NAD+
A central coenzyme in energy metabolism that has been studied as a supplement and IV therapy for aging, fatigue, and metabolic health.
In plain English
NAD+ (nicotinamide adenine dinucleotide) is not technically a peptide — it is a coenzyme found in every cell of the body. It is included here because it is widely marketed alongside peptides in longevity and wellness clinics, often as IV infusions or as precursors like NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide). NAD+ falls with age and is essential for mitochondrial function, DNA repair, and sirtuin signaling. Human evidence is strongest for NR and NMN raising blood NAD+ levels. Whether this translates to meaningful changes in healthspan, fatigue, or metabolic outcomes remains an open question.
What it is
NAD+ is a coenzyme central to electron transfer in cellular metabolism. It is a substrate for sirtuins, PARPs, and CD38. Supplemental forms include NAD+ itself (IV), NR, NMN, niacin, and nicotinamide.
Mechanism (summary)
NAD+ shuttles electrons between cellular metabolic reactions and serves as cofactor for sirtuin deacetylation and PARP-mediated DNA repair. NAD+ levels decline with age, primarily due to increased CD38 activity.
Why people research it
- Age-related decline in cellular energy and DNA repair
- Mitochondrial function in chronic fatigue and aging
- Metabolic conditions including insulin resistance
- Neurodegenerative disease research
Human evidence
Multiple RCTs of oral NR and NMN show reliable increases in blood NAD+ levels and good short-term safety. Clinical-outcome effects (on insulin sensitivity, blood pressure, fatigue, walking endurance) have been modest and inconsistent. Direct IV NAD+ has very limited high-quality data despite widespread clinical use.
Animal / lab evidence
Rodent studies of NR and NMN show improvements in mitochondrial function, exercise capacity, and metabolic markers, plus extension of healthspan in some models.
Key studies
Each summary explains the design, what was found, and what it doesn't prove.
Older adults who took NR raised their NAD+ levels and some inflammation markers improved, but insulin sensitivity didn't budge.
Recreational runners on NMN showed slightly better aerobic capacity after 6 weeks than the placebo group.
Oral NR raised NAD+ levels and was well tolerated for 8 weeks in adults with overweight.
History
NAD+ was discovered in 1906. The modern wave of research into precursors began with NR (Chromadex) and NMN (multiple companies and academic labs) in the 2010s.
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