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Review
. 2023 Feb 15;15(4):962.
doi: 10.3390/nu15040962.

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

Veera Houttu  1   2 , Aldo Grefhorst  2 , Danny M Cohn  1 , Johannes H M Levels  2 , Jeanine Roeters van Lennep  3 , Erik S G Stroes  1 , Albert K Groen  2 , Tycho R Tromp  1
Affiliations
Review

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

Veera Houttu et al. Nutrients. .

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.

Keywords: LDL cholesterol; cardiovascular disease; carnivore diet; familial hypercholesterolemia; high-fat diet; ketogenic diet; low-carbohydrate diet.

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Conflict of interest statement

V.H., A.G., D.M.C., J.H.M.L., A.K.G. and T.R.T. declare no conflict of interest. J.R.v.L. reports research grants from Amryt and Novartis (all paid to the institution). E.S.G.S. reports consulting fees from Amgen, Sanofi, Regeneron, Esperion, Novartis, and Ionis/Akcea (all paid to the institution).

Figures

Figure 1
Figure 1
Results of the total cholesterol distribution in plasma after fast protein liquid chromatography (FPLC) profiling from patient 1 and patient 2 compared with that of pooled plasma from healthy subjects. The elution of the main lipoprotein classes is indicated for very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), respectively.
See this image and copyright information in PMC

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