Omega-3 Polyunsaturated Fatty Acids and Stroke Burden

Abstract

Stroke is a major leading cause of death and disability worldwide. N-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid and docosahexaenoic acid have potent anti-inflammatory effects, reduce platelet aggregation, and regress atherosclerotic plaques. Since the discovery that the Greenland Eskimo population, whose diet is high in marine n-3 PUFAs, have a lower incidence of coronary heart disease than Western populations, numerous epidemiological studies to explore the associations of dietary intakes of fish and n-3 PUFAs with cardiovascular diseases, and large-scale clinical trials to identify the benefits of treatment with n-3 PUFAs have been conducted. In most of these studies the incidence and mortality of stroke were also evaluated mainly as secondary endpoints. Thus, a systematic literature review regarding the association of dietary intake of n-3 PUFAs with stroke in the epidemiological studies and the treatment effects of n-3 PUFAs in the clinical trials was conducted. Moreover, recent experimental studies were also reviewed to explore the molecular mechanisms of the neuroprotective effects of n-3 PUFAs after stroke.

Keywords: docosahexaenoic acid; eicosapentaenoic acid; omega-3 PUFA; stroke.

Figure 1

Flow diagram of the systematic literature search. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram indicates the number of records identified, included, and excluded through the different phases of a systematic review.

Figure 2

Omega-3 polyunsaturated fatty acids and specific pre-resolving lipid mediators. Eicosapentaenoic acid (EPA) is converted to resolvin E1 and E2 by 5-lipoxgenase (LOX) and resolvin E3 by 15-LOX. Docosahexaenoic acid (DHA) is converted to resolvin D1 by cyclooxygenase (COX)-2/aspirin/15-LOX, and further 5-LOX, protectin D1 by COX-2/aspirin/15-LOX, and maresin 1 by 12-LOX.

Figure 3

Scheme of underlying mechanisms before and after stroke. Age, cardiovascular risk factors, atherosclerosis, lifestyle, and dietary habits could be implicated in the mechanisms of stroke development in humans. On the other hand, previous experimental studies showed that the blood–brain barrier (BBB), inflammation, oxidative stress, and pathologic signaling pathways contributed to the mechanisms after stroke. N-3 polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and its metabolites, resolvins, protectins, and maresins, suppressed these pathomechanisms, and reduced infarct size, induced angiogenesis and neurogenesis, and improved functional recovery. Bar-headed lines indicate an inhibition, and arrows represent a production and induction.