The effects of fasting duration on gastric emptying in man, an exploration of the role of the endocannabinoid system and inter-individual responsiveness

Background In animal studies, gut vagal afferent neurons express cannabinoid (CB1) receptors, whose expression is increased by fasting. We aimed to explore the possibility that similar effects might be relevant in man in controlling gastric emptying. Methods Fourteen healthy volunteers underwent measurements of gastric emptying using the 13C acetate breath test, after either a nutrient (skimmed milk) or non-nutrient (water) meal following both a 12 and 24 h fast. Further gastric emptying studies were performed with and without the CB1 receptor antagonist Rimonabant (20 mg or 80 mg). Because of the inter-individual variations observed, two subjects underwent additional studies with and without Rimonabant to determine intra-individual consistency. Gastric emptying was evaluated as cumulative C13 : C12 ratio values, measured at 5 min intervals for 30 min. Key Results In the group as a whole, fasting duration slowed gastric emptying for both the nutrient [120 +/- 30 (mean +/- SD) vs 101 +/- 34, P < 0.05] and non-nutrient [226 +/- 62 vs 177 +/- 47, P < 0.05] meals, but there was no effect of Rimonabant. However, there was consistent inter individual variation; thus while 12 subjects showed a slowing, two (14%) exhibited accelerated gastric emptying for both the nutrient and the non-nutrient meal after 24 h fasting and in one of whom, Rimonabant consistently reversed the fasting effect on the non-nutrient meal. Conclusions & Inferences Extended fasting alters the gastric emptying of liquid meals but there are consistent differences between individuals. Where there is an accelerated response to fasting, Rimonabant appears to reverse the effect.