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NMN and NR Side Effects: Incidence Rates Across Clinical Trials

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At a glance

  • NMN doses tested / 250 mg/day for up to 12 weeks through 1,250 mg once daily for 4 weeks [1][4]
  • NR doses tested / 100 to 1,000 mg/day for eight weeks [6], 2,000 mg/day for 12 weeks [5], 3,000 mg/day for four weeks [3]
  • Serious or severe adverse events / none reported in the trials that reported safety findings [3][4][5]
  • Mild adverse events / not counted consistently; two NR trials found no significant difference from placebo [3][6]
  • Homocysteine / slight initial rise in NR recipients at 3,000 mg/day in Parkinson's disease [3]; no 1-carbon dysregulation at 100 to 1,000 mg/day for 8 weeks [6]
  • Trial size and length / 12 to 140 participants, up to about 12 weeks [8]
  • Regulatory status / sold as dietary supplements in the US; neither is an FDA-approved drug [9]

What the Trials Actually Measured

The trials reported safety in different ways. Some counted adverse events, while others primarily reported whether severe events or clinically relevant laboratory changes occurred [7][3][4]. Several trials report only that no severe events occurred and that laboratory panels stayed normal, rather than counting individual symptoms, so per-symptom incidence is thin. The trials described on this page enrolled 12 to 140 people and ran up to about 12 weeks [8].

NMN: What Each Trial Reported

TrialParticipantsDose and durationAdverse events reported
Irie 2020 [10]10 healthy men100, 250 or 500 mg, single doseNo significant clinical symptoms; heart rate, blood pressure, oxygen saturation and temperature unchanged; bilirubin rose and creatinine, chloride and glucose fell, all within normal range
Yoshino 2021 [11]25 completers (13 NMN, 12 placebo)250 mg/day, 10 weeksNo adverse events reported
Okabe 2022 [1]30 (15 NMN, 15 placebo)250 mg/day, 12 weeksNo abnormalities on physiological or laboratory tests; no obvious adverse effects
Igarashi 2022 [12]Healthy older men250 mg/day, 6 or 12 weeksWell tolerated; no significant deleterious effect
Yi 2023 [2]80300, 600 or 900 mg/day, 60 daysNo safety issues on adverse-event, laboratory and clinical monitoring
Fukamizu 2022 [4]311,250 mg once daily, up to 4 weeksNo severe adverse events; no changes beyond physiological variation in hematology, biochemistry, urine or body composition

The highest NMN dose in the trials above is 1,250 mg once daily for up to four weeks in 31 healthy adults aged 20 to 65 [4]. A trial in 48 amateur runners used 300, 600 and 1,200 mg/day for six weeks, but its published report covers aerobic capacity rather than adverse-event counts [13]. A 108-person trial of 250 mg/day for 12 weeks focused its report on sleep, fatigue and physical performance [14].

NR: What Each Trial Reported

TrialParticipantsDose and durationAdverse events reported
Martens 2018 [7]30 randomized, 24 completers aged 55-79500 mg twice daily (1,000 mg/day), 2 x 6 weeks14 mild events in 7 participants (nausea, flushing, leg cramps, bruising); no serious events
Dollerup 2018 [5]40 obese men aged 40-701,000 mg twice daily (2,000 mg/day), 12 weeksNo serious adverse events; normal safety blood tests
Conze 2019 [6]Overweight, otherwise healthy adults100, 300 or 1,000 mg/day, 8 weeksNo reports of flushing; no significant difference in adverse events versus placebo or between doses
NR-SAFE 2023 [3]20 with Parkinson's disease (10 NR, 10 placebo)1,500 mg twice daily (3,000 mg/day), 4 weeksNo moderate or severe events; no significant difference in mild events
NADPARK 2022 [15]30 with newly diagnosed Parkinson's disease1,000 mg, 30 daysWell tolerated
Dellinger 2017 [16]120 adults aged 60-80NR plus pterostilbene (Basis), 8 weeksNo serious adverse events; combination product, not NR alone

The NR Crossover With the Most Detailed Adverse-Event List

Martens et al. randomized 30 adults aged 55 to 79 in a two-period crossover with six weeks per period, and 24 completed; the dose was 500 mg twice daily, or 1,000 mg/day [7]. Seven participants reported 14 mild adverse events in total, which were nausea, flushing, leg cramps and bruising, and there were no serious events [7]. The report describes chronic NR supplementation as well tolerated [7].

Does NR Raise Homocysteine?

The homocysteine finding in these trials is small. In the NR-SAFE trial, 10 people with Parkinson's disease received NR 1,500 mg twice daily (3,000 mg/day) for four weeks; NR recipients had a slight initial rise in serum homocysteine, and the investigators judged the methyl donor pool to be intact [3]. An eight-week trial of NR at 100, 300 and 1,000 mg/day reported no dysregulation of 1-carbon metabolism [6].

Do NMN or NR Cause Flushing?

One NR crossover listed flushing among its mild adverse events [7]. The eight-week dose-ranging trial of NR at 100, 300 and 1,000 mg/day recorded no reports of flushing at any dose [6].

Standard Blood Panels

Where trials reported laboratory data, they described values that stayed inside normal ranges. The 1,250 mg NMN study found no changes beyond normal physiological variation in hematology, biochemistry, urine or body composition [4]; the 250 mg NMN trial found no abnormalities on physiological or laboratory tests [1]; the 2,000 mg/day NR trial reported normal safety blood tests [5]. The single-dose NMN study saw a rise in serum bilirubin and falls in creatinine, chloride and glucose, all within the normal range and independent of dose [10].

What the Trials Cannot Tell You

Human safety data beyond about 12 weeks are lacking [8]. People with cancer, kidney disease or liver disease, and people who are pregnant or breastfeeding, were not studied in these trials, so safety in those groups is unknown [8].

Cancer risk with long-term NAD+ boosting has been raised as a theoretical concern; no human data were identified [8].

A PubMed search found no human drug-interaction studies of NMN or NR, whether CYP, transporter or pharmacodynamic, so no interaction with any specific prescription drug can be claimed or ruled out [8].

Regulatory Status

NMN and NR are sold in the US as oral dietary supplements, and neither is an FDA-approved drug [9]. FDA's response to a citizen petition, posted on 2025-09-29, is reported to conclude that NMN is not excluded from the dietary supplement definition, because FDA found evidence NMN was marketed as a supplement before it was authorized for drug investigation [9]. NMN remains a new dietary ingredient, so a maker must file an NDI notification before selling it [9]. For NR, FDA responded to a GRAS notice from ChromaDex (GRN 000635) with a no-questions letter dated 2016-08-03 and stated it had not made its own GRAS determination [20].

Frequently asked questions

What are the most common side effects of NMN?
No symptom stands out in the NMN trials: they reported no adverse effects or no abnormalities on laboratory testing at 250 mg/day for 12 weeks and at 1,250 mg once daily for 4 weeks [1][4]. The single-dose study saw only within-range laboratory shifts, including a rise in serum bilirubin [10].
What are the most common side effects of NR?
In a six-week crossover of 30 randomized adults (24 completed) at 1,000 mg/day, 7 participants reported 14 mild events: nausea, flushing, leg cramps and bruising, with no serious events [7]. An eight-week trial at 100, 300 and 1,000 mg/day reported no flushing and no significant difference in adverse events versus placebo, and no dysregulation of 1-carbon metabolism [6]. The trials do not show which symptom is most common across NR studies.
Are there any serious adverse events from NMN or NR in trials?
The trials that reported safety findings described none: the 1,250 mg NMN study reported no severe adverse events [4]; the 2,000 mg/day NR study reported no serious adverse events [5]; the 3,000 mg/day NR-SAFE trial reported no moderate or severe events [3].
Does NR raise homocysteine levels?
In NR-SAFE, 10 people with Parkinson's disease received NR 3,000 mg/day for four weeks, and NR recipients had a slight initial rise in serum homocysteine, with the methyl donor pool judged intact [3]. An eight-week trial of 100 to 1,000 mg/day found no dysregulation of 1-carbon metabolism [6].
Is there long-term safety data for NMN or NR?
Human safety data beyond about 12 weeks are lacking, and the trials enrolled 12 to 140 participants [8].
Can NMN or NR interact with prescription medications?
A PubMed search found no human drug-interaction studies of NMN or NR, including CYP, transporter and pharmacodynamic studies, so no interaction with a specific drug can be claimed or excluded [8].

References

  1. 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
  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. 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
  5. 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
  6. 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. Sci Rep. 2019;9(1):9772. 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
  7. 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
  8. 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
  9. Official web page. Official web page
  10. Irie J, Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocr J. 2020;67(2):153-160. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men
  11. 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
  12. Igarashi M, Nakagawa-Nagahama Y, Miura M, Kashiwabara K, Yaku K, Sawada M, et al. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. NPJ Aging. 2022;8(1):5. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men
  13. Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr. 2021;18(1):54. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study
  14. Kim M, Seol J, Sato T, Fukamizu Y, Sakurai T, Okura T. Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study. Nutrients. 2022;14(4). Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study
  15. Brakedal B, Dölle C, Riemer F, Ma Y, Nido GS, Skeie GO, et al. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metab. 2022;34(3):396-407.e6. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease
  16. Dellinger RW, Santos SR, Morris M, Evans M, Alminana D, Guarente L, et al. Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging Mech Dis. 2017;3:17. Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study
  17. 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
  18. 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
  19. Human Foods Complaint System (HFCS) | FDA. Human Foods Complaint System (HFCS) | FDA
  20. 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: Incidence Rates Across Clinical Trials