What are Pro-resolving Lipid Mediators?

Specialized pro-resolving mediators (SPMs) are produced in human blood, milk, and brain tissue from naturally-occurring omega-3 and omega-6 polyunsaturated fatty acids that help support the body’s innate immune response during the “resolution phase” of acute inflammation, clearance of pathogenic microbes, support a normal pain response and promote tissue regeneration. Researchers have discovered that these SPMs include a superfamily of endogenous lipid-based chemical mediators known as resolvins, maresins, protectins, and lipoxins. These unique metabolites actively down-regulate the inflammatory response without compromising a healthy immune system response.

SPMs themselves do not block the initial phases of acute inflammation, which is a vital response to injury, infection, and illness, but rather have been shown in research to evoke novel anti-inflammatory and pro-resolving mechanisms that aid in the process of resolving acute inflammation, accelerating the return to homeostatic balance within the body. This active resolution process controlled by SPMs is done so via targeting immune cells to stop actively responding to pro-inflammatory chemical mediators, thus limiting overall inflammation. More specifically, SPMs promote resolution by binding to G-protein coupled receptors that can modify cellular behaviors such as mediating pro-inflammatory chemokine, cytokine, and adipokine regulation, microRNA transcription and translocation, and cell traffic. At the site of inflammation, SPMs promote clearance of damaging byproducts, microbes, and debris by enhancing macrophage phagocytosis.

Resolution for Pain Management, Tissue Repair, & Inflammation

SPMs may help support a normal pain response caused by inflammation and injury. Evidence from research studies shows that SPM biosynthesis and concentrations are much lower in circulation among patients with chronic inflammatory conditions. An RCT observing a population who suffer from chronic headaches showed that increasing omega-3 fatty acid intake while reducing omega-6s raised serum SPM levels which significantly attenuated headache pain through increasing production of antinociceptive mediators and improving the overall quality of life. In an animal model of rheumatoid arthritis with significantly lower levels of resolvin D3 mediators (members of the SPM family), when mice were given resolvin mediators, they experienced significantly improved joint pain, stiffness, and inflammation due to lower levels of leukocytes and inflammatory eicosanoid infiltration.

In an in vitro animal model of peritonitis, upon administration of maresin lipid mediators, neutrophilic phagocytosis of E. coli and bacteria at the site of infection increased significantly, reducing the resolution interval by 10 hours.

Furthermore, in a clinical trial of obese women, those who supplemented with omega-3 fatty acids had statistically significantly higher concentrations of DHA-derived resolvins which activated specific genetic pathways that are responsible for up-regulating antioxidant enzymes and lipid metabolism in those subjects.

Why SPMs?

Unlike common anti-inflammatory drugs and medications, SPMs have favorable profiles and fortunately do not suppress immune system function as they are naturally-produced and involved in the biological process of inflammatory resolution. Direct supplementation may help in facilitating the body’s natural response to inflammatory challenges caused by aging, physical traumas, inflammatory-rich/nutrient-poor diets, chronic stress, infections, and other insults. Research suggests that supplementation with pro-resolving mediators may also be beneficial for those who have single nucleotide polymorphisms (SNPs) for enzymes involved in SPM biosyntheses, such as the ALX/FPR2 SNPs, dysfunctioning SPM receptors, and inflammatory autoimmune conditions, as well as for those whose diets are low in omega-3 essential fatty acids (e.g., wild-caught fatty fish, flaxseed, walnuts). A diet enriched in omega-3s, coupled with high-quality, highly-concentrated supplemental SPMs, is shown to have favorable effects in reducing overall inflammation.