Effects of very low-carbohydrate ketogenic diets on lipid profiles in normal-weight (body mass index < 25 kg/m²) adults: a meta-analysis

Context: Very low-carbohydrate diets or ketogenic diets (KDs) have garnered attention for weight loss in patients with overweight or obesity as well as for normal-weight adults, yet the adverse effects of KDs, such as dyslipidemia in normal-weight adults, have not been studied extensively. Objective: This meta-analysis aimed to identify the effects of KDs on the lipid profile in normal-weight (body mass index [BMI] < 25 kg/m²) adults from randomized controlled trials. Data Sources: PubMed and Embase databases were searched on November 21, 2021, using search terms representing KDs and lipid profiles. Two researchers independently screened articles according to PICOS inclusion criteria. Data Extraction: General study information, dietary data, and lipid profiles were extracted from eligible studies. Risk of bias was assessed using the Cochrane risk of bias 2 tool. Data Analysis: Fixed- or random-effects meta-analysis was performed to estimate the effects of KDs on total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, apolipoprotein A (apoA), and apolipoprotein B (apoB), considering heterogeneity across studies. The certainty of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. Results: Three studies were selected for meta-analysis. A KD significantly increased TC by 1.47 mmol/L (95%CI, 0.72–2.22 mmol/L), LDL-C by 1.08 mmol/L (95%CI, 0.37–1.79 mmol/L), and apoB by 0.35 g/L (95%CI, 0.06–0.65 g/L). In addition, a KD significantly increased HDL-C by 0.35 mmol/L (95%CI, 0.27–0.42 mmol/L) and apoA by 0.34 g/L (95%CI, 0.28–0.41 g/L) compared with control diets. Triglyceride levels were not significantly different between KDs and control diets (P ¼ 0.63). Conclusion: This study suggests unfavorable effects of KDs on TC and LDL-C in normal-weight adults. Although an increase in HDL-C can compensate for unfavorable changes in lipids, normal-weight individuals should consider the risk of hypercholesterolemia when consuming a KD. Results for triglycerides were inconsistent.