NMN (Nicotinamide Mononucleotide) vs Palmitoylethanolamide (PEA)

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

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.

Contraindications

• None established at standard doses