Effect of carbohydrate-restricted dietary interventions on LDL particle size and number in adults in the context of weight loss or weight maintenance: A systematic review and meta-analysis

Background: LDL particle size and number (LDL-P) are emerging lipid risk factors. Nonsystematic reviews have suggested that diets lower in carbohydrates and higher in fats may result in increased LDL particle size when compared with higher-carbohydrate diets. Objectives: This study aimed to systematically review available evidence and conduct meta-analyses of studies addressing the association of carbohydrate restriction with LDL particle size and LDL-P. Methods: We searched 6 electronic databases on 4 January, 2021 for randomized trials of any length that reported on dietary carbohydrate restriction (intervention) compared with higher carbohydrate intake (control). We calculated standardized mean differences (SMDs) in LDL particle size and LDL-P between the intervention and control groups of eligible studies, and pooled effect sizes using random-effects models. We performed prespecified subgroup analyses and examined the effect of potential explanatory factors. Internal validity and publication bias were assessed using Cochrane's risk-of-bias tool and funnel plots, respectively. Studies that could not be meta-analyzed were summarized qualitatively. Results: This review summarizes findings from 38 randomized trials including a total of 1785 participants. Carbohydrate-restricted dietary interventions were associated with an increase in LDL peak particle size (SMD = 0.50; 95% CI: 0.15, 0.86; P < 0.01) and a reduction in LDL-P (SMD = -0.24; 95% CI: -0.43, -0.06; P = 0.02). The effect of carbohydrate-restricted dietary interventions on LDL peak particle size appeared to be partially explained by differences in weight loss between intervention groups and exploratory analysis revealed a shift from small dense to larger LDL subclasses. No statistically significant association was found between carbohydrate-restricted dietary interventions and mean LDL particle size (SMD = 0.20; 95% CI: -0.29, 0.69; P = 0.37). Conclusions: The available evidence indicates that dietary interventions restricted in carbohydrates increase LDL peak particle size and decrease the numbers of total and small LDL particles. This review was registered at www.crd.york.ac.uk/prospero/ as CRD42020188745.