-α-tocopheryl acetate daily), both vitamins (CellaVie^®), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F₂-isoprostane concentration was lowered by 17.3% (95% CI 3.9–30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F₂-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.     

Influence of dietary vitamin E and C supplementation on vitamin E and C content and thiobarbituric acid reactive substances (TBARS) in different tissues of growing pigs

To investigate the influence and possible interactions of dietary vitamin E and C supplementation on vitamin content of both vitamins and oxidative stability of different pork tissues 40 Large White barrows from 25 kg to 106 kg were allocated to four different cereal based diets: Basal diet (B), dl-alpha-tocopherylacetate + 200 mg/kg (E), crystalline ascorbic acid + 300 mg/kg (C) or both vitamins (EC). At slaughtering samples of liver, spleen, heart, kidney, backfat outer layer, ham and M. tongissimus dorsi were obtained. Growth performance of the pigs and carcass characteristics were not influenced by feeding treatments. Dietary vitamin E supplementation had a significant effect on the vitamin E and alpha-tocopherol concentration in all investigated tissues. Backfat outer layer, liver, spleen, kidney and heart had higher vitamin E concentrations than ham and M. longissimus dorsi. Dietary vitamin C supplementation tended towards enhanced vitamin E levels except for ham samples. Therefore, some synergistic actions without dietary vitamin E supplementation between the two vitamins could be shown. The vitamin C concentration and TBARS were increased or at least equal in all tissues due to vitamin C supplementation. Dietary alpha-tocopherol supplementation resulted in lower TBARS in backfat outer layer (malondialdehyde 0.35 mg/kg in B vs. 0.28 mg/kg in E), but increased in heart and ham. When both vitamins were supplemented (EC) TBARS were lower in M. longissimus dorsi and backfat outer layer, equal in heart and higher in liver and ham compared to a single vitamin C supplementation. Rancimat induction time of backfat outer layer was 0.3 h higher in C compared to B and 0.17 h higher in EC than in E. Correlations between levels of both vitamins were positive for kidney (r = 0.169), M. longissimus dorsi (r = 0.499) and ham (r = 0.361) and negative for heart (r = -0.350). In liver and spleen no interaction could be found. In backfat outer layer vitamin E was positively correlated with rancimat induction time (r = 0.550) and negatively with TBARS (r = -0.202), but provided no evidence that dietary vitamin E supply led to better oxidative stability.     

Update on nutrients involved in maintaining healthy bone

Osteoporosis is a leading cause of morbidity and mortality in the elderly and influences quality of life, as well as life expectancy. Currently, there is a growing interest among the medical scientists in search of specific nutrients and/or bioactive compounds of natural origin for the prevention of disease and maintenance of bone health. Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, a recent research has clarified the importance of several additional nutrients and food constituents. Based on this review of the literature, supplementation with vitamins B, C, K, and silicon could be recommended for proper maintenance of bone health, although further clinical studies are needed. The results of studies on long-chain polyunsaturated fatty acids, potassium, magnesium, copper, selenium, and strontium are not conclusive, although studies in vitro and in animal models are interesting and promising.     

Folic acid - vitamin and panacea or genetic time bomb?

We live in a health-conscious age - many of us supplement our diet with essential micronutrients through the discretionary use of multivitamin pills or judicious selection of foods that have a health benefit beyond that conferred by the nutrient content alone - the so-called 'functional foods'. Indeed, the citizens of some nations have little choice, with a mandatory fortification policy in place for certain vitamins. But do we ever stop to consider the consequences of an increased exposure to micronutrients? We examine this issue in relation to the B-group vitamin folic acid, and ask whether supplementation with this vitamin could introduce a strong genetic selection pressure - one that has the side effect of increasing the prevalence of some of the most significant, human life-threatening diseases. Are we affecting our genetics - is this a case of human evolution in progress by altering our diet?     

Breath alkanes as a marker of oxidative stress in different clinical conditions

We assessed oxidative stress in three different clinical conditions: smoking, human immunodeficiency virus (HIV) infection, and inflammatory bowel disease, using breath alkane output and other lipid peroxidation parameters such as plasma lipid peroxides (LPO) and malondialdehyde (MDA). Antioxidant micronutrients such as selenium, vitamin E, C, beta-carotene and carotenoids were also measured. Lipid peroxidation was significantly higher and antioxidant vitamins significantly lower in smokers compared to nonsmokers. Beta-carotene or vitamin E supplementation significantly reduced lipid peroxidation in that population. However, vitamin C supplementation had no effect. In HIV-infected subjects, lipid peroxidation parameters were also elevated and antioxidant vitamins reduced compared to seronegative controls. Vitamin E and C supplementation resulted in a significant decrease in lipid peroxidation with a trend toward a reduction in viral load. In patients with inflammatory bowel disease, breath alkane output was also significantly elevated when compared to healthy controls. A trial with vitamin E and C is underway. In conclusion, breath alkane output, plasma LPO and MDA are elevated in certain clinical conditions such as smoking, HIV infection, and inflammatory bowel disease. This is associated with lower levels of antioxidant micronutrients. Supplementation with antioxidant vitamins significantly reduced these lipid peroxidation parameters. The results suggest that these measures are good markers for lipid peroxidation.     

Vitamin production in transgenic plants

Plants are a major source of vitamins in the human diet. Due to their significance for human health and development, research has been initiated to understand the biosynthesis of vitamins in plants. The pathways that are furthest advanced in elucidation are those of provitamin A, vitamin C and vitamin E. There is little knowledge about the regulation, storage, sink and degradation of any vitamin made in plants, or the interaction of vitamin biosynthetic pathways with other metabolic pathways. Researchers as well as life science companies have endeavoured to manipulate levels of vitamins in order to create functional food with enhanced health benefits, and even with the goal of achieving levels worth extracting from plant tissues. Thus far, metabolic engineering has resulted in transgenic plants that contain elevated levels of provitamin A, vitamin C and E, respectively. Additional research is necessary to identify all relevant target genes in order to further improve and tailor plants with elevated vitamin contents at will.     

La vitamine D : effets « classiques », « non classiques » et évaluation du statut du patient

Knowledge about vitamin D has greatly improved during the last few years. Vitamin D cannot any more be considered as exclusively necessary to prevent ricket/osteomalacia. Its role in the prevention of some osteoporotic fractures in the elderly (in association with calcium nutrition) is now well-demonstrated and many epidemiologic and laboratory data argue for a role in the prevention of several diseases or anomalies (cancer, auto-immune diseases, cardiovascular events, sarcopenia…). A few intervention studies confirming some of these effects also exist. Vitamin D status can easily be assessed by measuring serum 25-OH vitamin D level. However, many experts have claimed that the population-based reference values for 25OHD are too low and that the cut-off value below which vitamin D insufficiency can be present is somewhere between 20 and 40 ng/mL with a clear tendency to target values above 30 ng/mL (75 nmol/L). The main consequences are that vitamin D insufficiency is highly frequent whereas the currently recommended supplementation doses are not sufficient.     

Vitamin E and heart disease: basic science to clinical intervention trials

A review is presented of studies on the effects of vitamin E on heart disease, studies encompassing basic science, animal studies, epidemiological and observational studies, and four intervention trials. The in vitro, cellular, and animal studies, which are impressive both in quantity and quality, leave no doubt that vitamin E, the most important fat-soluble antioxidant, protects animals against a variety of types of oxidative stress. The hypothesis that links vitamin E to the prevention of cardiovascular disease (CVD) postulates that the oxidation of unsaturated lipids in the low-density lipoprotein (LDL) particle initiates a complex sequence of events that leads to the development of atherosclerotic plaque. This hypothesis is supported by numerous studies in vitro, in animals, and in humans. There is some evidence that the ex vivo oxidizability of a subject's LDL is predictive of future heart events. This background in basic science and observational studies, coupled with the safety of vitamin E, led to the initiation of clinical intervention trials. The three trials that have been reported in detail are, on balance, supportive of the proposal that supplemental vitamin E can reduce the risk for heart disease, and the fourth trial, which has just been reported, showed small, but not statistically significant, benefits. Subgroup analyses of cohorts from the older three trials, as well as evidence from smaller trials, indicate that vitamin E provides protection against a number of medical conditions, including some that are indicative of atherosclerosis (such as intermittent claudication). Vitamin E supplementation also produces an improvement in the immune system and protection against diseases other than cardiovascular disease (such as prostate cancer). Vitamin E at the supplemental levels being used in the current trials, 100 to 800 IU/d, is safe, and there is little likelihood that increased risk will be found for those taking supplements. About one half of American cardiologists take supplemental vitamin E, about the same number as take aspirin. In fact, one study suggests that aspirin plus vitamin E is more effective than aspirin alone. There are a substantial number of trials involving vitamin E that are in progress. However, it is possible, or even likely, that each condition for which vitamin E provides benefit will have a unique dose-effect curve. Furthermore, different antioxidants appear to act synergistically, so supplementation with vitamin E might be more effective if combined with other micronutrients. It will be extremely difficult to do trials that adequately probe the dose-effect curve for vitamin E for each condition that it might affect, or to do studies of all the possible combinations of other micronutrients that might act with vitamin E to improve its effectiveness. Therefore, the scientific community must recognize that there never will be a time when the science is "complete." At some point, the weight of the scientific evidence must be judged adequate; although some may regard it as early to that judgement now, clearly we are very close. In view of the very low risk of reasonable supplementation with vitamin E, and the difficulty in obtaining more than about 30 IU/day from a balanced diet, some supplementation appears prudent now.