Science behind the cardio-metabolic benefits of omega-3 polyunsaturated fatty acids: biochemical effectsvs. 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.

Diet, Lifestyle and Cardiovascular Diseases: Linking Pathophysiology to Cardioprotective Effects of Natural Bioactive Compounds

“…In vitro studies showed that LCn-3PUFA improved endothelial function [143]. Although a fall in mortality from CVDs, most deaths are caused by sudden cardiac deaths associated with fatal arrhythmia [144]. The antiarrhythmic actions of LCn-3PUFA have been shown in vitro using cultured neonatal cardiac myocytes.…”

Platelet Responses in Cardiovascular Disease: Sex-Related Differences in Nutritional and Pharmacological Interventions

“…The main finding emerging from different studies is that ω-3 PUFAs counterbalance CVD risk factors in a genderspecific manner, both in primary and secondary prevention [103]. A meta-analysis indicated that dietary intake of fish and ω-3 PUFAs was correlated with lower incidence and mortality of stroke, especially in women and those with body mass index ðBMIÞ < 24 kg/m 2 [104].…”

Functions of Omega-3 and Omega-6 in Prevention and Fighting Cardio-Metabolic Complications

“…Omega-6 and Omega-3 supplements can as well be manufactured from laboratories and sold as pharmaceutical medicine. Sufficient consumption of foods rich in PUFAs, such as Omega-3 and Omega-6, influences the occurrence of inflammation in the body as well as cardio-metabolic health status in individuals [14].…”