Comparison of 50- and 100-g L -tryptophan depletion and loading formulations for altering 5-HT synthesis: pharmacokinetics, side effects, and mood states

Abstract

Rationale: Differences in 5-hydroxytryptamine (5-HT) function have been the subject of extensive research in psychiatric studies. Many studies have manipulated L -tryptophan (Trp) levels to temporarily decrease (depletion) or increase (loading) 5-HT synthesis. While most researchers have used a 100-g formulation, there has been ongoing interest in using smaller-sized formulations.

Objectives: This study examined the time course of multiple plasma indicators of brain 5-HT synthesis after a 50-g depletion and loading as a comparison to the corresponding 100-g formulations that are typically used.

Materials and methods: Plasma was collected from 112 healthy adults at seven hourly intervals after consumption of either a 50- or 100-g depletion or loading. Self-ratings of mood and somatic symptoms were completed before and after Trp manipulations.

Results: The primary findings were that (1) the 50- and 100-g formulations produced the expected changes in plasma indicators after both depletion (-89% and -96%, respectively) and loading (+570% and +372%, respectively); (2) the 100-g depletion showed more robust effects at the 4, 5, and 6 h measurements than the 50-g depletion; (3) there was significant attrition after both the 100-g depletion and loading, but not after either of the 50-g formulations; and (4) both the 50- and 100-g depletions produced increases in negative self-ratings of mood and somatic symptoms, while loading significantly increased negative ratings after the 100 g only.

Conclusions: There are important considerations when choosing among formulation sizes for use in Trp manipulation studies, and the complete 7-h time-course data set of the typical plasma Trp measures presented here may help researchers decide which methodology best suits their needs.

Figure 1

Time-course of plasma free L-tryptophan [Free Trp], total L-tryptophan [Total Trp], and the sum of the competing amino acids [CAA] following both 50 and 100g L-tryptophan depletion (left panels) and loading (right panels) amino-acid formulations. Error bars represent SEM.

Figure 2

Time-course of the [Free Trp] / [CAA] and [Total Trp] / [CAA] bioavailability ratios following both 50 and 100g L-tryptophan depletion (left panels) and loading (right panels) amino-acid formulations. Comparisons of the raw data for both depletion and loading formulations were conducted and statistically significant differences between the 50 and 100g formulations are marked with an *. Error bars represent SEM.