Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults

This was a set of human interventional studies in overweight adults, including a first-in-human acute study and a 24-week randomized trial. The long-term trial enrolled men and women aged 40 to 65 years with BMI 25 to 40 kg/m2 and excluded clinically significant illness, including diabetes; 25 participants were assigned to inulin-propionate ester and 24 to inulin control among those analyzed at 24 weeks.

Inulin-propionate ester was given orally to target propionate delivery to the human colon. In the acute study, participants received a single 10 g dose before a standardized breakfast; in the 24-week trial, participants received 10 g/day for 24 weeks, compared with inulin control.

Overall, targeted colonic propionate delivery produced a beneficial effect on appetite regulation and weight/adiposity outcomes. Acutely, the supplement reduced energy intake from 1175 kcal (95% CI 957 to 1392) to 1013 kcal (95% CI 816 to 1210) and increased PYY and GLP-1 responses versus control, with PYY ΔAUC 240-420 min of 3349 min×pmol/L versus 429 min×pmol/L and GLP-1 ΔAUC of 10 801 min×pmol/L versus 3495 min×pmol/L, both p<0.05. Over 24 weeks, fewer participants in the inulin-propionate ester group gained weight of at least 3% of baseline (1 of 25 vs 6 of 24, p=0.036) or at least 5% (0 of 25 vs 4 of 24, p=0.033), and intra-abdominal adipose tissue distribution changed less favorably than control (p=0.027). Weight change was -1.02 kg (95% CI -2.10 to 0.04) with inulin-propionate ester versus 0.38 kg (95% CI -0.95 to 1.72) with control (p=0.099); postprandial PYY and GLP-1 were not different after 24 weeks, suggesting the long-term effect may involve mechanisms beyond sustained gut-hormone elevation.

The trials were relatively small, especially after attrition in the 24-week study, which reduces precision and limits generalizability. Some long-term outcomes were only trends rather than statistically significant, including overall weight change and intrahepatic lipid content, and the mechanism for the sustained benefit remained unclear because postprandial PYY and GLP-1 were not different at 24 weeks. The population was restricted to overweight adults without major illness, so applicability to other groups is limited.