Intraduodenal Calcium Enhances the Effects of L-tryptophan to Stimulate Gut Hormone Secretion and Suppress Energy Intake in Healthy Males: a Randomized, Cross-Over, Clinical Trial

Background In humans, intraduodenal infusion of L-tryptophan (Trp) increases plasma concentrations of gastrointestinal hormones and stimulates pyloric pressures, both key determinants of gastric emptying and associated with potent suppression of energy intake. The stimulation of gastrointestinal hormones by Trp has been shown, in preclinical studies, to be enhanced by extracellular calcium and mediated in part by the calcium-sensing receptor. Objective To determine whether intraduodenal calcium can enhance the effects of Trp to stimulate gastrointestinal hormones and pyloric pressures, and if so, whether it is associated with greater suppression of energy intake, in healthy males. Methods Fifteen males with normal weight (mean±SD; age: 26±7 years; body mass index: 22±2 kg/m2), received on three separate occasions, 150-min intraduodenal infusions of 0, 500 or 1000 mg calcium (Ca), each combined with Trp (load: 0.1 kcal/min, with submaximal energy intake-suppressant effects) from t=75–150 min, in a randomized, double-blind, cross-over study. Plasma concentrations of GI hormones (gastrin, cholecystokinin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY)), and Trp, and antropyloroduodenal pressures were measured throughout. Immediately post-infusions (t=150-180 min), energy intake at a standardized buffet-style meal was quantified. Results In response to calcium alone, both 500-mg and 1000-mg doses stimulated PYY, while only the 1000-mg dose stimulated GLP-1 and pyloric pressures (all P<0.05). The 1000-mg dose also enhanced the effects of Trp to stimulate cholecystokinin and GLP-1, and both doses stimulated PYY, but, surprisingly, reduced the stimulation of GIP (all P<0.05). Both doses substantially and dose-dependently enhanced the effects of Trp to suppress energy intake (kcal; Ca-0+Trp: 1108±70, Ca-500+Trp: 961±90, Ca-1000+Trp: 922±96; P<0.05). Conclusions Intraduodenal administration of calcium enhances the effect of Trp to stimulate plasma cholecystokinin, GLP-1 and PYY, and suppress energy intake, in health. These findings have potential implications for novel nutrient-based approaches to energy intake regulation in obesity. Clinical Trial Registry The trial was registered with the Australian New Zealand Clinical Trial Registry (www.anzctr.org.au; trial number: ACTRN12620001294943).