Tryptophan Supplementation in the Pharmacotherapy of Anorexia Nervosa

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The significance of diet in human health, behavior and therapeutics is becoming increasingly recognized. All amino acids, being building blocks to the synthesis of proteins, are critical for life, but scientific interest on the role of tryptophan, an essential amino acid, in the modulation of behavior and treatment of brain disorders emerged because tryptophan is the precursor of neurotransmitter 5-hydroxytryptamine (5-HT; serotonin). Tryptophan hydroxylase, the rate limiting enzyme of serotonin biosynthesis exists unsaturated with its substrate under normal physiological conditions. It can be speculated that tryptophan supplementation could boost serotonin synthesis and neurotransmission and may be effective in the treatment of serotonin deficiency disorder. Anorexia nervosa, an eating disorder, characterized by false body perception, intense fear of weight gain, hyperactivity and amenorrhea is associated with high risk of mortality. Excessive starvation and exercise in anorexia nervosa, despite its negative consequences, parallels some features of addiction. Evidence suggests that the efficacy of pharmacotherapy in anorexia nervosa is not satisfactory. This article draws attention towards improving pharmacotherapy in anorexia nervosa by tryptophan supplementation. Studies performed in our laboratory on rat models show that excessive dietary restriction and starvation decreases serotonin neurotransmission, firstly by decreasing the nutritional availability of the essential amino acid tryptophan, the precursor of serotonin and secondarily by an increase in the effectiveness of feedback control over the synthesis and release of serotonin. A deficiency of serotonin produces depression like effects while the release of dopamine neurotransmission from the inhibitory effects of serotonin may lead to hyperactivity and addiction like behavior observed in anorexia nervosa patients. It is suggested that tryptophan supplementation can improve efficacy of pharmacotherapy in anorexia nervosa by increasing availability of precursor for serotonin synthesis and normalizing feedback control over serotonin synthesis and release.