Time-dependent effects of L-tryptophan administration on urinary excretion of L-tryptophan metabolites.

We have previously reported that dietary supplementation with up to 5.0 g/d of L-tryptophan (L-Trp) for 21 d has no adverse effects, judging from the levels of general blood variables, in healthy women. We performed a randomized, double-blind, placebo-controlled, crossover intervention study in 17 apparently healthy Japanese women. The subjects were randomly assigned to receive a 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. We examined the 24-h urine profiles on days -1 (1 d before starting L-Trp), 7, 14, and 21 to determine whether administration of L-Trp at doses of up to 5.0 g/d affects time-dependent urinary excretion of L-Trp or its metabolites in healthy women. The urinary excretion of L-Trp, kynurenic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid, N(1)-methylnicotinamide, N(1)-methyl-2-pyridone-5-carboxamide, and N(1)-methyl-4-pyridone-3-carboxamide increased in an L-Trp dose-dependent manner on day 7. The amount of urinary excretion of these compounds was unchanged on days 14 and 21. The urinary excretion of serotonin, 5-hydroxyindole-3-acetic acid, 2-oxoadipic acid, and nicotinamide was unaffected by L-Trp at any of the doses tested. L-Trp doses had weak effects on the urinary excretion of kynurenine and anthranilic acid. Based on these findings, we conclude that there are no time-dependent effects of L-Trp administration in urinary excretion of L-Trp metabolites. Additionally, L-Trp and its metabolites do not accumulate in the body.

Urinary excretion levels of water-soluble vitamins in pregnant and lactating women in Japan.

Recent studies have shown that the urinary excretion levels of water-soluble vitamins can be used as biomarkers for the nutritional status of these vitamins. To determine changes in the urinary excretion levels of water-soluble vitamins during pregnant and lactating stages, we surveyed and compared levels of nine water-soluble vitamins in control (non-pregnant and non-lactating women), pregnant and lactating women. Control women (n=37), women in the 2nd (16-27 wk, n=24) and 3rd trimester of pregnancy (over 28 wk, n=32), and early- (0-5 mo, n=54) and late-stage lactating (6-11 mo, n=49) women took part in the survey. The mean age of subjects was ~30 y, and mean height was ~160 cm. A single 24-h urine sample was collected 1 d after the completion of a validated, self-administered comprehensive diet history questionnaire to measure water-soluble vitamins or metabolites. The average intake of each water-soluble vitamin was ≍ the estimated average requirement value and adequate intake for the Japanese Dietary Reference Intakes in all life stages, except for vitamin B6 and folate intakes during pregnancy. No change was observed in the urinary excretion levels of vitamin B2, vitamin B6, vitamin B12, biotin or vitamin C among stages. Urine nicotinamide and folate levels were higher in pregnant women than in control women. Urine excretion level of vitamin B1 decreased during lactation and that of pantothenic acid decreased during pregnancy and lactation. These results provide valuable information for setting the Dietary Reference Intakes of water-soluble vitamins for pregnant and lactating women.

Supplementing healthy women with up to 5.0 g/d of L-tryptophan has no adverse effects.

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.

Fate of dietary tryptophan in young Japanese women.

The purpose of this study was to determine, using the high-performance liquid chromatographic methods recently modified by us, the fate of dietary tryptophan in 17 healthy female Japanese adults who ate self-selected food. The experimental period was 22 days. The habitual intake of tryptophan was 3328.4 µmol/day. 24-hour urine samples were collected at the beginning of the experiment and then once per week. Blood was collected at the beginning and end of the experiment. Levels of tryptophan and its metabolites were measured in blood and urine. Tryptophan, nicotinamide and 2-oxoadipic acid were the major compounds of the blood. The urinary excretion amounts of tryptophan, 5-hydroxyindole-3-acetic acid, kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid and quinolinic acid were about 40, 20, 4, 1, 10, 4, 3, 5 and 20 µmol/day, respectively.