Objective  Ghrelin is a peptide hormone secreted primarily from the gastric mucosa. It plays a role in energy balance by stimulating appetite, thereby increasing food intake and enhancing weight gain and fat mass deposition. Plasma ghrelin concentrations increase with fasting and are suppressed by nutrient intake. The aim of this study was to examine in humans the relative contributions of small intestinal and gastric nutrient exposure to postprandial suppression of ghrelin, to determine whether gastric exposure is necessary for ghrelin suppression.

Patients  Twelve healthy older (age range 65–85 years) men (n = 7) and women (n = 5) were studied.

Design  On three separate days, equivolaemic (315 ml) intragastric (IG) and intraduodenal (ID) carbohydrate solutions (both 300 kcal) or intragastric water (control) were infused over 150 min.

Measurements  Food intake was quantified at a buffet meal offered immediately following each 150‐min infusion. Blood ghrelin, cholecystokinin and glucose concentrations were measured.

Results  There was a 25% suppression of mean plasma ghrelin concentrations following ID glucose (ID 2016 vs. control 2686 ng/l, P < 0·0001) and a 19% suppression following IG glucose (IG 2181 vs. control 2686 ng/l, P < 0·0001), with ghrelin concentrations slightly (7·6%) and nonsignificantly lower after ID than after IG glucose infusions (P = 0·2). There was no difference between the treatments for the amount of food consumed at the buffet meal (P = 0·88).

Conclusions  Although the primary source of ghrelin is the gastric mucosa, these results suggest that small intestinal nutrient exposure is sufficient for food‐induced plasma ghrelin suppression in humans, and that gastric nutrient exposure is not necessary for suppression.