Background

Short‑chain fatty acids (SCFAs) are products of microbial fermentation that have important roles in host metabolism and energy balance. The iPREVENT randomised-controlled trial investigated whether daily supplementation with 10 g inulin-propionate ester (IPE) for 12 months could prevent weight gain in adults aged 20-40 years at high risk of future weight accumulation. Although weight gain trajectories did not differ between IPE and the inulin control study arms, an increase in fat‑free mass (FFM) was observed in the IPE group. Evidence from animal studies indicates that SCFAs, can elevate circulating insulin‑like growth factor‑1 (IGF‑1), a hormone that promotes FFM accretion, particularly within musculoskeletal tissue. This secondary analysis therefore aimed to determine whether the increase in FFM with IPE supplementation was allied with changes in serum IGF-1 concentrations.

Methods

Stored fasting serum samples collected at baseline and 12 months from a subset of iPREVENT participants (N=78) were analysed for IGF‑1 using an Enzyme-linked immunosorbent assay (ELISA). Mean %CV of assay was 7.4%. Between group differences in change in IGF‑1 (ΔIGF‑1) concentrations at 12 months were assessed using analysis of covariance (ANCOVA), adjusting for age, sex, BMI, and IPE/inulin compliance. Associations between ΔIGF‑1 and change in FFM (ΔFFM) and the effect of study arms were evaluated using regression analysis.

Results

Baseline IGF‑1 concentrations were comparable between groups, (IPE (median [IQR]): 144.2 (67.81) ng/mL and inulin: 135.4 (57.22) ng/mL; p = 0.758). ANCOVA indicated that ΔIGF‑1 was not significantly influenced by study arm, age, sex, BMI, or IPE/inulin compliance. Regression analyses demonstrated that ΔIGF-1 did not predict ΔFFM (B = -0.015, p = 0.093), and there was no significant interaction between ΔIGF-1 and study arm (B = -0.001, p = 0.932).

Conclusions

Although evidence from animal studies indicates that microbial metabolites such as propionate may enhance circulating IGF-1 and thereby promote increases in FFM, this secondary analysis did not identify any significant increase in IGF-1 concentration between the IPE and inulin groups. Furthermore, changes in IGF-1 were not significantly associated with previously reported increases in FFM. These findings suggest that the IPE-related alterations in body composition are not mediated by IGF-1. Further research is warranted to identify alternative mechanisms driving the observed increases in FFM in response to IPE supplementation.