NAD+

NAD+ functions as a coenzyme in oxidation-reduction reactions, cycling between its oxidized (NAD+) and reduced (NADH) forms. In energy metabolism, it accepts electrons from substrates such as glyceraldehyde-3-phosphate and pyruvate, transferring them to the mitochondrial respiratory chain to generate ATP. Additionally, it acts as a substrate for:

• Sirtuins (SIRT1-7): NAD+-dependent deacetylases that regulate gene expression, DNA repair, and stress response.
• PARP (poly-ADP-ribose polymerase): An enzyme that consumes NAD+ to repair DNA damage, activated under genotoxic stress.
• CD38: An ectoenzyme that hydrolyzes NAD+ to generate cyclic ADP-ribose, a second messenger in calcium signaling.

• Anti-aging: Restore NAD+ levels to improve mitochondrial function and delay cellular aging.
• Metabolic health: Improve insulin sensitivity and glucose metabolism in conditions like type 2 diabetes.
• Neuroprotection: Protect against neurodegenerative diseases such as Alzheimer's and Parkinson's by reducing oxidative stress and inflammation.
• Athletic performance: Enhance endurance and muscle recovery through optimized energy metabolism.

Supplementation with NAD+ precursors can increase intracellular NAD+ levels, improving mitochondrial function, DNA repair, and sirtuin activity. This results in enhanced energy production, reduced oxidative stress, improved insulin sensitivity, and potential slowing of aging. Improved cognitive function and physical endurance have also been observed in animal models and preliminary human studies.

NAD+ is generally well tolerated, but may cause mild adverse effects such as nausea, fatigue, headache, or gastrointestinal discomfort, especially at high doses. It is not recommended in pregnant or breastfeeding women due to lack of studies. It may interact with drugs affecting NAD+ metabolism, such as some chemotherapeutics. Caution is advised in individuals with liver or kidney disease. Long-term supplementation is still under investigation.

NAD+ itself is not approved as a drug, but its precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are marketed as dietary supplements in the US and Europe, without FDA approval as medications. Some derivatives are in clinical trials for specific indications such as Alzheimer's disease and non-alcoholic steatohepatitis (NASH).

Typical doses of NAD+ precursors vary: nicotinamide riboside (NR) 250-500 mg/day, nicotinamide mononucleotide (NMN) 250-1000 mg/day, orally. For intravenous administration, doses of 100-500 mg of NAD+ in saline are used, typically in wellness clinics. Treatment duration ranges from weeks to months depending on the goal.

Store in a cool, dry place, protected from light and moisture. Ideal temperature is 2-8°C for lyophilized or powder forms. Once reconstituted, use within 24 hours and keep refrigerated. Do not freeze.