Is an excessive intake of vitamin E harmful?

“Vitamin E performs many critical roles in optimum health. As an antioxidant it protects polyunsaturated fatty acids from oxidation, may help protect other essential lipids (probably derived from highly polyunsaturated fatty acids such as docosahexaenoic acid), and has been studied for possible value in many degenerative diseases. Vitamin E does not have a known role as a cofactor or as an essential component of any enzymatic system. Alpha-tocopherol is the only vitamin E form of eight different forms synthesized by plants which is recognized by the US Food and Nutrition Board to meet human requirements (1). Higher than normal intake levels may be needed for some people who have certain health problems, and those who smoke which has also been shown to deplete vitamin E levels. The fat-soluble vitamin does not accumulate to toxic levels in the liver or other tissues. Thus, it was quite surprising that meta-analyses reported that consumption of vitamin E supplements (400 IU or more) by humans were associated with increased risk of dying (2, 3); although the accuracy of these statistical analyses do remain in dispute (4, 5). Indeed, when toxicologists searched for evidence of adverse effects of excess alpha-tocopherol, the only consistent finding was the observation that vitamin E caused increased bleeding tendencies, likely as a result of interference with vitamin K status (1). But no research has found this poses a health risk. Since two systems in the liver work to control the level of vitamin E in the body and routinely excrete excessive amounts, it is almost impos-sible to take a potentially harmful amount.

The liver plays a major role in vitamin E metabolism, which is one of the key mechanisms for limiting its accumulation and for the alpha-tocopherol preference compared to the other forms. Vitamin E, as supplied in the diet is in rela-tively low concentrations, especially compared with amounts in supplements, and dietary vitamin E from plants is usually present as multiple vitamin E forms. The vitamin E forms are absorbed from the intestinal lumen (in micelles), packaged into chylomicrons and then transported throughout the body via the circulatory system. Once in the liver alpha-tocopherol is preferably packaged into Very Low Density Lipoproteins (VLDL) and excreted back into the circulatory system, while mainly non-alpha-tocopherols are metabolized by cytochrome P450 oxidation systems in liver microsomes and are excreted (6). As the VLDL are broken down by lipoprotein lipase, Low Density Lipoproteins (LDL) are formed and from these lipoproteins alpha-tocopherol is transferred to High Density Lipoproteins (HDL) and eventually incorporated into either circulating lipoproteins or taken up by peripheral tissue.

With increasing doses of vitamin E taken the absorption rate is decreasing. Importantly, with high vitamin E adminis-tration (e.g. 400 IU from supplements), the liver secretion of alpha-tocopherol becomes limiting and elimination/ excretion rates go up: plasma concentrations do not increase more than 2-4 fold (7). Very high intakes achieved with supplementation only succeed in doubling the tissue levels of vitamin E, which is not harmful. I believe that past studies which have alleged adverse consequences from vitamin E have misinterpreted the data. Thus, taking too much vitamin E is not the real concern. A much more important issue is that more than 90 percent of people in the U.S. have inadequate levels of vitamin E in their diet (8). For those, consuming a healthy and balanced diet can be recommended and if necessary taking a daily multivitamin that has the full recommended dose of vitamin E.”

Based on: Traber M. G. Mechanisms for the prevention of vitamin E excess. Journal of Lipid Research. Published online April 2013.

1. Food and Nutrition Board, and Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids National Academy Press, Washington. 2000.
2. Bjelakovic G. et al. Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis. JAMA. 2007; 297:842-857.
3. Miller E. R. et al. Meta-analysis: high-dosage vitamin E supplementation may increase allcause mortality. Ann Intern Med.2005; 142:37-46.
4. Abner E. L. et al. Vitamin E and all-cause mortality: a meta-analysis. Current aging science. 2011; 4:158-170.
5. Berry D. et al. Bayesian model averaging in metaanalysis: vitamin E supplementation and mortality. Clin Trials. 2009; 6:28-41.
6. Traber, M.G. Vitamin E. In: Modern Nutrition in Health and Disease. Ninth Edition. Edited by Maurice Shils, James Olson, Moshe Shike, and A. Catharine Ross. Baltimore: Williams & Wilkins, 1999 p. 347-362.
7. Fuller C. J. et al. RRR-alphatocopheryl acetate supplementation at pharmacologic doses decreases low-densitylipoprotein oxidative susceptibility but not protein glycation in patients with diabetes mellitus. Am J Clin Nutr. 1996; 63:753-759.
8. Fulgoni V. L. et al. Foods, Fortificants, and Supplements: Where Do Americans Get Their Nutrients? The Journal of Nutrition. 2011.