Published: 13 October 2023

Increase colonic propionate as a method of preventing weight gain in adults aged 20-40 years.

Background: A major public health challenge is the development of effective strategies to prevent the weight gain that occurs throughout adult life at a population level. Young adults (25-35 years) experience the fastest weight gain of approximately 7-10kg over 10 years which is associated with a number of chronic diseases(1).The gradual long-term weight gain observed in adults can be explained by a small habitual positive energy balance of 50 kcal/day (2).

Short chain fatty acids (SCFA) are molecules produced by the fermentation of non-digestible carbohydrates (NDCs) by the gut microbiota in the colon (3). Recent evidence suggests that SCFA act through free fatty acid receptors (FFAR2) on enteroendocrine cells chiefly in the colon to stimulate release of the anorexic gut hormones peptide YY (PYY) and glucagon like peptide 1 (GLP-1)(4).

To predictably increase colonic SCFA release we have developed a colonic novel delivery vehicle inulin-propionate ester (IPE). We have conducted the first studies in man, demonstrating significant appetite suppression and increased plasma PYY and GLP-1 concentrations with IPE and have also completed a 24-week human intervention study which demonstrated significantly lower weight gain in overweight people compared with control subjects (5). In addition, our recent pilot data demonstrated that a one week supplementation period with IPE significantly increases fasting and postprandial energy expenditure by 7%.

Hypothesis: IPE supplementation will prevent weight gain compared with inulin control in young adults at higher risk of weight gain.

Design: A randomised, placebo-controlled double-blind study to investigate the impact of IPE on weight gain prevention.

Cohort: Male and female adults, 20-35 years, BMI 25-30 kg/m2 Environment: NIHR/Wellcome Trust Imperial CRF at Imperial College London and the Glasgow Biomedicine CRF at University of Glasgow.

Interventions: IPE vs control (inulin). The IPE and control will be given to participants in 10g sachets and they will be instructed to take one sachet per day with their normal diet for 12 months.

Outcomes: The primary outcome measure will be weight gain at 12 months. Weight will be measured at 0,2,6 and 12 months. Secondary outcomes will include assessments of physiological variables underpinning the improvements in body weight maintenance, including colonic metabolism, appetite regulation, energy expenditure and lipid oxidation.

Sample size: The proof of concept trial provided a difference between arms of 1.4kg (95% CI:(-0.3 to 3.1). This indicates 95% support for an underlying positive intervention effect. The enrichment of the cohort with young adults at risk of weight gain would allow 2kg effect size to be detected with 90% power, 5% significance level, SD 4.35kg, by randomising 270 participants, with 75% retention. A substudy (N=52) will provide in-depth data on energy expenditure, calorimetry, appetite regulation, breath hydrogen at oxidation and gut microbiota.

Statistical analysis: The primary outcome of weight gain at 12 months will be compared between the two groups using an intention-to-treat approach and a linear mixed effect model and sensitivity analysis for missing data. The main impact of this study will be a methodology to prevent weight gain at a population level. This has potential to make a major public health impact given the increased risk of diabetes, coronary heart disease and cancer that occurs with the accumulation of weight gain.

Funded by: NIHR

First published: 13 October 2023