Effect of ketone supplementation, a low-carbohydrate diet and a ketogenic diet on heart failure measures and outcomes: a systematic review and meta-analysis

The impact of ketone supplementation, low carbohydrate diets (LCDs) and ketogenic diets (KDs) on heart failure (HF) outcomes is largely unknown. This systematic review and meta-analysis investigated how these dietary changes impacted cardiac function and HF outcomes. A systematic search of MEDLINE, Embase, CINAHL and Web of Science was performed; last search on 19 November 2025. Randomised controlled trials (RCTs) and observational studies in humans receiving ketone supplementation, LCD and KD interventions were included. Studies were eligible if they reported at least one cardiac function/HF measure. Risk of bias was performed using RoB2 and ROBINS-I (Risk Of Bias In Non-randomised Studies of Interventions). Treatment effects were pooled, mean differences and 95% CIs calculated. Subgroup analysis was performed and heterogeneity was assessed. 14 studies were included in this systematic review. A meta-analysis was performed on six RCTs. Ketone supplementation increased left ventricular ejection fraction by 3.12% (95% CI 0.95% to 5.30%, p<0.01), with greater improvement in patients with HF with reduced ejection fraction (HFrEF); 4.25% (95% CI 1.99% to 6.51%, p<0.001). In patients with HFrEF, ketone supplementation increased peak systolic annular velocity (0.60% (95% CI 0.17% to 1.02%, p<0.01)) and cardiac output (1.24 L/min (95% CI 0.24 to 2.24, p<0.05)), compared with controls. Due to small cohorts and different treatment durations, assessment of certainty was low to high. Meta-analysis could not be performed on LCD or KD studies, due to low study numbers. Ketone supplementation significantly improved cardiac function compared with controls, especially in people with HFrEF. More research is needed to determine how low carbohydrate and ketogenic diets affect HF outcomes. CRD42024615367.