Tryptophan Catabolism and Vitamin B-6 Status Are Affected by Gender and Lifestyle Factors in Healthy Young Adults

Background: Abnormalities of tryptophan (Trp) metabolism through the kynurenine (Kyn) pathway have been reported in various diseases; however, nutritional and lifestyle factors that affect this pathway in healthy individuals are not well documented. Objective: Our aim was to examine the effect of vitamin B-6 status and lifestyle factors including the use of vitamin B-6 supplements, alcohol, smoking, and oral contraceptives On Trp and its Kyn metabolites in a cohort of 2436 healthy young adults aged 18-28 y. Methods: Anthropometric and lifestyle data were collected by questionnaire. Participants provided blood samples for analysis of Tip, Kyn, anthranilic acid, kynurenic acid (KA), 3-hydroxykynurenine (HK), 3-hydroxyanthranilic acid (HAA), and xanthurenic acid (XA). Vitamin B-6 species were also measured. Results: Serum Tip metabolites were 10-15% higher among men (n = 993) compared with women (n = 1443; P < 0.0001), except for HK and XA. In all participants, serum Tip was positively associated with plasma pyridoxal 5'-phosphate (PLP; r= 0.28, P< 0.0001), reaching a plateau at PLP concentrations of similar to 83 nmol/L. HK was inversely associated with PLP (r= -0.14, P< 0.01). Users of vitamin 8-6 supplements (n = 671) had 6% lower concentrations of HK than nonusers (n = 1765; P = 0.0006). Oral contraceptive users (n = 385) had lower concentrations of KA (20.7%) but higher XA (24.1%) and HAA (9.0%) than did nonusers (n = 1058; P <,0.0001). After adjustment for gender and other lifestyle variables, XA concentrations were 16% higher in heavy drinkers In = 713) than in never or occasional drinkers In = 975; P = 0.0007). Concentrations of 2 other essential amino acids, methionine and arginine, also were positively associated with serum Trp (r = 0.65 and 0.33, respectively; P < 0.0001). Conclusions: In this population of healthy young adults, gender has the largest influence on serum Kyn metabolite concentrations. The significant covariance of Trp with unrelated amino acids suggests that protein intake may be an important consideration in evaluating Kyn metabolism.