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

BACKGROUND

People commencing a carbohydrate-restricted diet (CRD) experience markedly heterogenous responses in LDL cholesterol, ranging from extreme elevations to reductions.

OBJECTIVES

The aim was to elucidate possible sources of heterogeneity in LDL cholesterol response to a CRD and thereby identify individuals who may be at risk for LDL cholesterol elevation.

METHODS

Hypothesis-naive analyses were conducted on web survey data from 548 adults consuming a CRD. Univariate and multivariate regression models and regression trees were built to evaluate the interaction between body mass index (BMI) and baseline lipid markers. Data were also collected from a case series of five clinical patients with extremely high LDL cholesterol consuming a CRD.

RESULTS

BMI was inversely associated with LDL cholesterol change. Low triglyceride (TG) to HDL cholesterol ratio, a marker of good metabolic health, predicted larger LDL cholesterol increases. A subgroup of respondents with LDL cholesterol ≥200 mg/dL, HDL cholesterol ≥80 mg/dL, and TG ≤70 mg/dL were characterized as "lean mass hyper-responders." Respondents with this phenotype ( = 100) had a lower BMI and, remarkably, similar prior LDL cholesterol versus other respondents. In the case series, moderate reintroduction of carbohydrate produced a marked decrease in LDL cholesterol.

CONCLUSIONS

These data suggest that, in contrast to the typical pattern of dyslipidemia, greater LDL cholesterol elevation on a CRD tends to occur in the context of otherwise low cardiometabolic risk.