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 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.

Dietary habits of pregnant and lactating women have a critical impact on the health of future infants. For this reason, the Japanese Dietary Reference Intakes regarding the amounts of addition of water-soluble vitamins have been set (1). The additional intake amounts for pregnant and lactating women were calculated based on data concerning the changes in the metabolic characteristics of vitamins in pregnant women and the loss of vitamins as a result of lactation. However, there is little information about whether nutritional statuses of water-soluble-vitamins in Japanese pregnant and lactating women are good or not. Therefore, we examined the nutritional status of pregnant and lactating women and speculated about the validity of the additional amount of some water-soluble vitamins in the dietary reference intakes for pregnant and lactating women.A potential approach for determining the validity for the additional amounts is based on the observation that a water-soluble vitamin or its catabolite(s) can be detected in the urine (2-11). Using this approach, the urinary excretion of a water-soluble vitamin or its catabolite(s) occurs when the dietary intake exceeds an individual necessary amount. MATERIALS AND METHODSSubjects. Japanese pregnant (16-40 wk gestation) or lactating women (0-11 mo postpartum) were recruited from a parenting circle in The University of Shiga Prefecture between April 2010 and February 2012. Japanese married non-pregnant, non-lactating women also were recruited as controls through the parenting circle to match the mean ages and heights of the pregnant and lactating women. The purpose and protocol of this study was explained to all participants before joining the study, and written informed consent was obtained from each participant. We excluded participants diagnosed with a cold or influenza, and those who had taken multi-vitamin supplements at least once during the previous month. In addition, we excluded participants whose 24-h urine collection was considered incomplete: a collection time outside the 22-26-h range, urine volume ,250 mL, or extremely low or high energy intake (,500 or .4,000 kcal/d) (12). Twenty-four of the 2nd trimester pregnant (16-27 wk gestation) and 32 of the Bunkyo-ku, Tokyo 113-0033, Japan (Received December 17, 2012) Summary 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 (n537), women in the 2nd (16-27 wk, n524) and 3rd trimester of pregnancy (over 28 wk, n532), and early-(0-5 mo, n554) and late-stage lactating (6-11 mo, n549) 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 comple...

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