title: Supplementing healthy women with up to 5.0 g/d of L-tryptophan has no adverse effects.
abstract: Because of the frequent use of L-tryptophan (L-Trp) in dietary supplements, determination of the no-observed-adverse-effect-level is desirable for public health purposes. We therefore assessed the no-observed-adverse-effect-level for L-Trp and attempted to identify a surrogate biomarker for excess L-Trp in healthy humans. A randomized, double-blind, placebo-controlled, crossover intervention study was performed in 17 apparently healthy Japanese women aged 18-26 y with a BMI of ≈ 20 kg/m(2). The participants were randomly assigned to receive placebo (0 g/d) or 1.0, 2.0, 3.0, 4.0, or 5.0 g/d of L-Trp for 21 d each with a 5-wk washout period between trials. Food intake, body weight, general biomarkers in blood and urine, and amino acid composition in blood and urine were not affected by any dose of L-Trp. Administration of up to 5.0 g/d L-Trp had no effect on a profile of mood states category measurement. The urinary excretion of nicotinamide and its catabolites increased in proportion to the ingested amounts of L-Trp, indicating that participants could normally metabolize this amino acid. The urinary excretion of L-tryptophan metabolites, including kynurenine (Kyn), anthranilic acid, kynurenic acid, 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid, and quinolinic acid (QA), all of which are intermediates of the L-TRP→Kyn→QA pathway, was in proportion to L-Trp loading. The response of 3-HK was the most characteristic of these L-Trp metabolites. This finding suggests that the urinary excretion of 3-HK is a good surrogate biomarker for excess L-Trp ingestion.
authors.affiliation: Department of Food Science and Nutrition, School of Human Cultures, The University of Shiga Prefecture, Shiga, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Hiratsuka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fukuwatari
authors.forename: Mitsue
authors.initials: M
authors.lastname: Sano
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shibata
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015992:Body Mass Index; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007736:Kynurenic Acid / Q000652:urine; D007737:Kynurenine / Q000031:analogs & derivatives / Q000652:urine; D009536:Niacinamide / Q000652:urine; D010919:Placebos; D014364:Tryptophan / Q000008:administration & dosage* / Q000009:adverse effects* / Q000378:metabolism; D055815:Young Adult; D062367:ortho-Aminobenzoates / Q000652:urine
chemical_list: D015415:Biomarkers; D010919:Placebos; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D009536:Niacinamide; C005045:3-hydroxykynurenine; D007737:Kynurenine; D014364:Tryptophan; D007736:Kynurenic Acid