On the biological activity of vitamin E

Department of Medicine New York University School of Medicine 550 First Avenue New York, NY 10016

Dear Sir:

The recent review article by Vatassery et al (1) on the use of vitamin E in the aged perpetuates an old and outmoded set of values for the comparative bioavailability of the 2 commonly available forms of vitamin E, RRR--tocopherol (natural vitamin E) and all-rac--tocopherol (synthetic vitamin E).

The original method for determining a quantitative value for vitamin E was a tedious biological system based on the amount of the vitamin that was effective in preventing fetal resorption in rats that were vitamin E deficient. Initially described as international units, quantitative milligram values were established for the 2 forms of the vitamins on the basis of these studies in rats, supported by studies on muscular dystrophy in vitamin E–deficient rats, chicks, and rabbits. The comparative functional analysis from these studies resulted in a value of 1.36 bioavailability of natural versus synthetic. Vatassery briefly acknowledged the publication by Burton et al (2) in which the 2 kinds of vitamin E were fed to humans and the tissue concentrations were obtained at 2 doses in 2 men, 1 given 30 mg daily for 360 d and the other 300 mg daily for 615 d. The data in that report (published in the Journal) conclusively established that all of the tissue concentrations of the natural and synthetic vitamin E (measured by deuterium label) yielded a ratio of 2, and the study additionally established that the brain concentrations of RRR--tocopherol could be increased 2–3-fold in the subject taking the higher dose for the longer period. We do not dispute that the studies in rats give the value of 1.36 but resist the suggestion that it would be "prudent" to continue to use the value obtained in rats or in any other species other than humans. Your readers may want to review an earlier set of letters on this subject that was published after the article by Burton et al (3, 4).

Although an effort was made by the manufacturing companies to simplify the relation between the 2 forms by using international units, this has served only to amplify the differences in effective bioavailability, because 1 mg synthetic vitamin E has only 12.5% as much as true RRR--tocopherol, and the effective value of the other R isomers (RSS, RSR, and RRS) in humans is not known. It is clear that the tocopherol transfer protein in the liver is the major discriminating locus for selecting RRR-tocopherol for secretion into plasma lipoproteins, both newly ingested vitamin E and recycled vitamin E. Many of us who use and study vitamin E in our investigations would like to discard the use of international units and the poorly understood RRR -tocopherol equivalent and accept milligram labeling, with the knowledge that 1 mg natural vitamin E is equal to 2 mg synthetic vitamin E for human use, as originally suggested by Horwitt in 1980 (5).

The authors could have provided additional information about vitamin E metabolism by reviewing articles on the excretion of the vitamin in human urine as the water-soluble glucuronide conjugate of -CEHC [2,5,7,8 tetramethyl-2(ß carboxyl ethyl)-6-hydroxy chroman]. Such articles suggest that the limitation in increasing plasma -tocopherol concentration beyond 3-fold is due to the urinary excretion of this metabolite and that supplements providing >150–200 mg daily may not promote higher tissue concentrations (6).

To buttress the importance of the putative role of -tocopherol in human brain disorders, attention should be drawn to a recent article describing immunohistochemical studies with an antibody to human -tocopherol transfer protein (7). The protein was found in the Purkinje cells of the cerebellum in patients with vitamin E deficiency (abetalipoproteinemia, cholestatic liver disease, and the genetic disorder ataxia with vitamin E deficiency), as well as in the brain of patients with central nervous system disease due to oxidative stress (Alzheimer disease and Down syndrome.) It was not possible to show that the protein was present in the healthy human (aged) brain by these techniques. The function of the -tocopherol transfer protein in the brain is of importance in identifying the role of vitamin E in the brain and the central nervous system.

REFERENCES

1. Vatassery GT, Bauer T, Dysken M. High doses of vitamin E in the treatment of disorders of the central nervous system in the aged. Am J Clin Nutr 1999; 70:793–801.
2. Burton GW, Traber MG, Acuff RV, et al. Human plasma and tissue -tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E. Am J Clin Nutr 1998; 67:669–84.
3. Cohn W. Evaluation of vitamin E potency. Am J Clin Nutr 1999; 69:156–7 (letter).
4. Burton GM, Ingold KU, Traber MG, Kayden HJ. Reply to W Cohn. Am J Clin Nutr 1999; 69:157–8 (letter).
5. Horwitt M. Relative biological value of d--tocopheryl acetate and all-rac-d--tocopheryl acetate in man. Am J Clin Nutr 1980;33: 1856–60.
6. Schultz M, Leist M, Petrizika M, Gassmann B, Brigelius-Flohe R. A novel urinary metabolite of -tocopherol, 2,5,7,8-tetramethyl-2(2' carboxyethyl)-6-hydroxychroman, as an indicator of adequate vitamin E supply? Am J Clin Nutr 1995;62(suppl):1527S–34S.
7. Copp RP, Wisniewski T, Hentati F, Larnout A, Ben Hamida M, Kayden HJ. Localization of -tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders. Brain Res 1999;822:80–7.