NMN (Nicotinamide Mononucleotide) vs Omega-3 (EPA/DHA)

Mechanism

NMN is a direct biosynthetic precursor to NAD+ via the salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT). Elevated NAD+ activates sirtuins (SIRT1-7), PARP DNA repair enzymes, and CD38/CD157 signaling. SIRT1 activation deacetylates PGC-1alpha (mitochondrial biogenesis), FOXO transcription factors (stress resistance), and NF-kB (anti-inflammatory). NMN also enters cells via the Slc12a8 transporter, recently identified in the gut.

Standard Dosing

500-1000mg daily

Timing

Morning on empty stomach. Sublingual absorption bypasses first-pass metabolism.

Cycle Duration

ongoing

Side Effects

• Mild GI discomfort
• Flushing (rare, unlike niacin)
• Mild headache during initial use

Contraindications

• Active cancer (theoretical concern: NAD+ may fuel rapidly dividing cells)
• Pregnancy/lactation (insufficient data)
• Theoretical concern in active cancer (NAD+ fuels all rapidly dividing cells)

Best Stacking Partners

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)

Best Stacking Partners