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

People commencing a carbohydrate-restricted diet (CRD) experience markedly heterogenous responses in LDL-cholesterol (LDLc), ranging from extreme elevations to a reduction.To elucidate possible sources of heterogeneity in LDLc response to a CRD and, thereby, identify individuals who may be at risk for LDLc elevation.Hypothesis-naive analyses were conducted on web survey data from 597 adults consuming a CRD. Univariate and multivariate regression models and regression trees were built to evaluate the interaction between BMI and baseline lipid markers. Data were also collected from a case series of five clinical patients with extremely high LDLc consuming a CRD.BMI was inversely associated with LDLc change. Low TG/HDLc ratio, a marker of good metabolic health, predicted larger LDLc increases. A sub-group of respondents with LDLc ≥200 mg/dL, HDLc ≥80 mg/dL, and TG ≤70 mg/dL were characterized as “Lean Mass Hyper-Responders.” Respondents with this phenotype (n = 112) had lower BMI and, remarkably, similar prior LDLc versus other respondents. In the case series, moderate reintroduction of carbohydrate produced a marked decrease in LDLc.These data suggest that, in contrast to the typical pattern of dyslipidemia, greater LDLc elevation on a CRD tends to occur in the context of low cardiometabolic risk.