Are You Resolving Inflammation?

Chronic inflammation is connected to degenerative aging.

This has prompted scientists to coin the term “inflammaging” to describe this destructive process.¹

Recent discoveries shed light on our understanding of inflammaging.²

Research shows that resolution of inflammation may be as important as inhibition of inflammation in the fight against age-related disorders.

The field of inflammation resolution is generating increasing interest.

This led scientists to identify compounds that help resolve inflammation. They are named:

Specialized pro-resolving mediators (SPMs)

Increasing SPM levels in preclinical models yields compelling findings.³

Clinical trials are currently recruiting participants and publishing results.⁴

How SPMs Resolve Inflammation

Specialized pro-resolving mediators are derived from polyunsaturated fatty acids, predominantly found in fish.³

In response to certain conditions, such as inflammation, small amounts of omega-3 fatty acids are converted to even more beneficial compounds: SPMs.³

Chronic inflammatory conditions such as inflammaging, have been associated with lower concentrations of SPMs in the body.⁵

SPMs resolve inflammation by three mechanisms:^6-8

• Removing dead and dying cells through a process in which macrophage immune cells engulf and digest dying or dead cells. This helps clean up the aftermath of inflammatory cascades.
• Restoring inflammation balance by decreasing pro-inflammatory mediators, while increasing compounds that have anti-inflammatory activity.
• Renewing damaged tissue by promoting cellular regeneration.

These benefits promise to help prevent many chronic aging disorders including deposition of plaque in the arteries (atherosclerosis).⁹

Inflamed Arteries

Inflammation is a key player in the development of heart disease.

Atherosclerosis is partially driven by an imbalance between pro-inflammatory and inflammation-resolving mechanisms in the artery inner walls.⁹

Atherosclerosis can begin when LDL cholesterol (the “bad” cholesterol) particles get trapped inside the endothelium (lining of the arteries).

Macrophages enter the endothelium to clear out these oxidized LDL particles. If there is a lack of pro-resolving mediators, these macrophages will change into foam cells.⁹

This is a dangerous state that generally results in the foam cells dying and releasing their contents, creating an even greater pro-inflammatory environment.⁹

SPMs come into play here by initiating the removal of dead cells and foam cells through a process called efferocytosis.

If these cells are not removed, they contribute to plaque progression, which leads to atherosclerosis that endangers the heart, kidneys, and brain.^9,10

How SPMs Differ from Omega-3s

The process of converting omega-3 fatty acids into SPMs requires several steps in the body.

When one eats cold water fish or takes fish oil supplements, tiny amounts may be converted to pro-resolving mediators (SPMs).

To meaningfully resolve inflammaging, higher amounts of standardized SPMs are often required beyond what can be obtained with fish oil.

Preclinical Research on SPM Precursors

In preclinical studies, SPMs and SPM precursors have been shown to have a variety of biological benefits.

Studies in mice have demonstrated impressive resolution benefits in a variety of disease models using the SPM precursor 18-HEPE.

SPM precursors enable formation of specialized pro-resolving mediators (SPMs) in the body.

One study involved a rodent model that mimics some of the complications related to cardiovascular disease. Following surgery, researchers injected mice with the SPM precursor 18-HEPE every three days.¹²

The mice that received 18-HEPE were significantly shielded from damaging complications brought on by the surgical procedure.

Another study used a mouse model of melanoma metastasis. Researchers pretreated mouse melanoma cells with the SPM precursor 18-HEPE while controls were not treated.

Healthy mice were then administered the SPM precursor 18-HEPE-treated melanoma cells and received additional 18-HEPE injections every other day. The SPM precursor-treated mice had significantly less formation of tumor colonies compared to controls.¹³

Another group of researchers found that treatment with the SPM precursor 17-HDHA was able to reverse pain behavior in two rat models of osteoarthritis.¹⁴

New Human Trial of SPM Precursors

A human trial of SPM precursors was published in January 2020 and showed remarkable results.

In this study, 22 healthy volunteers aged 19 to 37 were randomized. One group received an enriched fish oil supplement containing omega-3 PUFAs plus a combination of SPM precursors, including 18-HEPE, 17-HDHA, and 14-HDHA. The other group received a placebo.¹⁸

Researchers separated the participants into different dosing groups and performed a series of tests. They were able to conclude that the SPM precursors:

• Significantly increased cell surface proteins involved in reversing inflammation and platelet aggregation (which leads to harmful clotting) caused by the addition of a pro-inflammatory stimulus in the drawn blood of the patients.
• Increased clearance of Staphylococcus aureus and E. coli, by immune cells, which was highest at the final measurement, after 24 hours.
• Decreased platelet activation, a central part of the process that leads to a blood clot, in association with an increased level of resolvins.
• Increased the expression of genes linked to immune responses, recruitment of immune cells that fight infection and other diseases, and cellular metabolism in peripheral blood cells.

Omega-3s Help Resolve Inflammation

Because the original sources of SPMs are primarily the omega-3 fatty acids EPA and DHA, increasing the intake of these healthy fats will assist in resolving inflammation.^19-21

In a recent clinical trial, researchers showed that in response to a pro-inflammatory stimulus, EPA and DHA intake leads to the formation of more SPMs.²¹

For five months, participants were given either EPA and DHA or a placebo daily, before receiving a pro-inflammatory stimulus. Blood was collected daily for five days after receiving the stimulus.

By the fifth day, the group that received the EPA and DHA had 229% higher SPM levels than the placebo group. The levels of systemic inflammation, as measured by C-reactive protein, were significantly lower in the EPA/DHA treatment group compared to placebo.

The researchers repeated this testing using slight variations with their methods. Results consistently showed that EPA and DHA intake increases the level of SPMs in response to a pro-inflammatory stimulus.

This is great news for those who eat lots of cold-water fish and/or take high-potency fish oil supplements. Those with potential inflammaging issues may want to supplement with SPM Precursors:

• 18-HEPE
• 17-HDHA
• 14-HDHA

Summary

Chronic inflammation is so strongly correlated with age that scientists describe it as inflammaging.¹

For decades, researchers have been studying how to better inhibit inflammation. They are now also beginning to understand the importance of resolving inflammation.

An abundance of preclinical data has demonstrated substantial potential benefits of having higher levels of specialized pro-resolving mediators (SPMs) or SPM precursors.

Polyunsaturated fatty acids, particularly the omega-3 class, can be made into SPMs in your body. However, taking SPM precursors directly may be more effective.

Those concerned about chronic inflammation and persistently elevated inflammatory markers (like C-reactive protein and interleukin-6) may want to add a multi-SPM formula to their intake of omega-3 fatty acids.

Several clinical trials on SPM precursors are underway, with some completed and some still recruiting participants.⁴

Life Extension^® is also now recruiting generally healthy people for a clinical trial. If you are in the Fort Lauderdale area and are interested in participating, please call 1-866-517-4536.

If you have any questions on the scientific content of this article, please call a Life Extension^® Wellness Specialist at 1-866-864-3027.

References

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