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Specialized Pro-Resolving Mediators Supplementation in Adults With Obesity

A Clinical Trial Summary

Patients with obesity suffer from chronic, low-grade inflammation.1 That’s partly due to dysfunctions in the ability to endogenously create specialized pro-resolving mediators (SPMs).1 SPMs communicate with immune cells, telling them the inflammatory process is no longer needed and to finish the job.2 However, in many conditions, including obesity, the capability to send these potent signaling molecules can diminish, and so too can their effects.1-3 As a result, inflammation smolders and further perpetuates a vast array of associated conditions such as insulin resistance and atherosclerosis.1-3

For decades we assumed inflammation gradually faded away after being activated; however, we now know this resolution phase of the inflammatory cycle is carefully orchestrated by distinct signals from SPMs.2 Without their signals, inflammatory processes continue, often at the expense of our health.2

In a recent nonrandomized uncontrolled clinical trial, adults with obesity took 2 g/d of a proprietary SPM supplement for four weeks to determine if it would increase circulating levels of SPMs.3 The researchers demonstrated an increase in six different SPM precursors and two important SPMs.3 Of particular interest, resolvin E1 (RvE1) increased by 350%, and maresin 1 (MaR1) increased by 470% after supplementation with SPMs.3

SPM synthesis blunted in obese patients

In a previous clinical study comparing obese patients with metabolic syndrome to healthy controls, each group took 2.4 g/d of omega-3 fatty acids (SPM precursors), and SPM levels were monitored.1 While researchers didn’t find a difference in baseline SPMs between the two groups, obese patients with metabolic syndrome showed a blunted SPM production capacity despite being given parent compounds (omega-3s), compared to their healthy controls.1

Interesting effects of SPMs most elevated in this study

The researchers in the recent study in obese patients draw attention to the increase in a particular SPM, RvE1, because it has a role in glucose regulation and has been linked to plaque reversal in patients with coronary artery disease.3 These findings are especially important as “over 80% of coronary heart disease patients are overweight or obese,” obesity hastens the progression of the disease, and insulin insensitivity increases risks of complications from heart disease.4 Preclinical research in animals and human adipocytes suggests MaR1 (the other drastically increased SPM in the obesity study) may mitigate the insulin resistance induced by proinflammatory cytokines and reduce hyperglycemia from eating a high-fat diet, though these findings are relatively new, and we’re yet unsure if they will translate into clinical medicine.3,5

Other effects noticed from the current study in obese patients: Three compounds called hydroxyeicosatetraenoic acids or HETEs were reduced from baseline.3 Some HETEs are associated with insulin resistance, increases in BMI, and serum leptin levels—so decreasing these would likely benefit obese patients clinically.3 Also, immune cells (B-cells) isolated from subjects and stimulated with a cytokine (IL-4) produced less proinflammatory IgG (but not IgM) antibodies, which may be an observation of the inflammatory response resolving, while not interfering with IgM production, which typically signals an active infection is being fought.3

Conclusions

The findings from this most recent study of administering a proprietary SPM supplement to obese patients represents a significant milestone. This study demonstrates that not only was this particular blend well-absorbed by obese patients, but also important SPM compounds that may provide far-reaching benefits can be drastically increased rather quickly, without adverse effects.3  The study tested a single proprietary SPM oil blend, which to date is the only commercially available product with published human, randomized, placebo-controlled trials to support its use.3,6-8

There are limitations to the findings of this study as the authors acknowledge: There was no placebo control, subjects were not randomized, there were not enough participants to detect sex differences (of which, we know there are likely to be), and the average age of the subjects (56 years old) may be higher than the ideal age to be preventing complications from obesity.3

The demand for SPM supplements is swelling, and it is unclear if all SPM products will produce the same clinical results. Nonetheless, this is an exciting advancement, and if you’re a clinician looking to learn more about SPMs, their mechanisms, and clinical utilization please see this resource to learn more.

 

Citations:

  1. Barden AE et al. Specialized proresolving lipid mediators in humans with the metabolic syndrome after n-3 fatty acids and aspirin. Am J Clin Nutr. 2015;102(6):1357-1364.
  2. Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. 2014;510(7503):92-101.
  3. Al-Shaer AE et al. Enriched marine oil supplement increases specific plasma specialized pro-resolving mediators in adults with obesity. J Nutr. 2022;152(7):1783-1791.
  4. Ades PA et al. Obesity in coronary heart disease: An unaddressed behavioral risk factor. Prev Med. 2017;104:117-119.
  5. Martínez-Fernández L et al. Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice. J Physiol Biochem. 2021;77(1):167-173.
  6. Souza PR et al. Enriched marine oil supplements increase peripheral blood specialized pro-resolving mediators concentrations and reprogram host immune responses: a randomized double-blind placebo-controlled study. Circ Res. 2020;126(1):75-90.
  7. Schaller MS, et al. Treatment with a marine oil supplement alters lipid mediators and leukocyte phenotype in healthy patients and those with peripheral artery disease. J Am Heart Assoc. 2020;9(15):e016113.
  8. Callan N et al. Early evidence of efficacy for orally administered SPM-enriched marine lipid fraction on quality of life and pain in a sample of adults with chronic pain. J Transl Med. 2020;18(1):401.

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