By Georgia Marrion MNut, BHSci, Adv. Dip Health Sci (Nat)
The ω-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (ω-3 DPA, 22:5) is an intermediate metabolite in the endogenous fatty acid pathway with unique mechanistic and functional effects.1-3
The bidirectional conversion from eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) via ω-3 DPA, which is variable both inter-individually and within different cells and tissues, is the biological basis of ω-3 DPA’s role as a transitional reserve of EPA and DHA, particularly in major metabolic organs including the brain and heart.1,2,4-7 In addition, ω-3 DPA is a precursor for specialised pro-resolving mediators (SPMs), a class of 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, lymph nodes, plasma and serum.1,8-11 This is demonstrated by pharmacokinetic analyses following DPA supplementation resulting in increases in ω-3 DPA, EPA, DHA and SPM resolvins D5n-3DPA (RvD5n-3DPA), maresins (MaR)-1 and protectins in plasma triacylglycerol fractions and red blood cell phospholipids.2,4,6,12,13
Figure 1: Biosynthetic pathway from EPA to DHA via DPA. 24:5, n-3, tetracosapentaenoic acid; 24:6, n-3, tetracosahexaenoic acid.2
While ω-3 DPA is present in small concentrations in seafood, poultry, red meat and eggs, population data has found that average DPA intake levels are significantly low, particularly in women and individuals aged below 19 years of age.3,4,14 Factors that can adversely affect endogenous ω-3 and DPA concentrations and tissue activity include suboptimal intake, high-fat or fructose diets, chronic inflammation, aging, endotoxin exposure and the presence and severity of diseases.15-18
While research is ongoing, current evidence indicates that ω-3 DPA’s chemical structure is responsible for unique and common (to EPA and DHA) physiological mechanisms that translate to significant therapeutic benefits in relation to inflammation, immunity, cardiovascular and nervous system health.2,4,19
DPA MECHANISMS
Immune Health and Inflammation
The appropriate initiation and resolution of an inflammatory response to restore homeostasis in the body and limit tissue damage is a key aspect of healthy immune system functionality.1,16,19,20
The importance of ω-3 DPA and its lipid mediators (LMs) in this process is emphasised by elevated levels observed during acute inflammation and infection in vivo and its immunoresolvent properties (the capacity to promote inflammation resolution and tissue repair without inhibiting immunological activity).7,8,10,15,21
Immunoresolvent mechanisms demonstrated by ω-3 DPA LMs include reducing the time to inflammation resolution, inhibiting neutrophil infiltration and leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) synthesis and downregulating the expression and synthesis of pro-inflammatory mediators/modulators (nuclear factor-kappa B (NF-κB), metalloproteinase-2 (MMP-2) and MMP-9)) and cytokines (IL-6, IL-1β, iNOS, COX-2, TNF-α) at the site of inflammation.1,2,7,18,22-24 ω-3 DPA LMs also upregulate pro-inflammatory cytokines (IL-10) and promote macrophage phagocytosis.22,24
Cardiovascular Health
Chronic inflammation is a primary factor in cardiovascular disease (CVD) risk and onset, with increasing evidence demonstrating the significance of impaired resolution signaling and function in CVD pathogenesis (initiation, progression, consolidation).1,25-28
ω-3 DPA LMs play a key role in cardiovascular health, with low levels associated with elevated C-reactive protein (CRP), plaque formation and peripheral blood neutrophil, monocyte, platelet activation and an increased risk of cardiovascular disease onset and progression.13,14,23,29
Conversely, high levels have been shown to reduce platelet aggregation, inhibit angiogenesis, modulate endothelial cell function (stimulating vascular endothelial growth factor) and reduce vascular thromboxane B2 concentrations, aortic lesions and carotid arterial wall thickness.1,2,18,29,30 Further, ω-3 DPA ameliorates hypertriglyceridaemia by downregulating the expression of fat-synthesis genes (sterol-regulatory element-binding protein-1c (SREBP-1c), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), acetyl coenzyme A carboxylase (ACC-1), and fatty acid synthase (FASn)).1,18
Nervous System Health
Unresolved inflammation (‘neuroinflammation’) is a central pathophysiological process in central nervous system (CNS) dysfunctionality including cognitive impairment and neurodegenerative disease onset and progression.31-35
ω-3 DPA LMs anti-inflammatory mechanisms are considered central to its modulation of neuroinflammation and its physiological and functional consequences.36 Specific neuroprotective effects of ω-3 DPA LMs include ameliorating synaptic function loss caused by age-related oxidative stress and microglia activation, key processes involved in declining cognitive health.30,36
Such mechanisms underlie the clinically relevant benefits of ω-3 DPA (see Table 1).
