Coenzyme Research

NAD+: Coenzyme Research Data

A conservative review of NAD+: what the coenzyme is, how cells make and use it, what the age-decline evidence shows, how thin the direct human data are, and where regulators stand in 2026.

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Fact-checked · Reviewed by Remy Research Editorial Board
Update History ▾
October 6, 2026: Initial publication, built from a source-by-source check of the NAD+ literature, FDA compounding and safety records, EU novel-food decisions and WADA. It separates direct NAD+ studies from precursor (NR and NMN) studies.
Research-use-only framing applied throughout in line with Remy editorial standards.
TL;DR — Research Summary

NAD+ is not a peptide: it is a coenzyme, the dinucleotide at the centre of cellular energy metabolism, and the human evidence for administering it directly is thin. Its biology is well established — it carries electrons in metabolism and is consumed by sirtuins, PARPs and CD38 — and tissue NAD+ falls with age in mice and in some human tissues.[1][2] Most human trials test the precursors NR and NMN, which reliably raise blood NAD+ but have produced mixed or null clinical results.[3][4] A 2026 systematic review found no outcome trials of intravenous or intramuscular NAD+ itself.[5]

NAD+ is not an approved medicine in the US, and FDA has issued an alert and a Class I recall over endotoxin in injectable NAD+ products.[6][7] Material supplied by Remy Research is for in-vitro laboratory research only — not for human or veterinary use.

Compliance note: this page is a research review, not a treatment guide. It does not provide human-use dosing, therapeutic recommendations, or any clinical-use instructions, and should be read in the same non-therapeutic frame required across Remy's research content.

What Is NAD+?

NAD+ (nicotinamide adenine dinucleotide, also called nadide or coenzyme I) is a coenzyme, not a peptide: two nucleotides — an adenine nucleotide and a nicotinamide nucleotide — joined by a diphosphate bridge, with no amino acids. PubChem lists it as C21H27N7O14P2, with a molecular weight of about 663.4 g/mol, CAS number 53-84-9, and PubChem CID 5892.[8]

NAD+ and NADH are the oxidized and reduced forms of the same coenzyme. NAD+ accepts electrons during the breakdown of nutrients and NADH delivers them to the mitochondrial respiratory chain; in that redox role the coenzyme is recycled rather than used up.[1]

How Cells Make and Use NAD+

Cells build NAD+ three ways: from the amino acid tryptophan (the de novo route), from nicotinic acid (the Preiss–Handler route), and by recycling nicotinamide through the salvage pathway, in which NMN is the immediate precursor and NR is converted to NMN.[1] NAD+ is consumed by three enzyme families — the sirtuins, the PARPs involved in DNA repair, and the glycohydrolases CD38 and CD157 — which links it to metabolism, DNA repair and immune-cell function.[1]

NAD+ supplied from outside the cell is a separate question. In human cell studies, extracellular NAD+ was largely broken down outside the cell into smaller precursors that then entered it.[9]

Does NAD+ Decline With Age?

The answer depends on species and tissue:

No human study shows that falling NAD+ causes ageing; the causal case rests mainly on model organisms.

Human Data on NAD+ Itself

Published human studies of administered NAD+ are few and small:

None of these studies measured clinical benefit. Of 12 registered studies that test NAD+ itself on ClinicalTrials.gov, none has posted results.[18]

What the Precursor Trials Show

Most human NAD research uses the oral precursors NR and NMN. They reliably raise blood NAD+, and a 2026 head-to-head trial found them comparable over 14 days.[19][20][21] Clinical results are mixed:

The animal record is similarly mixed. NMN mitigated age-related physiological decline in mice, but in the National Institute on Aging's multi-site test NR did not extend lifespan in either sex.[23][24] These precursor findings cannot be transferred to NAD+ given directly.

What Has Been Published on Safety

FDA has also described NAD as degrading substantially with light, moisture, alkaline pH or room temperature, which makes product stability a real quality question.[28]

Regulatory Status in 2026

Where NAD+ stands as of October 6, 2026.
  • United States. No FDA-approved NAD+ drug product was found. NAD sits in 503A Category 1, "under evaluation", which lets compounders use it under an interim policy, even though FDA's advisory committee voted against listing it in 2017 and FDA proposed not to list it in 2019.[29][28] Separately, FDA concluded in September 2025 that the precursor NMN is not excluded from the dietary-supplement definition.[30]
  • European Union. NR chloride is an authorised novel food. NMN received a positive EFSA safety opinion in 2026 but had no Commission authorisation as of October 6, 2026.[31][32]
  • China. A 2026 paper describes an injectable NAD+ product, "Coenzyme I for Injection", as an approved drug there.[33]
  • United Arab Emirates. No NAD+-specific UAE registration or rule was found.
  • Sport. NAD+ is not named on WADA's Prohibited List, but method M2.2 prohibits intravenous infusions or injections of more than 100 mL in 12 hours, whatever the substance, outside hospital, surgical or diagnostic settings.[34]

What the NAD+ Literature Does Not Yet Give You

These gaps are not arguments against studying NAD+. They are arguments against overselling it.

Where NAD+ Fits in an RUO Research Catalog

For research use, NAD+ belongs with the metabolic and mitochondrial research tools: a defined coenzyme for cell-culture and model work on redox metabolism, sirtuin and PARP activity, and NAD+ turnover. Remy Research lists the Genovare NAD 500mg AQ pen and the Genovare NAD 1000mg AQ pen, supplied for in-vitro laboratory research only. Neither listing is framed for human use, veterinary use or treatment.

For researchers reading this page as a starting point, the most useful adjacent references on this site are the MOTS-c mitochondrial review, the SS-31 review, the COA and HPLC purity guide, and the Dubai legality brief.

Our Research Standards

This article prioritizes primary literature, systematic reviews and regulatory records, and keeps direct NAD+ evidence separate from precursor evidence. Where the human record is thin, we say so directly. No therapeutic, anti-aging, human-use, or veterinary-use claim is made here. Read our editorial policy →

RP
Editorial Review

Editorial Board, Remy Research

The Remy Research Editorial Board reviews Remy's peptide research library, with a focus on analytical verification, clinical-trial interpretation, and compliance-safe scientific communication.

About the editorial team →

NAD+ Research FAQ

Is NAD+ a peptide?

No. NAD+ is a coenzyme: a dinucleotide made of an adenine nucleotide and a nicotinamide nucleotide joined through phosphate groups, with a molecular weight of about 663. It contains no amino acids.[8]

What is the difference between NAD+ and NADH?

They are the oxidized and reduced forms of the same coenzyme, differing by two hydrogens. NAD+ accepts electrons during metabolism and NADH passes them to the mitochondrial respiratory chain.[1]

What is the difference between NAD+, NMN and NR?

NMN and NR are precursors that cells convert into NAD+ through the salvage pathway. Most human trials use oral NR or NMN, which raise blood NAD+ comparably; human data on NAD+ given directly are limited to a few small studies.[1][21]

Does NAD+ really decline with age?

In mice, tissue NAD+ falls modestly with age. Some human tissues, such as skin and brain, show lower NAD+ with age, but a 2026 multi-cohort study found whole-blood NAD+ stable. No study shows the decline causes human ageing.[2][11][13]

Is there human evidence for NAD+ IV drips or injections?

Very little: a small pharmacokinetic pilot, an industry-funded preprint and a small retrospective chart review. None measured clinical benefit, and a 2026 systematic review found no outcome trials of intravenous or intramuscular NAD+.[14][15][16][5]

Is NAD+ FDA-approved?

No FDA-approved NAD+ drug product was found. NAD sits in FDA's 503A Category 1, under evaluation, although FDA proposed in 2019 not to add it to the permanent compounding list. A 2026 paper describes an injectable NAD+ drug approved in China.[29][28][33]

Is NAD+ safe?

Long-term safety is not established. FDA has warned about endotoxin reactions after injectable NAD+ made from food-grade material, an injectable product was recalled, and two studies reported frequent infusion-related symptoms with intravenous NAD+.[6][7][16]

Is NAD+ banned in sport?

NAD+ is not named on WADA's Prohibited List, but method M2.2 prohibits intravenous infusions or injections of more than 100 mL in 12 hours, whatever the substance, outside hospital, surgical or diagnostic settings.[34]

Sources

  1. 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. doi: 10.1038/s41580-020-00313-x · PMID: 33353981 ↩
  2. McReynolds MR, Chellappa K, Chiles E, et al. NAD+ flux is maintained in aged mice despite lower tissue concentrations. Cell Syst. 2021;12(12):1160-1172.e4. doi: 10.1016/j.cels.2021.09.001 · PMID: 34559996 ↩
  3. Dollerup OL, Christensen B, Svart M, et al. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr. 2018;108(2):343-353. doi: 10.1093/ajcn/nqy132 · PMID: 29992272 ↩
  4. Martens CR, Decker KP, DeConne TM, et al. A phase-II randomized controlled pilot study of nicotinamide riboside supplementation in older adults with amnestic mild cognitive impairment. Alzheimers Dement. 2026;22(7):e71605. doi: 10.1002/alz.71605 · PMID: 42478598 ↩
  5. Gallagher C, Emmanuel OO. NAD+ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence. Ageing Res Rev. 2026;116:103057. doi: 10.1016/j.arr.2026.103057 · PMID: 41655607 ↩
  6. U.S. Food and Drug Administration. FDA reminds compounders to use ingredients suitable for sterile compounding (alert on food-grade NAD+ used in intravenous products and endotoxin-type adverse events), October 30, 2024. fda.gov ↩
  7. U.S. Food and Drug Administration. Enforcement report: Class I recall D-0094-2026, NAD+ (nicotinamide adenine dinucleotide) for injection, elevated endotoxin (classified October 21, 2025). accessdata.fda.gov ↩
  8. National Center for Biotechnology Information. PubChem Compound Summary for CID 5892, NAD+ (nadide). pubchem.ncbi.nlm.nih.gov/compound/5892 ↩
  9. Nikiforov A, Dölle C, Niere M, Ziegler M. Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation. J Biol Chem. 2011;286(24):21767-21778. doi: 10.1074/jbc.M110.213298 · PMID: 21504897 ↩
  10. Camacho-Pereira J, Tarragó MG, Chini CCS, et al. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 2016;23(6):1127-1139. doi: 10.1016/j.cmet.2016.05.006 · PMID: 27304511 ↩
  11. Massudi H, Grant R, Braidy N, et al. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi: 10.1371/journal.pone.0042357 · PMID: 22848760 ↩
  12. Zhu XH, Lu M, Lee BY, et al. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci U S A. 2015;112(9):2876-2881. doi: 10.1073/pnas.1417921112 · PMID: 25730862 ↩
  13. Trętowicz MM, Scantlebery AML, Schomakers BV, et al. Human whole-blood NAD+ levels do not vary with age or lifestyle interventions. Nat Metab. 2026;8(6):1282-1290. doi: 10.1038/s42255-026-01537-5 · PMID: 42135539 ↩
  14. Grant R, Berg J, Mestayer R, et al. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. Front Aging Neurosci. 2019;11:257. doi: 10.3389/fnagi.2019.00257 · PMID: 31572171 ↩
  15. Hawkins J, et al. Randomized, double-blind, placebo-controlled pilot comparing intravenous NAD+ with intravenous and oral nicotinamide riboside. medRxiv preprint, 2024 (industry-funded; not peer reviewed). doi: 10.1101/2024.06.06.24308565. medrxiv.org ↩
  16. Reyna K, Heinzen G, Patel N, et al. Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting. Front Aging. 2026;7:1652582. doi: 10.3389/fragi.2026.1652582 · PMID: 41704678 ↩
  17. Kornilov SA, Hastings WJ, McGrath LF, et al. Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial. GeroScience. 2026. doi: 10.1007/s11357-026-02399-1 · PMID: 42530810 ↩
  18. ClinicalTrials.gov search for NAD+ as the intervention, run October 6, 2026 (267 raw results; 12 registered studies test NAD+ itself, none with posted results). clinicaltrials.gov ↩
  19. Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. doi: 10.1038/s41467-018-03421-7 · PMID: 29599478 ↩
  20. 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. doi: 10.1038/s41598-019-46120-z · PMID: 31278280 ↩
  21. Christen S, Redeuil K, Goulet L, et al. The differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans. Nat Metab. 2026;8(1):62-73. doi: 10.1038/s42255-025-01421-8 · PMID: 41540253 ↩
  22. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. doi: 10.1126/science.abe9985 · PMID: 33888596 ↩
  23. Mills KF, Yoshida S, Stein LR, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016;24(6):795-806. doi: 10.1016/j.cmet.2016.09.013 · PMID: 28068222 ↩
  24. Harrison DE, Strong R, Reifsnyder P, et al. 17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging Cell. 2021;20(5):e13328. doi: 10.1111/acel.13328 · PMID: 33788371 ↩
  25. Nacarelli T, Lau L, Fukumoto T, et al. NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol. 2019;21(3):397-407. doi: 10.1038/s41556-019-0287-4 · PMID: 30778219 ↩
  26. Maric T, Bazhin A, Khodakivskyi P, et al. A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism. Biosens Bioelectron. 2023;220:114826. doi: 10.1016/j.bios.2022.114826 · PMID: 36371959 ↩
  27. Jiang Y, Luo Z, Gong Y, et al. NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling. Oncogene. 2023;42(11):808-824. doi: 10.1038/s41388-023-02592-y · PMID: 36690678 ↩
  28. Federal Register. Amendments to the list of bulk drug substances that can be used to compound drug products in accordance with section 503A (proposed rule; NAD evaluated and not proposed for inclusion), September 5, 2019. federalregister.gov ↩
  29. U.S. Food and Drug Administration. Bulk drug substances nominated for use in compounding under section 503A: Categories 1–3 (updated May 14, 2026; NAD and NADH in Category 1). fda.gov/media/94155 ↩
  30. U.S. Food and Drug Administration. Response to citizen petition FDA-2023-P-0872 concluding that NMN is not excluded from the dietary-supplement definition (September 2025). regulations.gov ↩
  31. European Commission. Implementing Regulation (EU) 2022/1160 extending the authorised uses of the novel food nicotinamide riboside chloride (first authorised by Regulation (EU) 2020/16). eur-lex.europa.eu ↩
  32. EFSA Panel on Nutrition, Novel Foods and Food Allergens. Safety of beta-nicotinamide mononucleotide as a novel food. EFSA Journal 2026 (no Commission authorisation found as of October 6, 2026). doi: 10.2903/j.efsa.2026.10007. efsa.europa.eu ↩
  33. Non-clinical safety evaluation of Coenzyme I (NAD+) for injection, describing it as a drug approved in China. Biomed Pharmacother 2026;204:119934. doi: 10.1016/j.biopha.2026.119934. sciencedirect.com ↩
  34. World Anti-Doping Agency. 2027 Prohibited List (in force January 1, 2027); NAD+ is not named, and method M2.2 prohibits IV infusions or injections of more than 100 mL per 12 hours outside hospital, surgical or diagnostic settings. wada-ama.org ↩

For catalog details, see the Genovare NAD 500mg AQ pen and the Genovare NAD 1000mg AQ pen. For compliance context, continue to the Dubai legality brief and the research standards page.

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Mitochondrial MOTS-c Mitochondrial Peptide Research→ Mitochondrial SS-31 (Elamipretide) Research→ Catalog Genovare NAD 500mg AQ Pen→ Catalog Genovare NAD 1000mg AQ Pen→ Metabolic AICAR AMPK Activator Research→ Verification Peptide COA & HPLC Purity Guide→ Compliance Are Peptides Legal in Dubai?→ Catalog Research Peptide Catalog→ Profile SLU-PP-332: ERR Agonist Research Data →