Severe Dyslipidemia Mimicking Familial Hypercholesterolemia Induced by High-Fat, Low-Carbohydrate Diets: A Critical Review

Abstract

Emerging studies in the literature describe an association between high-fat, low-carbohydrate diets and severe hypercholesterolemia consistent with the levels observed in patients with (homozygous) familial hypercholesterolemia (FH). High levels of low-density lipoprotein cholesterol (LDL-C) may result from the reduced clearance of LDL particles from the circulation, the increased production of their precursor, or a combination of both. The increased intake of (saturated) fat and cholesterol, combined with limited to no intake of carbohydrates and fiber, are the main features of diets linked to hypercholesterolemia. However, several observations in previous studies, together with our observations from our lipid clinic, do not provide a definitive pathophysiological explanation for severe hypercholesterolemia. Therefore, we review these findings and possible pathophysiological explanations as well as opportunities for future research. Altogether, clinicians should rule out high-fat, low-carbohydrate diets as a possible cause for hypercholesterolemia in patients presenting with clinical FH in whom no mutation is found and discuss dietary modifications to durably reduce LDL-C levels and cardiovascular disease risk.

Association of a Low-Carbohydrate High-Fat Diet With Plasma Lipid Levels and Cardiovascular Risk

“…Previous studies have reported lower, higher, or similar apoB or LDL-C 5 , 6 , 8 , 9 , 10 , 11 , 12 , 24 , 25 levels in individuals consuming a LCHF diet. These conflicting findings may be due to study design, short duration of observation, and lack of uniform diet composition, reflecting variations in quantity and quality of carbohydrate and fat intake.…”

“…This may help explain the observed clinical heterogeneity in lipid level responses among individuals on carbohydrate-restricted diets encountered in clinical practice. 8 , 9 , 10 , 11 , 12 , 13 …”

Study on the Impact of Dietary Patterns on Cardiovascular Metabolic Comorbidities among Adults

“…Conversely, excessive fruit intake can lead to the accumulation of uric acid precursors, increasing glyconeogenesis and the pentose phosphate pathway, ultimately resulting in elevated serum uric acid levels and renal dysfunction. Dietary recommendations for individuals with dyslipidemia often involve reducing macronutrient intake, particularly carbohydrates [ 42 ]. As grains are a primary source of carbohydrates, reducing their consumption is typically advised to manage dyslipidemia.…”

A protein-rich meal provides beneficial glycemic and hormonal responses as compared to meals enriched in carbohydrate, fat or fiber, in individuals with or without type-2 diabetes

“…However, a systematic review examining protein diets in T2D did not conclusively confirm this effect ( 34 ). Additionally, it is crucial to note that individuals at risk of developing dyslipidemia should steer clear of a diet high in fat ( 35 ), although the composition of fats may influence this risk ( 36 ). The disparities observed between the T2D and ND groups regarding the benefits of transitioning from carbohydrates to other macronutrients may, to some extent, be influenced by the greater variation in HbA1c levels among individuals diagnosed with T2D.…”