Overview
Omega-3 fatty acids — eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) — are anti-inflammatory polyunsaturated fatty acids that counterbalance the pro-inflammatory effects of omega-6 arachidonic acid. They act through multiple mechanisms: competitive COX-2/5-LOX substrate (reducing prostaglandin/leukotriene production), precursors to specialized pro-resolving mediators (SPMs) (resolvins, protectins, maresins), and direct microbiome modulators.
Microbiome Effects
- Omega-3 supplementation increases Lactobacillus and Bifidobacterium while reducing Proteobacteria — shifting the microbiome toward an anti-inflammatory composition bi 2017 omega3 pufa ameliorate t1d autoimmunity.
- EPA/DHA enhance intestinal barrier integrity, reducing endotoxemia.
- The microbiome-mediated effects may explain why omega-3 supplementation has broader anti-inflammatory effects than expected from direct COX inhibition alone.
Condition-Specific Evidence
- T1D autoimmunity: Ameliorates autoimmune diabetes in NOD mice via microbiome + immune modulation bi 2017 omega3 pufa ameliorate t1d autoimmunity.
- ED: Improves endothelial function in chronic pelvic ischemia shim 2016 omega3 erectile dysfunction chronic pelvic ischemia; altered FA profiles in diabetic ED ben khedher 2017 fatty acids diabetic erectile dysfunction.
- MS: Dietary omega-3 studied for neuroinflammation modulation katzsand 2018 diet ms mechanistic review hoffman 2023 dietary strategies eae ms.
- Depression/sexual dysfunction: Systematic review evidence for anti-inflammatory interventions including omega-3 malekpour 2025 anti inflammatory interventions mental health sexual performance.
- Hashimoto's: Part of dietary prevention strategies puszkarz 2018 food nutrition hashimotos prevention.
Cross-References
- polyunsaturated fatty acids — PUFA umbrella concept
- arachidonic acid — pro-inflammatory omega-6 counterpart
- inflammation — omega-3 reduces NF-kB/COX-2/IL-6
- interleukin 6 — reduced by omega-3 supplementation
- endothelial dysfunction — omega-3 improves endothelial NO signaling
- lipid peroxidation — PUFAs as both target and defense substrate