Am J Clin Nutr. 2025 Sep 9:S0002-9165(25)00528-3. doi: 10.1016/j.ajcnut.2025.09.012. Online ahead of print.

ABSTRACT

BACKGROUND: Carbohydrate-restricted diets (CRDs) are widely promoted for improving cardiovascular and body composition outcomes, yet evidence remains mixed across dietary patterns, populations, and study designs.

OBJECTIVES: This meta-analysis evaluated the effects of CRDs on cardiovascular and anthropometric outcomes and examined whether these effects varied by diet type, macronutrient replacement, participant characteristics, and study features.

METHODS: Following PRISMA 2020 guidelines, 174 randomized trials (n=11,481) from 27 countries were included. Eligible studies compared CRDs (≤45% of energy from carbohydrates) to higher-carbohydrate diets in adults and reported cardiovascular or anthropometric outcomes. Random-effects models estimated standardized mean differences (SMDs) and 95% confidence intervals (CIs). Subgroup analyses explored differences by CRD type (ketogenic, low-carb, moderate-carb), replacement macronutrient (fat, protein, or combination), sex, weight status, diabetes status, intervention delivery, caloric intakes, and study design. Meta-regressions assessed the effects of intervention duration.

RESULTS: CRDs significantly reduced triglycerides (SMD: -15.11 mg/dL; 95% CI: -18.76, -11.46), systolic (SMD: -2.05 mmHg; 95% CI: -3.13, -.96) and diastolic blood pressure (SMD: -1.26 mmHg; 95% CI: -1.94, -.57)), various lipid profile ratios, and inflammatory markers (CRP, TNF-α), while increasing HDL (SMD: 2.92 mg/dL, 95% CI: 2.10, 3.74). LDL and total cholesterol increased modestly (SMD: 4.81, 95% CI: 2.58, 7.05; and SMD: 4.32 mg/dL, 95% CI: 1.66, 6.97, respectively). All measured body composition markers showed significant reductions. Moderate-carbohydrate diets offered balanced benefits, while ketogenic diets produced greater weight loss but greater increases in LDL and total cholesterol. Combined fat and protein replacements yielded the most comprehensive improvements. Benefits were most pronounced in females and individuals with overweight or obesity. Longer interventions amplified effects on lipid ratios and inflammatory markers.

CONCLUSIONS: CRDs improved cardiovascular health and body composition, especially in diets with combined macronutrient replacement. Potential adverse effects, including LDL elevation and lean mass loss, warrant clinical monitoring.

REGISTRATION NUMBER: For body composition: PROSPERO: CRD420251043066 (https://www.crd.york.ac.uk/PROSPERO/view/CRD420251043066); for cardiovascular health: CRD420251011748 (https://www.crd.york.ac.uk/PROSPERO/view/CRD420251011748).

PMID:40935153 | DOI:10.1016/j.ajcnut.2025.09.012

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