Increased lipid peroxidation during long-term intervention with high doses of n-3 fatty acids (PUFAs) following an acute myocardial infarction

Objective: To assess the oxidative burden of a highly concentrated compound of n-3 PUFAs as compared to corn oil by measuring thiobarbituric acid-malondialdehyde complex (TBA-MDA) by HPLC. We also studied the influence on TBA-MDA of statins combined with n-3 PUFAs or corn oil. Design: A prospective, randomised, double-blind, controlled study. Setting: One hospital centre in Stavanger, Norway. Subjects: A total of 300 subjects with an acute myocardial infarction (MI). Interventions: Gelatine capsules, containing 850-882 mg EPA and DHA as concentrated ethylesters, or 1 g of corn oil, were ingested in a dose of two capsules twice a day for at least 1 y. Alpha-tocopherol (4 mg) was added to all capsules to protect the PUFAs against oxidation. Results: After 1 y TBA-MDA increased modestly in the n-3 PUFA group (n = 125), as compared to the corn oil group (n = 130), P = 0.027. Multiple linear regression analyses of fatty acids in serum total phospholipids (n = 56) on TBA-MDA measured after 12 months intervention, showed no dependency. Performing best subsets regression, serum phospholipid concentration of arachidonic acid (20:4 n-6 PUFA) was identified as a predictor of TBA-MDA at 12 months follow-up, P = 0.004. We found no impact of statins on TBA-MDA. Conclusion: TBA-MDA increased modestly after long-term intervention with n-3 PUFAs compared to corn oil post-MI, suggesting biological changes induced by n-3 PUFAs, rather than simply reflecting their concentration differences. The peroxidative potential of n-3 PUFAs was not modified by statin treatment. Sponsorship: Pharmacia A/S and Pronova A/S, Norway.