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.

The tryptophan utilization concept in pregnancy

“…Whereas pregnancy outcome in mice whose diet was supplemented with 2% Trp was similar to that in un-supplemented controls, The 5% Trp-supplemented diet was, however, associated with lower placental weight and high mortality rates in pups (see further below). It is noteworthy that supplementing healthy women with 5 g of Trp daily does not cause any adverse effects on pregnancy [35]. …”

Tryptophan-Restriction Diets Help to Maintain L-Tryptophan Homeostasis in Tryptophan 2,3-Dioxygenase Knockout Mice

“…Hence, humans can catabolize ≈ 1 g of L-Trp every day. Our research team reported that supplementation of 5 g/day of L-Trp in adult Japanese women caused high urinary excretion of 3-hydroxykynurenine in some subjects 19. Such a finding suggests hereditary variance of L-Trp-kynurenine catabolism in humans.…”

The Urinary Ratio of 3-Hydroxykynurenine/3-Hydroxyanthranilic Acid Is an Index to Predicting the Adverse Effects of D-Tryptophan in Rats

“…In addition, we showed that supplementation with #5.0 g/d of l-Trp produces no adverse effects, and that the response of 3-hydroxykynurenine (3-HK) is the most characteristic of l-Trp metabolites in healthy women (4). This finding suggests that the urinary excretion of 3-HK is a good surrogate biomarker for excess ingestion of l-Trp (4).…”

“…We also reported that the urinary excretory ratio of anthranilic acid (AnA)/kynurenic acid (KA) could be a useful index to monitor excessive intake of l-Trp in rats (3). In addition, we showed that supplementation with #5.0 g/d of l-Trp produces no adverse effects, and that the response of 3-hydroxykynurenine (3-HK) is the most characteristic of l-Trp metabolites in healthy women (4). This finding suggests that the urinary excretion of 3-HK is a good surrogate biomarker for excess ingestion of l-Trp (4).…”