NAD+

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in every living cell and is essential to hundreds of metabolic reactions. While technically a coenzyme rather than a peptide in the traditional sense, NAD+ is widely categorized alongside peptide therapies in regenerative and longevity medicine due to its injectable administration protocols and overlapping clinical applications. NAD+ exists in two interconvertible forms: the oxidized form (NAD+) and the reduced form (NADH). Its primary biological role is as an electron carrier in cellular respiration, shuttling electrons from metabolic substrates to the mitochondrial electron transport chain to generate ATP.

Beyond energy metabolism, NAD+ functions as a critical signaling molecule and substrate for several enzyme classes. Sirtuins (SIRT1-7), a family of NAD+-dependent deacetylases, use NAD+ to regulate gene expression, DNA repair, mitochondrial biogenesis, and metabolic homeostasis.^[1] Poly(ADP-ribose) polymerases (PARPs), which repair DNA strand breaks, are also major consumers of cellular NAD+. CD38, an enzyme involved in immune cell signaling and calcium homeostasis, is another significant NAD+ consumer that becomes increasingly active with age and chronic inflammation, further depleting available NAD+.

A central finding driving clinical interest in NAD+ supplementation is the well-documented decline of cellular NAD+ levels with age. Tissue NAD+ levels fall progressively across the lifespan, and this decline is mechanistically linked to mitochondrial dysfunction, impaired DNA repair capacity, increased oxidative stress, and the accumulation of senescent cells.^[2] Animal studies in which NAD+ was restored pharmacologically showed reversal of multiple aging biomarkers, extension of lifespan in some models, and improvements in physical function, cognition, and metabolic health.

Clinical research in humans is more limited but encouraging. A pharmacokinetic study showed that oral nicotinamide riboside (NR) is uniquely and bioavailable in humans and produces dose-dependent increases in blood NAD+ levels.^[3] Injectable NAD+ produces more immediate and pronounced increases in tissue NAD+ levels compared to oral precursors, which must be converted through multiple enzymatic steps. Patients in clinical settings frequently report rapid improvements in energy, mental clarity, and sleep quality within 24-48 hours of intravenous or subcutaneous NAD+ administration, consistent with acute mitochondrial activation and nervous system recalibration.