NMN Clinical Trials in Humans: What the Evidence Actually Shows

TL;DR

Human trials consistently show that oral NMN raises blood NAD+ levels, usually within two to four weeks, and the doses studied so far have been well tolerated in the short term. Evidence for effects you can feel or measure, such as endurance, walking speed, insulin sensitivity and fatigue, is mixed and depends heavily on who was studied. No human trial has shown that NMN prevents disease or extends lifespan.

What human trials show about NMN

Most of the excitement around nicotinamide mononucleotide (NMN) started in mice. Older animals given NMN showed better blood vessel function, more efficient mitochondria and improved insulin sensitivity, results that made headlines before NMN had been tested in people.

Since the first single-dose safety study in 2020, research teams in Japan, China and the United States have run randomised, placebo-controlled trials in young adults, middle-aged adults and people over 65.

The picture is clearer than the marketing suggests, and more modest. NMN reliably raises NAD+ (nicotinamide adenine dinucleotide), the coenzyme cells rely on for energy production and repair, and which declines with age.

The table below summarises the evidence on the main outcomes trials have measured. This is our editorial summary of the published human trials, not a formal grading system.

Outcome	What human trials show	Evidence level
Blood NAD+ levels	Consistent, dose-related increases in blood NAD+ and its breakdown products, usually within two to four weeks.	Consistent
Short-term safety	No serious adverse events reported at the doses and durations studied, up to 12 weeks.	Consistent
Aerobic capacity	Better oxygen use at the ventilatory threshold in runners alongside exercise. Little data in sedentary groups.	Emerging
Muscle insulin sensitivity	Improved in one trial of postmenopausal women with prediabetes. Not seen in broader healthy groups.	Mixed
Walking and strength	Some gains in walking endurance and speed. Grip strength results vary.	Mixed
Energy and fatigue	Modest drops in self-reported drowsiness and fatigue in older adults, using measures that differ between trials.	Emerging
Disease and lifespan	No human trial has measured disease rates or lifespan.	No human evidence

Why mouse results don’t transfer directly to people

Mouse studies mapped how NMN works, but they are a poor guide to what a capsule will do for a person. The animals are genetically identical, tightly controlled and often given far higher doses.

Dose is the clearest example. Scaling a typical mouse dose of 300 to 500 mg per kg of body weight by body surface area gives roughly 1.5 g to 3 g a day for an adult. That is several times the 250 mg to 500 mg most supplements provide.

Where in the body the molecule is measured differs as well.. Mouse studies sample tissue directly, while human trials mostly measure NAD+ in blood. How the molecule is absorbed is also questioned. SLC12A8 is an intestinal NMN transporter identified in mice, however, its presence in humans, as well as how effectively it transports the molecule, is still being investigated.

The table summarises the main differences between the two bodies of evidence.

Factor	Rodent studies	Human trials
Subjects	Genetically identical, inbred strains	Genetically diverse adults

Environment	Controlled diet, light and activity	Everyday diet, sleep and lifestyle
Typical dose	Often 300 to 500 mg per kg of body weight	Roughly 3 to 15 mg per kg (250 to 1,000 mg a day)
Duration	Months, sometimes lifelong	Single dose to around 12 weeks
What is measured	Organ tissue such as liver, muscle and brain	Mainly blood, with occasional muscle biopsies

The key human NMN trials at a glance

These are among the most widely cited published human trials of oral NMN. They differ in size, dose and population, so their findings need reading side by side.

Trial	Who took part	Dose and duration	Main finding
Irie et al., 2020 [1]	10 healthy Japanese men	Single dose of 100, 250 or 500 mg	Safe, with dose-related rises in NMN breakdown products in the blood
Yoshino et al., [2] 2021	25 postmenopausal women with prediabetes	250 mg a day for 10 weeks	Improved muscle insulin sensitivity and insulin signalling
Liao et al., 2021 [3]	48 recreationally trained runners	300, 600 or 1,200 mg a day for 6 weeks	Improved aerobic capacity alongside training, more at higher doses
Huang, 2022 [4]	Healthy middle-aged adults	300 mg a day for 60 days	Raised blood NAD+, with gains in walking endurance
Fukamizu et al., 2022 [5]	Healthy adults	1,250 mg a day for 4 weeks	No safety concerns at the highest sustained dose tested
Kim et al., 2022 [6]	Older Japanese adults	250 mg a day for 12 weeks	Afternoon intake linked to better lower-limb function and less drowsiness
Igarashi et al., 2022 [7]	42 men aged 65 and over	250 mg a day for 12 weeks	Raised blood NAD+, partial gains in gait speed
Yi et al., 2023 [8]	80 adults aged 40 to 65	300, 600 or 900 mg a day for 60 days	Dose-related NAD+ rise and better six-minute walk distance

NAD+ levels: the most consistent human finding

If one result remains consistent, it’s that oral NMN raises NAD+ in the blood. This has been demonstrated. in young, middle-aged and older adults and in trained athletes.

The rise also appears to scale with dose. In Yi and colleagues’ 2023 trial, adults taking 600 or 900 mg a day saw larger increases than those taking 300 mg. Igarashi’s trial in men over 65 found NAD+ stayed raised across 12 weeks on 250 mg a day, rather than spiking and falling away.

Trials also record rises in NAD+ breakdown products such as 2-PY and 4-PY. Less clear is how much of an oral dose reaches tissues intact, since some NMN is likely converted to nicotinamide riboside (NR) or nicotinamide in the gut first. For where NMN sits in the NAD+ pathway, see our NMN and NAD+ guide and our comparison of NMN vs NR vs niacin.

Performance, energy and metabolic health: what trials show

Physical performance and walking ability

The strongest effect signal comes from trained runners. In Liao’s 2021 trial, runners taking NMN for six weeks alongside training saw their oxygen use at the ventilatory threshold, a marker of aerobic capacity, improve more than in the placebo. VO2 max itself did not change significantly.

In older adults, the effects are smaller. Trials giving 250 mg a day to people over 65 reported modest gains in walking. speed and lower-limb function, however, grip strength results were inconsistent. None of the trials found a meaningful change in muscle mass.

Energy and fatigue

NMN shows some evidence. as an energy supplement. A few placebo-controlled trials in older adults reported modest reductions in daytime drowsiness and self-reported fatigue, but as secondary measures in small groups.

NMN has not been tested as a treatment for chronic fatigue syndrome (ME/CFS) or post-viral fatigue, and supporting cellular energy production is not the same as relieving tiredness you can feel.

Insulin sensitivity and metabolic markers

The most cited metabolic result comes from Yoshino’s 2021 trial, published in Science. In 25 postmenopausal women with prediabetes who were overweight or obese, 250 mg a day for ten weeks improved muscle insulin sensitivity by about 25% compared with placebo.

That finding has not carried over to healthy people. Trials in healthy middle-aged adults have mostly found no significant change in fasting glucose, HbA1c or blood lipids. A few report modest changes in arterial stiffness or blood pressure, but only as secondary outcomes.

How safe is NMN in human trials?

Oral NMN has been well tolerated at the doses and durations tested. No trial has reported a serious adverse event linked to NMN, and minor complaints such as mild stomach upset or headache occur at similar rates in placebo groups.

The table shows the main dose ranges studied and what researchers found.

Daily dose	Duration studied	Reported findings
250 mg	Up to 12 weeks	No serious adverse events. Liver and kidney markers stayed within normal ranges.
300 to 900 mg	Up to 60 days	Well tolerated, with occasional mild digestive symptoms.
1,250 mg	4 weeks	No clinically meaningful changes in blood tests and no serious adverse events.
2,000 mg (1,000 mg twice daily)	14 days	Well tolerated in a short trial of the NMN formulation MIB-626.

Methyl groups are small chemical structures made of one carbon and three hydrogen atoms. They act like biological switches, attaching to other molecules to regulate essential functions like gene expression, detoxification, and neurotransmitter production. Clearing excess nicotinamide, a waste product of NMN, uses up methyl groups; NMN trials of up to 12 weeks have not reported signs of methyl group depletion. For dose limits and who should avoid NMN, see Is NMN safe? and how much NMN to take.

NMN is a supplement, not a medicine. If you are pregnant or breastfeeding, have a medical condition, are having cancer treatment or take prescribed medication, speak to your GP or pharmacist before taking it.

Where the evidence falls short

Whilst trials are so far. encouraging the are limited: small, short and focused on blood markers rather than health outcomes.

The table below identifies bottlenecks in NMN research.

Limitation	Why it matters	What would fix it
Small samples	Most trials enrolled 10 to 60 people per group, so chance findings are more likely.	Multi-centre trials with hundreds of participants
Short duration	No trial has run much beyond three months, too short to show long-term effects.	Multi-year studies tracking safety and health outcomes
Varied doses and formats	Doses from 100 mg to over 1,000 mg, in powders and capsules, make trials hard to compare.	Standardised doses and formats across trials
Industry funding	Many trials are supported by ingredient makers. Huang’s 2022 trial used UTHEVER® NMN with support from its manufacturer, Effepharm.	More independent, publicly funded research
Surrogate endpoints	Blood NAD+ is a marker, not an outcome such as disease or lifespan.	Trials measuring health outcomes and validated ageing markers
Few comparisons	There is little direct testing of NMN against NR, niacin or exercise.	Head-to-head trials with active comparators

What the trials mean if you take NMN

Read together, the trials support a limited narrative: NMN raises NAD+, safely, in the short term. Anything beyond that is promising at best.

In practice, trials that found effects mostly used 250 to 600 mg a day for eight to 12 weeks, with no evidence that much higher doses add benefit (see our NMN dosage guide). Changes are unlikely to be felt quickly, and NMN works alongside exercise, sleep and diet rather than replacing them.

The table sets common NMN marketing claims against the human evidence.

Claim	Human evidence	Verdict
Raises NAD+ levels	Consistent across trials and populations	Supported
Boosts energy	Small, self-reported effects in older adults	Not established
Improves endurance	Seen in trained runners alongside exercise	Limited
Controls blood sugar	One trial in a specific group. No change in fasting glucose in healthy adults	Not supported
Reverses ageing	No human trial has measured the rate of ageing	Not supported
Extends lifespan	Evidence comes from animal studies only	Not supported

Quality matters too. Youth & Earth’s finished NMN capsules are tested for identity, potency, purity, heavy metals and microbial safety, while stability testing is carried out by Effepharm on its UTHEVER® raw material. Our guide to the NMN Certificate of Analysis explains what to look for in any brand’s testing.

Choosing an NMN supplement?

Youth & Earth NMN capsules are made with UTHEVER® NMN and tested for identity, potency, purity, heavy metals and microbial safety.

→ Explore Youth & Earth NMN

→ Compare the best NMN supplements in the UK

Frequently asked questions

Has NMN been tested in humans?

Yes. As early as 2016, NMN has been studied in published human trials ranging from single-dose safety studies to randomised, placebo-controlled trials in young, middle-aged and older adults.

Does NMN increase NAD+ levels in humans?

Yes. Raised blood NAD+ is the most consistently replicated finding in human NMN trials. It usually appears within two to four weeks of daily use, with larger rises at higher doses.

Does NMN improve physical performance?

The evidence is mixed. Trained runners improved aerobic capacity when NMN was combined with training, and older adults showed modest gains in walking speed, but muscle mass and grip strength have rarely changed.

Is NMN proven to extend lifespan?

No. No human trial has shown that NMN extends lifespan or prevents age-related disease. Lifespan findings come from animal studies and cannot be applied directly to people.

How strong is the evidence for NMN?

It is strong for raising blood NAD+ and for short-term safety. For endurance, insulin sensitivity, walking ability and fatigue, it is limited and inconsistent.

Are there published NMN safety trials in humans?

Yes. Trials have tested oral doses from 100 mg to 1,250 mg a day, and 2,000 mg in one short study, without serious adverse events.

References

[1] 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. DOI: https://doi.org/10.1507/endocrj.EJ19-0313

[2] 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. DOI: https://doi.org/10.1126/science.abe9985

[3] 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. DOI: https://doi.org/10.1186/s12970-021-00442-4

[4] Huang H. A multicentre, randomised, double blind, parallel design, placebo controlled study to evaluate the efficacy and safety of Uthever (NMN supplement), an orally administered supplementation in middle aged and older adults. Front Aging. 2022;3:851698. DOI: https://doi.org/10.3389/fragi.2022.851698

[5] 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. DOI: https://doi.org/10.1038/s41598-022-18272-y

[6] 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):755. DOI: https://doi.org/10.3390/nu14040755

[7] 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. DOI: https://doi.org/10.1038/s41514-022-00084-z

[8] Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, et al. The efficacy and safety of β-nicotinamide mononucleotide 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: https://doi.org/10.1007/s11357-022-00705-1