Atherosclerosis, 2024, 2024 Apr 23:117562. doi: 10.1016/j.atherosclerosis.2024.117562

Dietary n-3 alpha-linolenic and n-6 linoleic acids modestly lower serum lipoprotein(a) concentration but differentially influence other atherogenic lipoprotein traits: A randomized trial

Nuotio P Lankinen MA Meuronen T et al.

Diets enriched with either n-3 alpha-linolenic or n-6 linoleic acid decrease serum Lp(a)
concentration by 7–10 %. Alpha-linolenic acid may have more beneficial effect on other
atherogenic lipoprotein traits, compared to linoleic acid. The FADS1 rs174550 genotype does
not modulate diet-induced changes in Lp(a) concentration or other lipoprotein traits.

Abstract
Background and aims: Lipoprotein(a) [Lp(a)] is a causal, genetically determined cardiovascular
risk factor. Limited evidence suggests that dietary unsaturated fat may increase serum Lp(a)
concentration by 10–15 %. Linoleic acid may increase Lp(a) concentration through its
endogenous conversion to arachidonic acid, a process regulated by the fatty acid desaturase
(FADS) gene cluster. We aimed to compare the Lp(a) and other lipoprotein trait-modulating
effects of dietary alpha-linolenic (ALA) and linoleic acids (LA). Additionally, we examined
whether FADS1 rs174550 genotype modifies Lp(a) responses. Methods: A genotype-based
randomized trial was performed in 118 men homozygous for FADS1 rs174550 SNP (TT or CC).
After a 4-week run-in period, the participants were randomized to 8-week intervention diets
enriched with either Camelina sativa oil (ALA diet) or sunflower oil (LA diet) 30–50 mL/day
based on their BMI. Serum lipid profile was measured at baseline and at the end of the
intervention. Results: ALA diet lowered serum Lp(a) concentration by 7.3 % (p = 0.003) and LA
diet by 9.5 % (p < 0.001) (p = 0.089 for between-diet difference). Both diets led to greater
absolute decreases in individuals with higher baseline Lp(a) concentration (p < 0.001).
Concentrations of LDL cholesterol (LDL-C), non-HDL-C, remnant-C, and apolipoprotein B were
lowered more by the ALA diet (p < 0.01). Lipid or lipoprotein responses were not modified by
the FADS1 rs174550 genotype. Conclusions: A considerable increase in either dietary ALA or
LA from vegetable oils has a similar Lp(a)-lowering effect, whereas ALA may lower other major
atherogenic lipids and lipoproteins to a greater extent than LA. Genetic differences in
endogenous PUFA conversion may not influence serum Lp(a) concentration.

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