Reviewed & approved by Dr. Nova Reyes · Last checked 2026-10-15. ← Back to Evidence Library

NAD+: what the evidence says

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

---

What is it?

NAD+ is a coenzyme (a helper molecule enzymes need to work). Levels fall with age in animals. That led to the idea that "boosting" NAD+ might slow aging. In rodents, raising NAD+ often improved metabolism and other measures. Whether that carries over to people is the open question. ^R6

You can raise NAD+ in two ways: - Oral precursors. NR and NMN are forms of vitamin B3 that the body converts into NAD+. They are sold as dietary supplements. - NAD+ itself. Given by IV drip, or as an injection under the skin (subcutaneous) or into muscle, mostly at wellness and "longevity" clinics. ^{R5, R6}

Does it work? Oral NR and NMN (supplements)

Human Raising NAD+ levels: yes. Placebo-controlled trials of NR and NMN consistently raise NAD+ and related molecules in blood, compared with placebo (a dummy pill). A 2026 systematic review of 33 human studies called this "consistent" target engagement, meaning the supplements reliably reach and raise the molecule they aim at. But a higher NAD+ level in blood is not the same as a health benefit. Whether it improves health is a separate question, covered next. ^{R1, R2, R6}

Human Health outcomes: mostly null or small. - Insulin sensitivity: in obese, insulin-resistant men, 12 weeks of NR did not improve insulin sensitivity or glucose metabolism vs placebo. In a small trial in overweight women with prediabetes, NMN improved muscle insulin sensitivity vs placebo. ^R2 - Metabolism overall: a 2026 meta-analysis (a study that pools the results of several trials) of NMN RCTs (randomized controlled trials, where people are assigned to groups by chance) found no significant effect on body weight, BMI, fasting glucose, HbA1c (average blood sugar), cholesterol or systolic blood pressure. Diastolic blood pressure fell slightly. ^R3 - Muscle in older adults: a 2025 meta-analysis found NMN had no significant effect on muscle mass, grip strength or walking speed. The authors concluded the evidence "does not support" NR or NMN for preserving muscle in adults over 60. ^R3 - Parkinson's disease: in a 30-person phase 1 trial (a small first study in people, focused mainly on safety and how the body handles the drug), NR for 30 days raised brain NAD+ levels and was well tolerated. There was "mild clinical improvement" in people whose brain NAD+ rose. This was an early safety study, not proof it works. ^R2

Does it work? IV and injected NAD+

Human We don't know. A 2026 systematic review found no outcome trials of IV or intramuscular NAD+ for anti-aging or wellness. ^R6 What exists: - A pilot study in 11 healthy men tracked what happens to NAD+ in blood during a 6-hour drip. Surprisingly, blood NAD+ did not change for the first 2 hours. The body cleared it rapidly. It measured no health outcomes. ^R4 - A chart review from a commercial IV clinic chain mainly looked at how well infusions were tolerated. Caution Only 6 people got IV NAD+ (8 others got IV NR), there was no placebo, and every author worked for the clinic company, which also funded the study. ^R5 - We found no published controlled human study of NAD+ injected under the skin or into muscle. ^R6

Is it safe?

Oral NR and NMN

• Human Short term, generally well tolerated. In a 2026 meta-analysis of NMN RCTs, NMN did not increase overall adverse events (problems reported after use, which may or may not have been caused by the drug), serious adverse events, or dropouts because of adverse events, compared with placebo. It did not raise liver enzymes (ALT, AST). Trials lasted 14 days to 24 weeks. ^R3
• Human In the 12-week NR trial in obese men, there were no serious adverse events due to NR, and safety blood tests were normal. ^R2
• Unknown Long-term safety (years) has not been studied.

IV NAD+

• Caution Infusion reactions. In the clinic chart review (only 6 people got NAD+; written by the clinic company's own employees), all 6 people who got IV NAD+ reported moderate to severe abdominal cramping, diarrhea, nausea, vomiting, faster heart rate, throat pain, congestion and chest pressure during the drip. The symptoms stopped as soon as the infusion ended. Clients controlled their own drip speed and slowed it down because of the symptoms. NAD+ infusions averaged 97 minutes vs 37 minutes for IV NR. ^R5
• Caution Linked to infusion speed? Anecdotal only. The link between drip speed and side effects comes from anecdotal reports cited by the chart review, whose authors say formal studies are lacking. In the 6-hour pilot (8 people on NAD+, slow drip), no adverse events were observed. But that study was also run with a NAD+ clinic company. ^{R4, R5} No study has tested infusion speeds against each other, so no safe rate is established.
• Caution The general risks of any IV procedure (infection, vein irritation) apply. "Procedural risks" are noted in a 2026 review of IV longevity therapy. ^R10
• Unknown No placebo-controlled safety data and no long-term data.

Injected NAD+ (under the skin / into muscle)

• Unknown No published human safety data found. ^R6

What we don't know

• Unknown Whether raising NAD+ in blood improves any health outcome in people
• Unknown Whether IV or injected NAD+ does anything that oral precursors don't
• Unknown Long-term safety for any route
• Unknown What is actually in a given clinic or online NAD+ vial (strength, sterility)

Is it legal?

• NMN: in 2022, FDA said NMN could not be sold as a dietary supplement because it had first been studied as a drug. In letters dated Sept 29, 2025, FDA reversed this. It now concludes NMN "is not excluded from the definition of dietary supplement," because NMN was sold as a supplement in the US before it was authorized for drug study. On Dec 2, 2025, FDA sent follow-up letters to NMN ingredient makers reinstating their earlier supplement notifications. This is not FDA approval of NMN's safety or effectiveness. Supplements are not reviewed by FDA for effectiveness before sale. ^R7
• IV and injectable NAD+: we found no FDA-approved NAD+ drug. Pharmacies compound it (prepare it for individual patients, with a prescription) under FDA's interim policy: NAD is listed in Category 1, "under evaluation," for the 503A bulks list (updated May 14, 2026). That means FDA has not finished deciding whether it belongs on the list. It is not an approval. ^R8
• Athletes: NAD+, NR and NMN are not named on WADA's 2026 Prohibited List. But IV infusions or injections of more than 100 mL per 12 hours are a banned method (M2.2) outside hospital care, surgery or diagnostic tests, whatever is in the bag. ^R9

As of Oct 15, 2026.

What's in the vial or bottle?

We found no published lab testing of retail NAD+ injections or NMN/NR supplements. Unknown For fake (counterfeit) or "research use only" vials, the contents are unknown. We test retail products blind under the Open Peptide Standard. See results at /tests/. A passing test covers one batch, tested on one date. It does not mean the compound itself is safe.

What do users report?

Self-report, not evidence.

Unknown TBD. We'll only list this once we can cite a public source.

Study details

^{R1, R2} Human Human studies: oral NR and NMN

Dose amounts are the study arms used, not recommendations.

Study	People	Route	Study arm	Follow-up	Reported	Limitations	Citation
Martens 2018, healthy adults 55–79	30 randomized, 24 completed (per full text)	Oral NR	NR 500 mg twice daily (1000 mg/day) vs placebo, crossover (per full text)	2 × 6 wk	Well tolerated; raised NAD+ metabolism; blood pressure / arterial stiffness flagged for future trials only. Mild self-reported AEs occurred in both NR and placebo periods (flushing was reported in both)	Small; exploratory outcomes	PMID 29599478 R1
Dollerup 2018, obese insulin-resistant men 40–70	40	Oral NR	NR 1000 mg twice daily vs placebo	12 wk	No improvement in insulin sensitivity, glucose metabolism, energy expenditure or body composition; no serious AEs due to NR	Small; men only	PMID 29992272 R2
Yoshino 2021, postmenopausal women with prediabetes, overweight/obese	25 (13 NMN, 12 placebo; per full text)	Oral NMN	NMN 250 mg/day vs placebo (per full text)	10 wk	Muscle insulin sensitivity increased on NMN, not on placebo	Small; one population; one author receives NMN patent-licensing fees, another holds an NMN patent application	PMID 33888596 R2
Igarashi 2022, healthy older men (65+)	42 (21 NMN, 21 placebo; per full text)	Oral NMN	NMN 250 mg/day vs placebo	6 or 12 wk	Raised blood NAD+; "nominally significant" gait speed and left grip improvements; no effect on body composition	Small; nominal results need validation; supplier mix-up swapped products for 22 men at week 6, so their 12-week data were excluded (per full text); 3 authors employed by Mitsubishi Corporation Life Sciences	PMID 35927255 R2
Brakedal 2022 (NADPARK), newly diagnosed Parkinson's	30	Oral NR	NR 1000 mg vs placebo	30 days	Well tolerated; brain NAD+ rose (variable); mild clinical improvement in those with brain NAD+ rise	Phase 1; short; two authors filed a patent application on NR in Parkinson's	PMID 35235774 R2

^{R3, R6} Human Systematic reviews and meta-analyses

• ^R3 Yang 2026 (NMN, Nutrients): 15 RCTs, 10 in safety analyses; study arms varied by trial (see the trials in the table above and the review), 14 days–24 weeks. No increase in overall, serious or withdrawal-related adverse events vs control; no ALT/AST rise; no significant effect on weight, BMI, fasting glucose, HbA1c, lipids or systolic BP; diastolic BP slightly lower; HOMA-IR non-significant trend. PMID 42514320.
• ^R3 Prokopidis 2025 (NMN and NR, muscle, J Cachexia Sarcopenia Muscle): RCTs vs placebo, mean age 60.9–83. NMN: no significant effect on skeletal muscle index, grip strength, gait speed or chair-stand test. NR: longer 6-minute walk in peripheral artery disease; lower SPPB and slower chair-stand in mild cognitive impairment. PMID 40275690.
• ^R6 Gallagher 2026 (Ageing Res Rev): 33 human intervention studies (28 randomized) and 80 rodent studies, 2010–Oct 2025. Oral NR/NMN: consistent target engagement, generally well tolerated; functional and metabolic outcomes "heterogeneous and often null." "No eligible outcomes trials evaluated intravenous or intramuscular NAD⁺." PMID 41655607. First author owns a management company serving an aesthetics clinic (which does not offer NAD+).

^{R4, R5} Human Human studies: IV NAD+

Study	People	Route	Study arm	Design	Reported	Limitations	Citation
Grant 2019, healthy men 30–55	11 randomized: 8 NAD+, 3 saline (per full text)	IV	750 mg NAD+ over 6 h (~3 µmol/min) vs saline (per full text)	Pilot pharmacokinetics	No change in plasma NAD+ or metabolites until after 2 h; NAD+ "rapidly and completely removed from the plasma"; no adverse events observed in either group (full text)	Tiny; no outcomes; funded by NAD+ Research Inc.; one author directs it and is medical director of a clinic selling IV NAD+, another took its consulting fees; NAD+ donated by the compounding pharmacy (per full text)	PMID 31572171 R4
Reyna 2026, clients of a commercial IV clinic	14: only 6 NAD+ IV, 8 NR IV (per full text)	IV	500 mg NAD+ or 500 mg NR, 4 consecutive days	Retrospective chart review, no placebo	NAD+ IV: all 6 reported moderate–severe GI symptoms, faster heart rate, chest pressure; resolved at infusion end; mean infusion 97 vs 37 min (NR). No significant changes in ALT, AST, hsCRP, BUN/creatinine, TSH; HDL-C fell in NAD+ group	Caution COI: all 7 authors employed by Restore Hyper Wellness, which funded the study; NR donated by Niagen Biosciences (per full text). Clients set their own infusion rate; retrospective; tiny; groups differed in age	PMID 41704678 R5

^R7–R10 Regulatory and other sources (as of Oct 15, 2026)

• ^R7 NMN status: FDA response to NPA/ANH citizen petition, Docket FDA-2023-P-0872, dated Sept 29, 2025 (the letter's own header misprints the year as "2029"). Verified on Regulations.gov (document FDA-2023-P-0872-2754, "Response Letter from FDA HFP to Natural Products Association and Alliance for Natural Health USA," posted Sept 29, 2025): "we now conclude that NMN is not excluded from the definition of dietary supplement" (text via AHPA copy). The letter recounts FDA's Oct 11 and Nov 4, 2022 letters excluding NMN. Coverage: NutraIngredients, Sept 30, 2025; Dec 2, 2025 follow-up letters to SyncoZymes and Inner Mongolia Kingdomway: NutraIngredients, Dec 9, 2025, Nutraceuticals World, Dec 10, 2025. UNVERIFIED The Dec 2, 2025 letters were seen only in trade-press coverage, not on FDA.gov. No later reversal found as of Oct 15, 2026 (absence not proof).
• ^R8 Compounding: FDA, Bulk Drug Substances Nominated for Use in Compounding Under Section 503A (updated May 14, 2026): "Nicotinamide Adenine Dinucleotide (NAD)" and NADH listed in Category 1 (under evaluation); a "Beta-Nicotinamide Adenine Dinucleotide Disodium Salt Trihydrate" nomination is in Category 3 (nominated without adequate support). Policy explained at FDA's 503A bulks page. Not FDA-approved: no match for NAD+ (nadide) in an openFDA Drugs@FDA search, Oct 15, 2026 (absence not proof).
• ^R9 WADA: 2026 Prohibited List (in effect Jan 1, 2026; checked against the official PDF): NAD+, NR, NMN not named. M2.2 (prohibited at all times, a Specified Method) prohibits "Intravenous infusions and/or injections of more than a total of 100 mL per 12-hour period except for those legitimately received in the course of hospital treatments, surgical procedures or clinical diagnostic investigations." Unknown Not checked: 2026 Monitoring Program, 2027 list.
• ^R10 Godic 2026, review of IV longevity therapy (including NAD+): placebo-controlled trials "scarce and underpowered"; notes "procedural risks"; should be "regarded as an experimental intervention." PMID 41915584.

Full reference list (all verified on PubMed, Oct 15, 2026)

• Martens CR, et al. Nat Commun. 2018;9(1):1286. doi:10.1038/s41467-018-03421-7. PMID 29599478
• Dollerup OL, et al. Am J Clin Nutr. 2018;108(2):343-353. doi:10.1093/ajcn/nqy132. PMID 29992272
• Yoshino M, et al. Science. 2021;372(6547):1224-1229. doi:10.1126/science.abe9985. PMID 33888596
• Igarashi M, et al. NPJ Aging. 2022. doi:10.1038/s41514-022-00084-z. PMID 35927255
• Brakedal B, et al. Cell Metab. 2022;34(3):396-407.e6. doi:10.1016/j.cmet.2022.02.001. PMID 35235774
• Yang W, et al. Nutrients. 2026;18(14):2251. doi:10.3390/nu18142251. PMID 42514320
• Prokopidis K, et al. J Cachexia Sarcopenia Muscle. 2025;16(3):e13799. doi:10.1002/jcsm.13799. PMID 40275690
• Gallagher C, Emmanuel OO. Ageing Res Rev. 2026;116:103057. doi:10.1016/j.arr.2026.103057. PMID 41655607
• Grant R, et al. Front Aging Neurosci. 2019;11:257. doi:10.3389/fnagi.2019.00257. PMID 31572171
• Reyna K, et al. Front Aging. 2026;7:1652582. doi:10.3389/fragi.2026.1652582. PMID 41704678
• Godic A, Townsend J. Acta Dermatovenerol Alp Pannonica Adriat. 2026;35(1):39-43. PMID 41915584

---

Disclaimer

This page is for education and harm reduction. It is not medical advice and not a recommendation to use NAD+, NR or NMN. Please talk to a clinician you trust, especially if you are pregnant, have heart, liver or kidney disease, or take other medicines. Stop an IV drip and seek care for chest pain, trouble breathing or fainting, and report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).