Acute decrease in the plasma tryptophan-to-large-neutral-amino-acids ratio attenuates the effects of L-tryptophan on gut hormones and energy intake in healthy males: a randomized, cross-over, exploratory trial.

BACKGROUND

L-tryptophan ("Trp") and L-leucine ("Leu"), when administered intraduodenally, increase plasma cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1) and stimulate pyloric pressures, which all slow gastric emptying and suppress subsequent energy intake. The circulating Trp-to-large-neutral-amino-acids ("Trp/LNAAs") ratio is also inversely related to energy intake.

OBJECTIVES

This exploratory study characterized the impact of standardized changes in the plasma Trp/LNAAs ratio, achieved by combining a fixed-load intraduodenal infusion of Trp with increasing loads of Leu, on the appetite-inhibitory effects of enteral Trp.

METHODS

Twelve males of normal weight [mean ± standard deviation; age: 23 ± 2 y; body mass index (in kg/m2: 23±1)], received on 4 separate occasions, 90-min iso-osmotic intraduodenal infusions of 1) isotonic 0.9% saline ("control"), 2) Trp (0.15 kcal/min; "Trp"), 3) Trp + Leu (0.22 kcal/min; "Trp+Leu-0.22"), or 4) Trp + Leu (0.45 kcal/min; "Trp+Leu-0.45"), in a randomized, double-blind, cross-over fashion. Immediately postinfusion ad-libitum energy intake was quantified. Plasma CCK, GLP-1, amino acid concentrations, and antropyloroduodenal pressures were measured throughout.

RESULTS

Although there was a transient stimulation of CCK and GLP-1 by Trp + Leu - 0.45 (at t = 15 min), only Trp led to a sustained increase in plasma CCK (P = 0.04) and GLP-1 (P = 0.009) from t = 60-90 min, and stimulated pyloric pressures (P = 0.01), compared with control. Only Trp reduced energy intake [kcal (mean ± standard error of the mean); control: 1085 ± 49, Trp: 881 ± 75, Trp + Leu - 0.22: 963 ± 57, Trp + Leu - 0.45: 932 ± 60] compared with control (P = 0.008). The Trp/LNAAs ratio was dose-dependently decreased by Trp + Leu - 0.22 and Trp + Leu - 0.45, compared with Trp (all P = 0.001), and energy intake correlated inversely with the Trp/LNAAs ratio (R = -0.38; P = 0.02).

CONCLUSIONS

Acute reduction in the Trp/LNAAs ratio appears to be associated with a diminished capacity of Trp to stimulate CCK and GLP-1 and suppress energy intake. Although these observations should be interpreted with caution given the exploratory nature of the study, they attest to the complexity of the relationships between pre and postabsorptive mechanisms underlying Trp's appetite-inhibitory effect. This trial was registered at the Australian New Zealand clinical trial registry as ACTRN12620001275954.