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The vitamin B-6 requirement of young women consuming a high-protein diet (1.55 g/kg body wt) and the effect of protein quality on this requirement was studied. In addition, the response of clinical, functional, and biochemical measures of vitamin B-6 nutriture to short-term depletion and step-wise repletion of vitamin B-6 were evaluated. Eight healthy young women resided in a metabolic unit and were fed a formula depletion diet (< 0.05 mg vitamin B-6/d) for 11-28 d followed by either an animal-protein (AP) or plant-protein (PP) diet with successively increasing vitamin B-6 intakes (0.5, 1.0, 1.5, and 2.0 mg/d) for periods of 14-21 d. Animal proteins were primarily from dairy and poultry sources and plant proteins were primarily from legumes. Vitamin B-6 status measures were assessed at weekly intervals. Results showed that a PP diet does not elevate the vitamin B-6 requirement over that required for an AP diet given the high amount of dietary protein used in this study. It was also found that 0.015 mg vitamin B-6/g protein intake normalized most biochemical indexes of vitamin B-6 status (including those indicative of functional status), and that 0.020 mg/g protein normalized all biochemical measures except total urinary vitamin B-6. Adding a margin of safety to either the 0.015 or 0.020 mg/g protein intake would raise the vitamin B-6 requirement for young women above the currently recommended dietary allowance of 0.016 mg/g protein.

The catabolism of homocysteine through cystathionine synthesis requires pyridoxal-5'-phosphate, thus the effect of vitamin B-6 deficiency on plasma homocysteine concentrations was evaluated. Total fasting plasma homocysteine concentrations were measured in 11 elderly subjects aged 64.4 +/- 1.7 y (mean +/- SE) who consumed a vitamin B-6-deficient diet for less than or equal to 20 d. Only 1 of the 11 subjects was found to have elevated homocysteine concentrations even though all subjects exhibited high urinary xanthurenic acid concentrations after a tryptophan load, a measure indicative of vitamin B-6 deficiency. In a supporting study, fasting plasma homocysteine concentrations were measured in 3- and 23-mo-old rats fed vitamin B-6-deficient diets and were compared with those of vitamin B-6-replete, pair-fed controls. There was no difference in homocysteine concentrations between deficient and pair-fed animals after 6 wk of the dietary regimen for either age group; after 9 wk a modest elevation was observed in the 3-mo-old deficient rats whereas no difference was observed for the 23-mo-old rats. It is concluded that fasting plasma homocysteine concentrations are not initially elevated in vitamin B-6 deficiency and therefore fasting plasma homocysteine concentrations are not a good indicator of vitamin B-6 status.

Two groups of pregnant women belonging to a low socioeconomic group, one with oral lesions and the other without lesions, were studied in the 3rd trimester of pregnancy for vitamin B6 nutritional status. Both the groups showed evidence of abnormal tryptophan metabolism, and in pregnant women with clinical signs the postload xanthurenic acid excretion in urine was higher than in the other group, suggesting a severe deficiency of vitamin B6. Treatment with vitamin B6 cured the oral lesions and also corrected the abnormalities in tryptophan metabolism. Excretion of 4-pyridoxic acid was low in both the groups and more so in women with oral lesions. Administration of tryptophan load significantly elevated the excretion of 4-pyridoxic acid in urine. These results indicated that pregnant women belonging to a low socioeconomic group were, in general, deficient in vitamin B6. In pregnant women with oral lesions the deficiency of vitamin B6 was more severe than in those pregnant women without oral lesions. Whether the severity of vitamin B6 deficiency would precipitate clinical signs like oral lesions is not yet known.

The effect of an oral contraceptive agent on serum folate and vitamin B12 levels and on some aspects of tryptophan metabolism in the baboon has been investigated. Folate levels were not affected by this treatment. Vitamin B12 levels were lowered during oral contraceptive treatment (P smaller than 0.1) and increased during a 30-day period of pyridoxine supplementation (P smaller than 0.01). Trends indicating deterioration of glucose tolerance and abnormal tryptophan metabolism were also observed. Definite conclusions concerning the effect of oral contraceptive agents on nutritive parameters could not be made. This is in keeping with the vast volume of literature published on the effects of oral contraceptive agents in humans and other species. It is concluded that perhaps, due to the biologically variable responses to oral contraceptive agents by individuals of any species, studies of serum levels of vitamins and other superficial biochemical parameters. Further, we conclude that the baboon could be a useful model for the study of endocrine influences on nutritive parameters, first because endocrine parameters resemble those of humans and second, because experimental protocols can be rigidly adhered to.

Oral glucose tolerance, urinary xanthurenic acid excretion, and plasma pyridoxal phosphate concentrations were determined in nine women taking oral contraceptives and in four controls. The tests were repeated after 4 weeks ingestion of a vitamin B6-deficient diet, and again after pyridoxine supplementation. Vitamin B6 deficiency, as judged by an increased xanthurenic acid excretion and reduced plasma pyridoxal phosphate, was associated with a deterioration in the glucose tolerance of the contraceptive steroid-treated group despite normal or elevated plasma insulin levels. This abnormality was reversed by pyridoxine. There was no change in the glucose tolerance of the vitamin B6-deficient controls. The observed pyridoxine-responsive alteration in carbohydrate metabolism may involve the complexing of insulin with xanthurenic acid with a consequent loss of biological activity. In addition, oral contraceptives may enhance gluconeogensis.

Effects of low estrogen combination type oral contraceptives on some of the biochemical parameters used for assessing vitamin nutritional status were investigated in a group of women who had used the pill for 6 to 12 months. Another group of women was examined initially and then at one or more points of time within the first 6 months of treatment. Following changes were observed in women treated with oral contraceptives: 1) increased excretion of kynurenic acid and xanthurenic acid following tryptophan load; 2) increased EGOT activity and also an increase in vitro stimulation of EGOT with added PALP; 3) increased plasma vitamin A levels; 4) fall in erythrocyte folate levels; 5) fall in erythrocyte transketolase activity with no change in vitro stimulation with TPP; and 6) fall in erythrocyte riboflavin concentration associated with a decrease in erythrocyte glutathione reductase activity and increase in vitro stimulation with FAD. Most of these changes were observed during the first few cycles of oral contraceptive treatment.

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.