Increase in colonic PRopionate as a method of prEVENTing weight gain over 12 months in adults aged 20-40 years (iPREVENT): a multi-centre, double-blind, randomised, parallel-group trial.

Background: Obesity drives metabolic disease development. Preventing weight gain during early adulthood could mitigate later-life chronic disease risk. Increased dietary fibre intake, leading to enhanced colonic microbial fermentation and short-chain fatty acid (SCFA) production, is associated with lower body weight. Despite national food policy recommendations to consume 30 g of dietary fibre daily, only 9% of adults achieve this target. Inulin-propionate ester (IPE) selectively increases the production of the SCFA propionate in the colon. In previous studies, IPE has prevented weight gain in middle-aged adults over 6 months, compared with the inulin control. IPE is a novel food ingredient that can be added to various commonly consumed foods with a potential health benefit. This 12-month study aimed to determine whether using IPE to increase colonic propionate prevents further weight gain in overweight younger adults. Methods: This multi-centre randomised-controlled, double-blind trial was conducted in London and Glasgow, UK. Recruited participants were individuals at risk of weight gain, aged between 20 and 40 years and had an overweight body mass index. Sealed Envelope Software was used to randomise participants to consume 10 g of IPE or inulin (control), once per day for 12 months. The primary outcome was the weight gained from baseline to 12 months, analysed by an 'Intention to Treat' strategy. The safety profile and tolerability of IPE were monitored through adverse events and compliance. This study is registered with the International Standard Randomised Controlled Trials (ISRCT) Database (ISRCT number: 16299902). Findings: Participants (n = 135 per study arm) were recruited from July 2019 to October 2021. At 12 months, there was no significant difference in baseline-adjusted mean weight gain for IPE compared with control (1.02 kg, 95% CI: -0.37 to 2.41; p = 0.15; n = 226). Neither the IPE (+1.22 kg) nor the control arm (+0.07 kg) unadjusted mean gains in body weight reached the expected 2 kg threshold. In the IPE arm, fat-free mass was greater by 1.07 kg (95% CI: 0.21-1.93), and blood glucose elevated by 0.11 mmol/L (95% CI: 0.01-0.21). Compliance, determined by intake of ≥50% sachets, was reached by 63% of IPE participants. There were no unexpected adverse events or safety concerns. Interpretation: Our study indicates that at 12 months, IPE did not differentially affect weight gain, compared with the inulin control, in adults between 20 and 40 years of age, at risk of obesity. Funding: NIHR EME Programme (15/185/16).