Wednesday, September 9, 2009

Vitamin E


Vitamin E is actually a family of related compounds known as tocopherols and tocotrienols. Although alpha-tocopherol is the most common form found in dietary supplements, vitamin E also exists in foods with slightly different chemical structures, such as beta-, gamma- and delta-tocopherol as well as alpha-, beta-, gamma- and delta-tocotrienols. Vitamin E was discovered in the early 1930’s when rats fed a diet free of vegetable oils (the primary dietary source of vitamin E) developed reproductive problems. Although vitamin E doesn’t have exactly the same reproductive effects in humans, vitamin E is commonly thought of as a “virility” vitamin for men.

Vitamin E can be obtained as a supplement in natural or synthetic form. In most cases, the natural and synthetic form of vitamins and minerals are identical, but in the case of vitamin E, the natural form is clearly superior in terms of absorption and retention in the body. The natural form of alpha-tocopherol is known as “d-alpha tocopherol,” whereas the synthetic form is called “dl-alpha tocopherol.” The synthetic “dl-“ form is the most common form found in dietary supplements, although many manufacturers are switching over to the more potent (and expensive) natural “d-“ form because consumers are learning to look for it.

Dietary sources of vitamin E include vegetable oils, margarine, nuts, seeds, avocados and wheat germ. Safflower oil contains a good amount of vitamin E but there is very little vitamin E in either corn oil or soybean oil. For those individuals watching their dietary fat consumption, vitamin E intake is likely to be low, due to a reduced intake of foods with high fat content. As a point of reference, 60 almonds are needed to supply the recommended amount of vitamin E and about 400-800 almonds would be needed to provide the amount of vitamin E, 200-400 IU, associated with heart health benefits in most studies.

Dietary supplements containing vitamin E are generally promoted as antioxidants and specifically to reduce the risk of cardiovascular disease and cancer. Vitamin E has also been shown to play a role in immune function, in DNA repair, and other metabolic processes.


Natural (“d-“) alpha-tocopherol is clearly more bioavailable and preferentially retained by the body compared to the more common synthetic ("dl-") form of vitamin E. Unfortunately, although the natural form is 2-3 times more potent than the synthetic form, it is also about twice the price. It may be preferable to choose products that offer a balanced source of “mixed tocopherols,” including the natural forms of all eight of the vitamin E isomers (d-alpha, d-beta, d-gamma, and d-delta forms of both the tocopherols and tocotrienols).

A recent meta-analysis (Miller et al. 2005) that generated a great deal of media attention, combined the results of 19 clinical trials of vitamin E supplementation for various diseases, including heart disease, end-stage renal failure and Alzheimer's disease, and reported that adults who took supplements of 400 IU/day or more were 6% more likely to die from any cause than those who did not take vitamin E supplements. However, further breakdown of the risk by vitamin E dose and adjustment for other vitamin and mineral supplements revealed that the increased risk of death was statistically significant only at a dose of 2,000 IU/day, which is higher than the Tolerable Upper Limit for adults (1,500IU/day). This study is at odds with at least three other meta-analytical studies that combined the results of randomized controlled trials designed to evaluate the efficacy of vitamin E supplementation for the prevention or treatment of cardiovascular disease and found no evidence that vitamin E supplementation up to 800 IU/day significantly increased or decreased cardiovascular disease mortality or all-cause mortality. At present, there is no convincing evidence that vitamin E supplementation up to 800 IU/day increases the risk of death from cardiovascular disease or other causes.

Some of the reasons for the Miller et al. (2005) meta-analysis to come to the conclusions that it did include the fact that the research reviewed was conducted with older subjects who had chronic illnesses and might not apply to younger, healthy people and that there are various types and compounds of vitamin E, including synthetic and natural forms, which research shows to have varying effects (and are not addressed in this analysis or most of the studies included in the analysis). Overall, it is important to understand that the Miller et al study, like all studies of nutrition and dietary supplements, needs to be placed in context – that being that vitamin E has been studied for many years and in hundreds of clinical trials with solid evidence showing the benefits of vitamin E (400 to 800 IU of natural vitamin E) in the reduction of heart attacks.

Scientific Support

Of the different isomers of vitamin E, the alpha-tocopherol form is typically considered the “gold standard” in terms of antioxidant activity – although the most recent in vitro research suggests that the other chemical forms may possess equivalent or superior antioxidant protection (Moyad et al. 1999). Vitamin E deficiencies are related to a wide variety of health problems, including cataracts, heart disease, lung problems and liver damage.

Several studies published over the last several years have clearly shown that natural vitamin E, the "d-" form, is about 2-3 times more bioavailable than synthetic "dl-" vitamin E (Morris and Carlson 2003). The natural form of the vitamin is extracted from vegetable oils, mostly from soybeans, which are cheap and plentiful in the USA. Synthetic vitamin E, in contrast, is manufactured from petroleum by-products, resulting in a chemical mixture in which only one eighth of the mixture is the powerful "d-" isomer (the other 7/8’s are weaker vitamin E isomers).

A wide variety of epidemiological and prospective studies have shown health benefits associated with higher than average vitamin E consumption (Miller et al. 1997, Miller et al. 2004, Morris and Carlson 2003). In most cases, the level of vitamin E intake required for heart, lung, eye and cancer protection are 10-30 times higher than the current RDA levels. Although high dose alpha-tocopherol supplements are clearly a powerful antioxidant measure, concern has recently been raised because such supplements may displace body stores of the other naturally occurring vitamin E forms.

There is a strong inverse relationship between plasma vitamin E levels (which almost exclusively measure only alpha-tocopherol) and the incidence of coronary heart disease (Muntwyler et al. 2002, Shekelle et al. 2004, Stone 2000). However, several supplementation studies have failed to demonstrate a protective effect when alpha-tocopherol alone has been supplemented. In two large studies published in the New England Journal of Medicine (Kushi et al. 1996, Yusuf et al. 2000), vitamin E appeared to offer greater protection when obtained from the diet (which is primarily gamma-tocopherol) and not as dramatically when taken in supplements (which are primarily alpha-tocopherol). The strongest correlation was shown with the consumption of margarine, nuts and seeds – all of which are excellent sources of gamma-tocopherol. In addition, serum levels of gamma-tocopherol (but not alpha-) are reduced in heart disease patients and rise rapidly when chronic smokers quit. Because alpha-tocopherol supplementation reduces tissue levels of the gamma- form, a mixed tocopherol that better reflects the ratios found in our diet may be more useful as a supplement than the formulations of vitamin E currently available.

In other studies, heart disease patients have been shown to have normal serum alpha-tocopherol levels, but much lower gamma-tocopherol levels compared to a group of healthy control subjects. In one of the largest epidemiological studies (21,809 women), vitamin E consumption was inversely associated with the risk of death from coronary heart disease, but this link was strongest in the women who did not consume vitamin E supplements – but who got their vitamin E from foods (Eidelman et al. 2004).

Overall, it appears that at least some studies indicate that a balanced intake of each of the naturally occurring forms of vitamin E may be the most prudent approach in terms of overall health benefits. For example, high dose alpha-tocopherol supplements can reduce body stores of gamma-tocopherol, whereas a 50/50 intake of each maintains elevated tissues stores of both (Moyad et al. 1999). Such findings are potentially important, given that gamma-tocopherol is the major form of vitamin E in the U.S. diet and has been found to inhibit lipid peroxidation (cell membrane damage) more effectively than alpha-tocopherol (Moyad et al. 1999). This may mean that the different vitamin E forms may complement each other in the body.

Safety / Dosage

Side effects associated with vitamin E supplements are exceedingly rare. Unlike other fat-soluble vitamins, such as A, D and K, vitamin E is relatively non-toxic, even at doses many times the current daily value (DV) of 30 IU (international units). A caution is advised, however, in those individuals at risk for prolonged bleeding, such as those taking anticoagulant medications, because vitamin E supplements can decrease blood clotting ability (reduced platelet aggregation) and prolong bleeding time. The Daily Value for vitamin E is 30IU, but most research studies show that optimal intakes associated with health benefits are in the range of 100-800 IU – an amount that is unrealistic to be obtained from foods. The Institute of Medicine has set an upper tolerable intake level for vitamin E at 1,000 mg (1,500 IU) for any form of supplementary alpha-tocopherol per day because the nutrient can act as an anticoagulant and may increase the risk of bleeding problems. Upper tolerable intake levels “represent the maximum intake of a nutrient that is likely to pose no risk of adverse health effects in almost all healthy individuals in the general population.”


1.Eidelman RS, Hollar D, Hebert PR, Lamas GA, Hennekens CH. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med. 2004 Jul 26;164(14):1552-6.

2.Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med. 1996 May 2;334(18):1156-62.

3.Miller ER 3rd, Appel LJ, Levander OA, Levine DM. The effect of antioxidant vitamin supplementation on traditional cardiovascular risk factors. J Cardiovasc Risk. 1997 Feb;4(1):19-24.

4.Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality. Ann Intern Med. 2004 Nov 10; [Epub ahead of print].

5.Miller JW. Vitamin E and memory: is it vascular protection? Nutr Rev. 2000 Apr;58(4):109-11.

6.Morris CD, Carson S. Routine vitamin supplementation to prevent cardiovascular disease: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003 Jul 1;139(1):56-70.

7.Morris MC, Beckett LA, Scherr PA, Hebert LE, Bennett DA, Field TS, Evans DA. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord. 1998 Sep;12(3):121-6.

8.Moyad MA, Brumfield SK, Pienta KJ. Vitamin E, alpha- and gamma-tocopherol, and prostate cancer. Semin Urol Oncol. 1999 May;17(2):85-90.

9.Muntwyler J, Hennekens CH, Manson JE, Buring JE, Gaziano JM. Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality. Arch Intern Med. 2002 Jul 8;162(13):1472-6.

10.Pietinen P, Ascherio A, Korhonen P, Hartman AM, Willett WC, Albanes D, Virtamo J. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol. 1997 May 15;145(10):876-87.

11.Shekelle PG, Morton SC, Jungvig LK, Udani J, Spar M, Tu W, J Suttorp M, Coulter I, Newberry SJ, Hardy M. Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. J Gen Intern Med. 2004 Apr;19(4):380-9.

12.Stone NJ. The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione Trial on fish oil and vitamin E supplementation in myocardial infarction survivors. Curr Cardiol Rep. 2000 Sep;2(5):445-51.

13.Swain RA, Kaplan-Machlis B. Therapeutic uses of vitamin E in prevention of atherosclerosis. Altern Med Rev. 1999 Dec;4(6):414-23.

14.Virtamo J, Rapola JM, Ripatti S, Heinonen OP, Taylor PR, Albanes D, Huttunen JK. Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease. Arch Intern Med. 1998 Mar 23;158(6):668-75.

15.Willett WC, Stampfer MJ, Underwood BA, Taylor JO, Hennekens CH. Vitamins A, E, and carotene: effects of supplementation on their plasma levels. Am J Clin Nutr. 1983 Oct;38(4):559-66.

16.Woodall AA, Britton G, Jackson MJ. Dietary supplementation with carotenoids: effects on alpha-tocopherol levels and susceptibility of tissues to oxidative stress. Br J Nutr. 1996 Aug;76(2):307-17.

17.Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000 Jan 20;342(3):154-60.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

No comments: