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Letters to the Editor |
-tocopheryl and all-rac--tocopheryl acetate
Division of Geriatric Medicine Department of Internal Medicine St Louis University School of Medicine St Louis, MO 63104
Dear Sir:
The paper by Burton et al (1), a collaborative study from 4 institutions, dealt with the relative biological values of RRR-
-tocopheryl acetate and all-rac--tocopheryl acetate, the 2 forms marketed in terms designated by the US Pharmacopoeia (2) as d--tocopheryl acetate and dl--tocopheryl acetate, respectively. On the basis of an assay in pregnant rats, 1 mg of the natural form RRR--tocopheryl acetate is officially considered to have 1.36 times the activity of 1 mg of the synthetic product all-rac--tocopheryl acetate. The excellent studies by Burton et al made use of deuterium labeling to show that when RRR- and all-rac--tocopheryl acetate were fed, amounts of RRR--tocopherol in the tissues of human subjects were much higher than amounts of all-rac--tocopherol. Burton et al concluded that the present official ratio of the biological activity of RRR--tocopheryl acetate to all-rac--tocopheryl acetate of 1.36:1 is erroneous. The last sentence of their report reads, "It seems highly improbable that the official biopotency ratio is relevant to human needs, which might be better served by thinking in terms of a 2:1 ratio, as was first suggested 
18 y ago in this Journal" (3).
The relative biopotency of RRR- and all-rac--tocopheryl acetate has been controversial for many years. Very little vitamin E is required by adults (<8 mg/d) to prevent nutritional deficiency, and nutritional deficiency is rare. As an antioxidant, however, much more tocopherol is recommended to inhibit undesirable free radical reactions in the tissues. The current conflict regarding the relative potency of tocopherol compounds has produced strong disagreement that makes an interesting story, which I will try to summarize.
The original protocol of the fourth Elgin Project (4) sponsored by the Food and Nutrition Board of the National Research Council [the first 3 projects (5) dealt with thiamine, riboflavin, and niacin-tryptophan] was designed to determine whether vitamin E was required by humans. No consideration was given in the original protocol to use all-rac--tocopheryl acetate because almost pure RRR--tocopheryl acetate was already available. After some of the subjects had been consuming a controlled diet that contained 4 mg total tocopherols/d for 54 mo, the sponsoring committee approved supplementation of the remaining subjects. Two members of the committee insisted, against my preference, that the effects of all-rac--tocopheryl acetate as well as RRR--tocopheryl acetate be included in the study. Unexpectedly, the data obtained during 138 d of supplementation (6) showed that 15 mg RRR--tocopheryl acetate/d resulted in higher plasma concentrations than did 20 mg all-rac--tocopheryl acetate and that 50 mg RRR--tocopheryl acetate/d had much greater biological potency than 80 mg all-rac--tocopheryl acetate. To avoid controversy, I presented no analysis of these data in my summarizing presentation at a symposium on the role of vitamins in October 1959 (6). About 20 y later, when consumer use of vitamin E had grown considerably, I decided to report the data obtained after supplementation in greater detail (3).
To evaluate the conflicting evidence, a committee was organized by FT Perkins, who was then Chief of Biologicals at the World Health Organization. We met in Geneva in April 1981. In this meeting, the animal assays were given preference over data obtained in humans and no agreement was reached. Convinced that the human data were different from the data derived from experiments in pregnant rats, Coy Fitch, I, and others conducted a definitive experiment in 1983 on 20 healthy men and women (7). The design of the experiment was such that each of 5 different vitamin E compounds in gelatin capsules was tested sequentially in each of the subjects. Briefly, the subjects ingested 800 IU of a tocopherol compound plus 100 mL whole milk and serum tocopherol concentrations were measured at 0, 8, 24, and 48 h. The total lipid content of each serum sample was also measured because lipid concentrations strongly affect tocopherol concentrations in the blood (8). The protocol was blinded as much as possible. An experienced technician performed the analyses in a different department. Tocopherol concentrations in the 24-h serum samples increased twice as much after ingestion of RRR--tocopheryl acetate than after ingestion of all-rac--tocopheryl acetate. The largest difference between the 2 compounds was found in samples obtained 8 h after ingestion. Incidentally, RRR--tocopherol was absorbed faster than the acetates and higher concentrations were sustained in the serum, confirming previous studies in the literature.
The findings of Burton et al (1) should end the debate about the biological potency of the 2 vitamin E compounds most commonly purchased. Now in my 90th y, I doubt whether I will ever see the proper correction made in the official values of the tocopherols. Having introduced the term equivalent as used by committees of dietary allowance (9), I prefer that this designation be used to describe the potency of the tocopherols. In the recommended dietary allowances (10), l mg RRR--tocopherol has a biological value of 1.0 -tocopherol equivalents. Accordingly, in modified US Pharmacopoeia vitamin E units, RRR--tocopherol should have a value of 1.0, all-rac--tocopherol a value of 0.5, RRR--tocopheryl acetate a value of 0.91, and all-rac--tocopheryl acetate a value of 0.455.
REFERENCES
-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E. Am J Clin Nutr 1998;67:669–84.[Abstract]
-tocopheryl acetate and all-rac--tocopheryl acetate in man. Am J Clin Nutr 1980;33:1856–60.-tocopherol after ingestion of various vitamin E preparations. Am J Clin Nutr 1984;40:240–5.This article has been cited by other articles:
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  M. K Horwitt Critique of the requirement for vitamin E Am. J. Clinical Nutrition, June 1, 2001; 73(6): 1003 - 1005. [Abstract] [Full Text] [PDF]
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