The effect of L-tryptophan on daytime sleep latency in normals: Correlation with blood levels

Abstract

L-Tryptophan, an essential amino acid, is readily converted to serotonin, which is thought to be important for expression of slow wave sleep and possibly rapid eye movement (REM) sleep. A vast but often confusing literature exists on L-tryptophan effects on inducing, maintaining, or altering sleep. In this study we measured the effects of L-tryptophan on objective (multiple sleep latency) and subjective [Stanford Sleepiness Scale (SSS)] measures of sleepiness and examined their relationship to blood L-tryptophan levels. Ten healthy volunteers (eight men and two women; mean ± SD age 34 ± 10 years) received placebo or 1.2 or 2.4 g of L-tryptophan on separate days in random double-blind fashion. Sleep latency and SSS were measured initially and at 60 and 120 min after ingestion. Blood and urine were collected at regular intervals. Compared with placebo both L-tryptophan doses reduced sleep latency at 1 h, with the reduction persisting at 2 h for the 2.4-g dose only (p<0.05). There was a positive correlation between subjective and objective sleepiness measures but only with the 2.4-g dose (r(s) = 0.76, p<0.01). There was a highly significant correlation between blood L-tryptophan and sleep latency at 0, 60, and 120 min in all subjects for all drug conditions (r = 0.276, df = 79, p = 0.013). Very small amounts of free L-tryptophan or its metabolites were found in the urine, with the exception of kynurenic acid. We conclude that L-tryptophan consistently reduced sleep latency in normals and that this correlates with blood levels. Increased urinary excretion of kynurenic acid suggests that blood kynurenic acid was similarly elevated and that kynurenic acid, given its inhibitory effects on excitatory neurotransmission, may possible be involved with inducing sleep.