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Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan

Department of Anthropology, University of Oregon, Eugene, Oregon, United States
Pharmacology [?] Therapeutics (Impact Factor: 9.72). 04/2006; 109(3):325-38. DOI: 10.1016/j.pharmthera.2005.06.004
Source: PubMed

ABSTRACT

This paper reviews the preclinical and clinical evidence regarding the use of the dietary supplement 5-hydroxytryptophan (5-HTP) for the treatment of depression. In the absence of supplementation with exogenous 5-HTP, the amount of endogenous 5-HTP available for serotonin synthesis depends on the availability of tryptophan and on the activity of various enzymes, especially tryptophan hydroxylase, indoleamine 2,3-dioxygenase, and tryptophan 2,3-dioxygenase (TDO). Factors affecting each of these are reviewed. The amount of 5-HTP reaching the central nervous system (CNS) is affected by the extent to which 5-HTP is converted to serotonin in the periphery. This conversion is controlled by the enzyme amino acid decarboxylase, which, in the periphery, can be blocked by peripheral decarboxylase inhibitors (PDIs) such as carbidopa. Preclinical and clinical evidence for the efficacy of 5-HTP for depression is reviewed, with emphasis on double-blind, placebo-controlled (DB-PC) trials. Safety issues with 5-HTP are also reviewed, with emphasis on eosinophilia myalgia syndrome (EMS) and serotonin syndrome.

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    • "We also decided against the addition of carbidopa, which is known to prevent peripheral conversion of 5-HTP to 5-HT. As previously reported, the average systemic availability of oral 5-HTP was approximately 70% (Turner et al., 2006), and there is no consensus as to whether the addition of carbidopa increases the efficacy of 5-HTP (Zmilacher et al., 1988). "
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    • "This view was supported by injection of carbidopa, an inhibitor of the decarboxylation of the tyrosine oxidation product DOPA into the dopamine, which induced a phenotype on egg maturation very similar to that observed in PAH-silenced mosquitoes. Carbidopa can also inhibit the biosynthesis of serotonin from 5-Hydroxy-L-tryptophan [39] and we cannot exclude the possibility that the small but significant decrease in oviposition rate is also a behavioural effect due to serotonin imbalance. Concomitant to the egg development defects in PAH-silenced mosquitoes we observed an impaired ability of the mosquito to melanize Plasmodium berghei ookinetes upon the ingestion of an infected blood meal. "
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