The satiating effect of dietary protein is unrelated to postprandial ghrelin secretion

Context: Increasing dietary protein relative to carbohydrate and fat enhances weight loss, at least in part by increasing satiety. The mechanism for this is unclear. Objective: The objective of this study was to compare the effects of isocaloric test meals with differing protein to fat ratios on fasting and postprandial ghrelin, insulin, glucose, appetite, and energy expenditure before and after weight loss on the respective dietary patterns. Design: The study design was a randomized parallel design of 12 wk of weight loss ( 6 MJ/d) and 4 wk of weight maintenance (7.3 MJ/d) with meals administered at wk 0 and 16. Setting: The study was performed at an out-patient research clinic. Patients and Other Participants: Fifty-seven overweight ( body mass index, 33.8 +/- 3.5 kg/m(2)) hyperinsulinemic men (n = 25) and women (n = 32) were studied. Interventions: High-protein/low-fat (34 % protein/29 % fat) or standard protein/high-fat (18 % protein/45 % fat) diets/meals were given. Main Outcome Measures: The main outcome measures were weight loss and fasting and postprandial ghrelin, insulin, glucose, appetite, and energy expenditure before and after weight loss. Results: Weight loss (9.2 +/- 0.7 kg) and improvements in fasting and postprandial insulin and glucose occurred independently of diet composition. At wk 0 and 16, subjects wanted less to eat after the highprotein/low-fat than the standard protein/high-fat meal (P = 0.02). Fasting ghrelin increased (157.5 +/- 3.4 pg/ ml or 46.6 +/- 1.0 pmol/liter; P < 0.001), and the postprandial ghrelin response improved with weight loss (P = 0.043) independently of diet composition. Postprandial hunger decreased with weight loss (P = 0.018) and was predicted by changes in fasting and postprandial ghrelin (r(2) = 0.246; P = 0.004). Lean mass was the best predictor of fasting (r(2) = 0.182; P = 0.003) and postprandial ghrelin (r(2) = 0.096; P = 0.039) levels. Conclusions: Exchanging protein for fat produced similar weight loss and improvements in metabolic parameters and ghrelin homeostasis. The reduced appetite observed with increased dietary protein appears not to be mediated by ghrelin homeostasis.