HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Traber, M. G Search for Related Content PubMed Articles by Traber, M. G Agricola Articles by Traber, M. G

Reply to JG Bieri

Linus Pauling Institute 571 Weniger Hall Oregon State University Corvallis, OR 97331-6512 E-mail: maret.traber{at}orst.edu

Dear Sir:

This comment is in response to the letter from Bieri, a well-recognized leader in the vitamin E field and a member of the committee that set the 1989 recommended dietary allowances (RDAs; 1). The new dietary reference intakes (DRIs) take into account not only deficiency symptoms but also the amounts of vitamins and minerals that provide an optimum benefit across the life span. The "health benefit of vitamin E for humans" is the basis for the 2000 DRI for vitamin E (2). The in vitro peroxide-dependent erythrocyte hemolysis test was chosen as a marker of vitamin E status because vitamin E–deficient children with neurologic abnormalities were shown to have erythrocytes that are sensitive to peroxide-induced hemolysis in vitro and a faster in vivo erythrocyte turnover (3). All of these responses, including the neurologic abnormalities, were reversed or ameliorated by supplements containing -tocopherol (2). The erythrocyte hemolysis test was also used in the studies carried out by Horwitt et al (4) to evaluate vitamin E status in humans who had consumed vitamin E–deficient diets for >5 y and were then given vitamin E supplements containing either RRR- or all-rac--tocopherol. These data were used to set both the 1968 RDA (30 IU vitamin E) and the 2000 DRI (15 mg 2R--tocopherol, or 22 IU RRR--tocopherol, or 33 IU all-rac--tocopherol). The 2000 DRI takes into account that all-rac--tocopherol has one-half, not two-thirds, the activity of RRR--tocopherol.

Admittedly, the erythrocyte hemolysis test is flawed in that it is critically dependent on assay conditions. However, the 1989 RDA for vitamin E was based on the observation that humans do not readily show symptoms of vitamin E deficiency; therefore, the usual amount of dietary vitamin E must be adequate. Currently, this level of evidence is insufficient to set an RDA; dietary intakes could be used to set an AI (average intake).

-Tocopherol was included in the forms of vitamin E that met the 1989 RDA because of its abundance in the American diet. The justification for its biological activity is that high amounts fed to vitamin E–deficient pregnant rats prevent fetal resorption (5). Unfortunately, these tests were carried out >20 y ago, when the methods used to detect contaminating -tocopherol were not as sensitive as today's techniques. Therefore, the extent to which -tocopherol contaminated the -tocopherol used in the diets is unknown. This is especially important in light of the discovery that the -tocopherol transfer protein (-TTP) is critically important in the rodent uterus during pregnancy (6). Hepatic -TTP maintains plasma -tocopherol by facilitating its export from the liver to the periphery via the plasma lipoproteins; -TTP binds -tocopherol but has little affinity for -tocopherol (7). Humans with a defect in the -TTP gene become deficient in vitamin E (8), as do -TTP knockout mice (6,9). Importantly, administration of -tocopherol reverses human vitamin E deficiency symptoms, proving that humans require -tocopherol.

Most of the postulated health benefits of -tocopherol are based on in vitro studies testing whether -tocopherol nitration might protect against peroxynitrite injury. Ohrvall et al (10), however, reported that circulating -tocopherol but not -tocopherol concentrations were low in patients with coronary heart disease (CHD), suggesting that -tocopherol might be protective. Lemcke-Norojarvi et al (11) showed in Swedish women that changing from the usual Swedish diet (low in -tocopherol) to one containing corn oil (high in -tocopherol) raised -tocopherol by 64% but had no effect on serum -tocopherol. Furthermore, Ohrvall et al (12) showed in a double-blind crossover trial that a diet containing unsaturated fat (rapeseed oil) increased circulating -tocopherol by 7% and -tocopherol by 23%, whereas a diet containing saturated fat decreased -tocopherol by 5% and -tocopherol by 37%. Taken together, these data suggest that if patients with CHD switch to an unsaturated oil, such as corn oil, circulating -tocopherol will increase but -tocopherol will be unchanged. Perhaps, more importantly, the change from saturated to unsaturated fat will lower serum cholesterol and thereby CHD risk. Thus, serum -tocopherol may be a marker of a vegetable oil–containing diet that is lower in saturated fat and higher in unsaturated fat. These dietary changes lead to lower circulating cholesterol that will lower CHD risk. Thus, -tocopherol itself does not necessarily decrease CHD risk. With respect to the 2000 DRI, -tocopherol may have health benefits, but as of yet, these have not been shown in humans; therefore, only -tocopherol meets the human vitamin E requirement.

REFERENCES

1. National Research Council. Recommended dietary allowances. 10th ed. Washington, DC: National Academy Press, 1989.
2. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academy Press, 2000.
3. Farrell PM, Bieri JG, Fratantoni JF, Wood RE, di Sant'Agnese PA. The occurrence and effects of human vitamin E deficiency. A study in patients with cystic fibrosis. J Clin Invest 1977;60:233–41.
4. Horwitt MK, Harvey CC, Duncan GD, Wilson WC. Effects of limited tocopherol intake in man with relationships to erythrocyte hemolysis and lipid oxidations. Am J Clin Nutr 1956;4:408–19.
5. Machlin LJ, ed. Vitamin E, a comprehensive treatise. New York: Marcel Dekker, 1980.
6. Jishage K, Arita M, Igarashi K, et al. Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice. J Biol Chem 2001;273:1669–72.
7. Hosomi A, Arita M, Sato Y, et al. Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. FEBS Lett 1997;409:105–8.
8. Cavalier L, Ouahchi K, Kayden HJ, et al. Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families. Am J Hum Genet 1998;62:301–10.
9. Terasawa Y, Ladha Z, Leonard SW, et al. Increased atherosclerosis in hyperlipidemic mice deficient in alpha-tocopherol transfer protein and vitamin E. Proc Natl Acad Sci U S A 2000;97:13830–4.
10. Ohrvall M, Sundlof G, Vessby B. Gamma, but not alpha, tocopherol levels in serum are reduced in coronary heart disease patients. J Intern Med 1996;239:111–7.
11. Lemcke-Norojarvi M, Kamal-Eldin A, Appelqvist LA, Dimberg LH, Ohrvall M, Vessby B. Corn and sesame oils increase serum gamma-tocopherol concentrations in healthy Swedish women. J Nutr 2001;131:1195–201.
12. Ohrvall M, Gustafsson IB, Vessby B. The alpha and gamma tocopherol levels in serum are influenced by the dietary fat quality. J Hum Nutr Diet 2001;14:63–8.

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Traber, M. G Search for Related Content PubMed Articles by Traber, M. G Agricola Articles by Traber, M. G