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Psychopharmacology (Berl). 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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  • 1Neurobehavioral Research Laboratory and Clinic, Department of Psychiatry, School of Medicine, The University of Texas Health Science Center at San Antonio, Mail Code 7793, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.



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.


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.


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.


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.


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.

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