The vitamin E family consists of four tocopherols and four tocotrienols, each designated as alpha, beta, gamma, or delta based upon slight differences in chemical structures.
Alpha-tocopherol is the only form of vitamin E that is actively maintained in the human body and is therefore the form of vitamin E found in the largest quantities in the blood and tissue.1
In the U.S. food supply, alpha-tocopherol provides 75% of the total vitamin E activity. Gamma-tocopherol supplies 20% and beta-tocopherol and alpha-tocotrienol together provide the remaining 5%.
Vitamin E is found in plants, animals, and in some green, brown and blue/green algae. The richest sources are unrefined edible vegetable oils. Approximately 50% of the vitamin E in vegetable oil is alpha-tocopherol
About 90% of the vitamin E stored in the body is in adipose tissue and the remaining 10% is stored in cell membranes throughout the body. The penetration of vitamin E into tissue is a slow process. Studies suggest that at least 2 years of vitamin E supplementation is necessary before changes in tocopherol concentrations can be identified.2
Male 9 to 13 years 14 to 18 years 19+ years Female 13 to 19 years 14 to 18 years 19+ years
11 15 15
11 15 15
600 800 1000
600 800 1000
Pregnancy <= 18 years 19 to 50 years
Lactation <= 18 years 19 to 50 years
The recommendations for vitamin E are provided in the Dietary Reference Intakes (DRIs) developed by the Institute of Medicine. Dietary Reference Intake is the general term for reference values used for planning and assessing nutrient intake for healthy people. The DRIs for vitamin E are listed as Alpha-Tocopherol Equivalents (ATE) to account for the different biological activities of the various forms of vitamin E. The table also lists vitamin E in International Units (IU) because food and some supplement labels list vitamin E in IUs (1 mg ATE vitamin E = 1.5IU).
Vitamin E intake of more than 1000 mg is contraindicated in people who have vitamin K deficiencies or who are at increased risk of coagulation problems (including those taking warfarin, heparin, dalteparin, tinzaparin, enoxaparin).
Dosing and Absorption Guidelines
Vitamin E supplements should be taken with food for optimal absorption (preferably taken with the highest fat meal of the day). 6
There are differences in absorption between natural vitamin E (d–alpha-tocopherol) and synthetic vitamin E (dl-alpha-tocopherol). Absorption of natural vitamin E can be twice as high as for synthetic vitamin E.7
The third National Health and Nutrition Examination Survey (NHANES III) examined blood levels of alpha-tocopherol in 16,295 adults and found that 27% of white participants, 41% of African Americans, 28% of Mexican Americans, and 32% of other participants had low blood levels of alpha-tocopherol.8
Suboptimal intake of some vitamins, above levels causing classic vitamin deficiency, has been found to be a risk factor for chronic diseases. These levels are common in the general population. 9
The World Health Organization (WHO) researchers determined that low levels of vitamin E are more closely linked to death from heart disease than such better-known risk factors as high cholesterol and high blood pressure. 10
Research on children’s diets (12 to 18 months old) indicates that many are deficient in key nutrients such as vitamin E, which could impact immune function.11
People with rare genetic abnormalities of the alpha-tocopherol transfer protein are at risk for vitamin E deficiency.12
Very low-birth weight (less than 3 pounds 4 oz.) premature infants are at risk for vitamin E deficiency.13,14
Since vitamin E is fat soluble, any condition affecting fat digestion, absorption or transport can lead to vitamin E deficiency with associated symptoms such as greasy stools or chronic diarrhea. This population may need a water-soluble form of vitamin E. Populations that experience fat malabsorption include: people with Crohn’s disease, people with cystic fibrosis, people with abetalipoproteinemia (a rare inherited disorder of fat metabolism that results in poor absorption of dietary fat and vitamin E)15, and people with ataxia caused by a genetic defect in a liver protein (responsible for maintaining normal alpha-tocopherol concentrations in the blood). 12
The Food and Nutrition Board of the Institute of Medicine has concluded that the Upper Limit (UL) of safety for vitamin E is 1000 mg, which is (1500 IU per day for natural vitamin E, or 1000 IU of synthetic vitamin E).14
Occasional side effects are seen with large doses of vitamin E (>2000 IU) such as headache, fatigue, nausea, double vision, muscular weakness and gastrointestinal distress. Relatively few side effects have been documented in double-blind studies of vitamin E, even at intakes of 3200 I.U./day.16
There has been some controversy regarding the effect of vitamin E on prevalence of cardiac arrhythmias. At a American Heart Association meeting, it was concluded that vitamin E is not linked to arrhythmias in people with pacemakers.
Primary deficiency may occur in early infancy, particularly in formulas high in unsaturated oils.
Protein-energy malnourished children may have low vitamin E concentrations.
Vitamin E malabsorption is often seen in people with Crohn’s disease, cystic fibrosis, abetalipoproteinemia (a rare inherited disorder of fat metabolism that results in poor absorption of dietary fat and vitamin E)15, and ataxia caused by a genetic defect in a liver protein (responsible for maintaining normal alpha-tocopherol concentrations in the blood). 12
Plasma levels of vitamin E may be lowered by anticonvulsants (phenobarbital, phenytoin and carbamazepine).
Vitamin E in large doses (> 1000 mg) may enhance effect of anticoagulants (warfarin, heparin, dalteparin, tinzaparin, enoxaparin).
High doses of vitamin E may potentiate the effects of antiplatelet drugs (aspirin, dipyridamole, eptifibatide, clopidogrel, and abciximab).
Vitamin E absorption may be decreased by: bile acid sequestrants (such as cholestyramine, colestipol, colesevelam), isoniazid (for treatment of tuberculosis), sucralfate (used to treat ulcers), and mineral oil.
The weight loss drug, orlistat (Xenical), alters fat absorption in the intestinal tract and has been shown to reduce the absorption of certain fat soluble vitamins such as vitamin E.
High intakes of supplementary polyunsaturated fatty acids (PUFAs) including alpha-linolenic acid, gamma-linolenic acid, docahexaenoic acid, icosapentaenoic acid and conjugated linolenic acid may increase vitamin E requirements.
The Melbourne Atherosclerosis Vitamin E Trial (MAVET): a study of high dose vitamin E in smokers.
The efficacy of vitamin E supplements to slow the progression of carotid atherosclerosis in heavy smokers was evaluated. In this randomized, placebo-controlled, double blind study, 409 smokers aged 55 years or more were randomized to consume 500 IU natural vitamin E daily for four years. While vitamin E supplementation was found to reduce LDL oxidation susceptibility, progression of carotid atherosclerosis was not different between the placebo and supplemented groups. 20
Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study.
In a randomized trial 26,779 women from the Women’s Health Study (WHS) were included in a study of vitamin E and venous thromboembolism (VTE). Participants allocated to receive either 600 IU natural vitamin E or a placebo on alternate days. After 10.2 years, 482 cases of VTE were reported. Of these, 213 were in the vitamin E supplemented group while 269 were in the placebo group. Vitamin E supplements were thus associated with a 21% reduction of risk for VTE. Among women who reported previous VTE at baseline, vitamin E supplements were associated with a 44% reduction in risk. Thus, vitamin E supplements may reduce risk for VTE in women. 21
Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial.
The Women’s Health Study (WHS) was conducted from 1992 to 2004 and was the longest, largest study ever conducted with vitamin E, involving nearly 40,000 healthy women. The WHS tested whether vitamin E supplementation decreased the risk of cardiovascular disease and cancer in healthy women. Participants received either 600 IU vitamin E or placebo, and aspirin or placebo, every other day. There was a non-significant 7% reduction of major cardiovascular events in the vitamin E group. The study clearly indicated a significant 24% reduction in cardiovascular deaths among the nearly 20,000 women taking vitamin E. In addition, women aged 65 years and older in the vitamin E group experienced a significant reduction in major cardiovascular events including a 34% reduction in heart attacks and 49% reduction in cardiovascular death. The authors did not recommend vitamin E supplements, however, since the results differed from the totality of evidence and requires further exploration.22
Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis.
In the Finnish Atherosclerosis Prevention (ASAP) Study, researchers examined the effect of vitamin E and vitamin C supplementation on the progression of carotid atherosclerosis over a period of three years. Study subjects (520 smoking and non-smoking men and postmenopausal women) received 136 IU of vitamin E (twice daily), 250 mg of slow-release vitamin C (twice daily), both, or placebo. The ratio of men with progression to without progression of carotid atherosclerosis was decreased by 75% with antioxidant supplementation. The combination of antioxidants slowed the progression of carotid atherosclerosis in men but not in women in this study.23
Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.
The Heart Outcomes Prevention Evaluation (HOPE) Study followed almost 10,000 patients who were at high risk for heart attack or stroke for 4.5 years. In this intervention study the subjects who received 265 mg (400 IU) of vitamin E daily did not experience significantly fewer cardiovascular events or hospitalizations for heart failure or chest pain when compared to those who received a placebo. The researchers suggested that it is unlikely that the vitamin E supplement provided any protection against cardiovascular disease in the HOPE study.24
Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial.
The Women's Angiographic Vitamin and Estrogen (WAVE) trial, studied 423 postmenopausal women at seven clinical centers in the United States and Canada. Postmenopausal women with heart disease, who took supplements providing 400 IU vitamin E and 500 mg vitamin C twice daily, either alone or in combination with hormones, did not have fewer heart attacks or deaths. There was also no change noted in progression of their coronary disease. In this trial, neither hormone replacement therapy nor vitamin supplements altered coronary disease progression.25
Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'I
One of the largest trials in Europe was the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico Prevenzione Study (GISSI-Prevenzione). The GISSI-Prevenzione trial involved 11,324 patients randomized within 3 months of experiencing a myocardial infarction to receive 300 mg/day of vitamin E (all-rac-alpha-tocopherol), 1 g/day of omega-3 fatty acids, both, or placebo in a 2 × 2 design. The primary combined efficacy endpoint was death, non-fatal myocardial infarction, or stroke. Treatment with omega-3 fatty acids, but not with vitamin E, significantly lowered the risk of death, myocardial infarction or stroke (the primary endpoint; relative-risk decrease 10%). However, the trial did find a reduced incidence of deaths related to heart disease for people assigned to take vitamin E, although there was no difference in nonfatal heart attacks.26
Risk of mortality with vitamin E supplements: the Cache County study.
A recent review of the results from the Cache County study investigated the associations between vitamin E use, cardiovascular disease, and mortality. A total of 4,416 participants were included in the study. At baseline, 10% of participants reported use of vitamin E supplements; at 3 year follow-up, 66% of participants reported use of vitamin E supplements. Overall, there was no association between vitamin E and mortality (Hazard Ratio 0.93). Stratification by previous cardiovascular disease or certain drug use revealed possible increases in risk or mortality for certain populations. Specifically use of vitamin E was associated with increased risk for those with previous stroke (HR 3.64), coronary bypass graft surgery (HR 4.40), myocardial infarction (HR 1.95), and those who consumed nitrates (HR 3.95), warfarin (HR 3.71), or diuretics (HR 1.83). Thus, vitamin E supplements were associated with a reduced risk of mortality for people without cardiovascular disease, but increased risk of mortality for people with a history of cardiovascular disease. 27
Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis.
A recent meta-analysis evaluated the impact of supplemental vitamin E on mortality rates. Sixty-eight randomized trials were included with a total of 232,606 participants. Analysis of the trials indicated a relative risk of mortality with vitamin E supplements of 1.04 (95% CI 1.01-1.07). The authors concluded that vitamin E supplements increase risk of mortality. The conclusions of this meta-analysis, however, have stimulated a vigorous debate. The results of this trial need further evaluation. 28
Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.
A prospective cohort study investigated the effect of serum concentrations of vitamin E on mortality in men. Data from the Alpha-Tocopherol, Beta-Carotene cancer prevention study were analyzed; 29,092 men aged 50 to 69 years participated in the study for up to 19 years. Serum vitamin E concentrations were analyzed by HPLC at baseline. Serum vitamin E concentrations in the highest quintile were associated with significant reductions in risk for total (relative risk (RR) 0.82) and cause-specific mortality (cancer RR 0.79, cardiovascular disease RR 0.81, and other causes RR 0.70) compared to those in the lowest quintile. Greatest risk reductions were found with increasing vitamin E concentrations up to approximately 13-14 mg/L, with no additional benefit at higher concentrations. The authors concluded that serum vitamin E concentrations in this high-normal range were associated with the greatest risk reductions for mortality.29
A prospective study on supplemental vitamin e intake and risk of colon cancer in women and men.
In a prospective study, 87,998 females from the Nurses' Health Study and 47,344 males from the Health Professionals Follow-up Study were evaluated to investigate the efficacy of vitamin E supplements for prevention of colon cancer. Men who consumed 300 - 500 IU/day vitamin E supplements for at least 4 years had lower risk for colon cancer versus those who had never taken vitamin E supplements. However, there was no evidence for an inverse association between vitamin E supplementation and risk of colon cancer for women.30
The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group.
The Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Trial was conducted by the U.S. National Cancer Institute (NCI) and the National Public Health Institute of Finland from 1985 to 1993. The ATBC study investigated risk factors and prevention of major chronic diseases such as cancer, cardiovascular disease, and diabetes in the Finnish population. The study population consisted of 29,133 male smokers aged 50 to 69 years who participated in a randomized placebo-controlled trial for 5 to 8 years. The study was to follow up the long-term effects of alpha-tocopherol (50 mg) and beta-carotene supplementation (20 mg) on the incidence of the risk factors for major chronic diseases such as cancer and heart disease. A 19% reduction in lung cancer incidence was observed in the highest versus the lowest quintile of baseline serum vitamin E levels. There was a stronger inverse association among younger men (< 60 years) and among men with less cumulative tobacco exposure.31 Prostate cancer incidence was 32% lower in the vitamin E group. The decreased incidence was evident in clinical prostate cancer but not in latent cancer. The lower prostate cancer incidence rates in participants taking alpha-tocopherol supplements during the trial returned toward normal soon after the trial ended, but remained below the placebo group rates throughout the six-year post-intervention period.32
The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals.
The largest longitudinal epidemiological study ever carried out in Europe, SU.VI.MAX,(SUpplémentation en VItamines et en Minéraux AntioXydants) aims to define the relationship between diet, health and disease. For a period of 8 years, 13,000 people throughout France are being nutritionally and medically monitored. Participants were randomly assigned to take either a daily capsule containing 120 mg of vitamin C, 30 mg vitamin E, 6 mg beta carotene, 100 mcg selenium and 20 mg of zinc, or a placebo. The participants were followed for an average of 7-1/2 years. The results showed that low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men (31% reduction) but not in women.33
Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women.
The American Cancer Society recently released the results of a long-term study that evaluated the effect of vitamin E and C supplements on bladder cancer mortality. The study followed 991,522 adults for a 15 year period and found that those who regularly consumed vitamin E supplements (dosages not reported) for at least 10 years were 40% less likely to die from bladder cancer. Regular use of vitamin E supplements for less than 10 years was not associated with a reduced risk of bladder cancer mortality.34
Relationship between vitamin and calcium supplement use and colon cancer
In a retrospective case-controlled study involving 450 colon cancer patients (aged 30-62 years) and a similar number of controls, the results showed that the use of multivitamins and vitamin E supplements was associated with a reduction in the risk of colon cancer. Subjects who used a multivitamin supplement daily for the 10 year period had half the risk of colon cancer compared to those who never used multivitamins during this period. And those who took an average of 200 IU or more of vitamin E per day over the 10 years had a 57% reduction in colon cancer risk compared to non-users of vitamin E.35
Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial.
A randomized, double-blind, placebo-controlled study included 451 subjects (65 years and older) living at a long-term care facility who consumed 200 IU of vitamin E or a placebo daily for 1 year. All subjects received a daily capsule containing half of the RDA of essential vitamins and minerals. The study found vitamin E reduced respiratory tract and upper respiratory tract infections. There was also a 20% lower incidence of common colds among vitamin E users.36
Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial.
A study investigated immune response in 88 free-living, healthy subjects (65 years or older) who were randomly assigned to a placebo group or to groups consuming 60, 200 or 800 mg/day of vitamin E for 235 days. Subjects taking 200 or 800 mg/day had higher antibody responses to hepatitis B vaccine and delayed-type hypersensitivity (DTH) skin response. The authors concluded that 200 mg/day or more of vitamin E significantly improved immune response.37
Immune function in aged women is improved by ingestion of vitamins C and E.
A Spanish study evaluated the effect of antioxidant supplementation on immune function in 30 older females (average age 72 years). Each subject took 200 mg vitamin E and 1,000 mg vitamin C daily for 16 weeks. Antioxidant supplementation produced significant improvement in parameters of immune function and a significant decrease in lipid peroxide levels in the women.38
Effect of vitamin E supplementation on the regular treatment of seasonal allergic rhinitis.
The effects of vitamin E on the symptoms of allergic rhinitis were investigated in 112 men and women. Participants were assigned to receive either 800 IU vitamin E per day or placebo for ten weeks, in addition to continuing on current anti-allergy medications as needed to control symptoms. The amount of medication used to alleviate symptoms and the occurrence of nasal symptoms (sneezing, itching, stuffiness, and runny nose) and eye symptoms (watering, itching, redness, and swelling) were recorded. Nasal symptoms were significantly less in the group receiving vitamin E than in the placebo group. In particular, the vitamin E group experienced much less nasal stuffiness than the placebo group. Eye symptoms were not changed by treatment with vitamin E, and the use of anti-allergy medications did not differ between the two groups.39
Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation.
The efficacy of vitamin for the prevention of paclitaxel-induced peripheral neuropathy (PIPN) during chemotherapy was assessed. Thirty-two patients receiving paclitaxel were randomly assigned to receive 300 mg vitamin E twice daily or chemotherapy alone. Neurological and electrophysiological exams were used to assess neurotoxicity. Neurotoxicity occurred in 18.7% of vitamin E supplemented patients and in 62.5% of patients who took paclitaxel alone. Vitamin E supplements effectively protected cancer patients from PIPN. Double-blind, placebo controlled trials are needed to support these data.40
Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study.
Researchers assessed the prevalence of dementia, Alzheimer’s disease (AD), and supplement use in 4,740 elderly (65 years or older) people from 1995 to 1997 with follow-up in 1998 to 2000 for new cases of dementia or AD. The researchers identified 200 cases of AD between 1995 and 1997, and 104 new cases of AD during follow-up. The researchers categorized participants into four groups: those taking (1) vitamin E - 400 IU, (2) vitamin C - 500 mg, (3) multivitamin users if they reported taking multivitamins containing lower doses of vitamin E or C, or (4) vitamin B-complex users. The researchers found the greatest reduction in incidence of AD in participants who used vitamin E and C supplements in combination, with or without an additional multivitamin. The use of vitamin E and C supplements together reduced AD prevalence by about 78%. The researchers suggest that vitamins E and C together may offer protection against AD.41
A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study.
In April 1997, a landmark study published in the New England Journal of Medicine suggested that the deterioration of patients who have moderate Alzheimer's disease may be slowed through treatment with vitamin E, selegiline (Eldepryl), or both. Three-hundred-forty-one patients were given daily doses of 2,000 IU vitamin E, 10 mg selegiline, both, or placebo, for two years. There was a significant delay (about 230 days) in disease progression, e.g., loss of ability to perform basic activities of daily living, severe dementia, institutionalization, and death, in patients who received daily doses of vitamin E, selegiline, or both.42
In a study in Chicago, investigators interviewed more than 6,000 people 65 and older about dietary habits and use of vitamins and supplements. Study participants also took a series of cognitive tests. The surveys were repeated over three years. At the end of the study period, patients having a high intake in vitamin E showed 36% less decline in cognitive function (in some cases, they even improved their test scores). Participants taking vitamin E supplements performed better than those who relied on food sources. Seniors consuming the lowest amounts of vitamin E experienced the most extensive cognitive decline.43
Dietary intake of antioxidants and risk of Alzheimer disease.
The association between dietary intake of antioxidants and the risk of Alzheimer's Disease (AD) was examined in a population-based study conducted in the Netherlands. At baseline (1990-1993), the 5,395 participants were aged 55 years or older, free of dementia, non-institutionalized, and had reliable dietary assessments. Subjects were monitored for incident dementia and were reassessed in 1993-1994 and 1997-1999. One-hundred-ninety-seven participants developed dementia; 146 had AD. High intakes of vitamin C and vitamin E were associated with lower risk for AD among current smokers. Adjusting for age, sex, baseline cognitive function, alcohol intake, education, smoking status, body mass index, total energy intake, presence of carotid plaques, and use of antioxidant supplements, education, and apolipoprotein E genotype did not change this association. Beta-carotene and flavonoid intakes were also associated with lower risk for AD among current smokers. Results suggest that high dietary intakes of vitamin C and vitamin E may lower the risk for AD.44
High-dose antioxidant supplements and cognitive function in community-dwelling elderly women.
Cognitive function and supplement use were evaluated for 14,968 female nurses participating in the Nurses Health Study. Data regarding lifestyle factors and use of vitamin E and vitamin C supplements were collected for 15 to 20 years. From 1995-2000 cognitive function examinations were administered by phone to the women who were 70-79 years of age at that time. Women who were taking supplements of both vitamin E (100 - 600 mg) and vitamin C (400-750 mg), and had done so for several years, performed better on the cognitive function tests compared with women who had never taken vitamin E or C supplements. Longer duration of supplement use was associated with a greater benefit (the greatest benefit was seen in those who took vitamin E and C supplements for more than 10 years). The benefit of supplement use was strongest among women who had low amounts of vitamin E in their diets, and was less pronounced among women taking just vitamin E with no vitamin C.45
Association of vitamin E and C supplement use with cognitive function and dementia in elderly men.
Data from the Honolulu-Asia Aging Study, which in 1965 began to study 8,006 Japanese-American males living in Hawaii, were evaluated. The researchers compared dementia and cognitive function in a sub-sample of 3,385 men (age range, 71 to 93 years) who had reported using vitamins C and E (dosage not reported) during a 1988 survey with that of the entire sample, who participated in a dementia prevalence survey from 1991 to 1993. Participants who used both vitamins C and E, had dramatically reduced rates of vascular dementia (88% reduction in frequency), but not Alzheimer's Disease, compared with the entire sample. A smaller, but still significant, decrease in frequency was also noted for mixed dementia. The use of supplements in the sub-sample had no significant effect on the incidence of stroke. Among those without dementia, use of either vitamin C or E in 1988 was associated with significantly better cognitive performance in 1991 to 1993.46
Antioxidant vitamin intake and risk of Alzheimer disease.
Researchers investigated the relationship between Alzheimer's Disease (AD) and the intake of carotenoids, vitamin C, and vitamin E in 980 elderly subjects who were free of dementia at baseline and were followed for a mean time of 4 years. Semi quantitative food frequency questionnaires were used to assess dietary quality and were administered between baseline and the first follow-up visit. Two-hundred-forty-two incident cases of AD were detected during 4,023 person-years of follow-up. No decrease in risk of AD was found for carotenoids, vitamin C, or vitamin E in this study.47
Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants.
Vitamins C and E may protect the lungs of asthmatic children from the effects of ozone pollution, recent study findings suggest. A study was conducted to determine whether antioxidant supplements could protect asthmatic children from air pollution in the metropolitan area of Mexico City. One-hundred-fifty-eight children involved in the study were randomly divided into one of two groups that received a daily supplement of either vitamins (50 mg/day of vitamin E and 250 mg/day of vitamin C) or an inactive placebo. They were then followed for 1.5 years. The investigators found that the vitamin supplements protected the study group from decreased forced expiratory flow, the amount of air dispelled from the lungs during a certain time period, and diminished peak expiratory volume, a measure of airway resistance. The data suggest that supplementation with vitamins C and E above the minimum dietary requirement in children with asthma with low intake of vitamin E provides some protection against the acute effects of ozone on their lungs.48
Effect of antioxidant supplementation on ozone-induced lung injury in human subjects.
Thirty-two healthy, non-smoking adults aged 18 to 35 consumed an antioxidant-restricted diet and either a placebo or 250 mg of vitamin C, 50 IU of alpha-tocopherol, and 12 oz of vegetable cocktail daily for 2 weeks. After a week during which they were exposed to filtered and purified air, lung function was assessed. For the next two weeks, half the subjects in the study were given antioxidant supplements, and the other half a placebo. All were exposed to 0.4 parts per million of ozone gas for two hours, while intermittently taking moderate exercise. Researchers then gave them a brochoalveolar lavage. Those who had consumed vitamin C and E supplements had 24% to 30% improvements in the various tests of lung function, compared to the group who did not take the supplements.49
Vitamin E and risk of type 2 diabetes in the women's health study randomized controlled trial.
To assess the efficacy of vitamin E supplements for the prevention of type 2 diabetes, 38,716 healthy women aged 45 years or more were randomized to receive 600 IU vitamin E on alternate days for 10 years. A non-significant 5% reduction in risk for type 2 diabetes was found. The authors concluded that 600 IU vitamin E on alternate days did not reduce risk for type 2 diabetes.50
Effect of high-dose vitamin E on insulin resistance and associated parameters in overweight subjects.
Eighty overweight individuals (BMI >27 kg/m2) consumed either 800 IU vitamin E per day or a matching placebo for 3 months. After 3 months, the vitamin E dose was increased to 1,200 IU for an additional 3 months. Indicators of oxidative stress such as plasma peroxides decreased by 27% at 3 months and by 29% at 6 months in the group that received vitamin E. Plasma peroxide concentrations were positively correlated with plasma vitamin E concentrations at the 6-month time point. Authors concluded that vitamin E can improve indicators of oxidative stress and hepatocellular function. Although insulin resistance also improved during the first 3 months of the study, this effect was transient and was no longer evident at the 6 month time point.51
The impact of vitamin and/or mineral supplementation on lipid profiles in type 2 diabetes.
In a randomized, double-blind, placebo controlled clinical trial, 69 people with Type 2 diabetes were randomly divided into four groups for three months, 200 mg Mg and 30 mg Zn (n = 16), 200 mg vitamin C and 150 mg vitamin E (n = 18), 200 mg Mg, 30 mg Zn, 200 mg vitamin C and 150 mg vitamin E (n = 17), or placebo (n = 18). After 3 months of supplementation mean serum levels of HDL and apo A1 increased significantly in the Mg, Zn, vitamin C and vitamin E group by 24% and 8.8% respectively. There were no significant changes in the levels of these parameters in the other three groups. Serum levels of total cholesterol, LDL, triglyceride, and apo B were not altered after supplementation in all four groups. The authors concluded that co-supplementation of Mg, Zn, and vitamins C and E significantly increased HDL-c and apo A1 and could be beneficial for people with Type 2 diabetes.52
Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus.
To investigate the effects of antioxidant vitamins on endothelial vasodilator function (EDV) and endothelium-independent vasodilation (EIV) in type 1 and type 2 diabetes, 49 people with diabetes and 45 healthy controls subjects were enrolled in a study. All subjects were randomly assigned to receive either 1000 mg vitamin C and 800 IU vitamin E per day or a placebo for 6 months. Both EDV and EIV were measured by vascular ultrasonography. At the beginning of the study, EDV was reduced in both type 1 and type 2 diabetics. Antioxidant therapy increased EDV only in type 1 diabetics. Vitamins C and E had no significant effect on EIV.53
Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study.
To evaluate the effect of vitamin E supplementation on impaired conduit and resistance vessel endothelial vasodilator function (EVF) and systemic arterial compliance (SAC), EVF and SAC were monitored before and after supplementation with 1000 IU vitamin E for 3 months in people with type 1 diabetes. Improvements in LDL susceptibility to oxidation, flow-mediated dilation, and response to acetylcholine were observed in the vitamin E group but not in the placebo group. It was concluded that short term supplementation with vitamin E improves EVF in subjects with type I diabetes.54
The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial.
The effect of vitamin E supplements on blood pressure, heart rate, and F2-isoprostane concentrations were investigated in 58 people with type 2 diabetes. Subjects were randomly assigned to receive 500 mg/day RRR-alpha-tocopherol, 500 mg/day mixed tocopherols (60% gamma-tocopherol), or a placebo for 6 weeks. After 6 weeks, systolic and diastolic blood pressure, pulse pressure, and heart rate were increased in both the RRR-alpha-tocopherol and the mixed tocopherol groups, relative to the placebo group. Plasma F2-isoprostane concentrations were decreased in both tocopherol groups; urinary F2-isoprostane concentration was not affected. The results of this study, contrary to earlier hypotheses, suggest that vitamin E supplements may adversely affect blood pressure in people with type 2 diabetes. The results of this trial need confirmation. 55
Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis.
A randomized, placebo controlled clinical trial investigated the efficacy of vitamin E or pioglitazone for nonalcoholic steatohepatitis (NASH). Two-hundred-forty-seven adults with NASH without diabetes participated in the 96 week trial. Participants were randomly assigned to receive pioglitazone (30 mg daily), vitamin E (800 IU daily), or a placebo daily. Compared with placebo, vitamin E had a statistically significant higher rate of improvement in NASH (43% vs. 19%, P=0.001). Pioglitazone treatment had a higher rate of improvement than placebo but the difference was not significant (34% vs. 19%, P=0.04). Both vitamin E and pioglitazone reduced serum alanine and aspartate aminotransferase levels compared to placebo (P<0.001 for both). Vitamin E and pioglitazone each reduced hepatic steatosis (P=0.005 for vitamin E and P<0.001 for pioglitazone) and lobular inflammation (P=0.02 for vitamin E and P=0.004 for pioglitazone). This study indicates that vitamin E may help improve NASH for adults without diabetes. Further trials are warranted. 56
A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8.
The Age-Related Eye Disease Study (AREDS) enrolled 3,640 participants between the ages of 55 and 80 and followed them over a six-year period. Each person had some degree of retinal changes, ranging from mild to severe. Participants were divided into groups to receive daily intakes of 500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of beta-carotene, 80 mg of zinc and 2 mg of copper, vitamin C, 400 IU of vitamin E, and 15 mg of beta-carotene, and 80 mg of zinc (no copper), or no supplements at all. Antioxidant vitamins and zinc therapy reduced the risk of developing advanced Age-related Macular Degeneration (AMD) in participants with intermediate and greater risk of developing AMD by 25%. The risk of vision loss of 3 lines or more on the logarithmic visual acuity charts also was reduced by 19% for these participants. For participants who developed AMD, the risk of such vision loss was reduced by 25%.57
Vitamin supplement use and incident cataracts in a population-based study.
A population-based study provides further evidence of the association between vitamin supplement use and reduced incidence of nuclear and cortical cataracts. 3,000 participants, 43 to 86 years old were followed for five years. Incidence of cataracts, determined by optometric photographic techniques, was evaluated at baseline and follow-up examination. At five-year follow-up, subjects who had used multivitamins or any supplement containing Vitamin C or E (dosage not determined) for more than 10 years were 60% less likely to suffer cataracts compared with nonusers.58
Vitamin E supplementation and cataract: randomized controlled trial.
One-thousand-two-hundred subjects were enrolled and followed for four years in a prospective, randomized, double-masked, placebo-controlled clinical trial of vitamin E and eye health. Subjects were assigned randomly to receive either 500 IU of natural vitamin E or a placebo. There was no difference in the rate of cataract extraction between the two groups. Researchers concluded that vitamin E given for 4 years at a dose of 500 IU daily did not reduce the incidence of or progression of nuclear, cortical, or posterior subcapsular cataracts.59
Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using solar simulated radiation.
To evaluate the effect of daily supplementation with vitamins E and C on solar skin damage, 40 healthy subjects consumed 2 g vitamin E and 3 g vitamin C daily for 50 days. The results showed significantly increased levels of the antioxidants in the epidermis and suppressed solar-stimulated irradiation-induced skin erythema (reddening of the skin). The researchers concluded that vitamins E and C in combination can suppress sunburn reaction.60
Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-alpha-tocopherol (vitamin E).
In a double-blind, placebo-controlled study, 10 subjects took a daily combination of 1000 IU vitamin E and 2 grams of ascorbic acid or a placebo. The sunburn reaction before and after 8 days of treatment were assessed by determining the minimal exposure to UV required to produce sunburn. The vitamin E and vitamin C combination reduced the sunburn effect compared to the placebo group.61
Evaluation of dietary intake of vitamin E in the treatment of atopic dermatitis: a study of the clinical course and evaluation of the immunoglobulin E serum levels
Eczema is a chronic skin condition that causes scaling, reddening, and thickening of areas of the skin. Researchers evaluated 96 people between the ages of 10 to 60 with moderate eczema. Subjects received either 400 IU vitamin E daily or a placebo daily for eight months. Subjects who took vitamin E had significantly greater improvement compared to those who took the placebo. Blood levels of IL-6 also decreased in the people who consumed vitamin E supplements.62
The relationship between reduced vitamin antioxidant concentrations and the systemic inflammatory response in patients with common solid tumours.
One study measured fasting circulating concentrations of antioxidants and C-reactive protein (CRP) in 30 normal subjects, 15 subjects with breast cancer, 15 subjects with prostate cancer, and 11 subjects with colorectal cancer. Concentrations of CRP were higher and antioxidants lower in the cancer patients compared to healthy subjects. The results showed an inverse association between antioxidants and the magnitude of inflammatory response. The relationship appeared to be independent of the presence and type of cancer.63
Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients
The effect of vitamin E supplementation (1200 IU/day) on plasma C-reactive protein (CRP) and interleukin -6 release from activated monocytes was investigated. Twenty-three people with macrovascular disease and type 2 diabetes, 24 people with type 2 diabetes without macrovascular disease, and 25 matched controls consumed 1200 IU vitamin E daily for three months. Vitamin E supplementation was found to significantly lower levels of CRP and monocyte IL-6 in all subjects in this study.64
Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes.
A randomized placebo-controlled study looked at 57 people with type 2 diabetes. All subjects consumed a placebo for four weeks and then were randomized to receive 800 IU/day vitamin E, 500 mg/day vitamin C, 250 mL tomato juice twice daily, or the placebo. The lag time for oxidation of isolated LDL by copper ions was significantly increased with tomato juice (42%) and vitamin E (54%) supplementation. Treatment with vitamin E significantly decreased plasma levels of C-reactive protein (CRP; 49% reduction). The decrease in plasma CRP during vitamin E supplementation may indicate an improvement in systemic inflammation and reduce risk for myocardial infarction in people with type 2 diabetes.65
Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients.
A randomized, prospective clinical study was conducted with 595 critically ill patients at risk for the development of inflammatory organ injury. Upon admission to the intensive care unit (ICU), patients were randomly chosen to receive either an antioxidant supplement (1000 IU vitamin E and 1000 mg vitamin C) or standard care with no antioxidant supplement. Antioxidants were continued for the duration of the ICU admission or for 28 days. Patients in the antioxidant group were found to have a decreased risk for pulmonary morbidity (ARDS and pneumonia), a decreased risk for developing multiple organ failure, and a shorter duration of mechanical ventilation and duration of stay in the ICU.66
Antioxidants as adjuvant therapy in rheumatoid disease. A preliminary study.
A study was conducted with 30 patients with rheumatoid arthritis (RA). Subjects were divided into three groups; group 1 received a standard treatment of medications, group 2 received the standard treatment plus a combination of antioxidants, group 3 patients received a high dose of vitamin E (400 IU 3 times daily) in addition to the standard treatment. Subjects receiving the standard treatment (group 1) reported improvement of symptoms after the second month. Subjects receiving antioxidants or high dose vitamin E in addition to standard treatment (groups 2 and 3) there were improvements in arthritis symptoms during the first month. Laboratory measurements (including rheumatoid factor, erythrocyte sedimentation rate, and glutathione peroxidase activity) also indicated improvements in RA. The results obtained from the study showed clinical improvement in RA with use of antioxidants and vitamin E along with standard therapies.67
Oxidative stress response to aerobic exercise: comparison of antioxidant supplements.
Forty-eight aerobically trained men and women participated in a study to evaluate antioxidant vitamin or fruit and vegetable juice for reduction of exercise-induced oxidative stress. Participants were randomly assigned to receive 400 IU vitamin E and 1 g vitamin C daily, fruit and vegetable juice concentrate, or a placebo. Blood samples were taken before and after participants ran for 30 minutes at 80% VO(2 max); participants were assessed before, after 2 weeks of supplementation, and after a 1 week washout period. The exercise-induced increase in protein carbonyls was significantly reduced by both vitamin and fruit and vegetable concentrate supplementation after two weeks of supplementation (21% and 17%, respectively) and after a one week washout period (13% and 6%, respectively). The reductions were not significantly different between the vitamin and fruit and vegetable concentrate groups. These data suggest that vitamins C and E and fruit and vegetable concentrate are effective for reducing exercise-induced oxidative stress.68
Antioxidant supplementation prevents exercise-induced lipid peroxidation, but not inflammation, in ultramarathon runners.
Traber and colleagues at the Linus Pauling Institute at Oregon State University recently reported that ultramarathon runners who used supplements of vitamins C and E for six weeks prior to their races prevented the increase in lipid oxidation that is otherwise associated with extreme exercise. Twenty-two runners who performed in a 50km 'ultramarathon' participated in the study. Half of the runners were given daily supplements of 1,000 mg vitamin C and 400 IU vitamin E for six weeks prior to the race, while the other half ate only their normal, healthy diet. An analysis of biomarkers in the control group showed significant increases in lipid peroxidation following the race. These biomarkers were at levels that are often seen after someone has had a heart attack. The runners taking vitamins C and E were comparatively normal. The study demonstrated that supplementation with vitamins C and E helped to attenuate the level of lipid oxidation associated with intense exercise.69
Effect of vitamin E and eccentric exercise on selected biomarkers of oxidative stress in young and elderly men.
A study of the effect of vitamin E and eccentric exercise on selected biomarkers of oxidative stress in men was completed at Tufts University. Young and older healthy men were randomly assigned to consume 1,000 IU day of vitamin E or placebo for 12 weeks and ran downhill for 45 minutes, before and following supplementation. Blood samples were taken at multiple hourly intervals post-exercise to monitor antioxidant status, muscle damage, lipid peroxidation, and DNA damage. Vitamin E supplementation decreased peak creatine kinase levels in young men. In older men levels of F(2alpha)-isoprostanes were decreased and the 24 hour post exercise increase in F(2alpha)-isoprostanes was suppressed. Vitamin E supplementation improved measures of exercise-induced oxidative stress.70
Effects of alpha-tocopherol, beta-carotene and ascorbic acid on oxidative, hormonal and enzymatic exercise stress markers in habitual training activity of professional basketball players.
In a study of professional basketball players, antioxidant supplements (600 mg alpha-tocopherol, 1000 mg ascorbic acid and 32 mg beta-carotene) were given to determine the effect of these supplements on exercise induced stress. After 35 days of antioxidant treatment, plasma lipid peroxides decreased about 28%. A significant decrease of lactate dehydrogenase serum activity was noted during the 24 hour recuperation time. Also during this time, the anabolic/catabolic balance increased about 30% in the antioxidant supplemented group but this change was not statistically significant.71
Vitamin E supplementation attenuates leakage of enzymes following 6 successive days of running training.
One study explored the potential effects of vitamin E on exercise-induced muscle damage. The double-blind, placebo-controlled study involved 14 male runners aged 18 to 24. The study period included four weeks of moderate exercise training immediately followed by six days of intense training during which subjects substantially increased their running distances. The subjects were randomized to receive either 1,200 IU d-alpha-tocopherol or placebo taken daily throughout the entire study period. Levels of serum creatine kinase, lactate dehydrogenase, and LDH isozymes (enzymes thought to be indirect markers of muscle damage) were measured before and after the six-day intense training period. Enzyme levels were increased in both groups following the intense training period, but levels were significantly lower in the vitamin E group compared to the placebo group. These results suggest 1,200 IU of vitamin E daily may be protective against exercise-induced muscle damage.72
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