The science behind NAD+ therapy is grounded in decades of peer-reviewed research. Below, we present the key studies that inform our physician-prescribed protocols.
decline in NAD+ levels by age 40 compared to age 20
decline in NAD+ levels by age 60 compared to youthful levels
It is essential for converting food into cellular energy, repairing damaged DNA, regulating circadian rhythms, and maintaining healthy immune function. NAD+ was first discovered in 1906 by Arthur Harden and William John Young.
Over a century later, it has become one of the most studied molecules in aging research, with over 30,000 published papers exploring its role in human health. Research shows that NAD+ levels decline progressively with age.
*Source: Verdin, E. Science (2015); Covarrubias et al. Nature Reviews (2021).
NAD+ decline is implicated in at least four of the recognized hallmarks of aging. Understanding these mechanisms is essential to understanding why NAD+ repletion may support cellular health.
NAD+ is essential for mitochondrial electron transport. As NAD+ declines, mitochondria produce less ATP and more reactive oxygen species, accelerating cellular aging.
DNA repair enzymes (PARPs) require NAD+ as a substrate. When NAD+ levels fall, DNA damage accumulates, increasing mutation rates and cancer risk.
Sirtuins, a family of NAD+ dependent enzymes, regulate gene expression and chromatin structure. NAD+ decline impairs sirtuin activity, disrupting the epigenome.
Sirtuins, a family of NAD+ dependent enzymes, regulate gene expression and chromatin structure. NAD+ decline impairs sirtuin activity, disrupting the epigenome.
Below are peer-reviewed studies from leading journals that form the scientific foundation for NAD+ therapy. Each study is linked to its original publication.
Verdin, E.—Science, 2015
This foundational review establishes that NAD+ levels decline with age across multiple tissues, and that this decline is a key driver of age-related metabolic dysfunction. The paper proposes NAD+ repletion as a therapeutic strategy for age-related diseases.
READ FULL STUDY ↗Covarrubias, A.J., Perrone, R., Grozio, A., & Verdin, E.—Nature Reviews Molecular Cell Biology, 2021
Comprehensive review of NAD+ metabolism across aging. Demonstrates that NAD+ is consumed by key enzymes (sirtuins, PARPs, CD38) and that age-related decline impairs DNA repair, mitochondrial function, and immune regulation.
READ FULL STUDY ↗Gomes, A.P., Price, N.L., Ling, A.J.Y., et al.—Cell, 2013
Landmark study showing that NAD+ decline disrupts the communication between the cell nucleus and mitochondria. Restoring NAD+ levels in aged mice reversed this dysfunction to levels comparable to young mice within just one week of treatment.
READ FULL STUDY ↗Lautrup, S., Sinclair, D.A., Mattson, M.P., et al.—Cell Metabolism, 2019
Reviews the evidence linking NAD+ depletion to neurodegenerative diseases including Alzheimer's and Parkinson's. Boosting NAD+ levels in preclinical models improved cognitive function, protected neurons from damage, and extended healthy lifespan.
READ FULL STUDY ↗Elhassan, Y.S., Kluckova, K., Fletcher, R.S., et al.—Cell Reports, 2019
Demonstrates that NAD+ precursor supplementation increases intramuscular NAD+ levels in older adults. Participants showed improved muscle function, reduced fatigue markers, and enhanced mitochondrial biogenesis compared to placebo controls.
READ FULL STUDY ↗Haigis, M.C. & Guarente, L.P.—Genes & Development, 2006
Seminal paper establishing the role of sirtuins — NAD+-dependent enzymes — in the regulation of aging and age-related disease. Sirtuin activity is directly linked to cellular stress response, metabolism, and longevity across species.
READ FULL STUDY ↗MEDICAL DISCLAIMER
*The information on this page is provided for educational purposes only and is not intended as medical advice. The studies referenced above represent the current state of scientific literature and do not constitute endorsement of any specific treatment protocol. NAD+ therapy should only be pursued under the supervision of a licensed physician who can evaluate your individual health profile. Individual results may vary. Always consult your healthcare provider before starting any new treatment.