Suppression of Energy Intake by Intragastric L-Tryptophan in Lean and Obese Men: Relations with Appetite Perceptions and Circulating Cholecystokinin and Tryptophan

Background: L-Tryptophan reduces energy intake in healthy men. The underlying mechanisms, including appetite, plasma cholecystokinin (CC K), tryptophan (Trp), and the ratio of Trp to large neutral amino acids (Trp:LNAAs ratio), and whether responses differ in lean and obese individuals, are uncertain. Objectives: We evaluated the effects of intragastric Trp on energy intake (primary outcome) and their potential mechanisms, pre- and postmeal, in lean men and those with obesity. Methods: Twelve lean men [mean +/- SD age: 30 +/- 3 y; BMI (in kg/m(2)): 23 +/- 11 and 13 men with obesity (mean +/- SD age: 31 +/- 3 y; BMI: 33 +/- 1) received, on 3 separate occasions, in double-blind, randomized order, 3 g (Trp-3) or 1.5 g (Trp-1.5) Tip, or control (C), intragastrically, 30 min before a buffet-meal. Energy intake from the buffet-meal, hunger, fullness, and plasma CCK and amino acid concentrations were measured in response to Tip alone and for 2 h postmeal. Data were analyzed using maximum likelihood mixed-effects models, with treatment, group, and treatment-by-group interaction as fixed effects. Results: Trp alone increased plasma CCK, Trp, and the Trp:LNAAs ratio (all P < 0.001), with no difference between groups. Tip suppressed energy intake (P < 0.001), with no difference between groups (lean, C: 1085 +/- 102 kcal, Trp-1.5: 1009 +/- 92 kcal, Trp-3: 868 +/- 104 kcal; obese, C: 1249 +/- 98 kcal, Trp-1.5: 1217 +/- 90 kcal, Trp-3: 1012 +/- 100 kcal). Postmeal, fullness was greater after Trp-3 than after C and Trp-1.5 (all P < 0.05), and in men with obesity than in lean men (P < 0.05). Plasma Trp and the Trp:LNAAs ratio were greater after Trp-3 and Trp-1.5 than after C (all P < 0.001), and tended to be less in men with obesity than in the lean (P= 0.07) (Trp:LNAAs ratio: lean, C: 1.5 +/- 0.2, Trp-1.5: 6.9 +/- 0.7 Trp-3: 10.7 +/- 1.4; obese, C: 1.4 +/- 0.1, Trp-1.5: 4.6 +/- 0.7 Trp-3: 7 8 +/- 1.3). There were inverse correlations of energy intake with plasma Trp and the Trp:LNAAs ratio in both groups (lean, both r= -0.50, P < 0.01; obese, both r= -0.40, P < 0.05). Conclusions: Intragastric Trp has potent energy intake-suppressant effects, in both lean men and those with obesity, apparently related to the Trp:LNAAs ratio.

Automated summary

In healthy men, intragastric tryptophan increases plasma cholecystokinin levels and effectively suppresses energy intake, leading to enhanced fullness after intake. Obese men showed less response to tryptophan compared to lean men.