Calcium Alpha-Ketoglutarate (Ca-AKG) vs NMN (Nicotinamide Mononucleotide)

Mechanism

AKG is a TCA cycle intermediate that declines with age. Supplementation reduces inflammatory cytokines, improves stem cell function, and extends healthspan in mice. Calcium salt form provides sustained release. Also supports collagen synthesis and reduces frailty markers.

Contraindications

• Hypercalcemia
• Kidney stones (calcium component)

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)

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