You must read and accept the disclaimer to use this site. Updated for monthly, 2011

Vitamin E

Changing the dogma of nutrition and medicine! This page is quite lengthy, though the key points are in large type below. However,the evidence for taking a vitamin E supplement is so overwhelming that many people take that supplement before taking others. So here is sufficient evidence to show how overwhelming the proof is that vitamin E is safe and proven likely to prevent serious diseases.

The micronutrient leading the revolution in nutrition is vitamin E. Despite Dr. Linus Pauling's effort to bring antioxidants to the fore by promoting the value of vitamin C, it is the overwhelming evidence for the value of vitamin E supplements for long-term health which is changing the way that nutritionists, physicians, and researchers view nutritional supplements. Unlike all other vitamins that have clear catalytic roles as cofactors to enzymes, vitamin E is a fat-soluble vitamin whose only apparent function is to act as an antioxidant. This vitamin may lower heart disease by 50%, boost immune function by 65%, reduce the buildup of plaque in your arteries, and much more. In recent years it has been as intensively studied and proven as safe as vitamin C. In numerous epidemiological, biochemical, and clinical studies, it is the micronutrient for which the evidence is most compelling that it is safe and should be taken as a supplement.

Vitamin E is unique among the vitamins, as it is the only one that does not function as part of an enzyme in catalyzing specific chemical reactions. Its function appears to be solely to act as an antioxidant! The US Daily Value for vitamin E is set at only 30 international units, which is the same as 30 mg of alpha-tocopherol. Vitamin E occurs naturally in plants in different forms, known as isomers, differing only in the position of the double bonds between the carbon atoms. The four forms are alpha-, beta-, gamma-, and delta-, as shown in figure 6. This is important because while most vitamin E supplements contain only the alpha-form, research shows it is important to get the gamma-form as well. I will show later that it is advantageous to be careful to purchase vitamin E that shows it contains "mixed tocopherols" on the label.

SAFE AND PROVEN! Numerous studies have been conducted showing that vitamin E can reduce the incidence of age- associated diseases. Here are a few significant findings:

Vitamin E levels are much lower in people with heart disease: "Vitamin E is potent and is the most readily available naturally occurring, lipid-soluble antioxidant carried in LDL...Plasma vitamin E levels were significantly lower in patients with active variant angina...suggesting an association between vitamin E deficiency and coronary artery spasm." Miwa, K., Miyagi, Y., Igawa, A., Nakagawa, K., and Inoue, H., "Vitamin E Deficiency in Variant Angina", Circulation 94:14-18 (1996)

Taking supplemental vitamin E reduces the rate of heart attacks: 2002 patients with atherosclerosis were given 800 or 400 IU daily. Vitamin E treatment significantly reduced the risk of the primary trial endpoint of cardiovascular death and non-fatal myocardial infarction (MI). "We conclude that in patients with ...atherosclerosis, vitamin E treatment substantially reduces the rate of non-fatal MI, with beneficial effects apparent after 1 year of treatment. Stephens, N. G., Parsons, A., Schofield, P.M., Kelly, F. Cheeseman, K., Mitchinson, M.J., and Brown, M.J., "Randomised Controlled Trial of Vitamin E in Patients with Coronary Disease: Cambridge Heart Antioxidant Study (CHAOS)", Preventive Medicine 347:781-5 (1996)

Vitamin E is effective in reducing the progression of Alzheimer's disease: This article is based on a study of 341 moderate Alzheimer's patients who were treated for two years with 2000 IU vitamin E per day. "In patients with moderately severe impairment from Alzheimer's disease, treatment with ...alpha-tocopherol slows the progression of disease." Sano, M. et al, "A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's Disease", New Eng. J. Med. 336: 1216-1222 (1997)

Vitamin E boosts the immune system to prevent infections: "Vitamin E status was negatively related to the number of past infections: [elderly] subjects with a high alpha-tocopherol plasma concentration had fewer infections during the last 3 years than those with a medium or a low concentration." Chavance, M. et al, "Vitamin Status, immunity, and infections in an elderly population", Eur J Clin Nutr 43: 827-835 (1989)

There is so much evidence that there are now numerous books by researchers documenting the multitude of studies. A couple of good ones are: 1) Frei, Balz, "Natural Antioxidants in Human Health and Disease", San Diego, Academic Press, 1994. This is my favorite recent compendium of many papers by hundreds of authors on the overwhelming evidence favoring role of vitamins C and E in protecting the nervous system, immune system, vision, circulatory system, etc. from free radicals. 2) Diplock, A. T., Machlin, L.J., Packer, L., and Pryor, W.A., Vitamin E: Biochemistry and Health Implications, New York Academy of Sciences, New York, 1989. This is a symposium on the scientific basis and medical evidence for effectiveness of vitamin E. The book provides the wide range of evidence and likely benefits.

c. How much vitamin E should I take?

Since 1995, three studies have provided a clear scientific basis for a specific dosage of vitamin E. Brown et al were the first to compare different dosages of vitamin E to determine what an optimal level is. "male nonsmokers (n=50).. during 20 wk of supplementation with 70, 140, 560, and 1050 mg of D-alpha-tocopherol/d... 560 was better than 1050 mg/d...in nonsmokers receiving 1050 mg, the susceptibility to peroxidation also increased. Thus, vitamin E may have prooxidant activity in nonsmokers at high and prolonged intakes." Brown, K.M., Morrice, P.C., and Duthie, G.G. "Erythrocyte vitamin E and plasma ascorbate concentrations in relation to erythrocyte peroxidation in smokers and nonsmokers: Dose response to vitamin E supplementation", Am. J. Clin. Nutr. 65: 496-502 (1997)

They determined that a dosage of 560 mg daily was superior to 140 mg, and that at 1050 mg daily vitamin E produced a pro-oxidant effect. There has been some criticism of this study because of the small number of participants and the high dropout rate. But what is especially useful is that these authors compared different dosages of a micronutrient, so that we can get some information about what a useful dosage is. After my study of vitamin C in 1994, others were beginning to seek practical dosages.

Brown's study was followed by one by Meydani et al that compared 60, 200, and 800 mg daily. They demonstrated that the 200 mg dosage was superior in elevating the immune response in elderly participants, and it is especially important to note that there were no adverse effects seen in this study, as has been consistently true for vitamin E. "88 free-living, healthy subjects at least 65 years old... were randomly assigned placebo or 60, 200, or 800 mg/d of vitamin E for 235 days... Subjects consuming 200 mg/d of vitamin E had a 65% increase in [immune cells]... No adverse effects were observed with vitamin E supplementation." Meydani, S.N., et al. "Vitamin E supplementation and in vivo immune response in health elderly subjects", JAMA 277: 1380-86 (1997))

Combining the results of the two studies, the optimal dosage of vitamin E is somewhere in the range of 200 to 560 mg daily. As many long-term clinical studies have been carried out at a dosage of 400 mg daily with no observed side effects, and 400 mg vitamin E tablets are readily available, a dosage of 400 mg daily is prudent based on the current evidence.

A further specification about the type of vitamin E to take is important. A study by Ames et al, demonstrated that it may be important to take vitamin E in the form of mixed tocopherols, as opposed to pure alpha-tocopherol. "Because large doses of dietary alpha-tocopherol displace gamma-tocopherol in plasma and other tissues, the current wisdom of vitamin E supplementation primarily with alpha-tocopherol should be reconsidered." "High doses of alpha-tocopherol can increase tumor formation in animals and displace gamma-tocopherol in plasma and other tissues." Christen, S., Woodall, A.A., Shigenanga, M.K., Southwell-Keely, P.T., Duncan, M.W., and Ames, B. N. "Gamma-tocopherol traps mutagenic electrophiles such as NOx and complements alpha-tocopherol: Physiological Implications", PNAS (USA) 94: 3217-3222 (1997)

Low density lipoprotein is maintained in a reduced state by various antioxidants, including alpha- and gamma-tocopherol. When LDL is oxidized, it is bound by receptors in the circulatory system and begins a cascade leading to the accumulation of plaque in the arteries. In this study, Ames discovered that supplementation with pure alpha-tocopherol, the commonly available form of vitamin E supplements, displaces gamma-tocopherol from LDL particles. They further showed that gamma- tocopherol traps different types of free radicals more effectively than alpha-tocopherol. On this basis any supplement with vitamin E would be better if it contained both the alpha- and gamma- forms of vitamin E. On the label of the supplement, this is usually listed as "mixed tocopherols". Be careful, because "blended" vitamin E is different, usually made from a mixture of "natural" pure alpha-tocopherol and synthetic pure alpha-tocopherol, neither of which contains gamma-tocopherol.

An editorial appearing with the report by Brown et al above points to the interactions between vitamins C and E, a synergistic effect that is very important.

"There is increasing evidence to support the heretic idea that ... tocopherols can have a prooxidant function, actually accelerating lipid peroxidation processes...the tocopherol radical can be reduced by ascorbate...this could conceivably explain the decreases in ascorbate with increasing tocopherol concentrations" - Editorial by Cross and Traber. Both vitamin E and C are essential, vitamin E to act in the lipid phase, as in LDL, and vitamin C to act in the aqueous phase to regenerate the vitamin C. A suggestion of the combined benefit is evident in the study of Losonczy et al, which was shown earlier. Note that vitamin C alone showed little benefit for the three outcomes measured. Vitamin E alone was very beneficial - it is indeed nature's master antioxidant. But when people took both vitamins C and E, the improvement was much greater than either alone - true synergy - because vitamin E traps many free radicals but vitamin C can regenerate the vitamin E so it can be recycled effectively. By the way, notice that those who took a multivitamin were worse off than those who took no supplements at all!

d. How conclusive is the evidence?

It has been the standard dogma in nutrition that we should obtain all the nutrients we need from our diet. Dr. Linus Pauling was the first to argue for "megadoses", based on the reasoning that long ago, when we lost the genes necessary to synthesize vitamins ourselves, our diets were substantially different than they are today. In that distant past, we might have been eating 16 oranges daily, which would provide that 1,000 mg of vitamin C per day. But it is simply not feasible to obtain even 200 mg of vitamin E in a normal diet today - a normal diet provides about 40 mg. Recognizing that vitamin E may be so beneficial at dosages of 200 mg or more, even distinguished but conservative journals like the Journal of the American Medical Association are starting to consider that supplements are required for optimal health. In response to the Meydani study above demonstrating that 200 mg of vitamin E daily boosts the immune system by 65% in elderly individuals, the following editorial appeared:

"nutrient supplements may be important for health promotion and prevention of certain chronic diseases. This view goes against the prevailing dogma in nutritional science that a balanced diet is sufficient to achieve all nutritional objectives." Chandra, R. K. "Graying of the immune system: Can nutrient supplements improve immunity in the elderly?", JAMA 277: 1398-99 (1997)

The conclusion is that 400 mg of mixed tocopherols (including alpha- and gamma-tocopherols) daily and 500 mg of vitamin C twice a day provide safe, proven dosages of these essential antioxidants. In combination with the B vitamins discussed elsewhere, taking vitamin C and E supplements is the easiest step we can all take to maintain our long term health!

e. As a final note, it is important always to keep in mind the issue of safety. Here is the latest review on the subject.

"There are several comprehensive reviews of the literature concerning the safety of vitamin E. The conclusions of these reports are that the use of supplements of vitamin E at dosages from 200-2400 IU/d ... administered for periods of up to 4.5 y is safe." Weber, P, et al, "Vitamin E and Human Health: Rationale for Determining Recommended Intake Levels", Nutrition 13: 450-60 (1997)

f. Reports on the mechanisms and benefits of Vitamin E

There are also many reports published about vitamin E. Below is just a sample of the overwhelming evidence with regard to our understanding of the safety, mechanism of action, and efficacy of this important vitamin.

"Vitamin E is potent and is the most readily available naturally occurring, lipid-soluble antioxidant carried in LDL" "Plasma vitamin E levels were significantly lower in patients with active variant angina...suggesting an association between vitamin E deficiency and coronary artery spasm." Miwa, K., Miyagi, Y., Igawa, A., Nakagawa, K., and Inoue, H., "Vitamin E Deficiency in Variant Angina", Circulation 94:14-18 (1996)

341 moderate Alzheimer's patients for two years. 2000 IU vitamin E per day. "In patients with moderately severe impairment from Alzheimer's disease, treatment with ...alpha-tocopherol slows the progression of disease." Sano, M. et al, "A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's Disease", New Eng. J. Med. 336: 1216-1222 (1997)

800 mg E for 30 days with 32 people "short term vitamin E supplementation improves immune responsiveness in healthy elderly individuals" Meydani, S.N., Barklund, M.P., Liu, S., Meydani, M., Miller, R.A., Cannon, J.G., Morrow, F.D., Rocklin, R., and Blumbery, J.B., "Vitamin E Supplementation Enhances Cell-Mediated Immunity In Healthy Elderly Subjects", Am J Clin Nutr 52: 557-63 (1990)

This paper provides evidence that in human plasma, the ratio of alpha- to gamma- tocopherol is about 20:1. Winklhofer-Roob, B. M., Van't Hof, M.A., and Shmerling, D. H., "Reference values for plasma concentrations of vitamin E and A and carotenoids in a Swiss population from infancy to adulthood, adjusted for seasonal influences", Clin. Chem. 43: 146-153 (1997)

"vitamin E may help to relieve the symptoms of premenstrual syndrome... vitamin E significantly reduced the PMS syndrome of anxiety, headache, cravings, and depression." London, R. S., "Newsfront: Vitamin E May Reduce PMS Symptoms", Modern Medicine 51: 15-16 (1986)

"in the present study the cross-cultural differences of Ischemic Heart Disease mortality are primarily attributable to plasma status of vitamin E, which might have protective functions." comparison of 16 European study populations. Gey, K. F., Puska, P., Jordan, P., and Moser, U.K., "Inverse Correlation Between Plasma Vitamin E And Mortality From Ischemic Heart Disease In Cross-Cultural Epidemiology", Am J Clin Nutr 53:326S-34S (1991)

Trial of 36,265 adults in Finland. "Individuals with a low level of vitamin E had about a 1.5-fold risk of cancer compared with those with a higher level" Knekt, P., Aromaa, A. Maatela, J., Aaran, R. Nikkari, T., Hakama, M. Hakulinen, T., Peto, R., and Teppo, L., "Vitamin E and Cancer Prevention", Am J Clin Nutr 53: 283S-6S (1991)

" In a crossover study on the effects of vitamin E on osteoarthritis, vitamin E supplementation was significantly more effective than was placebo in relieving pain. A double-blind study of patients with osteoarthritis also showed that vitamin E was significantly superior to placebo in regard to pain relief and necessity of additional analgesic medications and improvement of mobility." Packer, L. , "Protective Role of Vitamin E in Biological Systems", Am J Clin Nutr 53: 1050S-5S ( 1991)

In a study of 20 patients over 80 and 20 controls, "both Alzheimer's and multi-infarct dementia patients had significantly lower levels of vitamin E... than controls" Zaman, Z., Roche, S., Fielden, P., Frost, P.G., Niriella, D.C., and Cayley, A.C.D., "Plasma concentrations of vitamins A and E and Carotenoids in Alzheimer's Disease", Age and Ageing 21: 91-94 (1992)