Importance of SPMs to enhance therapeutic effects of EPA and DHA: cardiovascular, cognitive and pregnancy health

By Georgia Marrion MNut, BHSci, Adv. Dip Health Sci (Nat).

Acute inflammation is a normal immunological response to pathogenic infection or injury that protects body tissues from infection or further tissue damage.1-3 It is a complex cascade involving many mediators and cells that regulate the initiation and resolution phases in response to inflammation.3,4 Increasing evidence attributes chronic, uncontrolled, endogenous inflammation, a key aetiological factor in many disease states, to impaired functionality within the inflammatory resolution phase.1,5,6 Therefore, understanding these phases and the nutritional factors that influence their synthesis and function is important for clinically meaningful outcomes in inflammatory-mediated health issues.

Inflammation phases: initiation and resolution

Lipid mediators from polyunsaturated fatty acids (PUFAs) play a central role in the initiation and resolution of inflammation.2

Following exposure to an inflammatory-inducing stimuli, the initiation phase is activated and ω-6 derived arachidonic acid (AA) is converted by cyclooxygenases (COX) to chemical mediating eicosanoids including prostaglandins (E2), thromboxanes (A2) and leukotrienes (LTB4).3,4,7 LTB4’s significant chemoattractant properties stimulate an influx of polymorphonuclear leukocytes (PMNs) to affected tissues (PMN infiltration), where they phagocytose microbes and cellular debris and neutralise and clear pathogens via phagocytosis, apoptosis and efferocytosis.4,8,9 This process continues until PMNs are exposed to AA-derived PGE2, resulting in the preferential synthesis of lipoxin (LXA4 via 15-lipoxygenase) over LTB4 and the subsequent downregulation of PMN infiltration. This shift from pro- to anti-inflammatory signalling and lipid mediator biosynthesis characterises the onset of the inflammatory resolution phase.7,8

The biological aim of the resolution phase is to re-establish a homeostatic state in the body and limit tissue damage that naturally occurs as a consequence of the inflammatory response.2,3 This is an active process requiring optimal concentrations of a class of bioactive lipid mediators called specialised pro-resolving mediators (SPMs). SPMs promote inflammation resolution and self-limitation, thereby inhibiting the extensive tissue damage, infection and disease/pathology that can be caused by uncontrolled inflammatory processes.2,3,8,10


SPMs are potent, bioactive pro-resolving lipid mediators naturally occurring in human tissues (mainly immune and endothelial cells), fluids and exudates including the brain, cerebrospinal fluid, adipose cells, synovial fluid, lymph nodes, plasma, serum and breast milk.7,8,10 The ω-3 essential fatty acids are precursors for the structurally and functionally distinct SPM families: resolvins (from eicosapentanoic [EPA], docosahexaenoic acid [DHA] and n-3 docosapentanoic acid [DPA]); protectins and maserins (from n-3 DPA and DHA); and lipoxins (from ω-6 AA).6,7,10-12 Locally synthesised at different stages and concentrations of the inflammatory process in a cell-specific manner, SPMs utilise specific mechanisms in target tissues to promote the resolution of inflammation and tissue repair without inhibiting immunological activity (‘immunoresolvent’).1,7,10,13 (see Breakout Box 1)* 

As the PUFAs, EPA, DPA and DHA are essential precursors for endogenous SPM synthesis, regular intake of sufficient concentrations of these essential lipids from high quality exogenous sources is necessary to maintain optimal tissue levels to support their roles in maintaining normal physiological functionality and homeostasis as well as ameliorating inflammatory- mediated disease states.3,6,14,15 Factors that can adversely affect endogenous EPA, DHA and SPM concentration and tissue activity include suboptimal intake, chronic inflammation, ageing, endotoxin exposure and the presence and severity of diseases.1,3,6

*References available on request.