Gastrointestinal hormones and subjective ratings of appetite after low-carbohydrate vs low-fat low-energy diets in females with lipedema - a randomized controlled trial.

Background: Ketosis seems to attenuate, or prevent, the rise in both ghrelin concentrations and subjective hunger ratings that follow weight loss. However, most of the previous studies have employed very-low energy diets (VLED) and are therefore limited in terms of generalizability.

Objectives: To compare changes in ghrelin plasma concentrations after a low-carbohydrate (LCD) versus an isocaloric low-fat low energy diet (LED) in females with lipedema. Secondary objectives were to determine potential differences between diets in changes in satiety hormones, and subjective ratings of appetite.

Methods: Females with obesity and lipedema were randomized to either an LCD (75g carbohydrates) or low-fat diet (180g carbohydrates) for 8 weeks. Plasma concentrations of ghrelin, peptide YY, cholecystokinin (CCK), and glucagon-like peptide 1 (GLP-1), and subjective ratings of appetite were measured in the fasting and postprandial states, pre and post intervention.

Results: 55 females (30 in LCD) were included (age 47.9±11.3 years, BMI 36.8±5.1 kg/m²). Both LCD and low-fat groups lost weight (10.3%, P<0.001 and 7.3%, P<0.001, respectively), but the LCD lost significantly more. No within or between groups differences were found for ghrelin in the fasting state. A reduction in postprandial (tAUC) ghrelin was seen only in the LCD group (P=0.002), and this change was significantly different from the low-fat group (P=0.046). The LCD group also reported an increase in postprandial (both iAUC and tAUC) fullness ratings (P=0.035 and P=0.005, respectively), but this was not significantly different from the low-fat group (P=0.703 and P=0.365, respectively), despite the latter experiencing no change (P=0.127 and P=0.152, respectively). Conversely, only the low-fat group reported increased hunger in fasting (P=0.046), but changes were not significantly different from the LCD group (P=0.711). A decrease in postprandial (both tAUC and iAUC) CCK was observed in both LCD and low-fat diet groups (P≤0.005 for all).

Conclusion: Despite no changes in fasting ghrelin concentrations in either of the diet groups, a reduction in postprandial ghrelin and increased fullness was seen in the LCD group. These favorable changes in appetite in the LCD group might have contributed to the greater weight loss observed in this group.

Clinical trial registration: NCT04632810, Effect of Ketosis on Pain and Quality of Life in Patients With Lipedema (Lipodiet).