Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Omega-3 (EPA/DHA) | Palmitoylethanolamide (PEA) | |
|---|---|---|
| Category | Supplements | Supplements |
| Standard Dose | 2-4g combined EPA/DHA daily (targeting 2:1 EPA:DHA ratio for inflammation; 1:1 for cognitive) | — |
| Timing | With meals containing fat for absorption. Split dose AM/PM. | — |
| Cycle Duration | ongoing | — |
| Evidence Level | strong_human | Strong |
EPA and DHA incorporate into cell membrane phospholipids, modulating membrane fluidity and lipid raft signaling. EPA competitively inhibits arachidonic acid conversion via COX-2 and 5-LOX, reducing pro-inflammatory eicosanoids (PGE2, LTB4) while generating anti-inflammatory resolvins and protectins. DHA is critical for neuronal membrane integrity, modulating BDNF expression and synaptic plasticity via Nrf2 and NF-kB pathways.
2-4g combined EPA/DHA daily (targeting 2:1 EPA:DHA ratio for inflammation; 1:1 for cognitive)
With meals containing fat for absorption. Split dose AM/PM.
ongoing
Endocannabinoid-like lipid that activates PPAR-alpha and indirectly enhances endocannabinoid tone. Potent anti-inflammatory and analgesic without acting directly on CB1/CB2. Reduces mast cell activation, neuroinflammation, and chronic pain.
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