Omega-3 Fatty Acids (Fish Oil) in Oncology

Anti-inflammatory EPA and DHA with evidence for cancer cachexia, chemotherapy tolerability, and survival

Key Points

• EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) at 2–4 g/day significantly reduce cachexia — increasing lean body mass and hand-grip strength — in pancreatic and other GI cancers.
• The ESPEN guidelines recommend 2 g/day combined EPA+DHA for all cancer patients at nutritional risk or with cancer-associated cachexia.
• Incorporated into EPA-enriched oral nutritional supplements (ProSure, Supportan) validated in clinical trials for weight maintenance during treatment.
• Pre-clinical and limited clinical evidence for direct anti-tumor activity via resolvin/protectin pathway induction and NF-κB suppression.
• May enhance the efficacy of platinum-based chemotherapy and reduce neurotoxicity (oxaliplatin peripheral neuropathy).
• Antiplatelet effect at high doses (>3 g/day) — discontinue 7 days prior to surgery.

Mechanisms Relevant to Oncology

Omega-3 polyunsaturated fatty acids (EPA, C20:5n-3; DHA, C22:6n-3) are incorporated into cell membrane phospholipids, displacing the pro-inflammatory omega-6 arachidonic acid (AA). This membrane competition fundamentally alters eicosanoid production: prostaglandins and thromboxanes derived from EPA (3-series) and DHA (3-series) are less biologically active than their AA-derived (2-series) counterparts, resulting in a net anti-inflammatory shift. **Key mechanisms in cancer biology:** 1. **NF-κB suppression:** EPA and DHA reduce IκB kinase activation, lowering pro-inflammatory cytokine…

Clinical Evidence

**Cancer Cachexia:** This is the strongest and most clinically actionable evidence base for omega-3s in oncology. A landmark RCT (Fearon et al., Gut 2003) in pancreatic cancer patients demonstrated that EPA-enriched oral supplements (2.2 g EPA/day) stabilized weight and lean body mass compared to isocaloric/isonitrogenous controls. Subsequent meta-analyses confirm: - Significant preservation of lean body mass (mean difference +0.87 kg) - Improved hand-grip strength and functional status - Reduced IL-6 and CRP levels - Better overall survival in the highest-adherence patients **ESPEN…