Omega-3 Discoveries: New Lipids, New Benefits

May 11, 2017

Research on omega-3 polyunsaturated fatty acids (omega-3 LCPUFA) has grown tremendously over the past 10 years, and our knowledge about these LCPUFA—especially, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—has given way to new understandings of how they can benefit human health. 

In this article (the second in a two-part series), I will discuss how our understanding of omega-3 LCPUFA’s role in human health has evolved over time.


New Lipids Containing Omega-3s

Several new lipids containing omega-3 LCPUFA have received attention in the past decade.

Lysophospholipids containing DHA have taken a prominent place in our understanding of how DHA is transported between organs, ever since scientists discovered that the transporter Major Facilitator Superfamily Domain Containing 2A  (Mfsd2a) is a selective (sodium-dependent) transporter for DHA into the brain. This discovery was followed by the finding that Mfsd2a also transports DHA as lysophospholipid in the placenta and in the retina, suggesting that carrier-mediated uptake is an important component in the incorporation of DHA in some tissues with high demands for omega-3 LCPUFA. 

This discovery may have implications for the alleged higher efficacy for absorption and transport of omega-3 LCPUFA in the phospholipid form. (A number of studies so far have compared the bioavailability of different chemical forms of EPA and DHA upon oral intake, and if careful comparisons are made in the fed state over some reasonable period of time, little to no remarkable difference between digestion and absorption can be noted between triglycerides, ethyl esters, or phospholipids.)

Also, notable anti-inflammatory effects of EPA-monoglyceride and DHA-monoglyceride have been reported in the airways, colon, and joints.


Enzymatically Generated Oxygenated Derivatives

In addition to the growing appreciation for distinct biological activities and roles of various chemical forms of lipids containing omega-3, the last 10 years have seen more understanding about the enzymatically generated oxygenated derivatives of EPA and DHA, as well as docosapentaenoic acid (DPA). Many new studies have been published on the Specialized Proresolving Lipid Mediators (SPMs) that were uncovered from the beginning of the 2000s onwards. SPMs are endogenous derivatives of LCPUFA (lipid mediators) that activate a range of cellular changes that concertedly drive inflammatory responses towards their resolution. In other words, they are an important part of the body’s physiological mechanism to control the extent and magnitude of inflammation occurring in the body.

In the past decade, several SPMs that are made from omega-3 LCPUFA have been further characterized in terms of their chemical structure and biological activities, and new members, such as the DPA-derived 13S-series resolvins, and the DHA-derived protectin- and resolvin-sulfido conjugates, have been described. A newly uncovered DHA-derived metabolite, 19,20-epoxydocosapentaenoic acid, has potent activity in retinal and choroidal angiogenesis. Scientists have been busy elucidating the many biologically active derivatives of omega-3 fatty acids that regulate inflammation and tissue development in the body.

An increasing number of studies has addressed how dietary intake and supplementation with EPA/DHA-containing oils affects the formation and levels of these lipid mediators in the body. 

Also, the question of how specific nutrients affect the metabolism of EPA and DHA into these lipid mediators, and how omega-3 LCPUFA metabolism is dysregulated in diverse diseases, is gathering in force. For instance, obesity and aging are now recognized as exerting a negative influence on SPM-mediated healing responses after injury—for example, after myocardial infarction. Lipid mediators derived from omega-3 LCPUFA are now known not to be confined to the generation in local inflammatory reactions, but have been detected in saliva and in breast milk, suggesting important roles in protecting mucosal tissues and possibly in immunotolerance and gastrointestinal biotic health of infants. 

In a rabbit model of periodontitis, the local oral application of resolvin E1 was reported to have systemic anti-inflammatory effects. Further progress has been made in characterizing a more complete scope of immuno-resolvent actions that omega-3 LCPUFA-derived mediators exert in cells and tissues, in particular their endogenous antiseptic activity through the activation of phagocytosis of microbes. 


Omega-3s and Human Health

Ten years ago, it was quite clear that the role of omega-3 LCPUFA in the body is far more complex than simply influencing cell membrane properties. It was also known that omega-3 fatty acids played plausible roles in mediating tissue-protective and anti-inflammatory activities. Much more information is now available to support that omega-3 LCPUFA actually modulate disease risk. 

Ahead, we also look at what science has revealed about the implications of omega-3 LCPUFA intake on various aspects of human health.


Immune System

A shift in the way researchers think about the effects of omega-3 LCPUFA on the immune system has taken place in the last 10 years. Gradually, the poor classification that omega-3 PUFAs are immuno-suppressive is being replaced. 

Now, there is an understanding that omega-3 LCPUFA permit the execution of marked multi-cellular immuno-modulatory activities that can be interpreted as being immuno-stimulatory in nature—namely, specific parts of the immune system are triggered to become less active, and other immune cell types are activated to actively promote inflammation resolution.


Fatty Acid Distinction

Another notable change is a growing appreciation for the individual activities of distinct fatty acids in general. Even among omega-3 LCPUFA family members, there is recognition of distinct tissue distributions and, in some cases, notable differentiation in biological activities of EPA and DHA. 

Furthermore, omega-3s that are not EPA and DHA—for example DPA omega-3 and alpha-linolenic acid (ALA)—are increasingly being studied for their contributions to beneficial effects on health. 

With regard to ALA, although it is an essential fatty acid, no unique or distinct biological activity for this fatty acid itself has yet been identified; however, research nevertheless links the dietary intake of ALA to several benefits for health, in particular metabolic health, such as insulin sensitivity and body weight. 

Given the variable degrees of metabolic interconversion of the various omega-3 LCPUFA, their individual activities remain challenging to study and elucidate.