NR (Nicotinamide Riboside) vs Palmitoylethanolamide (PEA)

Mechanism

NR is converted to NMN by nicotinamide riboside kinases (NRK1/NRK2), then to NAD+ via the salvage pathway. Like NMN, elevated NAD+ activates sirtuins, PARPs, and CD38. NR has demonstrated ability to cross the blood-brain barrier and elevate brain NAD+ levels. It supports mitochondrial function, DNA repair, and circadian rhythm regulation through SIRT1-mediated deacetylation of BMAL1 and CLOCK proteins.

Standard Dosing

300-600mg daily

Timing

Morning with or without food.

Cycle Duration

ongoing

Side Effects

• Mild nausea
• Warmth/flushing (mild)
• GI upset
• Fatigue in some during initial days

Contraindications

• Active cancer (same theoretical NAD+ concern as NMN)
• Pregnancy/lactation
• Theoretical cancer concern shared with NMN

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