Resolution is an active program, not an absence
For decades, inflammation was thought to simply 'wear out' when the trigger ended. We now know that resolution is a distinct, actively-signaled biological program — as tightly regulated as the initial response. When resolution fails, inflammation persists.
NSAIDs suppress the initial cascade — and simultaneously block the synthesis of resolving mediators. Suppression is not resolution. This distinction is why chronic NSAID use paradoxically slows healing.
Specialized pro-resolving mediators
SPMs — resolvins, protectins, and maresins — are synthesized on demand from omega-3 fatty acids (EPA and DHA) at sites of inflammation. They actively terminate neutrophil recruitment, promote macrophage clearance of debris, and restore tissue homeostasis.
E-series resolvins derive from EPA; D-series from DHA. Both stop neutrophil infiltration and stimulate macrophage phagocytosis of dead cells — the housekeeping step required to end inflammation.
DHA-derived mediators that protect neural tissue and dampen T-cell responses. Low protectin capacity is implicated in neuroinflammatory and autoimmune conditions.
'Macrophage mediators in resolving inflammation.' Produced by macrophages themselves; potent at promoting tissue regeneration once the immune response is quenched.
Feeding the pathway
You cannot synthesize resolvins from substrate you do not eat. An Omega-3 Index above 8% is the practical benchmark that the raw material is present. Below 4% and the resolution machinery is running on fumes regardless of what else you do.
Achievable with 2–3 g combined EPA+DHA daily plus two fatty-fish meals per week. Retest at 90 days.
"You are not fighting inflammation. You are provisioning the pathway that ends it."
- Confirm your omega-3 supplement is triglyceride-form, molecularly distilled, and provides ≥ 2 g EPA+DHA.
- Eat fatty fish (salmon, sardines, mackerel) twice this week.
- Order or re-draw the Omega-3 Index at day 90; aim for ≥ 8%.
- Reduce industrial seed oils that shift the omega-6:3 ratio against you.
- Track how quickly minor injuries resolve — a subjective but real signal of resolving capacity.