NAD+
The coenzyme every cell runs on, now sold as IV drips and injections: one small 2026 trial in heart failure is the only controlled test of NAD+ itself, and a 2026 systematic review found no outcome trial of IV NAD+ for ageing or wellness.
Nicotinamide adenine dinucleotide carries electrons in energy metabolism and fuels enzymes such as sirtuins and PARPs. Its levels fall with age, which has made "NAD+ boosting" one of the busiest corners of longevity medicine. Most of the research is on oral precursors like nicotinamide riboside; the intravenous NAD+ that clinics sell has barely been tested.
What is it?
NAD+ is not a peptide. It is a coenzyme made from vitamin B3 and the amino acid tryptophan, and every cell needs it: it shuttles electrons in the reactions that turn food into energy, and it is the fuel that sirtuins, PARP DNA-repair enzymes and the enzyme CD38 consume. Reviews since 2018 describe how NAD+ levels decline with age and with inflammation and DNA damage, and how restoring them in old or diseased animals improves metabolism and, in some studies, lifespan.
That animal work launched a market. Most research, and most human trials, use oral precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which the body turns into NAD+. Isotope-tracing and metabolomics studies in mice have shown how indirect that is: taken by mouth, most NR and NMN is converted to nicotinamide in the liver or by gut bacteria before it becomes NAD+, while given intravenously they reach more tissues intact. A 2026 systematic review of 33 human intervention studies found oral NR and NMN reliably raised NAD-related metabolites in blood but had heterogeneous and often null effects on functional and metabolic outcomes.
Intravenous NAD+ itself, the product wellness clinics sell, has almost no controlled evidence. The same 2026 review found no outcome trial of intravenous or intramuscular NAD+ for anti-ageing or wellness at all. A 2026 retrospective review of a commercial clinic's records found four daily 500 mg NAD+ infusions caused moderate to severe gut symptoms, raised heart rate and chest pressure during infusion, which is why they took an average of 97 minutes.
The one randomised trial of NAD+ itself was in heart failure: 180 patients with ischaemic cardiomyopathy given 10 mg a day intravenously for seven days, on top of standard treatment, had a modestly better ejection fraction at one month than those on placebo, with non-significant trends in other outcomes. It is a single-centre study that needs repeating. In the United States, pharmacies may compound NAD+ under FDA's interim policy because FDA lists it in 503A Category 1, under evaluation; it is not an approved drug for any use.
Mechanism of Action
NAD+ works as a coenzyme and as a substrate. Raising it is meant to restore the enzymes that consume it, but how much of an injected or swallowed dose reaches cells intact is exactly what the research questions.
Redox carrier
NAD+ accepts and donates electrons in glycolysis, the citric acid cycle and oxidative phosphorylation. A 2021 mouse study found metabolic acidosis shifted the NAD redox state in kidney tubules and caused acute injury, which the precursor nicotinamide prevented.
Consumed by sirtuins, PARPs and CD38
DNA damage activates PARPs and chronic inflammation raises CD38, both of which burn through NAD+. Restoring NAD+ is meant to keep sirtuins, which regulate metabolism and stress responses, working.
Precursor routes
Cells make NAD+ from tryptophan (mainly in the liver) or recycle it from nicotinamide. Oral NR and NMN largely become nicotinamide or nicotinic acid first, via the liver or gut bacteria, before contributing to NAD+.
Downstream signals
In mice and human volunteers, nicotinamide riboside raised the exercise-linked hormone irisin through the NAD+-dependent enzyme SIRT2, and treated fatty liver in mice only when that pathway was intact.
Published Research
Our evidence set holds 50 papers that name NAD+ or nicotinamide adenine dinucleotide, most of them about its biology or its precursors rather than about taking NAD+. Thirteen name it in their titles and have an abstract; 10 are carded below: 2 studies in people, 5 in animals and 3 reviews. Only the two human studies gave NAD+ itself, and one of them was a retrospective review of clinic records.
NAD-boosting molecules in vivo
A review of NAD+ as a redox carrier and signalling molecule that controls hundreds of processes through NAD+-sensing enzymes, rising and falling with food intake, exercise and time of day. NAD+ declines with age, and restoring it in old or diseased animals can improve health and extend lifespan, prompting the search for safe NAD-boosting molecules.
Where NAD+ is made and used
Isotope tracers showed cells make NAD+ from nicotinamide and consume it mostly through PARPs and sirtuins. In mice, the liver made NAD+ from tryptophan and exported nicotinamide, fluxes varied widely between tissues, and intravenous NR or NMN reached many tissues intact while the same molecules taken orally were converted to nicotinamide in the liver.
NAD+ and age-related degenerative disease
A review of NAD+ in energy production, DNA repair, gene regulation, calcium signalling and immunity. It describes depletion through PARP activation after DNA damage and through CD38 during chronic inflammation, and proposes raising NAD+ as a strategy for age-related degenerative diseases, including in the brain.
Acidosis and kidney injury, mice
Acute metabolic acidosis shifted the NAD redox state in kidney tubule mitochondria, reduced maximal respiration, caused lipid build-up and damaged the tubules. Intravenous bicarbonate improved tubular function, and pretreatment with the NAD precursor nicotinamide was highly protective.
Irisin and fatty liver
Nicotinamide riboside raised the exercise hormone irisin in mice and in human volunteers. In mice on a high-fat diet it reduced weight gain, fatty liver, inflammation, insulin resistance and fibrosis, but not in mice lacking the irisin gene; the effect depended on the NAD+-dependent enzyme SIRT2 stabilising the irisin precursor.
How NR and NMN become NAD+
In mice, only a small part of oral NMN or NR was absorbed intact; most was converted by gut bacteria to nicotinic acid. Given intravenously, NMN and NR were rapidly broken down to nicotinamide, excreted in bile and converted by gut bacteria, so both reach NAD+ largely indirectly, with the liver the main user.
Restoring NAD+ in kidney injury
Ultrasound-responsive liposomes carrying plant thylakoid fragments, which contain an enzyme that makes NAD+, accumulated in injured kidneys after intravenous injection. They restored NAD+ synthesis, mitochondrial function and energy supply in tubular cells and prevented kidney damage in mice and piglets.
Heart failure, 180 patients
Adults with ischaemic cardiomyopathy, ejection fraction 45% or less and NYHA class II to III received intravenous NAD+ 10 mg a day or placebo for seven days with standard treatment. At one month ejection fraction was 45.4% against 42.4% (p = 0.024). Trends toward lower NT-proBNP, fewer heart-failure hospitalisations (13.5% vs 23.6%) and better NYHA class did not reach significance.
IV NAD+ vs IV NR in a clinic
A retrospective review of commercial clients given four daily 500 mg infusions of NAD+ or nicotinamide riboside found NAD+ caused moderate to severe gastrointestinal symptoms, faster heart rate and chest pressure during infusion, stretching infusions to 97 minutes against 37 for NR. Liver, kidney, thyroid and inflammation markers did not change; HDL cholesterol fell with NAD+.
Systematic review: NAD+ for ageing and wellness
Of 113 eligible studies from 2010 to 2025, 33 were human trials. Oral NR and NMN raised NAD-related metabolites and were well tolerated, but effects on functional, metabolic and vascular outcomes were heterogeneous and often null. No outcome trial evaluated intravenous or intramuscular NAD+ itself for anti-ageing or wellness; clinical effectiveness remains inconclusive.
What people say, and what was measured
NAD+ is sold as infusions and injections for ageing and energy. The underlying biology is real and busy. What is missing is any trial of infused NAD+ itself for the thing it is sold for, and a 2026 systematic review says so explicitly.
NAD+ infusions slow ageing and restore energy.
Heard in: A 2026 PRISMA-guided systematic review of NAD+ supplementation for anti-ageing and wellness, which searched for exactly these trials (read October 1, 2026). Source
That review is the answer to its own question: across the human and 80 rodent studies it screened, no eligible outcomes trial evaluated intravenous or intramuscular NAD+ itself for anti-ageing or wellness. Rodent work shows improvements across metabolic and mitochondrial measures, varying by model. PMID: 41655607, 29514064
Never tested in peopleInfusing NAD+ raises your NAD+ better than taking a precursor.
Heard in: Grey Peptides listing review, October 1, 2026: listings sell infusions as superior to oral NR or NMN. Sellers are not named.
A 2026 comparison ran the experiment: intravenous NAD+ against intravenous nicotinamide riboside over 30 days. The NR group showed a significant fall in HbA1c; the NAD+ group showed a fall in HDL cholesterol; neither changed fasting glucose or LDL. Flux work also shows precursors feeding NAD synthesis through defined routes rather than NAD+ simply arriving intact. PMID: 41704678, 29685734, 40117359
Tested in people; mixedIt protects the kidneys, liver and heart.
Heard in: Grey Peptides listing review, October 1, 2026: listings list organ protection among its benefits. Sellers are not named.
Each of those is an animal or mechanistic study: NAD and lipid changes driving acidosis-induced kidney injury, NAD-boosting therapy in fatty liver disease, NAD biosynthesis in acute kidney injury, and an animal study in ischaemic cardiomyopathy. None is a human outcome trial. PMID: 33478973, 33754067, 40461655, 40954388
Shown in animals or cells onlyIt is a vitamin derivative, so it is safe at any dose.
Heard in: Grey Peptides listing review, October 1, 2026: listings present high-dose infusions as nutritional rather than pharmacological. Sellers are not named.
The reviews treat NAD precursors as therapeutic targets with dose and route questions open, and the 2026 systematic review ends by calling for studies of dosage and effect beyond 30 days. Being derived from a vitamin says nothing about an intravenous dose given over hours. PMID: 29634344, 41655607
Measured, never givenEach claim is quoted from where it is said, never from a seller, and checked as of October 1, 2026 against the studies listed below.
Dosing Data
NAD+ has no approved dose. The only randomised trial used 10 mg a day intravenously for seven days in heart failure; wellness clinics typically infuse 250 to 1,000 mg over one to four hours, and the one study of clinic practice gave 500 mg on four consecutive days.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
→ Full NAD+ dosage guide — clinic infusion and injection ranges, the 10 mg dose in the only randomised trial, and why infusion speed matters
Side Effects & Contraindications
Reported Side Effects
From the two human studies above; neither was designed to catalogue side effects over the long term.
Contraindications & Cautions
No approved label exists. These cautions follow from the studies and from how NAD+ is sold.
Legal Status
NAD+ is not an approved drug anywhere. In the United States it sits on FDA's compounding list under evaluation.
Frequently Asked Questions
?Is NAD+ a peptide?
No. It is a coenzyme built from vitamin B3 and adenine nucleotides. It appears in peptide guides because clinics sell it as an injectable alongside peptides.
?Do IV NAD+ drips work?
There is no outcome trial showing they do anything for ageing or wellness. A 2026 systematic review found none, and the only randomised trial of NAD+ itself tested a much smaller dose (10 mg a day) in heart failure.
?Why do NAD+ infusions feel so uncomfortable?
In a 2026 review of clinic records, 500 mg infusions caused moderate to severe gut symptoms, a faster heart rate and chest pressure during the infusion, which is why clinics run them slowly; symptoms stopped when the infusion ended.
?Is NMN or NR better than NAD+?
They are different questions. Oral NR and NMN reliably raise NAD-related metabolites in blood, but their effects on health outcomes in trials have been mixed and often null, and in mice most of an oral dose is converted to nicotinamide or nicotinic acid first.
?Can a pharmacy compound NAD+?
In the United States, yes, under conditions: FDA lists NAD and NAD disodium in 503A Category 1, under evaluation, where its interim policy does not act against compounding. That is not an approval, and it can change when FDA completes its evaluation.
?Did NAD+ help heart failure?
In one single-centre trial of 180 patients, a week of 10 mg a day intravenously improved ejection fraction by about three points more than placebo at one month. Hospitalisations and symptoms trended better but not significantly; it needs repeating.
References
- [Review] Rajman L, et al. "Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence." Cell Metab, 2018;27(3):529-547. PMID: 29514064.
- [Animal] Liu L, et al. "Quantitative Analysis of NAD Synthesis-Breakdown Fluxes." Cell Metab, 2018;27(5):1067-1080.e5. PMID: 29685734.
- [Review] Braidy N, et al. "Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes." Antioxid Redox Signal, 2019;30(2):251-294. PMID: 29634344.
- [Animal] Bugarski M, et al. "Changes in NAD and Lipid Metabolism Drive Acidosis-Induced Acute Kidney Injury." J Am Soc Nephrol, 2021;32(2):342-356. PMID: 33478973.
- [Animal] Li DJ, et al. "NAD(+)-boosting therapy alleviates nonalcoholic fatty liver disease via stimulating a novel exerkine Fndc5/irisin." Theranostics, 2021;11(9):4381-4402. PMID: 33754067.
- [Animal] Yaku K, et al. "Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD(+) synthesis via enterohepatic circulation." Sci Adv, 2025;11(12):eadr1538. PMID: 40117359.
- [Animal] Lei Y, et al. "NAD(+) biosynthesis and mitochondrial repair in acute kidney injury via ultrasound-responsive thylakoid-integrating liposomes." Nat Biomed Eng, 2025;9(10):1740-1757. PMID: 40461655.
- [Human] Yu X, et al. "Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy: A Randomized, Placebo-Controlled Trial." Am J Cardiovasc Drugs, 2026;26(1):97-106. PMID: 40954388.
- [Human] Reyna K, 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. PMID: 41704678.
- [Review] Gallagher C, et al. "NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence." Ageing Res Rev, 2026;116:103057. PMID: 41655607.
Sources & Citations
Every citation on this page is PubMed-indexed and has been checked against its record; the compounding status was read on FDA's 503A category list. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.