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Vitamin E is a potent antioxidant that hypothetically may play a role in chronic disease prevention. Prospective epidemiological studies have found a supporting role for vitamin E in cardiovascular health. It appears that individuals taking higher vitamin E intakes (men > 60 IU, women >20 IU) are about 1/3 less likely to suffer heart disease than those taking low amounts (men<7.5 IU, women< 3 IU). However, the more rigorously designed clinical control studies have found little protective effect of vitamin E supplementation. Current research does not indicate a protective role for vitamin E in the prevention of cancer. Research on vitamin E and Dementia/Alzheimer’s disease is inconclusive. With respect to daily intake, I recommend consuming 30-100 IU/day.

Vitamin E

The chemical structure of α-tocopherol, the most bioavailable form of vitamin-E³⁴.

Previously, we discussed what antioxidants were and how they function in the body in the article, Understanding Antioxidants, Free Radicals and Oxidative Damage. In addition, we’ve examined the potential ergogenic role of vitamin E in the article Dietary Antioxidants: Vitamin E & Athletic Performance . In this article I’d like to discuss the role of vitamin E and its potential role in chronic disease prevention.

Cardiovascular Disease

A large amount of research has been dedicated towards the possible protective effect of vitamin E on cardiovascular disease (CVD). Esterbauer et al. examined this by adding various amounts of vitamin E and copper (capable of causing oxidative damage) to a sample of LDL cholesterol obtained from human blood¹³. Esterbauer et al. observed an inverse relationship between the rate of oxidative LDL damage provoked by copper and vitamin E concentration. In other words, as more vitamin E was added to the sample, a decreased rate of oxidation was observed in the LDL cholesterol. Encouraging evidence has also been obtained from animal studies with regard to vitamin E and CVD¹⁴¹⁵.

Positive results of vitamin E on CVD have also been shown in large prospective studies. The famous Nurses Health Cohort Study (NHCS), which involved >87,000 women between the ages of 34-59, looked at the development of CVD over the course of 8 years¹⁶. It was found that those taking of those taking >21 IU had a 34% lower risk of developing CVD vs. those taking < ~3 IU. A similar outcome was found in the Health Professionals Follow-up Study (HPFS) where men consuming >60 IU/day were 36% less likely to develop coronary disease vs. those taking < 7.5 IU/day¹⁷.

Despite population studies providing strong evidence of a relationship between these variables, most clinical controlled studies have failed to show vitamin E supplements decreasing the risk of developing CVD. For ~5000 individuals (mean age 64.4 years) with 1 risk factor for CVD, de Gaetano et al found that over a 3.6 year time span, those taking 300 IU/day of vitamin E had the same risk for CVD death as those taking placebo¹⁸. Sesso et al. randomly assigned ~15,000 healthy men (age>50), into groups that received either 300 IU/day of vitamin E or a placebo¹⁹. After 8 years, it was observed that vitamin E had no impact in preventing CVD death, nonfatal strokes or heart attacks vs. those in the control group. A third large scale trial, involving ~ 40,000 healthy women (mean age 45) from the Womens Health Study, it was found that those receiving 600 IU on an every other day routine for 10 years had the same risk for developing CVD vs. those not taking any supplement²⁰. On the other hand, a 24% reduction in CVD death rates was seen in study participants who were receiving the 600 IU supplement.

When examining the evidence regarding CVD and vitamin E, it’s apparent that some sort of relationship does appear to exist for these 2 variables. However, large scale clinical control trials mostly fail to show this type of relationship. This could be for a couple reasons. It’s possible that vitamin E may not have a protective effect on CVD. Rather, the protective effects seen in the NHCS and the HPFS prospective studies may be attributed to another nutritional compound that coincidentally occurs in foods high in vitamin E. One must remember, prospective studies (all epidemiology studies for that matter) show an association between variables; not a casual relationship. Only experimental trials, such as lab based or controlled studies can demonstrate a cause and effect relationship. A second possible explanation is the fact that these studies were mostly done on middle to older aged individuals. Although asymptomatic, most individuals will show some signs of arterial plaque buildup by their late teen and mid-twenties. Therefore, in order to truly assess the potentially protective effect of vitamin E, clinical control studies should be started in this population and followed through there middle years.

Cancer

One of the primary causes of cancer occurs when DNA is damaged and abnormal tissue growth (tumors) occurs, eventually spreading throughout the body. Thus, many researchers have examined a possible preventative relationship between cancer and vitamin E. Despite the theoretical basis for cancer prevention, very few studies have shown a protective effect of vitamin E supplementation. Besides looking at CVD in the Women’s Health Study, researchers also examined whether participants receiving vitamin E had a reduced risk of cancer [20]. After 10 years, the incidence of cancer was the same between both groups. In another controlled clinical study, the HOPE study, >9,000 men and women over the age of 55 were given either 400 IU/day of vitamin E or a placebo²¹. At the 7 year follow-up, there was no difference in new cancer events between either or the groups.

Alzheimer’s disease

A great fear for many individuals as they age is the thought of losing their memory. Although some loss in mental sharpness can be expected, it should not reach the level where it significantly impacts daily living activities²². When normal activities are interrupted due to loss of memory, it is termed as dementia. The disease that people most commonly associated with dementia is Alzheimer’s disease (AD). Although the exact cause of this disease has not yet been determined, some have hypothesized that it’s a multifactorial problem involving both genetics and excessive oxidative damage in the brain²³.

Various prospective studies have looked at the relationship between vitamin E intake and risk of developing AD and mixed results have been shown. One large scale study, conducted by Marianne et al, followed >5000 healthy individuals (age>55 years; mean age 67) over the course of 6 years²⁴. Study results indicated that those who consumed higher amounts of vitamin E (>22.5 IU) from whole food sources were 43% less likely to develop AD vs. those with consuming lower amounts (<7 IU). One limitation of the study is that they were looking at whole food sources. Thus, it’s hard to rule out the possibility of other antioxidants contributing to the results.

In another prospective study, involving healthy individuals >65 years of age (mean age 75), it was found that the likelihood of developing AD was similar between those taking vs. not taking a vitamin E supplement (25). The researchers, Luchsinger et al, hypothesized that discrepancies in their results vs. that of Marianne et al.²⁴, may have been caused by different age populations that were involved in each respective study. With a younger mean age, vitamin E may have a stronger protective effect against development of AD. To date, I’ve only ran across two controlled clinical trials that have looked at vitamin E’s impact on AD. In both studies, the mean age was 73, and those in the experimental group received 2000 IU of supplemental vitamin E for 2 years²⁶ or 3 years²⁷. Both studies failed to show a significant effect of vitamin E on either the prevention of AD or slowing down the progression of it.

As a whole, research on vitamin E and AD is inconclusive. From both a theoretical standpoint as well as research conducted on animals, it appears that vitamin E has a protective effect on developing AD. However, as seen in the previously mentioned studies, its possible that a protective effect may only be seen when taken at specific points in one’s life. This time dependent effect has been seen in animal studies²⁸. As such, more research is needed to better understand this relationship.

Recommended Daily Intake

The current adult RDA for vitamin E is beween 22.4-28.4 IU²⁹. Taken into account the evidence presented in this article, I’d try getting between 30-100 IU/day. Additionally, I’d try to meet these goals by consuming foods (presented below) that have higher vitamin E content. I’d be sure to include a daily multivitamin-mineral that at least minimally meets 100% of the daily value. Remember, vitamin E is a fat soluble vitamin. Therefore it’s better absorbed when ingested with dietary fat.

In general, I do not believe in taking large doses of a single vitamin or mineral unless one happens to be deficient in it. Thus, I believe that one should take supplemental vitamin E as part of a potent, well balanced daily multivitamin-mineral complex. In the human body, no compound acts alone; rather multiple factors are required for a biological reaction to occur. Being a fat soluble vitamin, the risk of toxicity is always present. However, there have been no reported cases of toxicity when obtained from food sources²⁹. One highly controversial study has been published indicating that > 400 IU of vitamin E/day increases the risk of mortality in individuals already suffering chronic disease³⁰. Until more research comes out that refuting this claim, I wouldn’t take any more than 400 IU of Vitamin E from supplemental sources.

Table 1 Food Sources of Vitamin E. Adapted from the USDA³¹³², top food sources of vitamin E (alpha-tocopherol) are:

Whole grains do contain some vitamin E. However, most whole grain products do not contain enough Vitamin E to be classified as a good (+ 10% Daily Value) or high(>+ 20% Daily Value) source. However, wheat germ is a solid source of vitamin E for individuals without wheat allergies/sensitivities. For instance, 2 tbsp of Kretschmer Toasted Wheat Germ contains 4.5 IU of vitamin E which is equivalent to 20% of the Daily Value³³. This can be sprinkled on various cereals, yogurt, etc.

Bottom Line

The research is relatively inconclusive with respect to vitamin E and most chronic disease. Prospective epidemiological studies have shown vitamin E to be protective for various conditions such as heart disease. However, most clinical trials fail to support this notion. Thus, it may be other compounds in food (that coincidentally are also high in vitamin E) are responsible for decreasing the risk for chronic disease development/progression. On the other hand, it may be that vitamin E (in amounts greater than the RDA) does alter the course of various chronic diseases, but only in a synergistic relationship with other dietary compounds. Thus I recommend getting vitamin E from whole food sources as well as a balanced multi-vitamin complex.

References

¹³ Esterbauer H, Dieber-Rotheneder M, Striegl G, et al. Role of vitamin E in preventing the oxidation of low-density lipoprotein. Am J Clin Nutr. 1991;53(Suppl):314S–321S.

¹⁴ Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary heart disease in women. N Engl J Med. 1993;328:1444–1449.

¹⁵ Ferre N, Camps J, Paul A, et al. Effects of high-fat, low cholesterol diets on hepatic lipid peroxidation and antioxidants in apolipoprotein E-deficient mice. Mol Cell Biochem. 2001;218:165–169.

¹⁶ Thomas S, Leichtweis S, Pettersson K, et al. Dietary cosupplementation with vitamin E and coenzyme Q(10) inhibits atherosclerosis in apolipoprotein E gene knockout mice. Arterioscler Thromb Vasc Biol. 2001;21:585–593.

¹⁷ Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993;328:1450–1456.

¹⁸ de Gaetano G; Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the PrimaryPrevention Project. Lancet. 2001;357:89–95.

¹⁹ Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA 2008;300:2123-33.

²⁰ Lee I-M, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA 2005;294:56-65.

²¹ Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR; HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005 Mar 16;293(11):1338-47.

²² Kelley RE, Minagar A. Memory complaints and dementia. Med Clin North Am. 2009 Mar;93(2):389-406, ix.

²³ Praticò D. Evidence of oxidative stress in Alzheimer’s disease brain and antio8xidant therapy: lights and shadows. Ann N Y Acad Sci. 2008 Dec;1147:70-8.

²⁴ Marianne J. Engelhart; Mirjam I. Geerlings; Annemieke Ruitenberg; et al. Dietary Intake of Antioxidants and Risk of Alzheimer Disease. JAMA. 2002;287(24):3223-3229.

²⁵ Luchsinger JA, Tang MX, Shea S, Mayeux R. Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol. 2003 Feb;60(2):203-8.

²⁶ Sano M, Ernesto C, Klauber MR, Schafer K, Woodbury P, Thomas R, et al. and members of the Alzheimer’s Disease Cooperative Study. Rationale and design of a multicenter study of selegiline and a-Tocopherol in the treatment of Alzheimer’s disease using novel clinical outcomes. Alzheimer Disease and Associated Disorders 1996;10(3): 132–40.

²⁷ Petersen RC, Thomas RG,GrundmanM, Bennett D,Doody R, Ferris S, et al. for the Alzheimer’s Disease Cooperative Study Group.Vitamin E and Donepezil for the treatment of mild cognitive impairment. The New England Journal of Medicine 2005;352(23):2379–2388.

²⁸ Sung S, Yao Y, Uryu K, Yang H, Lee VM, Trojanowski JQ, Praticò D. Early vitamin E supplementation in young but not aged mice reduces Abeta levels and amyloid deposition in a transgenic model of Alzheimer’s disease. FASEB J. 2004 Feb;18(2):323-5.

²⁹ Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000.

³⁰ U.S. Department of Agriculture, Agricultural Research Service. USDA National Nutrient database for Standard Reference, Release 16-1, 2004. http://www.ars.usda.gov/ba/bhnrc/ndl.

³¹ 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 2005;142:37-46.

³² U.S. Department of Agriculture, Agricultural Research Service. USDA National Nutrient database for Standard Reference, Release 22, 2009. http://www.nal.usda.gov/fnic/foodcomp/search/.

³³ Kretschmer Wheat Germ.Quaker Oats. Accessed on Dec 26, 2009 from:http://www.quakeroats.com/products/more-products-from-quaker/content/cereals/kretschmer-toasted-wheat-germ.aspx#NutritionalInfo.

³⁴ Accessed June 13, 2010 from: http://en.wikipedia.org/wiki/Vitamin_e