Dietary tryptophan depletion according to body weight - A new treatment option in acute mania?
ABSTRACT Decreased neurotransmission of serotonin (5-HT) was shown to be related to the development of depressive symptoms, whereas recent preliminary evidence suggests that acute mania may be related to a hyperserotonergic state. The reduction of central nervous 5-HT synthesis achieved by a new modification of the dietary rapid tryptophan depletion technique, with the relevant amino acids dosed according to body weight, is hypothesized by the authors to be a further option of treatment during acute mania, in particular in view of a decrease in adverse reactions, a reduced amount of amino acids needed for sufficient depletion, but also improved tolerability. However, ethical issues may limit such studies investigating this relationship in acutely manic patients, in particular in view of informed consent.
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ABSTRACT: The pellagragenic effect of leucine (Leu) has been proposed to involve modulation of L-tryptophan (Trp) metabolism along the hepatic kynurenine pathway. Here, we discuss some of the mechanisms suggested and report the effects in healthy volunteers of single doses of Leu (4.05-6.75 g) administered in a 16-amino acid mixture on concentrations of plasma Trp and its kynurenine metabolites. Flux of Trp through Trp 2,3-dioxygenase (TDO) is dose-dependently enhanced most probably by Leu and can be attributed to TDO activation. Trp oxidation is better expressed using plasma total kynure-nines, rather than kynurenine, and free, rather than total, Trp. Increased hepatic Trp oxidation may be an additional mechanism of action of branched-chain amino acids in the acute Trp depletion test. Inhibition of intestinal absorption or hepatic uptake of Trp by Leu can be excluded. Potential mechanisms of the aggravation of pellagra symptoms by Leu are discussed.
Brain Behavior and Immunity 08/2011; 25. DOI:10.1016/j.bbi.2011.07.084 · 6.13 Impact Factor
Dataset: Biskup et al. 2012 PLoS ONE