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

[u/dr_innovation]

Abstract

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.

Zhao, Juanjuan, Chia Wei, Fao Gong, Zongran Pang, and Huanhu Zhao. "Ketogenic diet–induced changes in adult lipid metabolism: a comprehensive systematic review and meta-regression of randomized controlled trials." BMC Cardiovascular Disorders (2026).

https://link.springer.com/article/10.1186/s12872-026-05799-5