Omega-3 (EPA/DHA) vs Resveratrol

Mechanism

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.

Standard Dosing

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

Side Effects

• Fishy burps/aftertaste
• Mild GI upset
• Loose stools at high doses
• Potential increased LDL in some individuals

Contraindications

• Active bleeding disorders
• Scheduled surgery (discontinue 2 weeks prior)
• Fish/shellfish allergy (use algal-derived)

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Mechanism

Resveratrol activates SIRT1 (the longevity sirtuin) via allosteric binding, promoting deacetylation of PGC-1alpha (mitochondrial biogenesis), FOXO3 (stress resistance), and p53 (DNA repair). It inhibits NF-kB and COX-2, reducing chronic inflammation. Resveratrol also activates AMPK independently of SIRT1 and inhibits phosphodiesterases (PDEs), raising cAMP levels. It improves endothelial function via eNOS upregulation and NO production.

Standard Dosing

250-500mg trans-resveratrol daily

Timing

Morning with a fat-containing meal. Often taken alongside NMN for synergistic sirtuin activation.

Cycle Duration

ongoing

Side Effects

• GI upset/diarrhea at high doses
• Headache
• Joint pain (rare)
• Insomnia (if taken late)

Contraindications

• Estrogen-sensitive cancers (theoretical ER agonism)
• Bleeding disorders
• Pregnancy/lactation

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