I

CLINICAL

NUTRITION 1

THE VITAMIN Be REQUIREMENT IN ORAL CONTRACEPTIVE USERS Controlled depletion, repletion studies suggest that daily intakes of less than 5 mg vitamin B6 may be adequate to meet the needs of oral contraceptive users.

Key Words: oral contraceptives, vitamin B6requirement, tryptophan metabolites, erythrocyte transaminases, plasma pyridoxal

Numerous studies show that tryptophan metabolism is affected in pregnant women as well as in women using estrogen-progestogen combination oral contraceptives (OC). These women have been found to excrete increased amounts of several metabolites arising from tryptophan catabolism, the most pronounced change being in xanthurenic acid (XA) and kynurenic acid (KA) excretion. The abnormality is largely corrected by the administration of pyridoxine, suggesting but not proving an increased requirement of vitamin BSin OC users. Earlier workers reported that more than 20 mg pyridoxine per day was required to normalize tryptophan metabolism in OC While a majority of malnourished and wellnourished women show the abnormality in tryptophan metabolism following OC use, investigators differ in their assessment of vitamin B6 status using other tests, and the question of vitamin Be deficiency in OC users is controversial. Two types of multiparameter assessment approaches have been used to elucidate the vitamin Bg requirement of OC users. In one study on malnourished Indian women,4 it was observed that daily supplements of 10 mg pyridoxine from the day of starting contraception largely prevented the development of the abnormality in tryptophan metabolism. This level of supplementation also prevented the OCmediated deterioration in vitamin B6 status as judged by erythrocyte aspartate aminotransferase activation. The women were examined at 344

NUTRITION REVIEWS VOL. 37. NO. 1 1 NOVEMBER 1979

different time points between two and six cycles of OC use. Administration of 20 mg pyridoxine mitigated the OC effects on tryptophan metabolism completely. Based on these results the authors concluded that the vitamin B6 requirement of OC users is 10 mg per day. In another type of multiparametric approach Brown et al.5 and Laklem et a1.6 measured the pyridoxine status of OC users on known intakes of the vitamin in a depletion followed by repletion study. Daily intake of 2 mg vitamin BSwas adequate to maintain normal levels of plasma pyridoxal phosphate (PLP) as well as erythrocyte alanine and aspartate aminotransferase activities. Higher intakes were found to be essential to normalize xanthurenic acid excretion. They concluded that the use of OC only mildly affects the requirement for vitamin Bs and is of doubtful clinical significance. In a similar more recent study738 college women using OC for one to 13 months were first stabilized on a diet containing 2.06 mg vitamin Be per day. They were then depleted of pyridoxine by feeding a diet providing 0.36 mg pyridoxine per day for 42 days and then repleted in a stepwise manner by increasing the vitamin B6 intakes to 0.96, 1.56 and 5.06 mg for eight, nine and seven days respectively. Vitamin Be nutriture was assessed by erythrocyte pyridoxal level, alanine and aspartate aminotransferase activities and in vitro stimulation of these enzymes with PLP. Excretion of 4-pyridoxic acid and post-load urinary excretion of tryptophan metabolites was also studied. The results were compared with a similar study earlier conducted by the same authors on nonOC u s e r ~ . ~

On the predepletion diet providing 2.06 mg vitamin B6, the OC users excreted markedly higher levels of tryptophan metabolites (after loading with 2 g tryptophan) compared with non-users, the XA excretion of users being almost three times that of non-users. The excretion was further raised on the low vitamin B6 diet, but started decreasing after supplementation. Normal levels were reached when the pyridoxine intake was 5 mg per day.8 Since predepletion levels for tryptophan metabolites were reached with an intake of 1.56 mg per day and 5.06 mg caused large amounts of vitamin B6 and Qpyridoxic acid to be excreted, the authors concluded that intake of 1.5 mg is adequate for OC users, particularly since other parameters of vitamin B6 nutrition status were normalized at that level of intake.7 Judging from xanthurenic acid excretion on 2.06 mg and 1.5 mg vitamin B6 per day in OC users compared with non-users the conclusion reached may not be justified. In any event, the requirement for vitamin B6 for OC users does not appear to be more than 5 mg per day in that study.738 Whether or not the normal level of metabolite excretion would have continued in OC users on 5 mg vitamin Bs per day for a longer period of time is a moot point. Since some of the PLP enzymes are induced by the vitamin, a different steady state may be attained after the levels of other apoenzymes are raised. This process may take longer than the seven to eight days stabilization period permitted by the authors.7>8 An often debated question relates to the need to normalize tryptophan metabolism in OC users. The principal effect of steroids is to induce tryptophane 2,Sdioxygenase which produces these “overflow” metabolites even in healthy persons. Are these metabolites harmful? Most workers believe they are not, but some suspect toxicity. Clinically, several investigators have claimed improvement in OC-associated changes in mood and glucose tolerance with vitamin BStherapy. Despite the controversy, it might be of some value to supplement women using OC with pyridoxine to ensure a daily intake of at least 5 mg vitamin Be. Higher intakes are not necessary and may even bring about undesirable

alterations in amino acid metabolism. Further studies to settle this controversy are needed.

1. A.L. Luhby, M. Brin, M. Gordon, P. Davis, M.

Murphy and H. Spiegel: Vitamin 6 6 Metabolism in Users of Oral Contraceptive Agents. I . Abnormal Urinary Xanthurenic Acid Excretion and Its Correction by Pyridoxine. Am. J . Clin. Nutr. 24: 684-693, 1971 2. S.A. Price, D.P. Rose and P.A. Toseland: Effects of Dietary Vitamin 6 6 Deficiency and Oral Contraceptives on the Spontaneous Urinary Excretion of 3-Hydroxyanthranilic Acid. Am. J . Clin. Nutr. 25: 494-498, 1972 3. D.P. Rose, R. Strong, P.W. A d a m and P.E. Harding : Experimental vitamin 6 6 Deficiency and the Effect of Estrogen-Containing Oral Contraceptives on Tryptophan Metabolism and Vitamin 6 6 Requirements. Clin. Sci. 42: 465477, 1972 4. F. Ahmad and M.S. Bamji: Vitamin Supplements to Women Using Oral Contraceptives. Contraception 14: 309-318, 1976 5. R.R. Brown, D.P. Rose, J.E. Leklem, H. Linkswiler and R. Anand: Urinary 4-Pyridoxic Acid, Plasma Pyridoxal Phosphate, and Erythrocyte Aminotransferase Levels in Oral Contraceptive Users Receiving Controlled Intakes of Vitamin &.Am. J . Clin. Nutr. 28: 10-19, 1975 6. J.E. Leklem, R.R. Brown, D.P. Rose, H. Linkswiler and R.A. Arend: Metabolism of Tryptophan and Niacin in Oral Contraceptive Users Receiving Controlled Intakes of Vitamin 6 6 . Am. J . Clin. Nutr. 28: 146-156, 1975 7. T.R. Bosse and E.A. Donald: The Vitamin 6 6 Requirement in Oral Contraceptive Users. I. Assessment by Pyridoxal Level and Transferase Activity in Erythrocytes. Am. J . Clin. Nutr. 32: 1015-1023, 1979 8. E.A. Donald and T.R. Bosse: The Vitamin 6 6 Requirement in Oral Contraceptive Users. II. Assessment by Tryptophan Metabolites. Vitamin 6 6 and Pyridoxic Acid Levels in Urine. Am. J , Clin. Nutr. 32: 1024-1032, 1979 9. E.A. Donald, M.H. McBean, M.H.W. Simpson, M.F. Sun and H.E. Aly: Vitamin 6 6 Requirement of Young Adult Women. Am. J. Clin. Nutr. 24: 1028-1041, 1971 10. G.T. Bryan: The Role of Urinary Tryptophan Metabolites in the Etiology of Bladder Cancer. Am. J. Clin. Nutr. 24: 841-847, 1971

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The vitamin B6 requirement in oral contraceptive users.

Women using oral contraceptives (OCs) have been found to excrete increased amounts of several metabolites arising from tryptophan catabolism, the most...
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