Alpha Lipoic Acid (ALA) vs NMN (Nicotinamide Mononucleotide)

Mechanism

ALA is a dithiol compound that functions as a cofactor for mitochondrial alpha-keto acid dehydrogenases (pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase). Both ALA and its reduced form DHLA are potent antioxidants capable of regenerating other antioxidants including vitamin C, vitamin E, and glutathione. ALA activates AMPK, improving glucose uptake via GLUT4 translocation, and modulates NF-kB-mediated inflammatory signaling. It chelates redox-active metals (Fe2+, Cu2+).

Standard Dosing

300-600mg R-ALA daily

Timing

On empty stomach, 30-60 min before meals. Split doses for higher amounts.

Cycle Duration

ongoing or cycle 12 weeks on, 4 weeks off

Side Effects

• GI upset/nausea
• Skin rash
• Hypoglycemia symptoms
• Body odor changes

Contraindications

• Thiamine (B1) deficiency (ALA increases thiamine demand)
• Hypoglycemia-prone individuals without monitoring
• Autoimmune thyroid conditions (monitor thyroid function)

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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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