title: Tryptophan catabolism and vitamin B-6 status are affected by gender and lifestyle factors in healthy young adults.
abstract: 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 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.
  
  
  RESULTS
  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).
  
  
  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.
authors.affiliation: Schools of Medicine and.
authors.forename: Oana M
authors.initials: OM
authors.lastname: Deac
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD;
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.affiliation: Nutritional Science and Toxicology, University of California, Berkeley, CA;
authors.forename: Barry
authors.initials: B
authors.lastname: Shane
authors.affiliation: Bevital AS, Bergen, Norway;
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.affiliation: Section of Pharmacology, Institute of Medicine, University of Bergen and Haukeland University Hospital, Bergen, Norway;
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Department of Biochemistry, Memorial University, Newfoundland, Canada;
authors.forename: John T
authors.initials: JT
authors.lastname: Brosnan
authors.affiliation: Department of Biochemistry, Memorial University, Newfoundland, Canada;
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Brosnan
authors.affiliation: Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland;
authors.forename: Eamon
authors.initials: E
authors.lastname: Laird
authors.affiliation: Institute of Food and Health, University College Dublin, Dublin, Ireland; and.
authors.forename: Eileen R
authors.initials: ER
authors.lastname: Gibney
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD;
authors.forename: Ruzong
authors.initials: R
authors.lastname: Fan
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD;
authors.forename: Yifan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
authors.affiliation: Schools of Medicine and Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland; amolloy@tcd.ie.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000097:blood; D015415:Biomarkers / Q000097:blood; D019587:Dietary Supplements; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007736:Kynurenic Acid / Q000097:blood; D007737:Kynurenine / Q000031:analogs & derivatives / Q000097:blood; D008019:Life Style; D008297:Male; D008715:Methionine / Q000097:blood; D011732:Pyridoxal Phosphate / Q000097:blood; D012737:Sex Factors; D011795:Surveys and Questionnaires; D014364:Tryptophan / Q000097:blood*; D025101:Vitamin B 6 / Q000008:administration & dosage* / Q000097:blood*; D014977:Xanthurenates / Q000097:blood; D055815:Young Adult; D062367:ortho-Aminobenzoates / Q000097:blood
chemical_list: D015415:Biomarkers; D014977:Xanthurenates; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D015095:3-Hydroxyanthranilic Acid; C005045:3-hydroxykynurenine; D007737:Kynurenine; C028330:xanthurenic acid; D011732:Pyridoxal Phosphate; D025101:Vitamin B 6; D014364:Tryptophan; D001120:Arginine; D008715:Methionine; D007736:Kynurenic Acid
keywords: 3-hydroxykynurenine; kynurenine; protein; pyridoxal 5′-phosphate; tryptophan; vitamin B-6
references.citation: Eur J Clin Nutr. 2002 Apr;56(4):313-20
references.pmid: 11965507
references.citation: J Neural Transm (Vienna). 2009 Nov;116(11):1403-9
references.pmid: 19618107
references.citation: Am J Clin Nutr. 1971 Jun;24(6):659-72
references.pmid: 4253043
references.citation: Arch Physiol Biochem. 2011 Dec;117(5):254-8
references.pmid: 22034910
references.citation: Mol Neurobiol. 2013 Oct;48(2):294-301
references.pmid: 23813101
references.citation: Cancer Epidemiol Biomarkers Prev. 2014 Mar;23(3):461-8
references.pmid: 24357106
references.citation: Biosci Biotechnol Biochem. 2014;78(10):1757-60
references.pmid: 25273143
references.citation: Med Sci Monit. 2001 Jul-Aug;7(4):742-5
references.pmid: 11433204
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):588-93
references.pmid: 23267103
references.citation: Nutr Rev. 2013 Apr;71(4):239-44
references.pmid: 23550784
references.citation: Cancer Res. 2012 Nov 15;72(22):5649-57
references.pmid: 23144293
references.citation: Clin Chem. 2010 May;56(5):755-63
references.pmid: 20299681
references.citation: Nicotine Tob Res. 2009 Jan;11(1):12-24
references.pmid: 19246437
references.citation: Am J Clin Nutr. 1990 Jun;51(6):1058-61
references.pmid: 2349919
references.citation: Clin Chem. 2006 Jul;52(7):1318-24
references.pmid: 16690736
references.citation: J Nutr. 2011 Apr 1;141(4):611-7
references.pmid: 21310866
references.citation: Amino Acids. 2011 Nov;41(5):1195-205
references.pmid: 20872026
references.citation: Neurotoxicology. 2013 Jan;34:189-204
references.pmid: 23219925
references.citation: Br J Nutr. 2011 Jul;106(2):183-95
references.pmid: 21486513
references.citation: Am J Clin Nutr. 2012 May;95(5):1072-8
references.pmid: 22492365
references.citation: FEBS J. 2012 Apr;279(8):1355
references.pmid: 22251552
references.citation: J Med Chem. 2009 Jan 22;52(2):389-96
references.pmid: 19143568
references.citation: J Nutr. 1985 Dec;115(12):1663-72
references.pmid: 4067657
references.citation: J Neural Transm (Vienna). 2012 Feb;119(2):197-209
references.pmid: 21744051
references.citation: Nat Rev Neurosci. 2012 Jul;13(7):465-77
references.pmid: 22678511
references.citation: Am J Clin Nutr. 2013 Oct;98(4):934-40
references.pmid: 24004893
references.citation: Circulation. 2001 Jun 12;103(23):2788-91
references.pmid: 11401933
references.citation: Ann Clin Biochem. 2011 May;48(Pt 3):195-7
references.pmid: 21555538
references.citation: Am J Clin Nutr. 1975 Jan;28(1):10-9
references.pmid: 1115011
references.citation: PLoS One. 2011;6(7):e21851
references.pmid: 21765920
references.citation: Stroke. 2004 Jan;35(1):12-5
references.pmid: 14657454
references.citation: Am J Clin Nutr. 1972 May;25(5):494-8
references.pmid: 5021929
references.citation: Clin Exp Immunol. 2013 Jul;173(1):121-30
references.pmid: 23607723
references.citation: Am J Clin Nutr. 1971 Mar;24(3):297-303
references.pmid: 5548735
references.citation: Rapid Commun Mass Spectrom. 2009 May;23(9):1371-9
references.pmid: 19337982
references.citation: Obstet Gynecol. 2012 Jun;119(6):1243-50
references.pmid: 22617590
references.citation: BMC Gastroenterol. 2009;9:6
references.pmid: 19154614
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Oct;19(10):2549-61
references.pmid: 20813848
references.citation: J Nutr. 2010 Jan;140(1):103-10
references.pmid: 19906811
references.citation: Lancet. 1970 May 23;1(7656):1117-8
references.pmid: 4191995
references.citation: Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):698-704
references.pmid: 21183733
references.citation: Am J Clin Nutr. 2011 Aug;94(2):495-500
references.pmid: 21653798
references.citation: Am J Clin Nutr. 1971 Jun;24(6):699-703
references.pmid: 5581006
references.citation: World J Cardiol. 2014 Jun 26;6(6):462-77
references.pmid: 24976919
references.citation: Ann N Y Acad Sci. 1969 Sep 30;166(1):170-83
references.pmid: 4391266
references.citation: Am J Clin Nutr. 2014 Jul;100(1):250-5
references.pmid: 24808485
references.citation: Am J Clin Nutr. 1971 Jun;24(6):704-8
references.pmid: 5581007
references.citation: Handb Clin Neurol. 2013;113:1811-7
references.pmid: 23622403
references.citation: Am J Clin Nutr. 2013 Oct;98(4):863-4
references.pmid: 23985806
references.citation: Curr Pharm Des. 2014;20(6):840-9
references.pmid: 23701561