Pharmacology Biochemistry & Behavior, Vol. 31, pp. 149-152. © Pergamon Press plc, 1988. Printed in the U.S.A. 0091-3057/88 $3.00 + .00 The Effect of Lowering Plasma Tryptophan on Food Selection in Normal Males SIMON N. YOUNG,*t 1 SMADAR V. TOURJMAN,* KAREN L. TEFF,t ROBERT O. PIHL*$ AND G. HARVEY ANDERSON§ *Department of Psychiatry, tThe Div&ion of Experimental Medicine, Department of Medicine and the SDepartment of Psychology, McGill University, Montreal, Canada and §the Department of Nutritional Sciences, University of Toronto, Toronto, Canada Received 11 December 1987 YOUNG, S. N., S. V. TOURJMAN, K. L. TEFF, R. O. PIHL AND G. H. ANDERSON. The effect of loweringplasma tryptophan onfood selection in normalmales. PHARMACOL BIOCHEM BEHAV 31(1) 149-152, 1988.--The effects of a tryptophan deficient amino acid mixture on food selection were studied using a double-blind counterbalanced crossover design in normal male subjects. The subjects ingested tryptophan deficient or nutritionally balanced amino acid mixtures in the morning after an overnight fast. Five hours after the trypotphan deficient amino acid mixture plasma tryptophan was only 19% of the level found five hours after the nutritionally balanced amino acid mixture. After both mixtures subjects were allowed to select lunch from a buffet. The tryptophan-deficient mixture was associated with a modest but significant decline in protein selection with no significant alteration in selection of carbohydrate, fat or total kcal. Our results suggest that 5-hydroxytryptamine is involved in the control of protein selection in humans. Tryptophan 5-Hydroxytryptamine Amino acids Protein Carbohydrate Fat THERE is a large literature concerned with the effect of altered 5-hydroxytryptamine (5HT) function on feeding in experimental animals [1, 3, 12]. Results vary somewhat de- pending on the particular experimental paradigm, but in gen- eral 5HT acts to suppress food intake. Fluctuations in 5HT can also, in some circumstances, be involved in the modula- tion of macronutrient selection, with elevated 5HT increas- ing protein intake or decreasing the ratio of carbohydrate to protein in the diet. The possible involvement of 5HT in macronutrient selec- tion may help to explain why 5HT is altered by dietary intake [1, 3, 12]. The rate of synthesis of 5HT depends in part onthe level in brain of its precursor tryptophan. The effect of acute dietary intake on brain tryptophan is not what might intui- tively be expected. Thus, ingestion of protein, which con- rains tryptophan, lowers rat brain tryptophan and 5HT. This is because all the large neutral amino acids compete for transport across the blood-brain barrier. Protein ingestion increases plasma levels of the other large neutral amino acids more than tryptophan. This increased competition for the transport system results in a lowering of tryptophan in the brain. On the other hand carbohydrate, which contains no tryptophan, causes an increase in brain tryptophan and 5HT. This is because insulin enchances uptake of branched chain amino acids into muscle, thus decreasing their plasma level and competition at the blood-brain barrier. As protein and carbohydrate have opposite effects on brain 5HT, and 5HT may control relative intakes of protein and carbohydrate, 5HT may be part of a system ensuring that an animal takes in adequate supplies of both these macronutrients. A possible role of 5HT in food selection in humans has been studied by giving tryptophan. Tryptophan was given over a 2-week period to obese subjects with a craving for carbohydrate snacks. It significantly diminished carbo- hydrate intake in three of the eight subjects, and increased it in one subject. It did not significantly modify snacking pat- terns in the group as a whole [11]. Tryptophan was also tested against placebo in a double-blind crossover study of eight refractory carbohydrate-craving obese subjects in a weight loss program. Weight loss during the six weeks on tryptophan was not significantly different from the six weeks on placebo [10]. Tryptophan was also tested against placebo in a double-blind crossover study in healthy lean men. Tryp- tophan in doses from 1 to 3 g, or placebo, was given 45 min 1Requests for reprints should be addressed to Dr. S. N. Young, Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, Canada, H3A IA1. 149