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NMN and NR Side Effects: Potentially Permanent Risks You Should Know

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At a glance

  • What they are / NAD+ precursors sold as oral dietary supplements in the US; neither is an FDA-approved drug [8]
  • Longest controlled trials / 12 weeks, at NMN 250 mg/day and NR 1,000 mg twice daily [5][6]
  • Highest doses tested / NMN 1,250 mg once daily for 4 weeks; NR 1,500 mg twice daily, 3,000 mg/day, for 4 weeks [1][3]
  • Serious adverse events in these trials / None reported [1][2][9][3]
  • Reported complaints / 14 mild events in 7 of 30 people in one six-week NR crossover: nausea, flushing, leg cramps, bruising [9]
  • Groups not studied / pregnant or breastfeeding women, children, people with cancer or kidney or liver disease [7]
  • Cancer risk / Theoretical; no human data identified [7]
  • Regulatory status / May be lawfully marketed as a dietary supplement after FDA's 2025 petition response; not approved as a drug [8]

Do NMN or NR cause permanent side effects?

The trials described on this page recorded no serious adverse events, but they cannot establish whether NMN or NR causes lasting effects [1][9][3][7]. The studies are short, 21 days in one NR trial and up to 12 weeks in others, and small, enrolling between 12 and 140 people [4][7].

NAD+ is a coenzyme in cellular energy metabolism and a substrate for sirtuins and PARP enzymes, and NMN and NR are precursors the body converts to NAD+ [10]. Oral NMN and oral NR both raise NAD+ or NAD+ metabolites in human blood in randomized trials [5][2][9][3].

What the human trials actually reported

NMN, 1,250 mg once daily. A randomized, double-blind, placebo-controlled study gave 31 healthy adults aged 20 to 65 up to 1,250 mg of NMN daily for up to 4 weeks. There were no severe adverse events and no changes beyond normal physiological variation in hematology, biochemistry, urine or body composition [1].

NMN, 250 mg/day for 12 weeks. Thirty healthy adults took 250 mg/day or placebo (15 per group). Investigators found no abnormalities in physiological and laboratory tests and no obvious adverse effects [5].

NMN, 300 to 900 mg/day for 60 days. In 80 healthy middle-aged adults randomized to placebo or NMN, adverse-event reporting, laboratory tests and clinical monitoring turned up no safety issues [2].

NR, 500 mg twice daily. A 2 x 6-week crossover trial in 30 randomized adults aged 55 to 79 described NR as well tolerated; seven participants reported 14 mild events (nausea, flushing, leg cramps, bruising) and there were no serious adverse events [9].

NR, 1,000 mg twice daily for 12 weeks. In 40 sedentary obese men aged 40 to 70, there were no serious adverse events and safety blood tests were normal [6].

NR, 3,000 mg/day for 4 weeks. In 20 people with Parkinson's disease, NR produced no moderate or severe adverse events and no significant difference from placebo in mild events [3].

NR, 1 g/day for 21 days. In 12 men aged 70 to 80, no clinical adverse events were reported [4].

Is cancer risk a real concern with NMN or NR?

Cancer risk with chronic NAD+ boosting has been raised as a theoretical concern, and no human data were identified; people with cancer were not among the populations studied [7]. One cell-biology study linked NAMPT-driven NAD+ metabolism to a proinflammatory process with tumour-promoting effects, and its authors wrote that anti-aging NAD+ augmentation should be administered with precision [11]. That research did not test whether NMN or NR causes cancer in people.

Homocysteine and methylation

In the 4-week NR trial in Parkinson's disease, NR recipients had a slight initial rise in serum homocysteine; the authors judged the methyl donor pool intact despite it [3].

The related metabolic observation comes from the 21-day muscle study: NR 1 g/day raised nicotinamide-methylation products about 5-fold in muscle, indicating that excess nicotinamide is cleared through methylation [4].

Liver, blood and other laboratory findings

The laboratory monitoring in the NMN trials covered hematology, biochemistry and urine, and none found clinically relevant changes [1][5][2]. The 12-week NR trial in obese men reported normal safety blood tests [6].

Who has not been studied

Pregnancy, breastfeeding, children, and people with cancer, kidney disease or liver disease were not studied in these trials, so safety in those groups is unknown [7].

Do NMN or NR interact with prescription drugs?

A PubMed search found no human drug-interaction studies of NMN or NR covering CYP enzymes, drug transporters or pharmacodynamic interactions [7]. That means there is no human basis for saying either supplement is safe alongside a specific medicine, or that it changes that medicine's levels.

Is NMN banned or FDA-approved?

Neither. NMN and NR are sold in the US as oral dietary supplements, and no NAD+-precursor product is FDA-approved to treat aging or any disease [8].

A citizen petition about NMN was filed in March 2023 [12]. On 2025-09-29 the FDA posted its response, recorded as a partial petition approval and denial; law-firm and trade reports say it concludes NMN is not excluded from the dietary supplement definition because FDA found evidence NMN was marketed as a supplement in the US before drug investigation [8]. NMN remains a new dietary ingredient, so makers must file an NDI notification or rely on a prior one [8].

For NR, the FDA's only action was a 2016 'no questions at this time' letter on a company's GRAS notice (GRN 000635); the agency stated it had not made its own GRAS determination [13].

Frequently asked questions

Can NMN or NR cause permanent damage?
No human trial has shown permanent damage from NMN or NR, but the studies lasted only 21 days to 12 weeks, so long-term safety beyond about 12 weeks is unknown [4][7].
Does NMN raise cancer risk?
Human trials of NMN and NR have not reported cancer outcomes, and people with cancer were not studied [7]. One cell-biology study linked NAMPT-driven NAD+ metabolism to a proinflammatory process with tumour-promoting effects, and its authors called for precision in anti-aging NAD+ use [11].
Does NR raise homocysteine?
In a 4-week trial of NR 1,500 mg twice daily in 20 people with Parkinson's disease, NR recipients showed a slight initial rise in serum homocysteine, and the authors judged the methyl donor pool intact [3].
What side effects were reported in NMN and NR trials?
Mild adverse events were reported in one NR trial, including nausea, flushing, leg cramps and bruising; no serious events occurred [9]. A six-week crossover NR trial in 30 adults described NR as well tolerated, with no serious adverse events [9]. NMN trials at 250 to 1,250 mg/day reported no obvious adverse effects and no changes beyond normal physiological variation on laboratory testing [5][1].
Is NMN FDA-approved or banned?
Neither. NMN is sold as a dietary supplement and no NAD+ precursor is FDA-approved for aging or any disease [8]. Reports on FDA's 2025-09-29 petition response say it concludes NMN is not excluded from the dietary supplement definition, subject to new dietary ingredient notification rules [8].
Can you take NMN or NR with prescription drugs?
A PubMed search found no human drug-interaction studies of NMN or NR, including CYP, transporter or pharmacodynamic studies [7]. Without such studies there is no human basis for describing either supplement as interacting with, or as safe with, a named medicine.

References

  1. Fukamizu Y, Uchida Y, Shigekawa A, Sato T, Kosaka H, Sakurai T. Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Sci Rep. 2022;12(1):14442. Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women
  2. Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, 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. 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
  3. Berven H, Kverneng S, Sheard E, Søgnen M, Af Geijerstam SA, Haugarvoll K, et al. NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease. Nat Commun. 2023;14(1):7793. NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease
  4. Elhassan YS, Kluckova K, Fletcher RS, Schmidt MS, Garten A, Doig CL, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019;28(7):1717-1728.e6. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures
  5. Okabe K, Yaku K, Uchida Y, Fukamizu Y, Sato T, Sakurai T, et al. Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects. Front Nutr. 2022;9:868640. Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects
  6. Dollerup OL, Christensen B, Svart M, Schmidt MS, Sulek K, Ringgaard S, et al. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr. 2018;108(2):343-353. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects
  7. Freeberg KA, Udovich CC, Martens CR, Seals DR, Craighead DH. Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions. J Gerontol A Biol Sci Med Sci. 2023;78(12):2435-2448. Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions
  8. Official web page. Official web page
  9. Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
  10. Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
  11. Nacarelli T, Lau L, Fukumoto T, Zundell J, Fatkhutdinov N, Wu S, et al. NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol. 2019;21(3):397-407. NAD+ metabolism governs the proinflammatory senescence-associated secretome
  12. Official web page. Official web page
  13. Agency Response Letter GRAS Notice No. GRN 000635 | FDA. Agency Response Letter GRAS Notice No. GRN 000635 | FDA
Evidence overview for NMN and NR Side Effects: Potentially Permanent Risks You Should Know