# NAD+ References: The Cited Studies Behind the Coenzyme Digest

> Every NAD+ study cited on this site, with DOIs and PubMed links: the precursor trials, the CD38 and sirtuin mechanism work, the age-decline data, and the 2025 clinical-evidence review.

The peer-reviewed sources behind the readout — precursor trials, mechanism work, and the honest-gap review — with DOIs and PubMed links.

## How to read this list

Every quantitative claim in this NAD+ digest resolves to one of the numbered studies below. Each entry gives the authors, journal, year, DOI and a PubMed link so any figure — the `+142%` whole-blood NAD+ rise, the `~50%` age decline, the `250 mg/day` insulin-sensitivity dose — can be checked at source. Human trials, mouse studies, mechanism work and review articles are all listed together; the body pages tag which is which (CONFIRMED, PRECLINICAL, or GAP). Where a claim derives from the compound's compliance and dose record rather than a single indexed trial — the FDA Class I endotoxin recall, the contested NMN status, the IV protocol ranges — that is noted in the prose rather than as a numbered citation.

## References

[1] PubChem. Nicotinamide adenine dinucleotide (NAD+), CID 5893. Compound record (molecular weight 663.43 Da; formula C21H27N7O14P2; CAS 53-84-9; FDA UNII 0U46U6E8UK; ChEBI 15846). National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/5893
[2] Camacho-Pereira J, Tarragó MG, Chini CCS, Nin V, Escande C, Warner GM, Puranik AS, Schoon RA, Reid JM, Galina A, Chini EN. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 2016;23(6):1127-1139. https://pubmed.ncbi.nlm.nih.gov/27304511/
[3] Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience. 2023;45(1):29-43. https://pubmed.ncbi.nlm.nih.gov/36482258/
[4] Conze D, Brenner C, Kruger CL. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep. 2019;9(1):9772. https://pubmed.ncbi.nlm.nih.gov/31278280/
[5] Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141. https://pubmed.ncbi.nlm.nih.gov/33353981/
[6] Gomes AP, Price NL, Ling AJY, Moslehi JJ, Montgomery MK, Rajman L, et al. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013;155(7):1624-1638. https://pubmed.ncbi.nlm.nih.gov/24360282/
[7] Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471. https://pubmed.ncbi.nlm.nih.gov/24786309/
[8] Imai S, Guarente L. NAD+ and sirtuins in aging and disease — the sirtuin family (SIRT1-7) as NAD+-dependent deacylases regulating metabolism, DNA repair and lifespan. Trends Cell Biol. 2014;24(8):464-471. https://pubmed.ncbi.nlm.nih.gov/24786309/
[9] Covarrubias AJ, Kale A, Perrone R, Lopez-Dominguez JA, Pisco AO, Kasler HG, et al. Senescent cells promote tissue NAD(+) decline during ageing via the activation of CD38(+) macrophages. Nat Metab. 2020;2(11):1265-1283. https://pubmed.ncbi.nlm.nih.gov/33199924/
[10] Mendelsohn AR, Larrick JW. The NAD+/PARP1/SIRT1 Axis in Aging. Rejuvenation Res. 2017;20(3):244-247. https://pubmed.ncbi.nlm.nih.gov/28537485/
[11] Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. https://pubmed.ncbi.nlm.nih.gov/33888596/
[12] Shim DW, Cho HJ, Hwang I, Jung TY, Kim HS, Ryu JH, Yu JW. Intracellular NAD(+) Depletion Confers a Priming Signal for NLRP3 Inflammasome Activation. Front Immunol. 2021;12:765477. https://pubmed.ncbi.nlm.nih.gov/34987507/
[13] Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016;24(6):795-806. https://pubmed.ncbi.nlm.nih.gov/28068222/
[14] Vinten KT, Trętowicz MM, Coskun E, van Weeghel M, Cantó C, Zapata-Pérez R, Janssens GE, Houtkooper RH. NAD(+) precursor supplementation in human ageing: clinical evidence and challenges. Nat Metab. 2025. https://pubmed.ncbi.nlm.nih.gov/41083806/
[15] Cameron AM, Castoldi A, Sanin DE, Flachsmann LJ, Field CS, Puleston DJ, et al. Inflammatory macrophage dependence on NAD(+) salvage is a consequence of reactive oxygen species-mediated DNA damage. Nat Immunol. 2019;20(4):420-432. https://pubmed.ncbi.nlm.nih.gov/30858618/

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A signal-clean readout of the NAD+ literature — the precursor trials that actually moved whole-blood NAD+ logged in their own oral channel, plain oral NAD+ and the weak-evidence IV route kept on separate channels, and the unsettled NMN status reported as filed; no clinic behind this console and nothing here dosed, dispensed, or sold.