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NAD+ references

The trial results and the mechanisms come from different kinds of work. Here are the papers, with a few places to begin.

Human trials

The Conze NR trial is the starting point for the 22%, 51% and 142% blood NAD+ increases. Yi’s NMN trial adds six-minute walking distance and quality-of-life measures. Yoshino’s NMN study examines muscle insulin sensitivity in prediabetic, postmenopausal women.

I give the 2025 clinical review an early place in the pile. It brings the repeated blood findings into contact with the much less settled clinical outcomes and the scarcity of direct tissue measurements.

Mechanisms and mice

The NAD+ metabolism review lays out synthesis and consumption. CD38 in aging mice and senescent cells activating CD38-expressing macrophages examine why NAD+ supply can fall. The PARP1/SIRT1 account follows the competition between repair and other NAD-dependent work.

For the broad animal intervention result, the Mills NMN paper is the relevant experiment. The macrophage DNA-damage study and NAD+ depletion experiment ask narrower mechanistic questions in mouse cells.

Documents missing from this list

The list below contains neither the FDA notice naming the recalled compounded NAD+ injection nor the IV pilot as a separate paper. It also contains no later FDA decision settling present NMN supplement-sales status. Those omissions matter: the papers below cannot substitute for the underlying regulatory documents or provide a direct link to every IV observation.

I leave that gap visible. A correction would need to identify the misattributed claim or the exact missing document. The contact information explains the current limit on receiving one.

  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. ↗
  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. ↗
  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. ↗
  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. ↗
  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. ↗
  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. ↗
  7. Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471. ↗
  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. ↗
  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. ↗
  10. Mendelsohn AR, Larrick JW. The NAD+/PARP1/SIRT1 Axis in Aging. Rejuvenation Res. 2017;20(3):244-247. ↗
  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. ↗
  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. ↗
  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. ↗
  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. ↗
  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. ↗