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BACKGROUND: Animal experimental studies suggest that the amino acid valine may decrease brain serotonin (5-HT) function by inhibiting the transport of the 5-HT precursor, L-tryptophan, across the blood barrier. The aim of the present study was to assess whether valine could decrease brain 5-HT function in healthy subjects and provoke symptomatic relapse in recently remitted depressed patients taking antidepressant drug treatment. METHOD: We studied the effect of valine (30 g) on the prolactin (PRL) response to the 5-HT releasing agent, D-fenfluramine, in healthy male subjects and on the mood of 12 remitted depressed patients taking either selective serotonin re-uptake inhibitors (n = 10) or lithium and amitriptyline (n = 2). RESULTS: Valine significantly lowered the PRL response to D-fenfluramine in healthy subjects. In the remitted depressives, valine caused a mild but detectable lowering of mood on a number of measures but only one patient experienced a significant relapse in mood. CONCLUSIONS: Valine administration may decrease brain 5-HT neurotransmission in humans. This effect could explain the mild increase in depressive symptoms in patients taking 5-HT-potentiating drugs.


Journal article


Br J Psychiatry

Publication Date





238 - 242


Adult, Affect, Aged, Amino Acids, Branched-Chain, Amitriptyline, Antidepressive Agents, Blood-Brain Barrier, Cross-Over Studies, Depressive Disorder, Double-Blind Method, Drug Therapy, Combination, Female, Fenfluramine, Humans, Lithium, Male, Middle Aged, Personality Inventory, Prolactin, Recurrence, Reference Values, Serotonin, Serotonin Uptake Inhibitors, Tryptophan, Valine