No effect of omega-3 polyunsaturated fatty acid supplementation on inflammatory markers in familial hypercholesterolemia: a randomized crossover trial

Abstract

Individuals with familial hypercholesterolemia (FH) have increased cardiovascular risk despite lipid-lowering therapy, and additional therapy is warranted. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplements have demonstrated an effect on cardiovascular endpoints in some clinical trials. Platelet-modifying and anti-inflammatory properties are among the proposed beneficial effects of n-3 PUFA. We investigated the effect of a high-dose n-3 PUFA supplement on platelet function and inflammatory markers in FH subjects. We performed a randomized, double-blind trial with a crossover design. Inclusion criteria were genetically verified heterozygous FH, stable disease, statin treatment >12 months, and age 18-75 years. Trial participants were allocated to two treatment periods in random order. The treatment periods (three months each) were separated by a three-month washout period. N-3 PUFA (1840 mg eicosapentaenoic acid and 1520 mg docosahexaenoic acid) and placebo (olive oil) were administered in four capsules daily. Endpoints were platelet function and inflammatory markers, assessed by platelet function analyzer, soluble markers P-selectin, vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM), 27 cytokines, and hematological parameters. Thirty-four heterozygous FH individuals completed the trial. No treatment effect (p = 0.93) from n-3 PUFA on the platelet function analyzer was found (2 s, 95% CI [-13, 6]). In our FH population, n-3 PUFA did not influence the levels of P-selectin (-2.0, 95% CI [-5.0, 2.0], p = 0.41), VCAM (0, 95% CI [-14.2, 14.2], p > 0.99), ICAM (-27.0, 95% CI [-70.1, 16.5]; p = 0.21), cytokine levels, or hematological parameters. In statin-treated FH individuals, high dose n-3 PUFA supplement did not affect platelet function and inflammatory markers.