Cardiometabolic trade-offs of carbohydrate- and fat-focused diets: a network meta-analysis of randomised clinical trials.
Level 1 - systematic review of randomized trials
Network meta-analysis of randomized controlled trials
PubMed 42418007 · doi:10.1007/s00394-026-04028-1
What was done
A systematic review and random-effects frequentist network meta-analysis of literature from January 2013 to October 2025 compared carbohydrate- and fat-focused diets in adults aged 35–75 years with at least one cardiovascular disease (CVD) risk factor. Included trials were randomized clinical trials evaluating dietary interventions with explicit macronutrient targets. Diets were classified by fat and carbohydrate distribution, with low-fat-moderate-carbohydrate diets serving as the reference comparator. Evaluated outcomes included lipid profiles, adiposity, blood pressure, and glycaemic markers.
What was found
Forty-seven randomized trials (n = 3,450) were included. Compared with low-fat-moderate-carbohydrate diets, high-fat-low-carbohydrate diets were associated with modest reductions in body mass index [-0.48 kg/m² (95% CI: -0.74 to -0.22)]. Ketogenic diets showed the largest increases in LDL cholesterol [0.43 mmol/L (95% CI: 0.13 to 0.74)], total cholesterol [0.55 mmol/L (95% CI: 0.13 to 0.96)], and HDL cholesterol [0.12 mmol/L (95% CI: 0.06 to 0.18)]. High-carbohydrate diets increased triglycerides [0.24 mmol/L (95% CI: 0.04 to 0.43)]. Macronutrient composition had limited effects on waist circumference, blood pressure, and glycaemic markers.
Why it matters
These results establish clear cardiometabolic trade-offs: carbohydrate restriction improves triglycerides, HDL cholesterol, and BMI, but elevates LDL and total cholesterol. Because no single macronutrient distribution optimizes all cardiovascular markers, dietary advice must be tailored to individual baseline risk profiles.
Limits
The analysis was limited to surrogate biomarkers rather than hard cardiovascular outcomes or mortality. Interventions were categorized by broad macronutrient distributions rather than overall food source quality. The search was restricted to 2013–2025 in adults aged 35–75 with existing CVD risk factors, limiting generalizability to younger or lower-risk populations. Trial duration, participant adherence, and study-level risk of bias were not detailed in the abstract.
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