Ketogenic diet-induced changes in adult lipid metabolism: a comprehensive systematic review and meta-regression of randomized controlled trials

AIMS: The effects of the ketogenic diet (KD) on lipid metabolism remain controversial. We conducted a systematic review and meta-regression analysis of randomized controlled trials (RCTs) to evaluate the impact of KD on lipid profile parameters in adult populations. METHODS: Five electronic databases (PubMed/MEDLINE, Web of Science, Scopus, Embase, Cochrane Library) were systematically searched from inception through June 2025 for RCTs examining lipid-related outcomes following KD interventions (defined as > 45% fat, < 10% carbohydrate). The DerSimonian-Laird method was used to figure out pooled weighted mean differences (WMDs) and 95% confidence intervals (CIs) using random-effects models. We conducted meta-regression, subgroup analyses, sensitivity analyses, and assessed publication bias. Study quality was assessed using the Cochrane Risk of Bias 2 tool and the GRADE framework. RESULTS: Fifty-three RCTs met the inclusion criteria. Compared with control diets, KD significantly reduced triglycerides (WMD: -22.31 mg/dL; 95% CI: -28.90 to -15.72; p < 0.001; I2 = 69.8%, p < 0.001). HDL-C increased significantly (WMD: 3.52 mg/dL; 95% CI: 1.24 to 5.81; p < 0.001; I2 = 92.5%, p < 0.001). KD also raised LDL-C (WMD: 8.22 mg/dL; 95% CI: 5.08 to 11.40; p < 0.001; I2 = 59.9%, p < 0.001) and total cholesterol (WMD: 8.06 mg/dL; 95% CI: 3.04 to 13.07; p < 0.001; I2 = 72.3%, p < 0.001). Meta-regression revealed a significant negative correlation between changes in HDL-C and the duration of intervention (coefficient = − 0.125; p = 0.011). No evidence of publication bias was found, as Egger's test p-values exceeded 0.05 for all outcomes. According to the GRADE assessment, there is moderate certainty regarding TG and HDL-C, while certainty for LDL-C and TC remains low. CONCLUSIONS: KD causes an increase in HDL-C, LDL-C and total cholesterol while reducing triglycerides and. The long-term impact on heart and blood vessel health remains uncertain due to the lack of outcome data. These findings require careful interpretation and personalized monitoring.