Omega-3 Fatty Acids and Cardiovascular Disease

Omega-3 fatty acid supplementation exerts favorable effects on lipoprotein metabolism and inflammatory, oxidative, thrombotic, vascular, and arrhythmogenic factors implicated in cardiovascular disease.

“Omega-3 fatty acid supplementation exerts favorable effects on lipoprotein metabolism and inflammatory, oxidative, thrombotic, vascular, and arrhythmogenic factors implicated in cardiovascular disease. 5,6”

EPA and DHA are incorporated into phospholipid membranes of endothelial cells, where they influence membrane fluidity and receptor signaling.

“EPA and DHA are incorporated into phospholipid membranes of endothelial cells, where they influence membrane fluidity and receptor signaling [97].”

TG lowering by omega-3 fatty acids is linear with a dose-dependent effect such that greater absolute reduction is seen in individuals with higher baseline TG levels.

“The TG lowering is linear with a dose-dependent effect such that greater absolute reduction is seen in individuals with higher baseline TG levels”

A handful of studies have measured objective circulating or tissue ω-3 PUFA levels, but such findings could be limited by publication bias.

“A previous review1 also found that a handful of studies have measured objective circulating or tissue ω-3 PUFA levels, but such findings could be limited by publication bias.”

A review of experimental studies and randomized clinical trials found that ω-3 PUFAs protect against CHD risk pathways and clinical risk factors.

“A review1 of experimental studies and randomized clinical trials revealed a protective effect of ω-3 polyunsaturated fatty acids (PUFAs) on coronary heart disease (CHD) risk pathways and clinical risk factors.”

The paper's findings are consistent with prior experimental evidence that long-chain ω-3 PUFAs may stabilize membranes in ischemia-induced ventricular fibrillation and with observational evidence that fish consumption benefits relate most to arrhythmic events and fatal CHD.

“Our findings are consistent with prior experimental evidence that long-chain ω-3 PUFAs may have membrane stabilizing actions in the setting of ischemia-induced ventricular fibrillation1,38 and observational evidence indicating that benefits of fish consumption are most related to arrhythmic events39 and fatal CHD.40”

In randomized clinical trials, long-chain ω-3 PUFAs benefit multiple major cardiovascular risk factors, including triglyceride levels, blood pressure, heart rate, heart rate variability, endothelial function, and myocardial oxygen demand.

“In randomized clinical trials, long-chain ω-3 PUFAs benefit multiple major cardiovascular risk factors, including triglyceride levels, blood pressure, heart rate, heart rate variability, endothelial function, and myocardial oxygen demand.1,10”

EPA and DHA are more highly concentrated in phospholipids than other compartments, and phospholipids respond rapidly to dietary changes and may best reflect effects on membrane receptors.

“However, EPA and DHA are more highly concentrated in phospholipids than other compartments, and phospholipids also respond rapidly to dietary changes57,58 and may best reflect effects on membrane receptors.1”

Animal and epidemiologic research has suggested that the two main marine omega-3 fatty acids, EPA and DHA, may help prevent cardiovascular disease outcomes.

“Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, the 2 main omega-3 longchain polyunsaturated fatty acids of marine origin, have shown promise for the prevention of cardiovascular disease (CVD) outcomes in animal studies and epidemiologic studies. 1”

The G risk allele at rs10830963 in MTNR1B is associated with increased type 2 diabetes risk.

“The variant rs10830963 (G risk allele) in the melatonin receptor 1B (MTNR1B) gene increases the risk of type 2 diabetes.1”

Omega-3 PUFAs have electrophysiological, vascular, and antioxidative effects.

“have electrophysiological, vascular, and antioxidative effects”

These properties provide a mechanistic explanation for how omega-3 PUFAs may protect the heart.

“These properties offer a mechanistic framework by which omega-3 PUFAs exert cardioprotective effects”

Omega-3 PUFAs change the structure and function of cellular phospholipid membranes.

“Omega-3 PUFAs alter the structure and function of cellular phospholipid membranes”

Omega-3 fatty acids are integrated into biological membranes including those in atherosclerotic plaque where they influence signal transduction pathways involved in atherogenesis.

“Omega-3 fatty acids are integrated into biological membranes including those in the atherosclerotic plaque where they influence signal transduction pathways involved in atherogenesis (Calder, 2012;Mozaffarian and Wu, 2011).”

Available clinical evidence indicates that dietary consumption of long-chain omega-3 fatty acids correlates with reduced risk for cardiovascular mortality and morbidity.

“Available clinical evidence indicates that dietary consumption of long-chain, omega-3 fatty acids correlates with reduced risk for cardiovascular mortality and morbidity (Daviglus et al., 1997;Mozaffarian and Wu, 2011).”

The omega-3 fatty acids EPA and DHA may have a preventive role in the development and progression of atherosclerotic cardiovascular disease.

“The omega-3 (OM-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have a preventive role in the development and progression of atherosclerotic cardiovascular disease (ASCVD) [1–4].”

Dietary n-3 LCPUFA EPA and DHA have been associated with a decreased risk of chronic diseases, in particular CVD and cognitive decline.

“Dietary n-3 LCPUFA, eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3), have been associated with a decreased risk of chronic diseases, in particular CVD [3] and cognitive decline [4].”

Higher intakes of fish and omega-3 do not appear to appreciably reduce risk of fatal CHD further.

“In contrast, higher intakes do not appear to appreciably reduce risk further.”

Compared to little or no consumption, moderate consumption of fish (~2+ servings/week) and long-chain omega-3 (~250 mg/d) associates with lower risk of fatal CHD.

“Compared to little or no consumption, moderate consumption of fish (~2+ servings/week) and long-chain omega-3 (~250 mg/d) associates with lower risk of fatal CHD (Figures 6-7).200-202”

In meta-analyses of multiple controlled interventions, fish and omega-3 consumption improve major physiologic risk factors including BP, heart rate, endothelial function, triglycerides, and adiponectin.

“Notably, in meta-analyses of multiple controlled interventions, fish and omega-3 consumption improve major physiologic risk factors including BP, heart rate, endothelial function, triglycerides, and adiponectin.201, 205”

Omega-3's reduce inflammatory biomarkers, reduce myocardial oxygen utilization, and enhance cardiac function.

“Omega-3's also reduce inflammatory biomarkers, reduce myocardial oxygen utilization, and enhance cardiac function.201, 205”

Fish consumption has weaker associations with nonfatal cardiac events and stroke than with fatal cardiac events.

“Compared with fatal cardiac events, fish consumption has weaker associations with nonfatal cardiac events and stroke.201, 203, 204”

Farmed salmon have similar or higher levels of omega-3 fatty acids and likely similar net health benefits compared with wild salmon.

“Because farmed salmon are fed, while wild salmon hunt for their food, farmed salmon have similar or higher levels of omega-3 fatty acids201 and likely similar net health benefits.200”

The sum of evidence suggests that optimal levels of sodium intake are ~2000 mg/d and could be lower.

“Overall, while adverse effects of rapid sodium reduction cannot be excluded, and true optimal lower limits remain uncertain, the sum of evidence suggests that optimal levels of sodium intake are ~2000 mg/d193, 200-204 and could be lower.304”

Seafood is the major source of long-chain n-3 polyunsaturated fats, principally EPA and DHA.

“Seafood is the major source of long-chain n-3 polyunsaturated fats, principally EPA and DHA.201”

In clinical trials and meta-analyses, long-chain omega-3 PUFAs in fish reduced multiple CVD risk factors, including vascular resistance, BP, inflammation, serum lipids, and endothelial function.

“In clinical trials and meta-analyses of these trials the long-chain omega-3 polyunsaturated fatty acids in fish reduced multiple CVD risk factors, including vascular resistance, BP, inflammation, serum lipids, and endothelial function (197).”