Background Microbiota-derived short-chain fatty acid acetate has improved glucose metabolism and reduced appetite in animal studies and some preliminary human trials. However, other experiments show contradicting results, with acetate inducing hyperphagia and insulin resistance. Objective Study the effects of acute intravenous acetate infusion on postprandial insulin and glucose responses and on central responsivity in fasted state. Design We performed a randomised placebo-controlled crossover trial, including 18 lean individuals and 19 individuals with metabolic syndrome. We administered sodium acetate intravenously for 3 hours. We performed a standardised mixed meal test and employed a functional MRI (fMRI) paradigm, including a food-cue task and a food-receipt task. Results Acetate infusion did not significantly affect postprandial glucose or insulin levels or fasted fMRI results. Remarkably, plasma acetate levels decreased significantly after meal ingestion despite the constant acetate infusion rate. Fractional urinary acetate excretion significantly increased upon infusion but contained only 1–2% of the total amount of acetate infused. Conclusion Our data do not support effects of increased plasma acetate levels on glucose metabolism or blood oxygen level-dependent signal response to food-related stimuli in humans. These findings suggest that previously established positive effects of acetate are not dependent on acute rises in plasma acetate and may be primarily mediated through intestinal hormone release and the gut–brain axis—a route of effect that is bypassed in this current study. Finally, the decreasing acetate concentrations upon meal ingestion raise the question what tissues absorb or metabolise acetate in the postprandial phase. Trial registration number NL8381.
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Wijdeveld et al. (2026) studied this question.
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