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. 2022 Jul 27;10(8):1809.
doi: 10.3390/biomedicines10081809.

Effect of N-3 Polyunsaturated Fatty Acids on Lipid Composition in Familial Hypercholesterolemia: A Randomized Crossover Trial

Liv Nesse Hande  1   2 , Christian Kjellmo  1   2 , Kristin Pettersen  3 , Stefan Ljunggren  4 , Helen Karlsson  4 , Karin Cederbrant  5 , Maritha Marcusson-Ståhl  6 , Anders Hovland  1   7 , Knut Tore Lappegård  1   7
Affiliations

Effect of N-3 Polyunsaturated Fatty Acids on Lipid Composition in Familial Hypercholesterolemia: A Randomized Crossover Trial

Liv Nesse Hande et al. Biomedicines. .

Abstract

Individuals with familial hypercholesterolemia (FH) have an increased risk of cardiovascular disease. Treatment is mainly low-density lipoprotein cholesterol (LDL-C) reduction. How omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements affect lipoproteins in FH subjects is unknown. We hypothesized that a high-dose n-3 PUFA supplement would reduce atherogenic lipoproteins and influence the high-density lipoprotein cholesterol (HDL-C) function. We performed a randomized, double-blinded crossover study with 34 genetically verified FH individuals (18−75 years, clinically stable, statin treatment > 12 months). Treatment was 4 g n-3 PUFAs (1840 mg eicosapentaenoic acid and 1520 mg docosahexaenoic acid daily) or four capsules of olive oil for three months in a crossover design with a washout period of three months. The defined outcomes were changes in triglycerides, lipoproteins, lipoprotein subfractions, apolipoproteins, and HDL-C function. After treatment with n-3 PUFAs, total cholesterol, LDL-C, and triglycerides were reduced compared to placebo (p ≤ 0.01 for all). Total HDL-C levels were unchanged, but the subfraction of large HDL-C was higher (p ≤ 0.0001) after n-3 PUFAs than after placebo, and intermediate HDL-C and small HDL-C were reduced after n-3 PUFAs compared to placebo (p = 0.02 and p ≤ 0.001, respectively). No changes were found in apolipoproteins and HDL-C function. N-3 PUFAs supplements reduced atherogenic lipoproteins in FH subjects, leaving HDL-C function unaffected.

Keywords: cardiovascular disease; familial hypercholesterolemia; lipids; omega-3 fatty acids; randomized trial.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Graphical image of the Lipoprint LDL-C and HDL-C subfraction electrophoresis. VLDL: very low density lipoprotein. lbLDL: large, buoyant low-density lipoprotein cholesterol (LDL-C). sdLDL: small, dense LDL-C. HDL: high-density lipoprotein cholesterol. Int. HDL: intermediate HDL-C. Created with BioRender.com (accessed on 5 July 2022).
Figure 2
Figure 2
Participant flow diagram. N-3 PUFAs: omega-3 polyunsaturated fatty acids.
Figure 3
Figure 3
Total cholesterol (A), low-density lipoprotein cholesterol (LDL-C) (B), high-density lipoprotein cholesterol (HDL-C) (C), and triglycerides (D) after omega-3 polyunsaturated fatty acids (n-3 PUFAs) and placebo. IQR: interquartile range. ns = p > 0.05. ** = p ≤ 0.01. *** = p ≤ 0.001.
Figure 4
Figure 4
Large, buoyant low-density lipoprotein cholesterol (lbLDL-C) (A) and small, dense low-density lipoprotein cholesterol (sdLDL-C) (B) after omega-3 polyunsaturated fatty acids (n-3 PUFAs) and placebo. Large high-density lipoprotein cholesterol (large HDL-C) (C), intermediate HDL-C (D), and small HDL-C (E) after n-3 PUFAs and placebo. SD: standard deviation. IQR: interquartile range. ns = p > 0.05; * = p ≤ 0.05; *** = p ≤ 0.001; **** = p ≤ 0.0001.
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