Pro-Resolvin Mediators: Nature’s Inflammation-Resolving Molecules

---

What Are Pro-Resolvin Mediators?

Pro-resolvin mediators are a class of specialized bioactive lipid compounds that actively resolve inflammation. Unlike anti-inflammatory drugs that simply block inflammation, pro-resolving mediators (PRMs) are involved in turning off the inflammatory response and returning tissues to homeostasis.

These mediators include:

• Resolvins

• Protectins

• Maresins

• Lipoxins

Collectively, these compounds are part of a family called Specialized Pro-Resolving Mediators (SPMs), which are derived from omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). They act as brakes on the inflammatory process, preventing chronic inflammation, fibrosis, and tissue damage.

---

Inflammation: The Good, the Bad, and the Chronic

Inflammation is essential. It helps us fight infection, repair injury, and neutralize toxins. However, inflammation that doesn’t resolve properly becomes destructive, leading to a cascade of chronic diseases.

Diseases Associated With Chronic Inflammation:

• Cardiovascular disease

• Type 2 diabetes

• Autoimmune disorders (RA, lupus, MS)

• Neurodegenerative diseases (Alzheimer’s, Parkinson’s)

• Depression and anxiety

• Asthma and COPD

• Chronic pain syndromes

• Long COVID and post-viral fatigue

Resolution of inflammation is not passive. It’s not enough for inflammatory signals to stop; the body must actively shut down the response and repair the tissue. That’s where pro-resolvin mediators come in.

---

How Do Pro-Resolvin Mediators Work?

These powerful molecules orchestrate a return to homeostasis after injury, infection, or immune activation. Here's how:

1. Stop Neutrophil Infiltration

During acute inflammation, neutrophils flood the area. Resolvins and protectins signal a stop to further recruitment, preventing collateral damage.

2. Promote Clearance of Inflammatory Debris

Pro-resolvin mediators enhance efferocytosis—the removal of dead cells, pathogens, and apoptotic neutrophils by macrophages.

3. Switch Macrophages to a Healing Phenotype

They shift immune cells from a pro-inflammatory (M1) state to an anti-inflammatory, tissue-repairing (M2) state.

4. Inhibit Pro-Inflammatory Cytokines

They block the production of TNF-α, IL-1β, and IL-6, major drivers of systemic inflammation.

5. Promote Tissue Regeneration

Maresins and protectins contribute directly to cell proliferation, collagen deposition, and wound repair.

---

Types of Specialized Pro-Resolving Mediators (SPMs)

🔵 Resolvins

Derived from omega-3 EPA and DHA. Two main subtypes:

• E-series resolvins (from EPA)

• D-series resolvins (from DHA)

Key actions:

• Stop neutrophil infiltration

• Reduce pain by acting on nociceptors

• Enhance clearance of bacteria and damaged cells

🟢 Protectins

Derived from DHA.

Key actions:

• Potent anti-inflammatory effects in the brain and retina

• Neuroprotective

• Reduce oxidative stress

• Improve insulin sensitivity

🔴 Maresins

Derived from DHA in macrophages.

Key actions:

• Promote wound healing and tissue regeneration

• Improve resolution in chronic wounds and lung inflammation

• Enhance efferocytosis

🟠 Lipoxins

Derived from arachidonic acid (omega-6) via lipoxygenase pathways.

Key actions:

• One of the earliest discovered pro-resolving molecules

• Balance omega-6 pathways with resolution activity

• Work synergistically with omega-3 derived mediators

---

Why Are Pro-Resolving Mediators Important?

Most people associate inflammation control with blocking it—using NSAIDs, corticosteroids, or immune-suppressing drugs. But these tools do not restore balance, and often impair healing.

What Makes PRMs Different?

Feature	Anti-Inflammatory Drugs	Pro-Resolving Mediators
Block Inflammation?	✔️	❌
Resolve Inflammation?	❌	✔️
Promote Healing?	❌	✔️
Immune Suppression?	✔️	❌
Side Effects?	Common	Minimal
Support Tissue Regeneration?	❌	✔️

---

Conditions Benefiting from Enhanced Pro-Resolving Activity

SPMs are being researched in:

• Atherosclerosis: SPMs reduce plaque inflammation and support vascular repair.

• Arthritis: Reduce synovial inflammation and pain without GI side effects.

• Neuroinflammation: Alzheimer’s, brain fog, and mood disorders.

• Long COVID: Persistent immune activation may be calmed by resolvins.

• Liver Disease: SPMs support resolution of steatohepatitis and fibrosis.

• Asthma and COPD: Promote resolution of airway inflammation.

• Autoimmunity: Improve immune balance without suppressing defense.

---

Why Do People Become Deficient in Pro-Resolving Mediators?

Even though they are made from essential fatty acids, modern lifestyle factors reduce our ability to produce SPMs:

⛔ Common Causes of SPM Deficiency

• Low omega-3 intake (especially DHA)

• High omega-6 to omega-3 ratio

• Aging

• Chronic stress and high cortisol

• Persistent inflammation (depletes precursors)

• Poor liver function (affects conversion enzymes)

• Genetic SNPs affecting COX or LOX enzymes

---

How Can We Support Pro-Resolving Mediator Production?

A functional and integrative medicine approach offers powerful tools to enhance SPM levels naturally.

---

🐟 1. Increase Omega-3 Fatty Acids

Since SPMs are made from EPA and DHA, increasing omega-3 intake is step one.

Best sources:

• Wild-caught salmon

• Sardines and anchovies

• Cod liver oil

• Omega-3 supplements like Omega 1300

💡 Clinical note: Higher doses (2000–4000 mg/day of combined EPA+DHA) may be needed for those with high inflammation.

---

🧬 2. Direct SPM Supplementation

Several supplement companies now offer purified SPMs in capsule form—especially 17-HDHA, 18-HEPE, and MaR1.

• Shown in studies to reduce CRP and IL-6

• May improve pain, stiffness, and resilience after illness

---

🥗 3. Balance Omega-6 Intake

Too much linoleic acid (found in seed oils like corn, soybean, and sunflower) competes with omega-3s.

• Replace seed oils with olive oil, avocado oil, and grass-fed fats

• Choose organic, pasture-raised meats and eggs

---

🏋️ 4. Reduce Chronic Inflammation

SPMs are depleted in persistent inflammation. Address:

• Gut dysbiosis (use ProbioHealth 350)

• Blood sugar dysregulation

• Sleep deprivation

• Chronic infections or toxic exposure

• Stress (consider adaptogens like Hormone Balance)

---

💊 5. Support Enzyme Activity

SPM production depends on enzymes like COX-2, 5-LOX, and 15-LOX. These require:

• Zinc

• Magnesium

• Selenium

• Vitamin D

Support these with:

• ActiveMulti

• Multi-Mineral

• K2-D3 5000

---

🌿 6. Lifestyle Strategies

• Exercise: Moderate physical activity boosts SPM levels

• Fasting: Intermittent fasting may upregulate resolution pathways

• Sauna therapy: Reduces systemic inflammation and stimulates repair

• Cold exposure: Activates anti-inflammatory and mitochondrial pathways

---

Are There Risks or Side Effects?

SPMs are endogenously produced and appear safe in supplement form. They do not suppress immunity but help recalibrate it.

However:

• Direct SPM supplements are not yet FDA approved.

• Pregnant or breastfeeding individuals should consult their physician.

• Omega-3s at high doses may increase bleeding risk in certain individuals.

---

Summary: Why Pro-Resolvin Mediators Matter

Pro-resolvin mediators represent a paradigm shift in how we think about inflammation. Rather than blocking symptoms, they help the body complete the healing cycle.

They are the unsung heroes of immune resolution, tissue repair, and health restoration. Supporting your body’s production of SPMs through omega-3s, nutrient optimization, and anti-inflammatory lifestyle changes may be one of the most powerful tools in functional medicine.

---

Call to Action

At Revolution Health & Wellness, we specialize in root-cause, functional approaches to inflammation, pain, and chronic disease. If you want to harness the power of pro-resolving mediators to optimize your health, reduce inflammation, and enhance recovery:

📅 Book your consultation today and start your personalized inflammation resolution plan.

---

References

1. Serhan CN, et al. "Resolution of inflammation: state of the art, definitions and terms." FASEB J. 2007.

2. Chiang N, Serhan CN. "Specialized pro-resolving mediator network: An update on production and actions." J Allergy Clin Immunol. 2017.

3. Basil MC, Levy BD. "Specialized pro-resolving mediators: endogenous regulators of infection and inflammation." Nat Rev Immunol. 2016.

4. Clària J, et al. "Resolution of inflammation: a new therapeutic frontier in human disease." J Clin Invest. 2015.

5. Norris PC, Serhan CN. "Omega-3 fatty acids in inflammation resolution." Br J Clin Pharmacol. 2018.