Deac Oana M, Mills James L, Shane Barry, Midttun Øivind, Ueland Per M, Brosnan John T, Brosnan Margaret E, Laird Eamon, Gibney Eileen R, Fan Ruzong, Wang Yifan, Brody Lawrence C, Molloy Anne M
Schools of Medicine and.
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD;
J Nutr. 2015 Apr;145(4):701-7. doi: 10.3945/jn.114.203091. Epub 2015 Feb 18.
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.
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.
Anthropometric and lifestyle data were collected by questionnaire. Participants provided blood samples for analysis of Trp, Kyn, anthranilic acid, kynurenic acid (KA), 3-hydroxykynurenine (HK), 3-hydroxyanthranilic acid (HAA), and xanthurenic acid (XA). Vitamin B-6 species were also measured.
Serum Trp 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 Trp was positively associated with plasma pyridoxal 5'-phosphate (PLP; r = 0.28, P < 0.0001), reaching a plateau at PLP concentrations of ∼83 nmol/L. HK was inversely associated with PLP (r = -0.14, P < 0.01). Users of vitamin B-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 (n = 713) than in never or occasional drinkers (n = 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).
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.
已有报道称,在各种疾病中,色氨酸(Trp)通过犬尿氨酸(Kyn)途径的代谢存在异常;然而,影响健康个体该途径的营养和生活方式因素尚无充分记录。
我们的目的是在2436名年龄在18 - 28岁的健康年轻成年人队列中,研究维生素B - 6状态以及包括使用维生素B - 6补充剂、饮酒、吸烟和口服避孕药在内的生活方式因素对Trp及其Kyn代谢产物的影响。
通过问卷调查收集人体测量和生活方式数据。参与者提供血液样本,用于分析Trp、Kyn、邻氨基苯甲酸、犬尿酸(KA)、3 - 羟基犬尿氨酸(HK)、3 - 羟基邻氨基苯甲酸(HAA)和黄尿酸(XA)。同时也测量了维生素B - 6的种类。
除HK和XA外,男性(n = 993)的血清Trp代谢产物比女性(n = 1443;P < 0.0001)高10% - 15%。在所有参与者中,血清Trp与血浆磷酸吡哆醛(PLP;r = 0.28,P < 0.0001)呈正相关,在PLP浓度约为83 nmol/L时达到平台期。HK与PLP呈负相关(r = -0.14,P < 0.01)。服用维生素B - 6补充剂的人(n = 671)的HK浓度比未服用者(n = 1765;P = 0.0006)低6%。口服避孕药使用者(n = 385)的KA浓度较低(20.7%),但XA(24.1%)和HAA(9.0%)浓度高于未使用者(n = 1058;P < 0.0001)。在调整性别和其他生活方式变量后,重度饮酒者(n = 713)的XA浓度比从不饮酒或偶尔饮酒者(n = 975;P = 0.0007)高16%。另外两种必需氨基酸,蛋氨酸和精氨酸的浓度也与血清Trp呈正相关(分别为r = 0.65和0.33;P < 0.0001)。
在这群健康的年轻成年人中,性别对血清Kyn代谢产物浓度影响最大。Trp与不相关氨基酸的显著协方差表明,在评估Kyn代谢时,蛋白质摄入量可能是一个重要的考虑因素。