Coenzyme Active Human Trials
NAD+
Not a peptide — a coenzyme found in every cell, studied intensively for age-related NAD+ decline, mitochondrial function, and DNA repair. Delivered by IV infusion or subcutaneous injection in the wellness market.
In Plain English:
NAD+ (Nicotinamide Adenine Dinucleotide) is a molecule your cells use like a rechargeable battery — shuttling electrons to generate ATP energy and recharging enzymes that repair damaged DNA and regulate metabolism. Levels drop ~50% between ages 20 and 50, which researchers link to the hallmarks of aging: mitochondrial slowdown, poor DNA repair, and chronic inflammation. Supplementation (directly via IV or via precursors NMN/NR taken orally) can raise cellular NAD+ levels measurably, though whether this translates to meaningful anti-aging or disease outcomes in healthy humans remains an open question in 2025.
Research Maturity
Active Human Trials (~1,300 PubMed papers on NAD+ supplementation; 10 RCTs (489 participants) per 2024 review+ Studies)
Focus
Cellular Energy
Healthy Aging
Metabolic Health
Origin
Endogenous coenzyme synthesised in all living cells via the kynurenine (de novo), Preiss–Handler, and salvage pathways. Exogenous supplementation uses either direct NAD+ (IV/subcutaneous) or oral precursors NMN or NR that are converted intracellularly.
Mechanism
NAD+ serves as the primary electron carrier in oxidative phosphorylation (NADH → NAD+ cycle) and is the obligate substrate for three classes of NAD-consuming enzymes: sirtuins (SIRT1–7, deacetylases regulating gene expression and mitochondrial biogenesis), PARPs (poly-ADP-ribose polymerases, DNA strand-break repair), and CD38/cADPR signalling (calcium mobilisation). Age-related decline in NAD+ blunts all three systems simultaneously, contributing to mitochondrial dysfunction, impaired autophagy, and the senescence-associated secretory phenotype (SASP). Restoring NAD+ activates SIRT1/3, upregulates PGC-1α-driven mitochondrial biogenesis, suppresses NF-κB inflammatory signalling, and restores PARP-mediated genomic integrity.
Outcome
Measured outcomes in human trials include: increased blood/tissue NAD+ levels (10–139% with NR; up to 6× with NMN), modest reductions in inflammatory markers, improved insulin sensitivity and muscle insulin action, and small improvements in walking distance and muscular strength in specific patient populations (Parkinson's, ALS, ataxia telangiectasia). Cognitive and metabolic benefits have been demonstrated in animal models but not yet robustly replicated in healthy human RCTs. A 2025 Lancet eClinicalMedicine RCT showed NR improved NAD+ levels and symptom scores in long-COVID patients.
