Science behind the cardio-metabolic benefits of omega-3 polyunsaturated fatty acids: biochemical effects vs. clinical outcomes

Abstract

Lower incidence of cardiovascular disease (CVD) in the Greenland Inuit, Northern Canada and Japan has been attributed to their consumption of seafood rich in long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA). While a large majority of pre-clinical and intervention trials have demonstrated heart health benefits of LCn-3PUFA, some studies have shown no effects or even negative effects. LCn-3PUFA have been shown to favourably modulate blood lipid levels, particularly a reduction in circulating levels of triglycerides. High density lipoprotein-cholesterol (HDL-C) levels are elevated following dietary supplementation with LCn-3PUFA. Although LCn-3PUFA have been shown to increase low-density lipoprotein-cholesterol (LDL-C) levels, the increase is primarily in the large-buoyant particles that are less atherogenic than small-dense LDL particles. The anti-inflammatory effects of LCn-3PUFA have been clearly outlined with inhibition of NFkB mediated cytokine production being the main mechanism. In addition, reduction in adhesion molecules (intercellular adhesion molecule, ICAM and vascular cell adhesion molecule 1, VCAM-1) and leukotriene production have also been demonstrated following LCn-3PUFA supplementation. Anti-aggregatory effects of LCn-3PUFA have been a subject of controversy, however, recent studies showing sex-specific effects on platelet aggregation have helped resolve the effects on hyperactive platelets. Improvements in endothelium function, blood flow and blood pressure after LCn-3PUFA supplementation add to the mechanistic explanation on their cardio-protective effects. Modulation of adipose tissue secretions including pro-inflammatory mediators and adipokines by LCn-3PUFA has re-ignited interest in their cardiovascular health benefits. The aim of this narrative review is to filter out the reasons for possible disparity between cohort, mechanistic, pre-clinical and clinical studies. The focus of the article is to provide possible explanation for the observed controversies surrounding heart health benefits of LCn-3PUFA.