Carbohydrate-restricted diet types and macronutrient replacements for metabolic health in adults: A meta-analysis of randomized trials - PubMed
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CRDs, particularly LCDs and MCDs with mixed macronutrient replacements, confer significant metabolic benefits independent of energy intake. These findings support CRDs as a potential nutritional strategy in metabolic disease prevention and management. Clinical supervision is recommended.

Clin Nutr. 2025 Sep 13;54:27-41. doi: 10.1016/j.clnu.2025.09.005. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Carbohydrate-restricted diets (CRDs) are increasingly used in managing metabolic disorders, yet evidence remains mixed regarding their effectiveness beyond glycemic control and across diverse populations. To systematically evaluate the effects of CRDs, ketogenic (KD), low-carbohydrate (LCD), and moderate-carbohydrate diets (MCD), and different macronutrient replacements (fat, protein, or both) on metabolic health-related biomarkers, including glycemic, hepatic, renal, adipokine, and lipid metabolism indices.

METHODS: Five electronic databases, PubMed, MEDLINE, Embase, ERIC, and Web of Science, were used to identify relevant randomized trials. Outcomes analyzed included glucose, HbA1c, insulin, HOMA-IR, liver/kidney function markers, leptin, and beta-hydroxybutyrate (BHB). Subgroup analyses evaluated the effects of CRD type, macronutrient replacement, sex, diabetes status, weight status, study design (parallel vs. crossover), delivery mode (consultation vs. food provision), and calorie intakes (isocaloric vs. non-isocaloric).

RESULTS: 149 randomized controlled trials comprising 9104 adults across 28 countries were included. CRDs significantly improved glycemic control (including glucose: SMD = -2.94 mg/dL, 95 % CI: -4.19, -1.68; insulin: SMD = -8.19 pmol/L, 95 % CI: -11.04, -5.43; HOMA-IR = -0.54, 95 % CI: -0.75, -0.33), hepatic stress (GGT: SMD = -6.08 U/L, 95 % CI: -9.97, -2.20), renal function (UACR: SMD = -0.19, 95 % CI: -0.28, -0.10), and adipokine concentration (leptin: SMD = -3.25 ng/mL, 95 % CI: -4.91, -1.59), particularly in females, individuals with overweight/obesity, and people with T2DM. LCDs and MCDs showed the most consistent metabolic benefits. Combined fat and protein replacement yielded greater improvements. Isocaloric vs. non-isocaloric comparisons showed similar patterns, suggesting macronutrient composition alone may engender beneficial metabolic effects.

CONCLUSIONS: CRDs, particularly LCDs and MCDs with mixed macronutrient replacements, confer significant metabolic benefits independent of energy intake. These findings support CRDs as a potential nutritional strategy in metabolic disease prevention and management. Clinical supervision is recommended.

PMID:41004974 | DOI:10.1016/j.clnu.2025.09.005

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