Coenzyme Research

NAD+ Benefits and Side Effects: Research Data

What NAD+ does in cells, what human trials of NAD+ and its precursors found, how IV and oral study formats compare, and what is known about side effects.

·
Fact-checked · Reviewed by Remy Research Editorial Board
Update History ▾
October 27, 2026: Initial publication, built from the fact-checked NAD+ source set, re-checked PubMed records, FDA compounding and enforcement records, and the WADA 2027 Prohibited List.
Research-use-only framing applied throughout in line with Remy editorial standards.
TL;DR — Research Summary

NAD+ benefits are well established at the cellular level: NAD (nicotinamide adenine dinucleotide) is a coenzyme at the centre of energy metabolism and DNA repair in the body. The human evidence for supplying it directly, by NAD IV, injections or NAD supplements, is limited.[1] Most human clinical trials test the precursors nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which reliably raise blood NAD+ levels, while effects on health outcomes have been mixed and often null.[2][3][4]

For NAD+ itself there are a small intravenous pilot, an industry-funded intravenous comparison, a retrospective records review and a five-day oral trial. The intravenous studies reported gut symptoms, chest pressure and a rise in white cells.[5][6][7][8] NAD+ is not an FDA-approved drug and it is not a peptide. Remy Research supplies NAD+ for in-vitro laboratory research only.[9][10]

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+? A Coenzyme, Not a Peptide

NAD+ (nicotinamide adenine dinucleotide, nonproprietary name nadide) is a dinucleotide with the formula C21H27N7O14P2 and a molecular weight of 663.4.[10] Its building blocks are two nucleotides, not amino acids, so although it is sold beside peptides and discussed alongside peptide therapy, it is not a peptide.

NAD is a coenzyme. It carries electrons in redox reactions, which makes it central to energy metabolism, and it is a required cofactor for non-redox enzymes such as sirtuins, CD38 and poly(ADP-ribose) polymerases (PARPs). Through these enzymes nicotinamide adenine dinucleotide influences key cellular processes and cellular function: metabolic pathways, DNA repair, chromatin remodelling, cellular senescence and immune cell function.[1] For the full biochemistry, see the NAD+ research review.

NAD+ Levels and the Aging Process

The idea that NAD levels naturally decline with age drives most NAD+ marketing. A 2021 review describes a gradual fall in tissue and cellular NAD+ in rodents and humans and links it to age-related disease, including cognitive decline, metabolic disease and frailty.[1] Measured NAD levels give a more mixed picture across the body:

NAD+ Benefits: Potential Benefits Studied and Where the Evidence Varies

NAD+ — Claimed Benefits and the Evidence Behind Them
Claimed benefit What was reported Evidence type
Higher NAD levels NR and NMN reliably raise blood NAD+ Human RCTs (precursors)
Healthy aging (mice) NMN eased age-related decline over 12 months Animal
Life span NR did not extend lifespan in a multi-site test Animal, negative
Insulin sensitivity Better muscle insulin sensitivity with NMN; null with NR Human RCTs, mixed
Cognitive function No improvement in mild cognitive impairment Human RCT, negative
Energy and wellbeing No secondary endpoint held up in an oral NAD+ trial Human RCT, negative

Energy Production and Healthy Aging in Animal Studies

NAD+ supports energy production as the redox carrier of metabolism.[1] In mice given the precursor NMN for 12 months from normal ageing, the compound was quickly used to make NAD+ in tissues, suppressed age-associated weight gain, raised energy metabolism and physical activity, and improved insulin sensitivity, plasma lipids and eye function without obvious toxicity.[15] These animal models are the basis for claims that NAD+ boosters support healthy aging, cellular function or slow aging, but results in animal studies do not show the same effect on human health.

Life Span and Anti-Aging Claims

In a multi-site lifespan study in genetically heterogeneous mice, NR did not affect life span in either sex at the dose tested.[16] No human study has shown that raising NAD+ slows the aging process.[2]

Insulin Sensitivity and Metabolic Benefits

In postmenopausal women with prediabetes, NMN raised insulin-stimulated glucose disposal and insulin signalling in skeletal muscle.[17] In obese, insulin-resistant men, NR did not improve insulin sensitivity, glucose production, energy expenditure, lipolysis or body composition.[3] Metabolic benefits in people therefore depend on the compound, the population and the measure.

Cognitive Function

In 42 older adults with amnestic mild cognitive impairment, NR doubled blood NAD+ but did not improve cognitive function, total cerebral blood flow or blood pressure; a regional blood-flow signal was exploratory, and there were no serious adverse effects.[4]

NAD+ vs NR and NMN: How NAD Supplements Reach the Body

In human trials, the most-studied NAD supplements are not nicotinamide adenine dinucleotide itself but its precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which raise NAD+ in the body.[2][18] In human cells, nicotinamide, nicotinic acid and the matching nucleosides such as NR readily entered cells, while nucleotides such as NMN and NAD+ were broken down outside the cell first.[19] In a 2026 human study, NR and NMN raised circulating NAD levels to a similar degree, nicotinamide did not, and gut bacteria converted both precursors to nicotinic acid, so part of their effect on the body may run through the gut.[18]

For health claims, the form matters less than the outcome data. The systematic review found that precursors raise NAD levels consistently, while evidence for health outcomes is limited and varies by study.[2]

NAD+ IV and Injections vs Oral Supplements: How the Study Formats Compare

Search interest in NAD IV, NAD injections and NAD supplements is high, but the studies behind each format answer different questions, and the evidence for raising NAD levels does not translate into proven health benefits. The table compares study designs and findings only. It is not a guide to use.

NAD+ — Injectable and Oral Study Formats Compared
Study format What was reported Evidence type
NAD+ IV, pilot No plasma rise for 2 hours, then NAD+ and metabolites rose Human pilot, PK only
NAD+ IV vs NR IV NR IV gave higher blood NAD+ at 3 hours, with fewer symptoms Human RCT, preprint
IV records review Gut symptoms, raised heart rate and chest pressure on NAD+ Human, retrospective
Oral NAD+ Cell NAD up 53% at day 6; plasma NAD unchanged Human RCT, 5 days
Oral NR or NMN Blood NAD+ rises; outcome effects mixed Human RCTs
Outside the cell NAD is broken down before entering cells Cell

In human cells, extracellular nucleotides such as NAD were degraded outside the cell, and only smaller precursors readily entered.[19] That fits the intravenous pilot, in which plasma NAD+ and its metabolites did not change for the first two hours, as if NAD+ was rapidly removed.[5] In the industry-funded comparison, blood NAD+ three hours after IV infusions was higher with NR than with NAD+, and NR IV was better tolerated.[6] Among NAD supplements, the oral NAD+ trial raised NAD inside blood cells while plasma NAD stayed flat, and no secondary clinical, well-being or wearable endpoint held up after correction for multiple testing.[8]

A 2026 systematic review of 113 studies found that oral precursors consistently engage their target and were generally well tolerated over weeks to months, but effects on health outcomes were heterogeneous, and clinical effectiveness for anti-aging or wellness remains inconclusive.[2] The precursors may also act partly through gut bacteria, as described above.[18]

Human Clinical Trials of NAD+ Precursors

NR raised NAD+ in a crossover trial in healthy middle-aged and older adults and was well tolerated.[20] In healthy overweight adults, NR raised whole-blood NAD+ in a dose-dependent way within two weeks, with no difference in adverse events from placebo and no flushing.[21] In obese men, NR was generally safe, with no serious adverse events and normal safety blood tests, but produced no metabolic improvement.[3] Target engagement is clear in these human clinical trials; health benefits are not.

NAD+ Side Effects: Potential Side Effects and Safety Concerns

None of these studies was designed to define safe use, and no long-term human safety data exist for NAD+ itself.[2]

Is NAD+ FDA Approved? Regulatory Status

Where NAD+ stands as of October 28, 2026.
  • FDA approval. No approved NAD+ drug application was found in Drugs@FDA.[9]
  • Compounding. NAD and NADH sit in Category 1 (under evaluation) of FDA’s list of bulk substances nominated for 503A compounding.[24]
  • Sport. NAD+ is not named on WADA’s 2027 Prohibited List. Separately, method M2 prohibits intravenous infusions or injections of more than 100 mL per 12 hours outside hospital, surgical or diagnostic settings, whatever the substance.[25]
  • UAE. Remy Research sells NAD+ for in-vitro laboratory research only, not for human or veterinary use.

NAD+ vs Mitochondrial Peptides: Comparing Peptide Therapy Claims

NAD+ is often grouped with mitochondrial peptides such as SS-31 and MOTS-c. They are different molecule types: NAD+ is a coenzyme made from nucleotides, while SS-31 and MOTS-c are short chains of amino acids.[10] See SS-31 benefits and side effects, MOTS-c benefits and side effects and AICAR vs MOTS-c.

What NAD+ Research Does Not Yet Show

NAD+ for Laboratory Research

Remy Research supplies NAD+ for in-vitro research as the Genovare NAD+ 500mg AQ pen and the Genovare NAD+ 1,000mg AQ pen. Each product page carries its batch testing details.

Our Research Standards

This article prioritizes primary literature, systematic reviews and regulator records, and keeps cell, animal and human evidence apart. Industry funding and preprint status are stated where they apply. No therapeutic, dosing or administration guidance is given. Read our editorial policy →

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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+ Benefits and Side Effects FAQ

What are the benefits of NAD+?

In cells, NAD+ is a coenzyme for energy metabolism and a cofactor for enzymes involved in DNA repair. Precursors reliably raise blood NAD+, but health benefits in people have been mixed and often null.[1][2]

What are the side effects of NAD+?

In intravenous studies, NAD+ caused gut symptoms, raised heart rate, chest pressure and a rise in white cells. In a five-day oral trial, symptoms were similar to placebo.[7][6][8]

Is NAD+ FDA approved?

No approved NAD+ drug was found in Drugs@FDA. NAD sits in FDA’s 503A Category 1, under evaluation.[9][24]

Is NAD+ safe?

Short studies found oral precursors generally well tolerated. IV NAD+ caused frequent infusion symptoms, and FDA has linked some injectable NAD+ reactions to endotoxin. Long-term safety is unknown.[2][7][22]

Is NAD+ a peptide?

No. NAD+ is a dinucleotide coenzyme built from two nucleotides, with no amino acids.[10]

Is NAD+ injection better than a supplement?

No study shows that. In one industry-funded IV comparison, NR raised blood NAD+ more than NAD+ at three hours, and NAD+ is broken down outside cells.[6][19]

Do NAD levels decline with age?

Tissue NAD+ fell modestly in aged mice and was lower with age in human skin and brain. Whole-blood NAD+ stayed stable with age across seven human cohorts.[11][12][13][14]

Is NAD+ banned in sport?

NAD+ is not named on WADA’s 2027 List, but WADA prohibits IV infusions over 100 mL per 12 hours outside hospital settings.[25]

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. 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 ↩
  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. 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 ↩
  6. Hawkins J, Idoine R, Kwon J, et al. Randomized, placebo-controlled, pilot clinical study evaluating acute Niagen+ IV and NAD+ IV in healthy adults. medRxiv preprint, 2024 (not peer reviewed; funded by ChromaDex; NCT06382688). doi: 10.1101/2024.06.06.24308565. medrxiv.org ↩
  7. 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 ↩
  8. 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 ↩
  9. openFDA Drugs@FDA search for nadide / nicotinamide adenine dinucleotide, run October 28, 2026 (no matching approved application). api.fda.gov ↩
  10. National Center for Biotechnology Information. PubChem Compound Summary for CID 5892, nadide (NAD+), C21H27N7O14P2, 663.4 g/mol, checked October 28, 2026. pubchem.ncbi.nlm.nih.gov/compound/5892 ↩
  11. 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 ↩
  12. 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 ↩
  13. 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 ↩
  14. 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 ↩
  15. 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 ↩
  16. 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 ↩
  17. 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 ↩
  18. 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 ↩
  19. 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 ↩
  20. 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 ↩
  21. 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 ↩
  22. U.S. Food and Drug Administration. FDA reminds compounders to use ingredients suitable for sterile compounding (food-grade NAD+ used in intravenous products; adverse events consistent with excessive endotoxins), October 30, 2024, checked October 28, 2026. fda.gov ↩
  23. U.S. Food and Drug Administration. Enforcement report: recall D-0094-2026, NAD+ (nicotinamide adenine dinucleotide) for injection, elevated endotoxin, Class I (classified October 21, 2025; status ongoing), checked October 28, 2026. accessdata.fda.gov ↩
  24. 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, under evaluation). fda.gov/media/94155 ↩
  25. World Anti-Doping Agency. The 2027 Prohibited List (in force January 1, 2027); NAD+ is not named, and method M2 prohibits intravenous infusions and/or injections of more than 100 mL per 12-hour period outside hospital treatment, surgery or clinical diagnostic investigations. wada-ama.org ↩

For catalog details, see the Genovare NAD+ 500mg AQ pen and the Genovare NAD+ 1,000mg AQ pen. For editorial standards, continue to the editorial policy.

Research products mentioned in this article

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