Effect of Low-Carbohydrate Diets on C-Reactive Protein Level in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Chronic low-grade inflammation is a probable mediator between the quantity of carbohydrate intake and health outcomes. The aim of this systematic review and meta-analysis of randomized clinical trials (RCTs) was to summarize the effects of low carbohydrate diets (LCDs) as compared to control diets on c-reactive protein (CRP) levels in adults. A comprehensive search was conducted in several databases up to February 2024. In total, 60 eligible trials with 5511 adults were included in the meta-analysis. LCDs resulted in an average reduction of 0.18 mg/L in CRP levels compared to control groups (MD = 0.18; 95 CI: 0.032 to 0.03; p = 0.016); however, sensitivity analysis revealed that this significance was dependent on a single study (Abbaspour Rad et al.), with exclusion of which the effect became non-significant (MD = -0.14; 95 CI: -0.28 to 0.00; p = 0.052), indicating the fragility of the overall finding. Based on subgroup analyses, LCDs achieved greater lower CRP levels in trials of long-term duration (> 12.5 weeks) (MD = -0.24; 95 CI: -0.48 to -0.00; p = 0.046), in younger people (<= 49.6 years) (MD = -0.30; 95 CI: -0.51 to -0.10; p = 0.003) with baseline CRP concentrations of more than 4.5 mg/L (MD = -0.70; 95 CI: -1.13 to -0.26; p = 0.002), and in obese participants with BMI > 35 (MD = -1.21; 95 CI: -1.91 to -0.51; p = 0.001). Also, according to multivariate meta-regression analyses, baseline CRP level remained a strong predictor of the treatment effect of LCDs (p = 0.017). Evidence from our study showed that LCDs may modestly improve CRP levels in adults. However, the effect appears more pronounced in individuals with higher baseline CRP levels, greater BMI, and younger age, indicating that these factors may modify treatment response. Future well-designed RCTs are required, with particular attention to dietary confounders such as protein and fat sources and carbohydrate quality.