Omega-3 Polyunsaturated Fatty Acid Supplementation Improves Lipid Metabolism and Endothelial Function by Providing A Beneficial Eicosanoid-pattern in Patients with Acute Myocardial Infarction: a randomized, controlled trial
Meng Yuan Clinical Nutrition Articles in Press E-mail Alert - June 18, 2020
Highlights
• Our targeted metabolomics method showed that the metabolic status of eicosanoids changed when AMI occurred; most of the significantly changed eicosanoids were derived from ω-6 PUFA. Correlation analysis indicated that PGJ2, PGI2, 5-HETE, LTB4 and PGF2α would be key targets responding to the occurrence of AMI as compared with other metabolites.
• 2 g daily of ω-3 PUFA during the first 3 months after AMI significantly reduced TG, Apo B and Lp(a) levels in revascularized patients with AMI who received standard guideline-based medical care, meanwhile significantly increased NO production.
• ω-3 PUFA partially shifted the eicosanoid profile. Among the 13 metabolites with significantly changed content, the content of pro-inflammatory PGJ2 and LTB4 continuously decreased for 3 months after ω-3 PUFA treatment, while the content of EEQs and EDPs was increased.
• The degree of reduction in levels of TG, Apo B and Lp(a) was correlated with the degree of changes in content of DHA and EPA metabolite EEQs. And the increased NO production was correlated with the percentage change in content of DHA, EEQs and PGJ2.
Background and aims
Omega-3 polyunsaturated fatty acid (ω-3 PUFA) have been reported to have beneficial cardiovascular effects, but its mechanism of protection against acute myocardial infarction (AMI) who are under guideline-based therapy is not fully understood. Here, we used a metabolomic approach to systematically analyze the eicosanoid metabolites induced by ω-3 PUFA supplementation and investigated the underlying mechanisms.
Methods
Participants with AMI after successful percutaneous coronary intervention were randomized to 3 months of 2 g daily ω-3 PUFA and guideline-adjusted therapy (n=30, ω-3 therapy) or guideline-adjusted therapy alone (n=30, Usual therapy). Functional PUFA-derived eicosanoids in plasma were profiled by metabolomics. Clinical and laboratory tests were obtained before and 3 months after baseline and after the study therapy.
Results
By intent-to-treat analysis, the content of 11-HDoHE, 20-HDoHE and 16,17-EDP and that of epoxyeicosatetraenoic acids (EEQs), derived from docosahexaenoic acid and eicosapentaenoic acid, respectively, were significantly higher with ω-3 group than Usual therapy, whereas that of prostaglandin J2 (PGJ2) and leukotriene B4, derived from arachidonic acid, was significantly decreased. As compared with Usual therapy, ω-3 PUFA therapy significantly reduced levels of triglycerides (-6.3%, P<0.05), apolipoprotein B (-4.9%, P<0.05) and lipoprotein(a) (-37.0%, P<0.05) and increased nitric oxide level (62.2%, P<0.05). In addition, the levels of these variables were positively correlated with change in 16,17-EDP and EEQs content but negatively with change in PGJ2 content.
Conclusions
ω-3 PUFA supplementation may improve lipid metabolism and endothelial function possibly by affecting eicosanoid metabolic status at a systemic level during convalescent healing after AMI.