Meta-analysis finds modest cognitive improvement with exogenous ketone bodies in neuropsychiatric conditions
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Key Takeaway
Consider exogenous ketone bodies for modest cognitive support, but evidence is limited and warrants further trials.
This systematic review and meta-analysis examines the effects of exogenous ketone body supplementation on cognitive performance in healthy adults or individuals with neuropsychiatric conditions. It includes 38 studies with 1,602 participants (41 protocols), with 29 protocols (1,117 participants) eligible for meta-analysis. The intervention involved exogenous ketone bodies compared to placebo, focusing on cognitive performance as the primary outcome, though follow-up duration, setting, and safety data (adverse events, discontinuations) are not reported.
The key finding is a statistically significant improvement in cognitive performance, with a pooled effect size of SMD = 0.29 (95% CI 0.16–0.41), indicating modest improvements. The authors describe this as an association, avoiding causal claims, and note the certainty of evidence is limited to these modest effects. No absolute numbers, p-values, or secondary outcomes are detailed in the results.
Limitations highlighted by the authors include the need for further investigation in well-powered, long-term trials to confirm and extend these findings. The practice relevance is cautiously framed, suggesting support for exogenous ketone bodies as a flexible nutritional strategy for cognitive support, but this should be interpreted with restraint due to the observational nature and gaps in evidence. Funding or conflicts of interest are not reported.
View Original Abstract ↓
Cognitive function is closely linked to brain energy metabolism and may be compromised by aging, metabolic stress, and neuropsychiatric disease. Ketone bodies can serve as an alternative cerebral fuel and may also exert signaling effects relevant to cognition. Exogenous ketones (EK) offer a practical means of increasing circulating ketone concentrations without dietary carbohydrate restriction. However, the overall effect of EK supplementation on cognitive performance in humans has not been systematically quantified.
A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Web of Science, and Embase were searched through October 2025 for randomized controlled trials investigating the effects of EK on cognitive outcomes in healthy adults or individuals with neuropsychiatric conditions. Data extraction and quality assessment were performed independently by multiple reviewers using the PEDro scale. Standardized mean differences (SMD) were calculated using random-effects models. Subgroup and meta-regression analyses examined the influence of ketone formulation, intervention duration, dose, population type, and presence of acute cognitive stressors.
38 studies comprising 41 protocols (1,602 participants) were included in the systematic review, with 29 protocols (1,117 participants) eligible for meta-analysis. EK supplementation was associated with a statistically significant improvement in cognitive performance compared with placebo (SMD = 0.29, 95% CI 0.16–0.41; p
EK supplementation is associated with modest improvements in cognitive performance across diverse populations and study designs. These findings support EK as a flexible nutritional strategy for cognitive support and warrant further investigation in well-powered, long-term trials to clarify optimal dosing, formulation, and clinical applicability.
https://www.crd.york.ac.uk/PROSPERO/view/CRD42023471727, CRD42023471727.
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