NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in every living cell. It carries electrons in energy metabolism, and it is the fuel for several enzyme families involved in DNA repair, gene regulation and immune signaling. The body makes it from vitamin B3 and the amino acid tryptophan. Because tissue NAD+ levels fall with age, NAD+ has become a popular “longevity” product, most visibly as intravenous (IV) drips and injections sold by wellness clinics.

The single most important fact: NAD+ is not an FDA-approved drug for any use, and no controlled trial has shown that IV or injected NAD+ improves any health outcome. The published human data on IV NAD+ are limited to a small pharmacokinetic pilot, a retrospective chart review, a non-peer-reviewed preprint and uncontrolled case reports. The two studies that compared it with IV nicotinamide riboside found NAD+ infusions often uncomfortable.

This page covers NAD+ itself. The oral precursors have their own pages: NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside). This page summarizes what the clinical studies, reviews and regulators report. It is for education only and is not medical advice.

Property	Detail
Class	Endogenous coenzyme (dinucleotide); vitamin B3 metabolite
Chemistry	C₂₁H₂₇N₇O₁₄P₂, 663.4 g/mol; also called nadide
FDA status	Not an approved drug; IV and injectable products are compounded
Compounding status	Listed by FDA in 503A Category 1, “under evaluation” (May 2026)
Routes used	IV infusion, intramuscular injection, oral supplements
Doses in human IV studies	750 mg over 6 h (single); 500 mg daily for 4 days; 500 mg single dose
Half-life	No human plasma half-life published; infused NAD+ was cleared from plasma completely for at least the first 2 h of a slow infusion
Cell uptake	Not taken up intact; broken down outside cells into smaller precursors first (cell studies)
WADA	Not named; IV infusions over 100 mL per 12 h are prohibited at all times (M2.2)

What it is

NAD+ is a dinucleotide: two nucleotides joined through their phosphate groups. One carries an adenine base and the other carries nicotinamide, the vitamin B3 part that does the chemistry (PubChem). Its reduced form, NADH, carries electrons to the mitochondria for ATP production. NAD+ and NADH cycle back and forth without being used up.

NAD+ is also consumed as a substrate by three groups of enzymes, each of which releases nicotinamide (NAM) as a by-product (Covarrubias et al., Nat Rev Mol Cell Biol 2021):

sirtuins, enzymes that remove acetyl groups from proteins and help regulate metabolism and gene expression;
PARPs (poly-ADP-ribose polymerases), which mark and repair damaged DNA;
NAD+ glycohydrolases such as CD38, immune-cell enzymes that break NAD+ down.

Because NAD+ is constantly consumed, cells must keep rebuilding it. There are three routes:

Route	Starting material	Notes
De novo (kynurenine pathway)	Tryptophan	Mostly in the liver, which releases NAM into the blood for other tissues
Preiss–Handler pathway	Nicotinic acid (niacin)	Dietary vitamin B3
Salvage pathway	NAM, NR, NMN	Recycles the NAM released by NAD+-consuming enzymes

Severe dietary lack of these precursors causes pellagra, a disease of diarrhea, dermatitis and dementia that was found early in the 20th century to be curable with niacin-containing foods (Grant et al., Front Aging Neurosci 2019).

NAD+ and aging

The interest in NAD+ supplementation rests on observations that NAD+ falls with age:

In 49 samples of human pelvic skin from people aged 0–77, tissue NAD+ fell with age in both males (r = −0.706) and females (r = −0.537). In males, higher PARP activity tracked lower NAD+ (Massudi et al., PLoS One 2012).
In plasma from healthy adults across a wide age range, NAD+ and NADP+ declined with age while NAM and other breakdown products rose (Clement et al., Rejuvenation Res 2019).
In mice, expression and activity of the NAD+-degrading enzyme CD38 rose with age, and CD38 was required for the age-related NAD+ decline (Camacho-Pereira et al., Cell Metab 2016).

A 2021 review noted that many age-related diseases can be slowed or even reversed by restoring NAD+ in experimental models. It also stressed that it remains unknown whether NAD+ repletion is safe or beneficial in aging humans (Covarrubias et al., 2021).

How it behaves in the body

Why NAD+ does not simply enter cells

In studies of human cells in culture, only nicotinamide, nicotinic acid and their nucleosides (such as NR) readily crossed the cell membrane. Nucleotides, including NAD+ and NMN, were first broken down outside the cell into these permeable precursors, which the cell then used to rebuild NAD+ (Nikiforov et al., J Biol Chem 2011). In other words, injected NAD+ appears to work, if at all, as a source of precursors rather than as intact NAD+ delivered into cells.

In mice, isotope-tracing work found that NAD+ turnover differs widely between tissues: fast in the small intestine and spleen, slow in skeletal muscle. In cultured cells the turnover half-time was about 6–12 h. The same work found that NR or NMN given intravenously reached several tissues intact, whereas the same molecules given orally were mostly converted to NAM in the liver (Liu et al., Cell Metab 2018).

The only human IV pharmacokinetic study

The first study of what happens to infused NAD+ in people gave 8 healthy men aged 30–55 a 750 mg IV infusion over 6 hours (≈2 mg/min, or 3 µmol/min). Three men received saline (Grant et al., Front Aging Neurosci 2019). The dose was chosen to match a common regimen at the wellness clinic where the study was run.

Measure	Result
Plasma NAD+ during the first 2 h	No rise: infused NAD+ was removed from plasma rapidly and completely
Plasma NAD+ at end of infusion (6 h)	+398% vs baseline; still elevated 2 h later
Plasma nicotinamide (NAM) at 6 h	+409%
Plasma ADP-ribose at 6 h	+393%
Plasma NMN	+472%, only at 8 h (2 h after the infusion ended)
Urinary NAD+ excretion at 6 h	+538% vs the 30-minute value
Adverse events	None observed

The parallel rise of NAM and ADP-ribose points to rapid breakdown of NAD+ by enzymes such as CD38. Some intact NAD+ and methylnicotinamide (a NAM breakdown product) were lost in the urine. The study measured plasma and urine only, not NAD+ inside cells or tissues. One author was affiliated with the clinic that offers the infusions.

About “NAD+ half-life” figures. Some sources quote a plasma half-life for injected NAD+ in minutes. We could not find a published human study that measured one. The Grant study did not report a half-life; it showed that NAD+ disappears from plasma faster than a slow infusion can raise it during the first 2 hours.

Regulatory status

Not FDA-approved. No NAD+ product is approved as a drug in the US. IV and injectable NAD+ sold by clinics is made by compounding pharmacies (Reyna et al., Front Aging 2026). FDA states that compounded drugs are not FDA-approved, so the agency does not verify their safety, effectiveness or quality before they are marketed (FDA).
Compounding nominations. FDA’s list of substances nominated for 503A pharmacy compounding places NAD and NADH in Category 1, “bulk drug substances under evaluation.” A separately nominated salt form (beta-NAD disodium salt trihydrate) is in Category 3, “nominated without adequate support” (FDA 503A categories, May 2026). NAD+ has not been added to the final 503A bulks list (FDA).
Sport. NAD+ is not named on the WADA list. However, IV infusions or injections of more than 100 mL in total per 12-hour period are a prohibited method at all times, unless received legitimately during hospital treatment, surgery or clinical diagnostic investigations (WADA 2026 Prohibited List). The commercial infusions described below were diluted in 500 mL of saline.

What the research shows

Two recent systematic reviews frame the evidence:

A 2026 PRISMA-guided review identified 33 human intervention studies of NAD-related compounds. Oral NR and NMN reliably raised blood NAD+ markers, but effects on function, metabolism and other healthspan outcomes were mixed and often null. No eligible outcome trial of intravenous or intramuscular NAD+ itself was found (Gallagher & Emmanuel, Ageing Res Rev 2026).
A 2026 critical review of IV “longevity therapy” (including NAD+) concluded it should be regarded as experimental, citing scarce and underpowered placebo-controlled trials (Godic & Townsend, Acta Dermatovenerol APA 2026).

IV NAD+ compared with IV NR

Two small clinic-linked studies compared IV NAD+ with IV nicotinamide riboside at the same dose.

Study	Design	Arms	Main findings for IV NAD+
Reyna et al., 2026	Retrospective chart review, wellness clinic; 30-day follow-up	500 mg NAD+ IV (n = 6) vs 500 mg NR IV (n = 8), daily for 4 days	All 6 reported moderate to severe symptoms during infusion; mean infusion time 97 min vs 37 min for NR
Hawkins et al., 2024	Randomized, double-blind, placebo-controlled pilot (preprint, not peer reviewed)	Single 500 mg NR IV, 500 mg NAD+ IV, 500 mg oral NR, or saline; 37 + 16 participants analyzed	More and more severe infusion reactions than NR IV; tolerable infusion time for NR IV was 75% shorter; white cell and neutrophil counts rose; blood NAD+ at 3 h lower than after NR IV (p under 0.01)

In the chart review, clients set their own infusion rate based on tolerance. Over 30 days, HDL cholesterol fell by a mean of 5.8 mg/dL in the NAD+ group (p = 0.02) and alkaline phosphatase fell slightly, with values staying in the normal range. There were no significant changes in ALT, AST, hsCRP, kidney markers, TSH, fasting glucose or LDL. The study had no untreated control group and was funded and run by the clinic company. In the preprint, peak blood NAD+ rose 20.7% after NR IV; the comparison product (Niagen) is a branded NR.

Neither study measured a clinical benefit such as energy, cognition, body composition or disease risk.

Addiction and alcohol withdrawal

The clinic use of IV NAD+ traces back to a 1961 preliminary report on NAD (then called diphosphopyridine nucleotide, DPN) for drug addiction (O’Hollaren, West J Surg Obstet Gynecol 1961). The most-cited modern report is an uncontrolled series of 50 patients with substance use disorder who received infusions of NAD+ combined with an enkephalinase-inhibitor formula (Blum et al., Curr Psychiatry Res Rev 2022). Craving, anxiety and depression scores fell from baseline, but there was no control group, NAD+ was not tested alone, and the lead author holds patents on the enkephalinase therapy. The authors themselves called for randomized placebo-controlled trials. We found no randomized controlled trial of IV NAD+ for addiction or withdrawal.

Oral NAD+ and NADH

NAD+ itself is not thought to be absorbed intact from the gut or taken up intact by cells (Reyna et al., 2026). A 2026 randomized trial, whose authors include the developer’s chief executive and shareholders, in 50 analyzed adults aged 45–75 tested a modified oral NAD+ formulation for 5 days. Whole-blood NAD increased 53% versus placebo, but plasma NAD did not change, while the NAM breakdown products methylnicotinamide and N1-methyl-2-pyridone-5-carboxamide (2PY) rose sharply. Clinical and wellbeing endpoints did not differ after correction for multiple testing (Kornilov et al., GeroScience 2026).

The reduced form, NADH, has been tested orally at small doses. In a crossover trial in 26 people with chronic fatigue syndrome, 8 of 26 (31%) responded to 10 mg/day NADH for 4 weeks vs 2 of 26 (8%) on placebo (Forsyth et al., Ann Allergy Asthma Immunol 1999). A 2024 systematic review pooled 10 randomized trials with 489 participants, mostly of oral NADH or precursors, and found the products well tolerated, with clinical benefits that still need confirmation (Gindri et al., Am J Physiol Endocrinol Metab 2024).

For oral precursors, see the NMN and NR pages, which have a much larger trial base than NAD+ itself.

Side effects and risks

Infusion reactions

Discomfort during infusion is the most consistent finding with IV NAD+. In the 2026 chart review, all 6 clients given NAD+ reported moderate to severe symptoms during infusions, which stopped as soon as each infusion ended (Reyna et al., 2026):

abdominal cramping, nausea, vomiting and diarrhea;
faster heart rate and chest pressure;
throat pain and congestion.

Clinician reports cite these reactions as the reason NAD+ infusions are run slowly. The single-dose preprint reported the same pattern, with more and more severe reactions on NAD+ than on NR (Hawkins et al., 2024). The 6-hour, 750 mg infusion in the 2019 pilot produced no observed adverse events (Grant et al., 2019).

Possible inflammatory response

Extracellular NAD+ can act as a “danger signal” to the immune system, and the authors of the chart review suggest this may explain the infusion symptoms (Reyna et al., 2026). The preprint found rises in white blood cell and neutrophil counts after IV NAD+ but not IV NR, which its authors interpreted as an inflammatory response (Hawkins et al., 2024).

Lab changes

The available data are small and short:

750 mg over 6 h produced statistically significant but clinically minor changes in some liver tests (small falls in GGT, LD and AST; bilirubin up 2.75 µmol/L) (Grant et al., 2019).
Four daily 500 mg infusions were followed by a 5.8 mg/dL fall in HDL cholesterol at 30 days, in 6 people without a control group (Reyna et al., 2026).

Unknowns

Long-term safety. None of the published IV studies followed participants for more than about 30 days.
Product quality. Compounded NAD+ is not FDA-approved, so its identity, strength and sterility are not verified by FDA before sale (FDA).
Who was studied. The human IV studies enrolled small numbers of generally healthy adults; the chart review excluded pregnant clients. We found no IV NAD+ data in children or in people with heart, liver or kidney disease.

Key takeaways

An essential coenzyme, not an approved drug. NAD+ drives energy metabolism and fuels sirtuins, PARPs and CD38. No NAD+ product is FDA-approved, and clinic infusions are compounded.
Tissue levels fall with age. Human skin and plasma studies show lower NAD+ in older people; animal work links this to rising CD38 activity.
Infused NAD+ is broken down fast. It vanished from plasma during the first 2 hours of a slow infusion, and cell studies show it must be split into precursors before cells can use it.
No outcome trials. Systematic reviews found no controlled trial showing that IV or injected NAD+ improves any health or anti-aging outcome.
Infusions are often unpleasant. Cramping, nausea, chest pressure and a faster heart rate were reported by every NAD+ recipient in one clinic study; IV NR was tolerated better and raised blood NAD+ more in a preprint comparison.
Athletes face an IV limit. NAD+ is not banned by name, but IV infusions over 100 mL per 12 hours are prohibited by WADA outside legitimate medical care.

Sources

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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. PubMed.
Clement J, Wong M, Poljak A, et al. The plasma NAD+ metabolome is dysregulated in “normal” aging. Rejuvenation Res. 2019;22(2):121–130. PubMed.
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. PubMed.
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. PubMed.
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Blum K, Han D, Baron D, et al. Nicotinamide adenine dinucleotide (NAD+) and enkephalinase inhibition (IV1114589NAD) infusions significantly attenuate psychiatric burden sequalae in substance use disorder (SUD) in fifty cases. Curr Psychiatry Res Rev. 2022;18(2):125–143. PubMed.
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 (online ahead of print). PubMed.
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