Alpha Lipoic Acid (ALA) vs NR (Nicotinamide Riboside)

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

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

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