Vitamin B6 metabolism in users of oral contraceptive agents. I. Abnormal urinary xanthurenic acid excretion and its correction by pyridoxine

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Abstract
The response of the increased urinary xanthurenic acid (XA) excretion following a 2-g l-tryptophan load to oral doses of 2, 5, 10, and 20 mg pyridoxine hydrochloride was systematically studied in a group of women using oral contraceptive agents (OCA). This was done through three consecutive menstrual cycles in each subject. Vitamin B6 was given during the first and third cycles, whereas the middle cycle was a nonvitamin B6-supplemented control (placebo) period. Tryptophan load tests were done at the beginning, in the middle, and at the end of each menstrual cycle. None of 10 non-OCA using control subjects excreted over 35 µmoles XA/8 hr. The majority of OCA users excreted in excess of this amount with an average of 167 µmoles. Those with increased XA excretion, positive reactors, comprised 75% of the OCA using group. The 8-hr urine collection period was found to contain a relatively constant fraction (average, 63.4%) of the 24-hr xanthurenic acid excretion after a 2-g l-tryptophan oral load. As such, it was a valid and reliable urine collection period for this index of vitamin B6 inadequacy. Detrimental metabolic effects of various tryptophan metabolites in animal systems, interference with gluconeogenesis, oxidative phosphorylation, insulin metabolism, and in being carcinogenic, were pointed out. The 2-mg dose of pyridoxine hydroxychloride, equivalent to the Recommended Dietary Allowance (37, 38) of vitamin B6, was sufficient to correct only 10% of the women studied, whereas the 20-mg dose did not correct all subjects. A regression analysis of the dose-response data revealed that 25 mg would be required to correct all OCA using women. In view of the limited number of subjects studied, a dose of 30 mg (allowing 5 mg as a safety factor) is recommended to correct the altered vitamin B6-tryptophan metabolism resulting from OCA use.