NAD+

NAD+ (nicotinamide adenine dinucleotide) is a critical coenzyme present in every living cell, involved in over 500 enzymatic reactions. It plays a central role in energy metabolism, DNA repair, gene expression, and cellular signaling. NAD+ levels decline by approximately 50% between ages 40 and 60, contributing to mitochondrial dysfunction, impaired DNA repair, and metabolic decline. NAD+ can be administered directly via intravenous (IV) infusion or as an oral/sublingual powder. IV delivery provides 100% bioavailability, while oral NAD+ has limited absorption due to its large molecular structure. NAD+ is not a peptide but is widely included in longevity research alongside peptide bioregulators.

NAD+ functions as a coenzyme in redox reactions, carrying electrons between metabolic enzymes. It activates three key enzyme families: sirtuins (SIRT1-7, deacetylases regulating gene expression, metabolism, and stress responses), PARPs (poly-ADP-ribose polymerases for DNA repair), and CD38/CD157 (immune signaling). SIRT1 activation deacetylates PGC-1α (mitochondrial biogenesis), FOXO (stress resistance), and NF-κB (inflammation reduction). NAD+ is also essential for the electron transport chain in mitochondria, directly powering ATP production.

Aging and Longevity • Direct NAD+ restoration has been shown to extend lifespan in animal models • IV NAD+ infusions rapidly increase blood and tissue NAD+ levels with 100% bioavailability • Supports DNA repair, mitochondrial function, and sirtuin activation — key longevity pathways Metabolic Health • Enhances mitochondrial energy production and ATP synthesis • Improves insulin sensitivity and supports healthy glucose metabolism • Reduces chronic low-grade inflammation linked to metabolic syndrome Neurodegeneration • NAD+ depletion is closely linked to Alzheimer’s and Parkinson’s disease progression • IV NAD+ therapy is being studied for neuroprotective effects in neurodegenerative conditions • Supports neuronal energy supply and DNA damage repair in brain cells Cardiovascular Health • Promotes healthy endothelial function and blood vessel elasticity • Helps reduce arterial stiffness associated with aging • Supports cardiac energy metabolism and heart muscle contractility Addiction and Recovery • IV NAD+ therapy is being researched for substance abuse recovery support • May help reduce withdrawal symptoms and cravings • Supports neurochemical balance restoration

NAD+/SIRT1/PGC-1α for mitochondrial biogenesis. NAD+/PARP for DNA repair. NAD+/SIRT1/FOXO for stress resistance. NAD+/SIRT3 for mitochondrial protein deacetylation. CD38/NAD+ for immune function.

Well-tolerated in clinical trials at standard doses. Mild GI discomfort (nausea, bloating) at higher doses. Flushing with high-dose niacin (not with NMN/NR). Theoretical concern about cancer cell NAD+ metabolism, though not observed in human studies.

NMN and NR are relatively stable as dry powders. Store at room temperature in cool, dry conditions (some products recommend refrigeration). NMN is more stable than NR. Both are orally bioavailable. Enteric coating may improve delivery.

NR is FDA GRAS and available as a dietary supplement (Tru Niagen, Niagen). NMN regulatory status varies by country — available as supplement in US, recently restricted in some interpretations of FDA classification. Not WADA-prohibited.