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Comparative Study
. 2008 Jun;198(3):431-45.
doi: 10.1007/s00213-008-1163-2. Epub 2008 May 2.

Comparison of 50- And 100-g L -Tryptophan Depletion and Loading Formulations for Altering 5-HT Synthesis: Pharmacokinetics, Side Effects, and Mood States

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Free PMC article
Comparative Study

Comparison of 50- And 100-g L -Tryptophan Depletion and Loading Formulations for Altering 5-HT Synthesis: Pharmacokinetics, Side Effects, and Mood States

Donald M Dougherty et al. Psychopharmacology (Berl). .
Free PMC article

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.

Conflict of interest statement

Disclosure/Conflict of Interest

There are no conflicts of interest to report for any of the authors of this manuscript. This study was conducted in compliance with the Declaration of Helsinki and the current laws of the United States of America.

Figures

Figure 1
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
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.

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