Metabolic / SubQ / 100-500mg IV preferred; daily SubQ also used
NAD+*
NAD+ was the first coenzyme anyone described, in 1906, and its chemistry was settled over the following fifty years as a vitamin and redox story. The injectable has no comparable record: it reached patients through a 1961 preliminary report and then through private clinics, and nobody measured what an intravenous dose does in human plasma until 2019.
In plain words
NAD+ is a coenzyme every cell uses to run its energy chemistry; it was the first coenzyme ever described, in 1906. Its level in human skin falls steeply with age, and that observation is the idea behind putting it back by drip or injection. What the human measurements show is that an injected dose does not stay NAD+ for long: during a six-hour infusion in eight healthy men, plasma NAD+ did not change at all for the first two hours, and the pattern of breakdown products fit the molecule being cut apart outside cells and rebuilt inside from the pieces, since cells do not take NAD+ in whole. Randomized trials of the swallowed building blocks raise NAD+ in blood but did not raise it in muscle, where the surplus appeared to leave through disposal pathways instead of accumulating. There is no approved NAD+ injection in the United States, so every vial is a compounded preparation; the practice grew out of two brief 1961 reports that no controlled trial ever followed, and in practice the drip rate is limited by how it feels, with nausea, cramping, chest pressure and a raised heart rate reported during infusions and settling once they stop.
At a glance
| Half-life | 0.003 days |
|---|---|
| Tmax | 0.001 days |
| Route(s) | SubQ |
| Published dosing range | 100-500mg IV preferred; daily SubQ also used |
| Vial strengths | 500, 750, 1000 mg |
Reference data from the DosePlot canon -- not a protocol recommendation.
Serum curve
Single 300 mg dose by SubQ, rendered from the same engine that powers the interactive chart. Relative levels, not lab values.
What does the evidence show?
Two things are labeled separately here because they answer different questions. The tier is how a study was built. The distance chips are whether that study touched this molecule, by this route, in a population resembling the reader. A randomized trial of a different molecule keeps its tier and still says nothing about this compound.
| Finding | Tier | Distance from use | Study |
|---|---|---|---|
| NAD+ content in human skin falls steeply across the lifespan. Pelvic skin was taken during unrelated surgery from 49 people, newborns plus patients aged 15 to 77. The four age bands the authors tabulate hold 48 of those samples and leave a gap between age 1 and age 30: mean NAD+ was 8.54 ng per mg protein in newborns (n = 8), 2.74 at ages 30 to 50 (n = 12), 1.08 at 51 to 70 (n = 23), and 1.06 above 71 (n = 5). Across the same bands, activity of PARP, the DNA repair enzyme that consumes NAD+, rose from 2.52 to about 20 ng NAD+ used per hour per mg protein. NAD+ correlated negatively with age in both sexes (males r = -0.706, p = 0.001; females r = -0.537, p = 0.01). This is biochemistry on excised tissue rather than an interventional study, and it is cross-sectional in one tissue, so it describes an association, not a measured trajectory in any individual. | clinical | not recorded | Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.PLoS One 7(7):e42357, 2012 |
| Infused NAD+ does not appear in plasma as NAD+ for the first two hours. Eight healthy men received 750 mg of NAD+ intravenously over six hours, about 2 mg per minute, alongside three saline controls. Plasma NAD+, nicotinamide, ADP-ribose, methylnicotinamide and NMN were all unchanged through the two-hour sample. At the end of the infusion plasma NAD+ was 398 percent above baseline, nicotinamide 409 percent, ADP-ribose 393 percent and methylnicotinamide 350 percent; NMN rose 472 percent only at eight hours, two hours after the drip stopped. Urinary NAD+ excretion was 538 percent above the 30-minute rate at six hours. The authors read the pattern as cleavage by NAD+ glycohydrolase and NAD+ pyrophosphatase rather than delivery of intact NAD+. | clinical | not recorded | Grant R, Berg J, Mestayer R, Braidy N, Bennett J, Broom S, Watson J. A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+.Frontiers in Aging Neuroscience 11:257, 2019 |
| Cells do not take up NAD+ whole. In human cell lines, the only members of this family that cross the plasma membrane readily are nicotinamide, nicotinic acid, and their corresponding nucleosides. The nucleotides, NAD+ and NMN among them, are degraded outside the cell first, and the permeable fragments that result are what enter and get rebuilt into NAD+ inside. The same paper placed mitochondrial NAD+, a large share of the cellular total, as assembled on site from NMN by NMNAT3. That part of the 2011 model no longer stands. Three groups independently identified SLC25A51, also called MCART1, as a mammalian mitochondrial NAD+ transporter in 2020, and mice lacking NMNAT3 hold normal mitochondrial NAD+ in every tissue except red blood cells, so the mitochondrial pool is now read as largely imported rather than made in place. Those four studies are listed in the diagram sources on this page. | preclinical | not recorded | Nikiforov A, Dolle C, Niere M, Ziegler M. Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation.Journal of Biological Chemistry 286(24):21767-21778, 2011 |
| Tolerability, not chemistry, sets the infusion rate. A retrospective chart review at a commercial wellness chain compared four consecutive daily infusions of 500 mg NAD+ against 500 mg nicotinamide riboside. The NAD+ group reported moderate to severe gastrointestinal symptoms, raised heart rate and chest pressure during infusions, and averaged 97 minutes per bag against 37 minutes for nicotinamide riboside, whose symptoms were limited to tingling in the tongue, jaw and arm plus mild cramping. All symptoms resolved when the infusion ended. ALT, AST, hsCRP, BUN and creatinine, and TSH did not change over 30 days in either group. | clinical | not recorded | Reyna K, Heinzen G, Patel N, Ritter M, Siojo A, Legere H, Pojednic R. Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting.Frontiers in Aging 7:1652582, 2026 |
| Oral nicotinamide riboside raises whole blood NAD+ in proportion to dose. In an 8-week randomized, double-blind, placebo-controlled trial in overweight but otherwise healthy adults, 100, 300 and 1000 mg per day raised whole blood NAD+ by 22, 51 and 142 percent within two weeks, and the increases held for the rest of the study. No flushing was reported, adverse events did not differ from placebo, and LDL cholesterol was unaffected. | rct | not recorded | 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.Scientific Reports 9(1):9772, 2019 |
| Moving the blood number is not the same as moving muscle NAD+. Twelve aged men took 1 g of nicotinamide riboside daily for 21 days in a randomized, double-blind, placebo-controlled crossover trial with muscle biopsies. Muscle NAD+ itself did not rise (210 against 197 pmol per mg, p = 0.22). What rose was the traffic around it: NAAD doubled (0.73 against 0.35 pmol per mg, p = 0.004) and the methylated disposal products rose about fivefold. Mitochondrial bioenergetics, muscle protein acetylation and grip strength were unchanged, while circulating inflammatory cytokines fell. | rct | not recorded | Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures.Cell Reports 28(7):1717-1728, 2019 |
| One trial found a functional benefit from a precursor without any measurable change in muscle NAD+. Twenty-five postmenopausal women with prediabetes who were overweight or obese took 250 mg of NMN or placebo daily for 10 weeks. Insulin-stimulated glucose disposal on a hyperinsulinemic-euglycemic clamp rose with NMN and not with placebo, as did skeletal muscle AKT and mTOR phosphorylation. Muscle NAD+ content did not change in either group, while methylated NAD+ metabolites rose, which the authors read as faster turnover. Body composition, blood pressure, plasma glucose, insulin and lipids did not change. | rct | not recorded | Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.Science 372(6547):1224-1229, 2021 |
| Community practice treats the drip rate, not the milligram total, as the variable that has to be managed. Reported protocols run 250 to 1000 mg over two to four hours, slowed or paused when chest tightness, nausea or abdominal cramping start and resumed once they pass, often as a block of consecutive daily infusions followed by monthly maintenance. Subcutaneous injection is described as stinging at the site and is chosen mainly because it needs no line and no chair time. | anecdotal | not recorded | community reports aggregated from reddit, MESO-Rx, and similar forumsno study |
How did it get here?
- preclinical1906
- Harden and Young find that yeast juice stops fermenting sugar once it has been dialyzed, and starts again when boiled yeast juice, which contains no working enzymes at all, is added back. They name the heat-stable factor in the boiled fraction the coferment of yeast juice. It is NAD+, and it is the first coenzyme ever described.
- preclinical1936-1937
- Warburg and Christian identify the nicotinamide ring as the part of the molecule that carries hydrogen. A year later Elvehjem and colleagues show that nicotinic acid amide cures canine black tongue, tying the same ring to pellagra in humans. The coenzyme becomes a vitamin story, and nicotinamide becomes a cheap commodity chemical, which is why every later product in this family is built from it.
- preclinical1958
- Preiss and Handler identify the intermediates between nicotinic acid and NAD+, the first biosynthetic route to the molecule written down. The salvage route from nicotinamide, which turns out to carry most of the traffic in mammals, is mapped over the following decades.
- first-human1961
- One physician publishes two preliminary reports in a single year, both in the same regional surgical journal: pyridine nucleotides in problem drinkers in the March-April issue, then diphosphopyridine nucleotide, the old name for NAD+, in the prevention and treatment of drug addiction in the May-June issue. No controlled trial follows either. The practice survives in private clinics rather than in the literature, which is the whole reason the intravenous route arrived in the 2010s with almost no data behind it.
- preclinical2000-2004
- Three papers turn NAD+ from a redox carrier into a target. Imai and colleagues show that the longevity protein Sir2 is an NAD-dependent deacetylase, so consuming NAD+ becomes a signaling act. Revollo and Imai establish NAMPT as the rate-limiting step of the salvage cycle. Bieganowski and Brenner identify nicotinamide riboside and the NRK kinases as a separate entry into the same cycle. The oral precursor industry is built on these three results.
- grey-market2010s-2020s
- Intravenous NAD+ spreads from addiction clinics into wellness and drip-bar practice, supplied as a compounded preparation rather than an approved drug. Community reports put the amount at 250 to 1000 mg per infusion, above the 100 to 500 mg reference range DosePlot carries; no trial and no regulator sets either figure. The first human pharmacokinetic data appear in 2019, from a study run at one of the clinics that had already been giving the infusions for years, and they cover the intravenous route only. A head-to-head tolerability comparison against intravenous nicotinamide riboside appears in 2026.
How is it made?
Production happens in four stages.
1. Making the nicotinamide half. Nicotinamide is a commodity vitamin, produced industrially from 3-methylpyridine, oxidized to nicotinic acid and then amidated, or from 3-cyanopyridine using a bacterial nitrile hydratase. The starting material costs almost nothing next to the finished vial.
2. Building the dinucleotide. NAD+ is nicotinamide mononucleotide joined to adenosine monophosphate through a pyrophosphate bridge. Commercial routes are mostly enzymatic. A phosphoribosyltransferase attaches nicotinamide to a ribose phosphate to give NMN, and an adenylyltransferase couples that to ATP to close the bridge, either in enzyme reactors or inside engineered bacteria. Chemical coupling of NMN to an activated adenylate works, but it needs protecting groups and gives poorer yields.
3. Purifying and drying. The molecule is charged and water-soluble, so it is captured on ion-exchange resin, polished by preparative chromatography, and freeze-dried. The oxidized form is stable in acid and decomposes in alkali, so the process is run on the acid side. Release assays look for nicotinamide, AMP, ADP-ribose, and the reduced form NADH.
4. Filling the vial. There is no approved NAD+ injection in the United States. The powder is dissolved in water for injection or saline, pH-adjusted, sterile-filtered and filled by a compounding pharmacy or an outsourcing facility. The chemistry is ordinary. Outside regulated manufacturing what varies is sterility and endotoxin control, whether the batch was assayed at all, and how far a solution's real strength has drifted from the number on the label by the time it is hung.
Worth knowing
For its first thirty years NAD+ had no chemical identity, only a name for what it did. Harden and Young titled their 1906 paper for the coferment of yeast juice, an activity rather than a substance, because nobody could yet say what the substance was; the nicotinamide ring at its center was not pinned down until the 1930s. The name then changed twice more, to diphosphopyridine nucleotide and finally to NAD+, which is why the 1961 reports of the first human infusions are indexed under DPN and are easy to miss.
Harden A, Young WJ. The alcoholic ferment of yeast-juice. Part II. The coferment of yeast-juice.Proceedings of the Royal Society of London Series B 78:369-375, 1906
Intravenous NAD+ was first reported as an addiction treatment in 1961, under the molecule's old name, diphosphopyridine nucleotide. It was the second of a pair: the same author had already published a preliminary report on pyridine nucleotides in problem drinkers earlier that year, in the same journal (69:101-104, March-April 1961). The addiction report is three pages long and explicitly preliminary, as is the one before it. No controlled trial followed either, and the first measurements of what an intravenous dose actually does to plasma NAD+ in humans were published 58 years later, in 2019, by investigators working at a clinic that had been giving the infusions in routine practice.
O'Hollaren P. Diphosphopyridine nucleotide in the prevention, diagnosis and treatment of drug addiction. A preliminary report.Western Journal of Surgery, Obstetrics and Gynecology 69:213-215, 1961
There is no approved NAD+ injection to compare a compounded one against. On the FDA's list of bulk drug substances nominated for use by outsourcing facilities, beta-nicotinamide adenine dinucleotide sits in Category 1, still under evaluation, while beta-nicotinamide adenine dinucleotide disodium salt trihydrate sits in Category 3, nominated without enough supporting information for the agency to evaluate it. Both entries describe the raw powder. The finished vial is a compounded preparation in every case.
US Food and Drug Administration. Bulk drug substances nominated for use in compounding under section 503B of the Federal Food, Drug, and Cosmetic Act.FDA category list, updated March 21, 2025
Reconstitution
NAD+* ships lyophilized and is mixed before use; the published vial strengths are 500, 750, 1000 mg. The water volume you add sets the concentration, not the dose -- the calculator turns a vial size and a water volume into mg/mL, draw volume, and units on an insulin syringe.
Open in the reconstitution calculatorWritten and reviewed by Evan Marlow, developer of DosePlot · Updated 2026-08-27
Not medical advice. DosePlot is an informational tool, not a healthcare provider, and using it creates no provider-patient relationship. Do not start, stop, or change any protocol without the approval of a licensed healthcare professional.
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