Human research library · β-NMN
NMN Human Clinical Research: What Has Actually Been Studied
β-Nicotinamide mononucleotide (β-NMN) has been evaluated in more than 15 published randomized controlled trials in humans, alongside pharmacokinetic and safety studies. This library summarizes what was studied, how much NMN was used, for how long — and what happened.
What the human evidence shows
Oral β-NMN raises NAD+ in people
In randomized, placebo-controlled trials, daily oral β-NMN significantly increased blood NAD+ at intakes from 250 mg to 1,000 mg per day. At 1,000 mg/day, whole-blood NAD+ roughly doubled within 14 days compared with placebo (Christen et al., Nature Metabolism, 2026).
Studied across a wide daily range
The repeated-dose trials of standard β-NMN in this library used 250 mg to 1,250 mg per day; 1,250 mg/day was evaluated for safety over four weeks (Fukamizu et al., 2022). Separately, a 2026 meta-analysis of randomized trials — covering intakes of 250 to 2,000 mg/day, including a pharmaceutical crystalline form — found no increase in adverse events compared with placebo (Yang et al., Nutrients, 2026).
Promising, and still developing
Trials have reported improvements in muscle insulin sensitivity, walking speed, six-minute walking distance and aerobic thresholds. Other trials found no significant effect on their primary outcome, and pooled data show no consistent change in glucose or lipids.
Why this research matters for Novera
The molecule studied in these trials is β-NMN — the molecule in Novera.
Each trial used β-NMN from its own supplier, and we identify every study by its own materials and protocol. The compound investigated, however, is the same: β-nicotinamide mononucleotide (CAS 1094-61-7). Novera contains β-NMN of that molecular identity, supplied by BONTAC®. Novera lot 04.2029/NV101 was manufactured using BONTAC® β-NMN batch BT05L125B011, documented at 99.9% purity by HPLC on its raw-material certificate of analysis.
Novera provides 1,000 mg of β-NMN per daily serving, taken orally — and 1,000 mg/day has itself been evaluated in published human research. In a 2026 randomized, placebo-controlled trial, 1,000 mg/day of oral β-NMN roughly doubled whole-blood NAD+ within 14 days (Christen et al., Nature Metabolism, 2026).
Oral delivery: what the evidence supports
Conventional oral β-NMN has increased blood NAD+ in human clinical trials
Swallowed as ordinary capsules or tablets, β-NMN raised NAD+ in people: 125 mg tablets taken twice daily significantly increased whole-blood NAD+ versus placebo at 4, 8 and 12 weeks (Okabe et al., 2022); 150 mg capsules at 300–900 mg/day increased blood NAD+ at every dose and improved six-minute walking distance versus placebo (Yi et al., 2023); and 125 mg capsules at 250 mg/day raised NAD+ in blood immune cells from 25.5 to 41.4 pmol/mg in eight weeks (Yamaguchi et al., 2024).
None of these trials used delayed-release, enteric-coated or targeted-delivery technology. We found no published human head-to-head study showing that delayed-release or enteric NMN raises NAD+ more than conventional oral β-NMN.
A vegan HPMC capsule — an established pharmaceutical material
Novera uses a plant-based hypromellose (HPMC) capsule, an established material for oral pharmaceutical and supplement capsules. In a human comparative study, HPMC and gelatin capsules performed comparably for the formulation tested: peak blood level and total exposure did not differ significantly, although HPMC capsules opened slightly later (Cole et al., Pharmaceutical Research, 2004; DOI). That study tested a model drug, not NMN; the NAD+ evidence for oral β-NMN comes from the human trials described here.
The studies at a glance
16 published human studies of β-NMN, plus a meta-analysis of randomized trials. Results are labeled by what each study found on its own terms — positive, mixed, neutral or pharmacokinetic.
| Study | Participants | Daily NMN | Duration | Result |
|---|---|---|---|---|
| Irie J et al., 2020 Endocrine Journal |
10 Healthy Japanese men |
Single oral doses of 100, 250 and 500 mg | Single dose, 5-hour follow-up | Safety / pharmacokinetics |
| Yoshino M et al., 2021 Science |
25 Postmenopausal women with prediabetes and overweight or obesity |
250 mg/day | 10 weeks | Positive on primary outcome |
| Liao B et al., 2021 Journal of the International Society of Sports Nutrition |
48 Healthy amateur runners in regular training |
300, 600 or 1,200 mg/day | 6 weeks | Mixed results |
| Okabe K et al., 2022 Frontiers in Nutrition |
30 Healthy adults aged 20–65 |
250 mg/day (125 mg twice daily, oral tablets) | 12 weeks, plus 4-week follow-up | Safety / pharmacokinetics |
| Kim M et al., 2022 Nutrients |
108 Community-dwelling adults aged 65 and over |
250 mg/day (oral tablets) | 12 weeks | Mixed results |
| Igarashi M et al., 2022 npj Aging |
42 Healthy men aged 65 and over |
250 mg/day | 12 weeks | Mixed results |
| Fukamizu Y et al., 2022 Scientific Reports |
31 Healthy adults aged 20–65 |
1,250 mg/day | 4 weeks | Safety / pharmacokinetics |
| Huang H, 2022 Frontiers in Aging |
66 Healthy adults aged 40–65 |
300 mg/day (oral capsules) | 60 days | No significant effect on primary outcome |
| Pencina KM et al., 2023 The Journals of Gerontology: Series A |
32 Adults aged 55–80 with overweight or obesity |
1,000 mg once or twice daily (proprietary microcrystalline β-NMN tablets) | 14 days | Safety / pharmacokinetics |
| Yi L et al., 2023 GeroScience |
80 Healthy adults aged 40–65 |
300, 600 or 900 mg/day (standard oral capsules) | 60 days | Positive on primary outcome |
| Katayoshi T et al., 2023 Scientific Reports |
36 Healthy middle-aged adults |
250 mg/day (125 mg capsule twice daily) | 12 weeks | No significant effect on primary outcome |
| Akasaka H et al., 2023 Geriatrics & Gerontology International |
— Older adults with diabetes and impaired physical performance |
250 mg/day | 24 weeks | No significant effect on primary outcome |
| Yamaguchi S et al., 2024 Endocrine Journal |
9 Healthy men aged 40–60 |
250 mg/day (two 125 mg capsules) | 8 weeks | Mixed results |
| Morifuji M et al., 2024 GeroScience |
60 Healthy older adults |
250 mg/day | 12 weeks | Mixed results |
| Christen S et al., 2026 Nature Metabolism |
65 Healthy adults |
1,000 mg/day β-NMN (compared with nicotinamide riboside, nicotinamide and placebo) | 14 days | Comparative / mechanistic |
| Wakabayashi J et al., 2026 Scientific Reports |
13 Healthy young men |
Single 250 mg tablet, swallowed vs. held under the tongue | Single dose, 60-minute sampling | Comparative / mechanistic |
| Yang W et al., 2026 Nutrients |
— Adults in 15 randomized controlled trials of oral NMN |
250–2,000 mg/day across included trials | 14 days to 24 weeks across included trials | Safety / pharmacokinetics |
Study by study
Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men
Irie J, Inagaki E, Fujita M, et al. Endocrine Journal, 2020.
Question: Is a single oral dose of β-NMN safe in humans, and how is it metabolized?
What happened: The first published human study of oral β-NMN. Plasma levels of the NAD-pathway metabolites 2PY and 4PY rose significantly and in proportion to the dose, showing that orally ingested β-NMN is absorbed and metabolized.
Safety: No significant clinical symptoms and no changes in heart rate, blood pressure, oxygen saturation or body temperature. Small laboratory changes stayed within normal ranges.
Limitations
Small, single-dose, non-randomized study without a placebo group; it did not assess effects of daily use.
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
Yoshino M, Yoshino J, Kayser BD, et al. Science, 2021.
Question: Does daily β-NMN improve insulin sensitivity and metabolic function in people with prediabetes?
What happened: β-NMN increased skeletal-muscle insulin sensitivity (insulin-stimulated glucose disposal rose about 25% from baseline, with no change on placebo) and enhanced muscle insulin signaling. NAD+ metabolites increased in blood cells and muscle.
Safety: Well tolerated; no adverse effects attributed to NMN.
Limitations
Small trial in a specific population. Liver and fat-tissue insulin sensitivity, blood glucose, HbA1c, body composition and muscle NAD+ content did not change.
Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study
Liao B, Zhao Y, Wang D, et al. Journal of the International Society of Sports Nutrition, 2021.
Question: Does β-NMN improve aerobic capacity in people who train regularly?
What happened: Aerobic capacity measured at the ventilatory thresholds (oxygen uptake and power output) improved in the NMN groups, with larger gains at higher doses.
Safety: No abnormal ECG findings or adverse symptoms were reported.
Limitations
Peak measures such as VO2max did not differ significantly from placebo; small groups (12 per arm); all participants were also training.
Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects
Okabe K, Yaku K, Uchida Y, et al. Frontiers in Nutrition, 2022.
Question: Is daily oral β-NMN safe, and does it raise blood NAD+?
What happened: Whole-blood NAD+ was significantly higher than placebo at 4, 8 and 12 weeks, and returned to baseline 4 weeks after supplementation stopped — evidence that the increase was driven by daily intake.
Safety: No serious adverse events; liver, kidney, blood and metabolic markers showed no meaningful differences from placebo.
Limitations
Small sample; NAD+ measured in blood only; functional outcomes were not assessed. Sponsored by the NMN manufacturer.
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
Kim M, Seol J, Sato T, et al. Nutrients, 2022.
Question: Does the time of day β-NMN is taken affect sleep, fatigue and physical performance in older adults?
What happened: Lower-limb function (five-times sit-to-stand) showed a significant group-by-time effect, with the largest improvement in the evening NMN group. Drowsiness also improved most with evening intake.
Safety: No side effects of NMN were reported.
Limitations
Overall sleep-quality scores did not differ significantly between groups and placebo groups also improved; grip strength did not change; no blood biomarkers measured.
Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men
Igarashi M, Nakagawa-Nagahama Y, Miura M, et al. npj Aging, 2022.
Question: Does long-term β-NMN raise NAD+ and affect muscle function in older men?
What happened: Blood NAD+ and related metabolites rose significantly with NMN, and some measures of muscle performance, including walking speed, improved compared with placebo.
Safety: No obvious adverse effects were reported.
Limitations
Muscle mass did not change, not every performance measure improved, and the trial was small and limited to older men.
PubMed 35927255Full text (PMC9158788)DOI 10.1038/s41514-022-00084-z
Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women
Fukamizu Y, Uchida Y, Shigekawa A, et al. Scientific Reports, 2022.
Question: Is a higher daily intake of β-NMN (1,250 mg) safe?
What happened: Daily intake of 1,250 mg β-NMN for 4 weeks produced no changes beyond normal physiological variation in blood chemistry, hematology, urinalysis, body composition or vital signs. A standard mutagenicity (Ames) test of the material was negative.
Safety: No serious adverse events; the few minor events were judged unrelated to NMN.
Limitations
Short duration and small sample; NAD+ levels were not measured. Sponsored by the NMN manufacturer.
PubMed 36002548Full text (PMC9400576)DOI 10.1038/s41598-022-18272-y
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
Huang H Frontiers in Aging, 2022.
Question: Does 300 mg/day of β-NMN improve NAD+, walking endurance and well-being?
What happened: Blood NAD+/NADH rose 38% from baseline in the NMN group (vs. 14% on placebo), with within-group gains in walking distance and well-being scores. Differences versus placebo were not statistically significant.
Safety: Well tolerated; adverse events were mild and equally frequent in both groups.
Limitations
Small sample, a single lower dose and no statistically significant between-group differences. Single author employed by the ingredient supplier.
MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults
Pencina KM, Lavu S, dos Santos M, et al. The Journals of Gerontology: Series A, 2023.
Question: How does oral β-NMN affect circulating NAD+ and its metabolites, and is it safe at 1–2 g/day?
What happened: Oral β-NMN produced large, dose-related increases in blood NAD+ and its metabolites compared with placebo; twice-daily dosing produced higher exposure than once-daily dosing.
Safety: No serious adverse events; adverse-event rates were similar to placebo.
Limitations
Short, small study designed for pharmacokinetics, not efficacy. Used a specific pharmaceutical crystalline form of β-NMN. Sponsored by the formulation developer.
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
Yi L, Maier AB, Tao R, et al. GeroScience, 2023.
Question: How do different daily doses of β-NMN affect blood NAD+, physical performance and well-being?
What happened: Blood NAD+/NADH rose significantly at every dose at days 30 and 60, with no change on placebo; 600 mg raised levels more than 300 mg, and 900 mg added no further increase. Six-minute walking distance and SF-36 well-being scores improved versus placebo (walking distance most clearly at 600 and 900 mg). Blood-based biological age increased on placebo but not in the NMN groups.
Safety: No adverse events were judged NMN-related and none occurred in the 600 mg or 900 mg groups; no dropouts due to adverse events.
Limitations
60-day duration, single-country cohort, insulin resistance (HOMA-IR) showed no benefit versus placebo, and NAD+ was measured in serum. Co-sponsored by the ingredient manufacturer.
Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial
Katayoshi T, Uehata S, Nakashima N, et al. Scientific Reports, 2023.
Question: Does long-term β-NMN affect NAD metabolism and arterial stiffness?
What happened: Serum nicotinamide (an NAD-pathway metabolite) rose significantly with NMN. Arterial stiffness (baPWV) fell in the NMN group, but the difference from placebo was not statistically significant overall; it was significant in participants with higher BMI or blood glucose.
Safety: Well tolerated; no adverse events and no significant changes in blood tests.
Limitations
NAD+ itself could not be quantified in serum; the subgroup findings are exploratory; small sample. Sponsored by the product manufacturer.
Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study
Akasaka H, et al. Geriatrics & Gerontology International, 2023.
Question: Can β-NMN improve physical performance in older adults with diabetes and frailty-related decline?
What happened: No statistically significant improvement in grip strength, walking time, knee-extension strength or other physical-performance measures compared with placebo.
Safety: No adverse effects were reported.
Limitations
Very small sample of older patients with diabetes; underpowered to detect modest effects.
Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men
Yamaguchi S, Irie J, Mitsuishi M, et al. Endocrine Journal, 2024.
Question: Is 8 weeks of β-NMN safe, and does it increase NAD+ in blood cells and affect glucose metabolism or sleep?
What happened: NAD+ in blood immune cells (PBMCs) rose from 25.5 to 41.4 pmol/mg after 8 weeks of NMN (p = 0.0046), with no change during the placebo period.
Safety: No serious adverse events.
Limitations
Very small, open-label study without a concurrent control group; glucose metabolism, insulin sensitivity and sleep scores did not change significantly.
Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study
Morifuji M, Higashi S, Ebihara S, et al. GeroScience, 2024.
Question: Does β-NMN support physical function and sleep in older adults?
What happened: Blood NAD+ and its metabolites were significantly higher than placebo at 12 weeks. 4-meter walking time was significantly shorter than placebo, and greater NAD+ increases correlated with better walking times. Sleep-questionnaire scores (global PSQI and daytime dysfunction) improved versus placebo.
Safety: No adverse effects related to the test substance were observed.
Limitations
The primary outcome (stepping test) did not differ from placebo; walking-speed and sleep results are secondary outcomes. Funded by a food company that employs some of the authors.
The differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans
Christen S, Redeuil K, Goulet L, et al. Nature Metabolism, 2026.
Question: How do common NAD+ precursors compare in raising blood NAD+, and how are they processed in the body?
What happened: 1,000 mg/day of β-NMN raised whole-blood NAD+ by 43.1 µM versus placebo — roughly doubling baseline levels — comparable to nicotinamide riboside, while nicotinamide produced no sustained increase. Laboratory experiments suggest gut microbes help convert NMN into compounds the body uses to make NAD+.
Safety: Supplements were well tolerated over 14 days.
Limitations
Open-label, short duration, healthy young-to-middle-aged adults; the gut-microbe mechanism was shown in laboratory models. Most authors were employed by a nutrition company.
PubMed 41540253Full text (PMC12855009)DOI 10.1038/s42255-025-01421-8
Sublingual NMN administration increases early circulating terminal catabolites 2PY and 4PY compared with oral administration in healthy adult men
Wakabayashi J, Higashi S, Morifuji M Scientific Reports, 2026.
Question: Does sublingual β-NMN change early blood metabolites compared with swallowing it?
What happened: Sublingual intake produced a faster early rise in the NAD-pathway end-products 2PY and 4PY. Overall exposure to NMN, nicotinamide, NAD+ and NADP+ in the first hour did not differ significantly between routes.
Safety: No adverse events were considered related to the product.
Limitations
Single dose, 60-minute window, small sample; it did not measure longer-term NAD+ or clinical outcomes. Funded by a food company.
PubMed 42304075Full text (PMC13534420)DOI 10.1038/s41598-026-57552-9
Safety and Metabolism-Related Outcomes of Oral Nicotinamide Mononucleotide Supplementation in Adults: A Systematic Review and Meta-Analysis
Yang W, Huang J, Tang Z, et al. Nutrients, 2026.
Question: Across all randomized trials, is oral NMN safe, and does it change metabolic markers?
What happened: Pooling 10 placebo-controlled trials (383 participants), NMN did not increase overall, serious or treatment-related adverse events, and did not raise liver enzymes. Fasting glucose, HbA1c, lipids and body weight did not change; diastolic blood pressure fell slightly (about 2.4 mmHg).
Safety: No increase in adverse events versus placebo across pooled trials.
Limitations
Included trials were small and short; long-term and rare risks cannot be excluded; certainty of evidence ranged from moderate to very low.
PubMed 42514320Full text (PMC13414721)DOI 10.3390/nu18142251
Go deeper
- NMN human clinical trials: complete evidence review — every trial's primary endpoint, secondary findings and null results.
- NMN dosage: what human studies have actually used
- How NMN is absorbed and metabolized
- BONTAC® NMN: the documented source behind Novera
How to read this library
This library summarizes independent published human research investigating β-NMN. Studies are identified by their actual study materials and protocols; none were sponsored by Novera or used Novera product. Clinical research is not regulatory approval, and individual results vary.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.