LAUSR

Recently developed ketone (monoester or salt) supplements acutely elevate blood β-hydroxybutyrate (BHB) exogenously without prolonged periods of fasting or carbohydrate restriction. Previous (small-scale) studies have found a blood glucose-lowering effect of exogenous ketones. This study aimed to systematically review available evidence and conduct meta-analyses of studies reporting on exogenous ketones and blood glucose. We searched 6 electronic databases on December 13, 2021 for randomized and non-randomized trials of any length that reported on the use of exogenous ketones. We calculated raw mean differences (MD) in blood BHB and glucose in two main analyses: (I) after compared to before acute ingestion of exogenous ketones, and (II) following acute ingestion of exogenous ketones compared to a comparator supplement. We pooled effect sizes using random-effects models and performed prespecified subgroup analyses to examine the effect of potential explanatory factors, including study population, exercise, blood BHB, and supplement type, dosing, and timing. Risk of bias was examined using Cochrane's risk-of-bias tools. Studies that could not be meta-analyzed were summarized narratively. Forty-three trials including 586 participants are summarized in this review. Following ingestion, exogenous ketones increased blood BHB (MD = 1.73 mM, 95% CI: 1.26 mM to 2.21 mM, P < 0.001) and decreased mean blood glucose (MD = -0.54 mM, 95% CI: -0.68 mM to -0.40 mM, P < 0.001). Similarly, when compared to placebo, blood BHB increased (MD = 1.98 mM, 95% CI: 1.52 mM to 2.45 mM, P < 0.001) and blood glucose decreased (MD = -0.47 mM, 95% CI: -0.57 mM to -0.36 mM, P < 0.001). Across both analyses, significantly greater effects were seen with ketone monoesters compared to salts (P < 0.001). The available evidence indicates that acute ingestion of exogenous ketones leads to increased blood BHB and decreased blood glucose. Limited evidence on prolonged ketone supplementation was found.