NMN (Nicotinamide Mononucleotide)

Mechanism of Action

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.

Dosing Protocol

Notes

Central compound in David Sinclair's longevity protocol. The NMN vs NR debate continues — NMN may have advantages due to direct Slc12a8 transport. TMG co-supplementation is considered essential by most practitioners. First human RCTs (2021-2023) show improved insulin sensitivity and muscle function in older adults. The cancer concern is theoretical but warrants discussion with clients who have active malignancy or family history.

Stacking

• Resveratrol
• TMG (Betaine)
• Vitamin D3
• Quercetin

Interactions

• TMG (Trimethylglycine/Betaine) [LOW] — Recommended co-supplement: NAD+ metabolism consumes methyl groups; TMG replenishes the methyl pool
• Nicotinamide (niacinamide) [MEDIUM] — High-dose nicotinamide inhibits SIRT1 — avoid combining as it may counteract NMN benefits
• Synergistic with resveratrol for SIRT1 activation
• May interact with chemotherapy agents that rely on NAD+ depletion

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)

Side Effects

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

Key Papers

• 10.1126/science.aaf2693
• 10.1016/j.cmet.2019.11.013
• 10.1126/science.abm9354
• Yoshino et al. 2021 - NMN increases muscle insulin sensitivity in prediabetic women (Science)

Source Quality

Enzymatically produced NMN (>99% purity) preferred. Third-party tested for identity and purity (HPLC verified). Store cool and dry. Brands: ProHealth Longevity, DoNotAge, Renue By Science (liposomal/sublingual).

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