Critique of the requirement for vitamin E.

The Food and Nutrition Board of the Institute of Medicine recently published a comprehensive evaluation of antioxidants in human diets that includes dietary reference intakes for vitamin E. The new dietary reference intake is 15 mg (35 mol)/d for adults, which is 50% greater than the generous allowance in the 10th edition of Recommended Dietary Allowances published in 1989. Much of the data interpreted in these publications came from studies sponsored by the Committee of Nutritional Studies at Elgin State Hospital (Elgin, IL) of an earlier Food and Nutrition BOARD: The 50% increase in the recommended dietary allowances for vitamin E is not supported by any new data. It is possible that the publication of the Institute of Medicine did not take into consideration the effects of the oxidized lipids in the diets used to promote the development of vitamin E deficiency. If lipids, oxidized to remove tocopherols, had not been a part of the experimental diets, the minimum requirement for vitamin E would have been too small for possible evaluation. Studies on the different effects of saturated and oxidized lipids in the production of encephalomalacia in chicks and muscular dystrophy in rats are reviewed. The tolerable upper intake level of vitamin E supplementation is reported to be 1000 mg/d. It is possible that the universal consumption of aspirin may not have been taken into consideration when this level was determined. Vitamin E plus aspirin may increase the tendency to hemorrhage, which makes a lower upper intake level worth consideration.

Interpretations of requirements for thiamin, riboflavin, niacin-tryptophan, and vitamin E plus comments on balance studies and vitamin B-6.

Data from the long-term projects sponsored by the Food and Nutrition Board to determine the requirements for thiamin, riboflavin, niacin-tryptophan, and vitamin E are utilized to effect an opinion regarding the recommended dietary allowances for these vitamins. Based upon data obtained during these and subsequent research projects, comments on balance studies, changes in tissue lipids, and the requirements for vitamin B-6 are included. The possibility that antioxidants may have an effect on delaying oncogenesis is discussed.

The promotion of vitamin E.

Investigations that have influenced the promotion of vitamin E supplementation are reviewed. The various forms of vitamin E found in foods and the composition of synthetic vitamin E in common use are described with note of a frequent error of identification made in reports of studies on vitamin E. Recent communications on the use of antioxidants to delay carcinogenesis in animals and in humans are discussed. The publicity given the reports of cancer prevention by antioxidants will probably increase self-supplementations. It is therefore necessary to understand the pharmacological limits of such supplementation with vitamin E. Daily supplementation of adults with about 200 mg of d-alpha-tocopherol equivalents per day has not been proven to be harmful, but the effects of ingestion of more than 800 mg a day have not been studied sufficiently. Special precautions should be taken in administering emulsified vitamin E preparations intravenously to premature infants.

Serum concentrations of alpha-tocopherol after ingestion of various vitamin E preparations.

The rat-fetal-resorption test currently is used to assess the biological activity of vitamin E compounds. Previous studies in humans, however, suggest that rat assays underestimate the potency of free tocopherol relative to the acetate ester form and of RRR-alpha-tocopheryl acetate relative to all-rac-alpha-tocopheryl acetate. Therefore, we studied the serum concentrations of alpha-tocopherol after ingestion of RRR-alpha-tocopheryl acetate, all-rac-alpha-tocopheryl acetate, RRR-alpha-tocopherol, RRR-alpha-tocopheryl succinate, and RRR-alpha-tocopheryl acetate plus apple pectin by each of 20 adult human subjects. Measurements were made at 0, 8, 24, and 48 h after ingestion of 800 IU of the various preparations. The results at 24 h were representative of the differences observed. The mean increase in concentration of alpha-tocopherols (mg/g lipid) in 24 h was 71.2% after RRR-alpha-tocopherol, 63.3% after RRR-alpha-tocopherol acetate, and 41.2% after RRR-alpha-tocopherol succinate. Animal assay data do not correlate with data from studies of absorption and retention in serum of alpha-tocopherols ingested by humans.

Relative biological values of d-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate in man.

A reexamination of the biological potency of compounds with vitamin E activities has been made. Special attention has been paid to the relative potencies of d-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate since these two forms provide most of the dietary and clinical supplementations used. Distinctions have been drawn between the vitamin E requirements and metabolism of animals, from which most previous calculations have been made, and the ability of adult males to retain the tocopherols in their blood. Previously published data from analyses of plasma from vitamin E-depleted subjects, who had been quantitatively supplemented for 138 days with different levels of the tocopherols, were analyzed. The evaluations showed that all-rac-alpha-tocopheryl acetate may have no more than half the biological potency of d-alpha-tocopheryl acetate when used as a supplement for vitamin E-depleted adult subjects.

Vitamin E: a reexamination.

An attempt is made to place into proper perspective the relative values of the eight natural forms of vitamin E and the epimers of the synthetic products with regard to their biological activities. Since differences in activities reported are mostly in a function of different rates of biological turnover, feeding a non-alpha-tocopherol compound three times a day would be expected to give a different biological value than if the total were fed once a week or together with alpha-tocopherol. An analysis of data to support an increase in the current RDA for vitamin E is presented. Recent developments on the prolongation of blood clotting time by vitamin E are interpreted from the viewpoint that alpha-tocopherol is oxidized to tocopherylquinone, which is an inhibitor of vitamin K.

Relationship between levels of blood lipids, vitamins C, A, and E, serum copper compounds, and urinary excretions of tryptophan metabolites in women taking oral contraceptive therapy.

To evaluate which women using oral contraceptive agents might be at risk, biochemical indices known to be affected by the estrogens and progestogens were studied in women who take oral contraceptive agents, in women who do not use oral contraceptive agents, in women in third trimester of pregnancy and 6 weeks after parturition, and in men with normal and high blood lipid levels. The most consistent changes due to oral contraceptive agents were in serum levels of copper, triglycerides, and vitamin A and in the urinary excretion of xanthurenic acid and niacin derivatives before and after a tryptophan load test. There was only a slight suggestion, with no statistical significance, that serum vitamin C levels decreased when the serum levels of ceruloplasmin were high. The highest blood pressures and serum triglycerides and vitamin A levels were obtained in those women who ingested the highest level of estrogens. Pregnant women had the lowest levels of serum vitamin A. The oral contraceptive agents users had the lowest average levels of carotenoids corresponding to the highest average levels of vitamin A in the serum. Thus, estrogens not only increase the rate of change of tryptophan to niacin but may also increase the rate of conversion of carotene to vitamin A. Relative reactivity to oral contraceptive agents and possible risk to a patient might be evaluated by a profile of blood pressure and serum triglycerides, copper, and vitamin A.

PIP: To determine if methods can be developed which will show those patients for whom oral contraceptive agents (OCAs) constitute a hazard, data on blood lipids, serum levels of Vitamis-A, E, and C and copper are reported. Results of the tryptophan load test are also given. This tes t is related to the levels of pyridoxine in the tissues. The program was designed to show the relationship of any changes to each other, and to get a better understanding of their significance. Results are compared from subjects taking OCAs, from those not taking OCAs, from women in the last trimester of pregnancy, from women after parturition, and from males. All blood and urine samples were taken at 21 days after the beginning of subjects' menstrual periods, except for those who were pregnant and males. There were 49 women taking a variety of OCAs. 32 not taking OCAs served as controls. Included were 22 pregnant women in the last trimesters of their pregnancies. Of these, 11 were tested again 6 weeks postpartum. 9 men with high blood lipids and 12 men with normal lipid levels were also tested. Diastolic blood pressures averaged higher in the group taking OCAs (p less than .01), except for the males who were older or who wer known to have high lipids. Serum cholesterol levels in OCA users were unaltered. Serum phospholipids showed some increase in OCA users (p less than .05). Triglycerides show ed the greatest increase in OCA users (p less than .001), especially in those taking the most estrogen. The pregnant women had high serum levels of cholesterol, triglycerides, phospholipids, and total lipids. All of these levels were found to be less at 6 weeks postpartum. Serum copper levels were increased in all OCA users to above 1.5 mcg/ml but in only 2 of the nonusers to this level. Serum Vitamin-A was increased in the OCA user group (p less than .001). The pregnant women had relatively low levels of Vitamin-A. This increased by 6 weeks after parturition to the level of OCA users. An 8-hour urine collection after a 2-g tryptophan load showed at 6 times increased excretion of xanthurenic acid in those using OCAs as compared with nonusers. An increased ability of pregnant women to convert tryptophan to nictionic acid was shown. It is not known to what degree the biological changes caused by OCAs are undesirable. However, it is assumed that women showing the greatest changes are at greater risk. Analyses which may serve as incicators of potential risk include serum triglycerides, copper, and Vitamin-A levels. Carbohydrate intolerance and triglyceride elevation have been associated. Blood pressure measurements should be included in any profile.