Polyunsaturated fatty acids supplementation impairs anti‐oxidant high‐density lipoprotein function in heart failure

BACKGROUND: The underlying reasons for the highly inconsistent clinical outcome data for omega‐3‐polyunsaturated fatty acids (n3‐PUFAs) supplementation in patients with cardiac disease have not been understood yet. The aim of this prospective, randomized, double‐blind, placebo controlled study was to determine the effects of oral treatment with n3‐PUFAs on the anti‐oxidant capacity of HDL in heart failure (HF) patients. METHODS: A total of 40 patients with advanced HF of nonischaemic origin, defined by NT‐proBNP levels of >2000 pg/mL, NYHA class III or IV and a LVEF <35% who were on stable optimized medical therapy for ≥3 months, were consecutively enrolled into this prospective, double‐blind, placebo‐controlled trial and randomized in a 1:1:1 fashion to receive 1 g/day or 4 g/day of n3‐PUFA, or placebo, respectively, for 12 weeks. RESULTS: After 12 weeks of treatment, the anti‐oxidant function of HDL, measured by the HDL inflammatory index, was found significantly impaired in the treatment group in a dose‐dependent fashion with 0.67 [IQR 0.49‐1.04] for placebo vs 0.71 [IQR 0.55‐1.01] for 1 g/day n3‐PUFA vs 0.98 [IQR 0.73‐1.16] for 4 g/day n3‐PUFA (P for trend = 0.018). CONCLUSION: We provide evidence for an adverse effect of n3‐PUFA supplementation on anti‐oxidant function of HDL in nonischaemic heart failure patients, establishing a potential mechanistic link for the controversial outcome data on n3‐PUFA supplementation.