Summary:
This study is a meta-analysis of randomized controlled trials investigating the effects of carbohydrate-restricted diets (CRDs) on metabolic health. Metabolic syndrome (MetS) is a cluster of conditions including obesity, high blood sugar, high blood pressure, and abnormal lipid profiles that increase the risk of type 2 diabetes, cardiovascular disease, and certain cancers. Diet is a major contributor to MetS, and CRDs have been proposed to improve metabolic outcomes. The analysis included 149 trials with 9,104 adults. Outcomes assessed included blood glucose, HbA1c, insulin resistance, liver and kidney function markers, fat metabolism and more. Subgroup analyses examined the effects of CRD type, macronutrients (fat vs. protein vs. combined), sex, diabetes status, weight status and study design. Overall, CRDs significantly improved glycemic control, liver and kidney markers, and adipokine levels, particularly in women, individuals with overweight or obesity, and those with type 2 diabetes. Lower and moderate carbohydrate diets showed the most consistent benefits, and replacing carbohydrates with a combination of fat and protein appeared most effective. Benefits were observed regardless of total calorie intake, suggesting that macronutrient composition alone contributes to improvements. This study indicates that CRDs can be an effective nutritional strategy for improving metabolic health and reducing disease risk. Clinical supervision is advised to ensure safe implementation, particularly for long-term adherence.
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.
Article Publication Date: 13/09/2025
DOI: 10.1016/j.clnu.2025.09.005
