It’s well known that fatty acids mediate inflammation. Omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) found in cold water fish and fish oil supplements, produce metabolites in the body called specialized pro-resolving mediators (SPMs). SPMs include resolvins, maresins, lipoxins, and protectins, and help to resolve inflammation and restore homeostasis.
There is an important upstream step between omega-3 fatty acids and SPM production. SPM precursors are converted to SPMs in the cell membrane upon active inflammation. SPM precursor supplementation has been shown to increase SPM plasma concentration in human studies. Examples of SPM precursors include 18-HEPE (18-hydroxyeicosapentaenoic acid), a hydroxylated metabolite of EPA;17-HDHA and 14-HDHA, hydroxylated metabolites of DHA; and others.
Omega-3s (EPA, DPA, DHA) SPM Precursors (18-HEPE, etc.) SPMs (resolvins, etc.)
Importantly, SPMs and their precursors prevent acute inflammation from becoming chronic and can be applied in many clinical scenarios. So, is there a benefit to taking the SPM precursors in addition to omega-3s? Some research suggests that when comparing healthy individuals to those with pathology, such as metabolic syndrome, plasma SPM levels do not rise with high-dose fish oil, suggesting that SPM biosynthetic pathways may be dysregulated. Therefore, SPM precursor supplementation may be a more effective way to resolve inflammation in these individuals.
The Studies
A randomized, double-blind, placebo-controlled study evaluated the effect of SPM precursors 18-HEPE, 17-HDHA, and 14-HDHA on patients with knee osteoarthritis. Fifty-one patients were treated for 12 weeks, and pain change was assessed via a Visual Analog Scale (VAS). Other pain and quality of life (QOL) parameters were also measured. A statistically significant reduction (p=0.039) in VAS pain scores was observed after 8 weeks in patients consuming SPMs versus placebo. Patients treated with SPMs also experienced a decrease in intermittent pain after 12 weeks and improved QOL.
An open-label trial investigated the effect of SPM precursors 18-HEPE and 17-HDHA on 44 participants with chronic pain for 4 weeks. Eligible participants included those experiencing moderate to severe chronic pain. Quality of life was assessed using the PROMIS-43 (Patient Reported Outcomes Measurement Information System) questionnaire and the American Chronic Pain Association (ACPA) QOL scale. There were significant improvements in pain intensity and pain interference. Significant changes were seen in the subdomains of fatigue, sleep disturbance, and social functioning. There was also a decrease in depression and anxiety.
An open-label pilot study published in the Journal of the American Heart Association evaluated the effects of an omega-3 supplement containing EPA, DHA, DPA, and several SPM precursors on peripheral artery disease (PAD). PAD and associated atherosclerosis are characterized by excessive inflammation. The effects of supplementation on plasma lipid mediators, inflammatory biomarkers, and leukocyte phenotype were studied in 10 healthy individuals and 10 patients with PAD. The supplement was given once daily for 5 days, followed by a 9-day washout period, then repeated at higher doses. The study length totaled 33 days. Supplementation increased plasma levels of SPMs, macrophage phagocytic activity, reduced expression of pro-inflammatory markers, and induced a less inflammatory phenotype in PAD patients.
Conclusions
SPMs promote a healthy inflammatory response and may be beneficial in pain management, cardiovascular function, healing and tissue health, and healthy immune cell function. Clinical trials are underway studying SPMs for treatment-resistant depression, periodontal disease, and other conditions.
