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

Abstract

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.

Effect of high-fat diet and morning or evening exercise on lipoprotein subfraction profiles: secondary analysis of a randomised trial

“…There was increased concentrations of Apo-B in larger LDL particles (LDL-2 and LDL-3), again revealing a shift towards larger, more buoyant LDL particles after the HFD. These findings are in line with a systematic review and meta-analysis showing an overall trend for an increase in the larger subclasses of LDL and a decrease in the smaller, more dense LDL subclasses, after carbohydrate-restricted dietary interventions 11 . The circulation time of smaller LDL particles is longer than that of large LDL particles, with small dense LDL particles being more susceptible to atherogenic modifications, including glycation and oxidation 25 .…”

Elevated LDL Cholesterol with a Carbohydrate-Restricted Diet: Evidence for a “Lean Mass Hyper-Responder” Phenotype

“…In the Scandinavian Simvastatin Survival Study ( 23 ), individuals with isolated elevated LDL cholesterol, compared with those who also had high TG and low HDL cholesterol, were at lower risk for coronary events and benefited less from statins, findings consistent with other studies ( 24 ). Furthermore, a CRD tends to increase LDL particle size ( 25 ), resulting in a lipoprotein profile associated with lower risk at a given LDL cholesterol concentration ( 22 , 26 ) (although we do not have particle-size data for our respondents). In some circumstances, elevated LDL cholesterol on a CRD may be associated with reduced small LDL particle number ( 1 , 27 ).…”

The Effects of Carbohydrate versus Fat Restriction on Lipid Profiles in Highly Trained, Recreational Distance Runners: A Randomized, Cross-Over Trial

“…Fatty acid saturation, however, particularly SFA, has shown to have the largest influence on TC and LDL (including small density LDL) species, and is used more reliably to describe effects on blood cholesterol [ 34 , 37 , 42 ]. Although LDL particle size was not included in our analysis goals, the literature indicates that ketogenic diets may favor large, “buoyant” LDL species over smaller, pro-atherogenic “dense” LDL that correlate with cardiovascular injury [ 43 ], whereby HCLF may not promote buoyant LDL subclasses [ 34 , 42 ]. The plateau in TC and LDL concentrations at day 28 and thereafter suggests that no further increase was expected in these lipid parameters.…”