The effect of short-chain fatty acids on glycemic control in humans: A systematic review and meta-analysis

Background: Non-communicable disease development is related to impairments in glycaemic and insulinemic response, which can be modulated by fiber intake. Fiber's beneficial effect upon metabolic health can be partially attributed to the production of short-chain fatty acids (SCFAs) via microbial fermentation of fiber in the gastrointestinal tract. Objective: We aimed to determine the effect of the SCFAs, acetate, propionate, and butyrate on glycemic control in humans. Methods: CENTRAL, Embase, PubMed, Scopus and Web of Science databases were searched from inception to the 07/12/2021. Papers were included if they reported a randomized, controlled trial measuring glucose and/or insulin compared to a placebo in adults. Studies were categorized by the type of SCFA and intervention duration. Random effects meta-analyses were performed for glucose and insulin for those subject categories with ≥3 studies, or a narrative review was performed. Results: We identified 43 eligible papers, with 46 studies within those records (n = 913), 44 studies were included in the meta-analysis. Vinegar intake decreased acute glucose response, standard mean difference (SMD) and (95% CI) –0.53 (–0.92, –0.14) (n = 67) in individuals with impaired glucose tolerance or type 2 diabetes and in healthy (SMD) –0.27 (–0.54, 0.00) (n = 186). The meta-analyses for acute acetate as well as acute and chronic propionate studies had no significant effect. Conclusions: Vinegar decreased glucose response acutely in healthy and non-healthy. Acetate, propionate, butyrate, and mixed SCFAs had no effect on blood glucose and insulin in humans. Significant heterogeneity, risk of bias, and publication bias were identified in several study categories, including acute vinegar glucose response. As evidence was very uncertain, caution is urged when interpreting these results. Further high-quality research is required to determine the effect of SCFAs on glycemic control