n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: Principles, Practices, Pitfalls, and Promises - A Contemporary Review

Abstract

Amidst voluminous literature, inconsistencies and opposing results have confused rather than clarified cardiologists' ability to assess the potential benefits of n-3 polyunsaturated fatty acids (n-3 PUFA). In perspective, there are common themes that emerge from n-3 PUFA studies, even as imperfect as they may be. The approach taken was to identify and unite these themes into a manageable, cohesive, evidence-based, yet useful synthesis. In all reviews and meta-analyses, the selection of component studies and assumptions influences outcomes. This overarching principle must be combined with the totality of the data, particularly when evidence is incompletely understood and gaps in knowledge must be bridged. Both the older literature and the most recent rigorous meta-analyses indicate that n-3 PUFA are highly pleiotropic agents with many documented positive physiological effects. Concordance among preclinical, observational, randomized clinical trials and meta-analyses is impressive. These agents have modest, statistically significant benefits which accrue over time. Given their favorable safety profile, a risk reduction of about 10% justifies their potential use in cardiovascular disease.

Cholesterol Content, Fatty Acid Profile and Health Lipid Indices in the Egg Yolk of Eggs from Hens at the End of the Laying Cycle, Following Alpha-Ketoglutarate Supplementation

“…n-3 FA are among the most desirable FA, because they have been shown to have a positive effect on inflammation and the prevention of chronic diseases, including heart disease and dementia. The relationship between n-3 PUFA consumption and the lowering of the risk of coronary heart disease is complicated, since exceeding a certain amount of n-3 PUFA intake would not improve the risk [ 65 ]. On the other hand, excessive consumption of PUFA increases the concentration of very reactive free radicals formed during FA oxidation.…”

Beneficial Role of Phytochemicals on Oxidative Stress and Age-Related Diseases

“…Most of the positive effects were associated with modulation of lipid metabolism [99]. In any case, even a slight but significant reduction of 10% of morbidity and mortality for CVD associated with PUFA supplementation remains a significant clinical outcome [100].…”

Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection

“…Shifts in select inflammatory mediators and VEGF could participate in improved IPC with ALA, while excess TNF-α and HMGB1 are both linked to myocardial injury; TNF-α signaling is also implicated in cardiac preconditioning [131] and HMGB1 may additionally precondition hearts via up-regulating protective VEGF [132], which was augmented by ALA here. Finally, it is also notable that n-3 PUFAs are highly pleiotropic [133], and could influence IPC through cytochrome P450 (e.g., epoxyeicosanoid formation) and arachidonate metabolic pathways [134], inter-related endocannabinoid signaling [135], activation of key transcriptional regulators [136], and/or inhibition of oxidative stress [137].…”