No effect of n-3 fatty acids on high-sensitivity C-reactive protein after myocardial infarction: the Alpha Omega Trial

Background Persistent inflammation plays a role in the pathogenesis of atherosclerosis. n-3 Fatty acids may have anti-inflammatory effects. This study examined the effect of plant-derived alpha-linolenic acid (ALA) and marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on high-sensitivity C-reactive protein (hsCRP), a systemic marker of (low-grade) inflammation. Design/Methods A supplementary study in the Alpha Omega Trial: a multicenter, double-blind, randomized, placebo-controlled trial of low-dose n-3 fatty acids. Patients were enrolled from 2002 to 2006 and followed for 40 months. A total of 2425 patients, aged 60-80 years (79% men), with a history of myocardial infarction, were randomly assigned to margarines supplemented with a targeted additional intake of 400mg/day EPA and DHA, 2g/day ALA, EPA-DHA plus ALA, or placebo for 40 months. Results Patients consumed on average 19.8g margarine/day, providing an additional amount of 238mg/day EPA with 158mg/day DHA, 1.98g/day ALA, or both, in the active treatment groups. In the placebo group, the geometric mean hsCRP (95% confidence interval (CI)) was 1.84mg/l (95% CI: +1.70 to +2.00) at baseline and 1.98mg/l (95% CI: 1.82 to 2.15) after 40 months (p<0.0001). hsCRP levels were not affected by ALA (-5% versus placebo; 95% CI: -14% to +6%, p=0.37), EPA-DHA (-8% versus placebo; 95% CI: -17% to +2%, p=0.13), or EPA-DHA plus ALA (-3% versus placebo; 95% CI: -12% to +8%, p=0.62). Conclusions Long-term supplementation with modest amounts of EPA-DHA, whether or not in combination with ALA, did not affect hsCRP levels in patients with a history of myocardial infarction. Trial Registration ClinicalTrials.gov number NCT00127452