Stefan Pilz, PhD, Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Austria.
“The term vitamin E covers eight compounds found in nature, alpha-tocopherol being the most common and biologically most active form. Vitamin E is a powerful antioxidant that can be regenerated by vitamin C after oxidation. Due to its lipophilic nature, vitamin E localizes in lipid compartments, such as cell membranes, where it prevents both the peroxidation of lipids and oxidation of proteins. Incorporation of vitamin E into cell membranes may alter the activity of membrane-associated proteins. This in turn can change certain cellular signal transduction pathways. In addition, the vitamin contributes to healthy blood flow by regulating the opening of blood vessels and preventing cholesterol from building up on blood vessel walls. Moreover, vitamin E plays an important role in maintaining the immune system, especially in the elderly.
Current recommendations on vitamin E requirements vary considerably amongst countries, genders, and age groups. Generally, women, infants, children, and the elderly require a lower daily intake, while requirements for men and for pregnant and lactating women are higher. Of the eight naturally occurring forms of vitamin E, only alpha-tocopherol is maintained in human plasma. The Recommended Dietary Allowance (RDA) is therefore based solely on this form. In 2000, the RDA for adults was set at 15 mg alpha-tocopherol/day in the US (1). In Europe, recommendations for adults range from 4 to 25 mg alpha-toco- pherol equivalents (alpha-TE)/day for men and from 3 to 12 mg alpha-TE/day for women. According to intake surveys, more than 90% of Americans (2) and almost 50% of the adults in Germany (3) did not meet the daily dietary recommendations for vitamin E. Based on the adverse effect of increased tendency to hemorrhage, the Tolerable Upper Intake Level (UL) for adults has been set at 1,000 mg/day alpha-toco- pherol in the US (1).
More recent research suggests that the RDA should be higher. As vitamin E is vital to the prevention of polyunsaturated fatty acid (PUFA) oxidation in cell membranes, it has been calculated that the intake require- ment for alpha-tocopherol for PUFA protection is 12 to 14 mg per day (4). By preserving intracellular and cellular membrane integrity and stability, vitamin E plays an important role in the stability of erythrocytes and conductivity in central and peripheral nerves (5). In Austria, Germany and Switzerland, the reported plasma concentrations for vitamin E to preserve membrane integrity of erythrocytes and neurons and avoid hemolysis, ranges from 12 to 46 μmol/L. The lower part of this range can be questioned, as erythrocyte hemolysis occurs at alpha-tocopherol concentrations of 12 to 16 μmol/L, which is well within this recommen- ded range. The required dietary intake to reach the recommended plasma concentration range is 15 to 30 mg alpha-tocopherol equivalents/day for persons without particular oxidative stress (4). On the other hand, a minimum of 30 μmol/L has been suggested for prevention of cardiovascular diseases (CVD) and cancer in individuals with normal plasma lipid concentrations (6, 7). A daily intake of about 50 IU vitamin E would be required to achieve this desirable protective plasma concentration. Since vitamin E intake correlates very well with plasma concentration, the latter could be used as a stable indicator and therefore form the basis of further recommendations.
Previously published randomized controlled trials (RCTs) on potential health effects of vitamin E supplemen- tation might not be particularly useful in defining RDA, as they not only have many limitations whilst looking at very narrowly defined cohorts, but because they also suffer from using intakes that far exceed the nutri- tional-physiological range (8). Based on epidemiological evidence, RCTs should have been conducted involving participants with vitamin E plasma concentrations in the 20 μmol/L range or even lower. There has, however, been no study with such a design. Moreover, the risk of bias by meta-analysis of RCTs is significant (e. g., publication bias, search bias, selection bias, etc.) (9). In that respect, the value of the epidemiological studies appears to be currently underestimated in setting RDAs. In particular, observational studies might be useful for identifying target plasma concentrations associated with health benefit(s), which then can be trans- lated into respective intakes to achieve these plasma concentrations. It should however be acknowledged that a great need still exists for well-designed RCTs. More studies are required on the vitamin E intake needed to exert an optimal protection of cell membrane constituents that are susceptible to oxidation. This fundamental role of vitamin E should be considered in defining required daily vitamin E intakes. In addition, the desired plasma level of vitamin E will provide an important element to establish such recommendations.”
Based on: Péter S. et al. The Challenge of Setting Appropriate Intake Recommendations for Vitamin E: Considerations on Status and Functionality to Define Nutrient Requirements. Int. J. Vitam. Nutr. Res. 2013; 83(2):129–136.
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3. Troesch B. et al. Dietary surveys indicate vitamin intakes below recommendations are common in representative Western countries. Br. J. Nutr. 2012; 13:1–7.
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7. Knekt P. et al. Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts. Am. J. Clin. Nutr. 2004; 80:1508–1520.
8. Traber M. G. et al. Vitamin E revisited: do new data validate benefits for chronic disease prevention? Curr. Opin. Lipidol. 2008; 19:30–38.