NR (Nicotinamide Riboside)

Mechanism of Action

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.

Dosing Protocol

Notes

NR has more published human clinical trials than NMN as of 2024. The Niagen form has been used in most research. NR and NMN should not typically be stacked — choose one NAD+ precursor. NR may be preferred for those prioritizing brain NAD+ due to BBB penetration data.

Stacking

• TMG (Betaine)
• Pterostilbene
• CoQ10
• Vitamin D3

Interactions

• TMG (Betaine) [LOW] — Recommended co-supplement to maintain methylation capacity
• Nicotinamide [MEDIUM] — Excess nicotinamide may inhibit sirtuins, partially negating NR benefits
• Similar considerations as NMN
• May reduce efficacy of certain chemotherapeutics

Contraindications

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

Side Effects

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

Key Papers

• 10.1038/ncomms12948
• 10.1016/j.cmet.2018.02.010
• 10.1038/s41598-019-46120-z
• Martens et al. 2018 - NR supplementation in healthy middle-aged and older adults (Nature Communications)

Source Quality

Niagen (ChromaDex) is the most clinically studied form and holds GRAS status. TruNiagen brand uses this. Ensure third-party testing. Chloride salt form (NR chloride) is standard.

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