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NAD+, and what each way of taking it actually does

Injections, IV drips, nasal sprays, NAD+ capsules, NR and NMN all promise the same thing and reach your cells in very different ways, and for some of them nobody has ever measured what happens. Here is what NAD+ does in your body, what each route delivers, and which claims have a study behind them.

Every source on this page is a peer-reviewed journal article, an FDA document or a registered trial. No clinic pages, no supplement brands.

Before you read the rest

None of this is FDA-approved, and most of it has never been measured in a person

Nothing on this page is an FDA-approved treatment for anything. Not for aging, not for energy, not for brain fog, not for recovery. The capsules are sold as dietary supplements, which means the FDA does not review them for whether they work before they go on sale. The injections, the IV bags and the nasal sprays are compounded preparations, which is a different thing again: NAD+ is not an approved drug and it is not on the FDA's final list of substances approved for pharmacy compounding.

Here is the entire scientific case, stated plainly. NAD+ is genuinely central to how your cells make energy. It genuinely declines with age. Some oral precursors, NR most clearly and NMN less so, genuinely raise the amount of NAD+ measured in your blood, by a known amount, at a known dose, and oral NR has been shown to raise it inside muscle tissue too. That is the whole of what has been established in humans.

Everything after that is speculation. That more NAD+ in your cells does anything you would notice. That it slows aging, lifts energy, sharpens thinking, or repairs anything. That a shot or a drip beats a capsule. None of those have been shown in people, and several have been tested and did not hold up. In the two trials that raised muscle NAD+ successfully, muscle mitochondrial function and whole-body metabolism did not change. For the injection, the nasal spray and the swallowed NAD+ capsule, the speculation starts even earlier: nobody has published a measurement of whether the dose gets into you at all.

That does not make any of it worthless, and it does not mean people pushing it are lying. It means the honest label on almost all of this is "promising, unproven, unregulated," and you should know that before you decide what it is worth to you.

Compare the routes

Pick up to 4.

Search or click a route to see it on its own. Pick a second, third or fourth to put them side by side. They are grouped by how much human evidence stands behind each one, and nothing is shown until you choose, so you only read the ones you came for.

The dose question

Does your weight change your dose?

No. Not in any published evidence, anyway, and this is worth being blunt about, because dosing charts that scale NMN or NR to your body weight are everywhere.

Every human trial of every NAD+ precursor has used flat doses. Not milligrams per kilogram, not adjusted for height, not different for men and women. The 60-day NMN trial gave everyone 300, 600 or 900 mg regardless of size. The 8-week NR trial gave everyone 100, 300 or 1000 mg. Where sex was considered at all, it was used to balance the groups, not to set the dose.

There is also a biological reason not to expect weight scaling to help much. The largest NMN trial found 900 mg a day did no better than 600 mg on blood NAD+, which is what a saturating pathway looks like. Past a point the enzymes are busy and more raw material does not go anywhere.

So instead of inventing a number, here is the more useful question: is the dose in front of you inside the range anyone has actually studied?

Enter a dose to see whether it falls inside the published range.

What you feel, and what it tells you

Feeling something is the main reason people prefer injections and drips to capsules. It is worth separating which sensations have an explanation and what they do and do not indicate.

The flush

A true flush, hot and red and prickling across the face and chest, is a receptor effect of nicotinic acid, the old form of B3. It hits GPR109A on skin immune cells, which release prostaglandin D2, which opens the capillaries. NR does not do it: the 8-week trial that went to 1000 mg a day recorded no reports of flushing at any dose. If you flushed, that tells you which molecule you took.

The IV reaction

The cramping, nausea, racing heart and chest pressure during an NAD+ drip are well documented, and in one chart review all six people had them, and they stop when the infusion stops. That is a rate-of-infusion effect. It is the reason bags are run slowly, and it is not a sign the dose is working.

The energy buzz

No trial has measured it. There is no placebo-controlled study of subcutaneous NAD+ reporting energy or mood, so there is no way to say how much of the effect is the molecule. That is not a claim that people are imagining it. It is that the study that would settle it has not been done.

If you only take one thing from this page

The routes with the most human evidence are the cheapest ones, and the routes with the least are the ones sold in clinics. Oral NR has around 25 published trials and a known dose-response curve. Subcutaneous NAD+, intranasal NAD+ and swallowed NAD+ have no published human pharmacokinetic data at all.

And even for NR, raising NAD+ is not the same as improving health. Two trials got NAD+ up inside the muscle of aged and overweight people and found mitochondrial function and metabolic measures unchanged, and the 2023 review of every human NR trial concluded it "has displayed few clinically relevant effects." The biochemistry works. The benefits people are buying have mostly not been demonstrated yet.

And none of it is FDA-approved. The supplements were never reviewed for whether they work; the injectables and infusions are compounded preparations rather than approved drugs. There is no regulator standing behind any claim made about these products, and no approved dose for any of them.

None of this means NAD+ research is going nowhere. It means one narrow thing has been demonstrated, that some precursors raise blood NAD+, and everything people are actually buying it for is still speculation. The marketing has run a long way ahead of the evidence, and the gap is widest exactly where the price is highest.

This is education, not medical advice

NAD+ products are largely unregulated, and injectable and compounded NAD+ is not an FDA-approved drug. If you are considering any of this, particularly an injection or an infusion, talk to your prescriber first, especially if you take other medications or have a liver or kidney condition. This page is general education from Cozy Butter rather than clinical advice. Bring it to your appointment if it helps the conversation; do not use it in place of one.

Sources

25 references
  1. Liu L, Su X, Quinn WJ, et al. Quantitative analysis of NAD synthesis-breakdown fluxes. Cell Metabolism. 2018;27(5):1067–1080. doi:10.1016/j.cmet.2018.03.018. The isotope-tracing work behind the turnover figures: NAD+ half-life ranging from roughly 15 minutes to 15 hours across tissues, high flux in the small intestine and spleen and low flux in skeletal muscle, nicotinamide as the main circulating source for most tissues, and the finding that orally delivered NR and NMN are broken at the nicotinamide-ribose bond before reaching tissues.
  2. Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. 2021;22(2):119–141. doi:10.1038/s41580-020-00313-x. Background for the salvage pathway, the NAD+-consuming enzymes (sirtuins, PARPs, CD38), and the extracellular conversion of NAD+ to NMN and then to NR by CD73 before cellular uptake.
  3. Trammell SAJ, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature Communications. 2016;7:12948. doi:10.1038/ncomms12948. The first human pharmacokinetic trial of NR: single 100, 300 and 1000 mg doses producing dose-dependent increases in the blood NAD+ metabolome.
  4. 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. 2019;9:9772. doi:10.1038/s41598-019-46120-z. The 22%, 51% and 142% whole-blood NAD+ increases at 100, 300 and 1000 mg per day, appearing within 2 weeks and maintained; and the finding of no reports of flushing at any dose.
  5. 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. Nature Communications. 2018;9:1286. doi:10.1038/s41467-018-03421-7. 1000 mg per day for 6 weeks raising NAD+ by about 60% in adults aged 55–79.
  6. Damgaard MV, Treebak JT. What is really known about the effects of nicotinamide riboside supplementation in humans. Science Advances. 2023;9(29):eadi4862. doi:10.1126/sciadv.adi4862. A critical review of 25 published human NR trials, concluding that oral NR "has displayed few clinically relevant effects" and that the literature tends to exaggerate the importance and robustness of reported effects.
  7. 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. American Journal of Clinical Nutrition. 2018;108(2):343–353. PMID 29992272. 2000 mg per day for 12 weeks with no improvement in insulin sensitivity, endogenous glucose production, or glucose disposal.
  8. Remie CME, Roumans KHM, Moonen MPB, et al. Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. American Journal of Clinical Nutrition. 2020;112(2):413–426. doi:10.1093/ajcn/nqaa072. 1000 mg per day for 6 weeks with no effect on insulin sensitivity or ex vivo mitochondrial function in overweight and obese volunteers.
  9. Yi L, Maier AB, Tao R, et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience. 2023;45(1):29–43. doi:10.1007/s11357-022-00705-1. 80 adults aged 40–65 given placebo, 300, 600 or 900 mg NMN daily for 60 days: dose-dependent blood NAD+ increases, with 900 mg not significantly better than 600 mg, and improvements in six-minute walk distance and SF-36 score.
  10. Liao B, Zhao Y, Wang D, et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. Journal of the International Society of Sports Nutrition. 2021;18:54. doi:10.1186/s12970-021-00442-4. The 300, 600 and 1200 mg per day arms, the upper end of the studied oral NMN range.
  11. 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+. Frontiers in Aging Neuroscience. 2019;11:257. doi:10.3389/fnagi.2019.00257. The only published pharmacokinetic study of IV NAD+: no change in plasma NAD+ or its metabolites for the first 2 hours of a 3 µmol/min infusion, with increased urinary excretion of NAD+ and methylnicotinamide by 6 hours.
  12. 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. doi:10.1101/2024.06.06.24308565. The head-to-head comparison of 500 mg IV NR, 500 mg IV NAD+, 500 mg oral NR and saline placebo, finding significantly higher blood NAD+ at 3 hours with IV NR than with IV NAD+, and better tolerability. Flagged here as a preprint: it has not completed peer review.
  13. 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. Frontiers in Aging. 2026;7:1652582. doi:10.3389/fragi.2026.1652582. The infusion-reaction figures: all six people receiving 500 mg IV NAD+ reported moderate to severe cramping, diarrhea, nausea, vomiting, raised heart rate, throat pain and chest pressure during infusion, resolving on completion, against milder tingling in five of eight receiving IV NR; and mean infusion times of 97 minutes versus 37 minutes.
  14. Janssens GE, Grevendonk L, Perez RZ, et al. Healthy aging and muscle function are positively associated with NAD+ abundance in humans. Nature Aging. 2022;2:254–263. doi:10.1038/s43587-022-00174-3. NAD+ among the metabolites most clearly lower in the muscle of older adults, with abundance correlating with physical activity levels and muscle function.
  15. Chubanava S, Treebak JT. Regular exercise effectively protects against the aging-associated decline in skeletal muscle NAD content. Experimental Gerontology. 2023;173:112109. doi:10.1016/j.exger.2023.112109. A review of how exercise training stimulates muscle NAD biosynthesis, cited in step four for the training argument rather than for a new measurement.
  16. Kamanna VS, Ganji SH, Kashyap ML. The mechanism and mitigation of niacin-induced flushing. International Journal of Clinical Practice. 2009;63(9):1369–1377. PMC2779993. The GPR109A and prostaglandin D2 mechanism behind the nicotinic acid flush.
  17. 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. 2019;28(7):1717–1728.e6. doi:10.1016/j.celrep.2019.07.043. 1000 mg a day for 21 days in aged men raised the NAD+ metabolome inside skeletal muscle without altering mitochondrial bioenergetics, and with measures of muscle and whole-body metabolism unchanged. This is the trial behind the statement that the precursor does get in and then not much happens.
  18. Gallagher C, Emmanuel OO. NAD+ supplementation for anti-aging and wellness: a PRISMA-guided systematic review of preclinical and clinical evidence. Ageing Research Reviews. 2026;116:103057. doi:10.1016/j.arr.2026.103057. 113 studies screened, 33 of them human intervention studies. No eligible outcomes trial evaluated intravenous or intramuscular NAD+ itself for anti-aging or wellness; the one IV NAD+ pharmacokinetic pilot was counted as contextual evidence only.
  19. Grozio A, Mills KF, Yoshino J, et al. Slc12a8 is a nicotinamide mononucleotide transporter. Nature Metabolism. 2019;1:47–57, and the dispute of that claim in Schmidt MS, Brenner C. Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter. Nature Metabolism. 2019;1:660–661. doi:10.1038/s42255-019-0085-0. Both sides of the question of whether NMN can enter a cell without first being converted to NR. The page reports the CD73 route as the supported one and the direct transporter as disputed, which is where the literature stands.
  20. 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. The 250 mg per day dose at the bottom of the studied NMN range, and the finding that muscle insulin sensitivity improved without a detectable change in muscle NAD+.
  21. Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. New England Journal of Medicine. 2015;373(17):1618–1626. doi:10.1056/NEJMoa1506197. The 500 mg twice daily dose, under medical supervision, at the top of the studied nicotinamide range.
  22. Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, niacin chapter, and the NIH Office of Dietary Supplements niacin fact sheet. ods.od.nih.gov. The 35 mg per day tolerable upper intake level, which covers supplemental niacin in every form including nicotinamide, and the reports of nausea, vomiting and liver toxicity signs at nicotinamide intakes of 3000 mg per day.
  23. EFSA Panel on Nutrition, Novel Foods and Food Allergens. Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283. EFSA Journal. 2019;17(8):5775. doi:10.2903/j.efsa.2019.5775. The European safety assessment, which reviewed human studies from 100 mg for one day up to 2000 mg per day for 12 weeks without raising safety concerns.
  24. US Food and Drug Administration. Bulk drug substances used in compounding under section 503A of the FD&C Act. fda.gov. NAD+ is not on the final 503A list; the agency proposed in 2019 that it not be included.
  25. US Food and Drug Administration letters of 29 September 2025 confirming that nicotinamide mononucleotide is not excluded from the dietary supplement definition, reversing the agency's November 2022 position. Reported in NutraIngredients and summarized by Venable LLP. Trade and legal reporting on FDA correspondence, used only for the regulatory timeline.

Where this page says no study exists, for subcutaneous, intramuscular and intranasal NAD+, that reflects searches of the published literature together with the 2026 Gallagher and Emmanuel systematic review above, which screened 113 studies and found no eligible outcomes trial of injected NAD+. Absence of a published study is not proof that a thing does nothing; it means nobody has shown what it does. If a trial is published, this page gets updated.