NMN Clinical Studies (In Humans) – RENUE BY SCIENCE

Above is a comprehensive list of human trials for NMN to date. The pace of human trials has picked up considerably over the past year, showing greater efficacy as trial dosages have increased and better methods of testing have evolved.

Highlights of these studies include reduced LDL and non-HDL cholesterol, reduced body weight, lower diastolic blood pressure, reduced frailty, reduced triglyceride levels, reduced arterial thickness, improved walking speed and grip strength, improved insulin sensitivity, and improved aerobic capacity.

The most notable research so far includes a recent study performed by Metro Biotech, using their own version of NMN called MIB-626. In that study, a significant increase in daily dosage was used (2,000mg of NMN) to show that:

MIB-626 treatment was associated with a substantial increase in blood NAD level from baseline to days 14 and 28
Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and non-high–density lipoprotein (HDL) cholesterol levels decreased from baseline in the MIB-626 group
Body weight decreased in the participants randomized to the MIB-626 group and increased in those assigned to the placebo group; between-group difference in change in body weight was statistically significant
Diastolic blood pressure decreased from baseline in the MIB-626 group

Details of each study, including date, participants, duration, dosage, safety and efficacy

16 – Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial

Summary: NMN safely increased NAD+ levels and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure.

Date: February 2023
Participants: 36 healthy middle-aged participants
Type: Randomized, double-blind, placebo-controlled, parallel-group clinical trial
Duration: 12 weeks
Dosage: 125mg NMN or placebo twice daily
Results:

Supplementation of NAD+-boosting agents reduced blood vessel stiffness, suggesting that NMN supplementation potentially improves vascular health in middle-aged adults
NMN intervention significantly decreased diastolic blood pressure in participants with higher-than-mean blood glucose levels

15 – Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study

Summary: NMN safely increased NAD+ levels and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure.

Date: February 2023
Participants: Thirty overweight or obese adults, ≥ 45 years
Type: single-center, randomized, double-blind, placebo-controlled, parallel group, physiologic study
Duration: 28 days
Dosage: 2 NMN tablets each containing 500 mg twice daily
Results:

MIB-626 treatment was associated with a substantial increase in blood NAD level from baseline to days 14 and 28
Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and non-high–density lipoprotein (HDL) cholesterol levels decreased from baseline in the MIB-626 group
Body weight decreased in the participants randomized to the MIB-626 group and increased in those assigned to the placebo group; between-group difference in change in body weight was statistically significant
Diastolic blood pressure decreased from baseline in the MIB-626 group

14 – 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

Summary: NMN was shown to be safe, well tolerated, and significantly increased NAD+ levels in blood of middle-aged adults. NMN also had a positive impact on physical endurance in six-minute walk tests, blood biological age, and patient-reported outcomes.

Date: December 2022
Participants: 80 middle-aged healthy adults
Type: randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial
Duration: 60 days
Dosage: once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN
Results:

Blood NAD concentrations were statistically significantly increased among all NMN-treated groups at day 30 and day 60 when compared to both placebo and baseline.
Walking distance increase during the six-minute walking test was statistically significantly higher in the 300 mg, 600 mg, and 900 mg groups compared to placebo at both days 30 and 60.
Blood biological age increased significantly in the placebo group and stayed unchanged in all NMN-treated groups at day 60, which resulted in a significant difference between the treated groups and placebo.
The change of SF-36 scores (positive patient reported outcomes) at day 30 and day 60 indicated statistically significantly better health of all three treated groups when compared to the placebo group.

13 – Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study

Summary: NMN improved prevalence of frailty and retinal thickness in older male patients with diabetes and impaired physical performance. NMN supplementation for 24 weeks was safe and showed a trend toward improved grip strength and walking speed, although it was not significant, possibly due to the small study size.

Date: November 2022
Participants: 14 male patients with diabetes aged ≥65 years with reduced grip strength (<26 kg) or walking speed (<1.0 m/s)
Type: placebo-controlled, double-blinded study
Duration: 24 weeks
Dosage: 250mg NMN per day
Results:

NMN was safe and tolerable without any severe adverse events. (13)
NMN improved prevalence of frailty and central retinal thickness in older males. (13)
Researchers found a trend towards improved grip strength and walking speed, but it was not significant, possibly due to the small study size. (13)

12 – Nicotinamide Mononucleotide Is Safely Metabolized and Significantly Reduces Blood Triglyceride Levels in Healthy Individuals

Summary: “Injecting healthy individuals with NMN safely and effectively reduced blood fat (triglyceride) content and increased NAD+ levels.” (12)

Date: Sept 2022
Model: ten healthy individuals (age 20-70 years)
Duration: 1 day
Dosage: Intravenous injection of 300 mg of NMN
Results:

“A single injection of NMN reduces blood fat content by about 75%.” (12)

“NMN injections are safely metabolized and cause no discernible damage to the heart, kidney, or pancreas despite bypassing the body’s detoxifier – the liver.” (12)

“The injections boost blood NAD+ levels by about 20%.” (12)

11 – Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women

Summary: “Previous clinical studies with NMN have not reported on the safety of repeated daily oral administration of ≥ 1000 mg/shot in healthy adult men and women, and human clinical trials on NMN safety are limited. Therefore, we conducted a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety of 1250 mg of β-NMN administered orally once daily for up to 4 weeks in 31 healthy adult men and women aged 20-65 years.” (11)

Date: Aug 2022
Participants: 31 healthy adult men and women aged 20-65 years old
Type: randomized, double-blind, placebo-controlled, parallel-group
Duration: 4 weeks
Dosage: 1250 mg of NMN administered orally once daily
Results:

“Oral administration of β-NMN did not result in changes exceeding physiological variations in multiple clinical trials, including anthropometry, hematological, biochemical, urine, and body composition analyses. Moreover, no severe adverse events were observed during the study period.” (11)

“Our results indicate that β-NMN is safe and well-tolerated in healthy adult men and women in oral dose of 1250 mg once daily for up to 4 weeks.” (11)

10 – Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial

Summary: “Japanese scientists find that NMN reduces blood vessel stiffness in middle-aged adults with higher-than-average weight and blood glucose levels.” (10)

Date: July 29,2022
Number of Participants: 36 healthy middle-aged participants
Duration: 12-weeks
Type: randomized, double-blind, placebo-controlled, parallel-group clinical trial
Dosage: Participants received one capsule of either 125mg of NMN or placebo twice a day
Results:

“250 mg of NMN for 12 weeks tends to reduce artery stiffness — a risk factor for cardiovascular disease, dementia, and death — in healthy middle-aged adults.” (10)

“NMN significantly reduces artery stiffness in middle-aged adults with higher-than-average weight and blood glucose levels.” (10)

“Blood vessel age is reduced by 2 years with NMN treatment.” (10)

9 – Clinical evaluation of changes in biomarkers by oral intake of NMN

Summary: “A new study finds that NMN improves the metabolism, hormone levels, and skin of postmenopausal women.” (9a)

Date: June 2022
Model: Postmenopausal women between 50 and 80 years old
Duration: 12 weeks
Dosage: 300 mg/day of oral NMN
Results:

“Supplementing older women with 300 mg of oral NMN improves sugar and cholesterol metabolism.” (9a)

“NMN improves hormone levels as measured by the “mother hormone” – dehydroepiandrosterone sulfate (DHEA-s).” (9a)

“Treatment with NMN reduces a process called glycation in the skin.” (9a)

8 – Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men

Summary: Japanese scientists show administering NMN to aged men more than doubles blood NAD+ levels and enhances walking speed and grip strength.

Date: May 2022
Model: Men aged 65 years and older
Duration: 12 weeks
Dosage: 250 mg per day of oral NMN
Results:

250 mg of NMN per day for 12 weeks more than doubles blood NAD+ levels in healthy males older than 65.
The supplementation regimen improves walking speed and grip strength in the aged men.
These findings suggest NMN supplementation may be used to ameliorate age-related muscle deterioration.

7 – 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

Summary: Study to evaluate the efficacy of NMN in stimulating NAD+ metabolism and its effect on middle-aged and older subjects, several parameters such as blood NAD+/NADH concentration in serum, 6 minute walking tests, blood pressure, pulse pressure, and the SF36 questionnaire on well being.

Date: May 2022
Participants: 66 adult and elderly subjects
Type: Multicentre, randomised, double blind, placebo controlled
Duration: 60 days
Dosage: 2 capsules of 150mg NMN or starch powder per day
Results:

At day 30, NAD+/NADH levels in the serum showed a noteworthy increase, i.e., by 11.3%, whereas the placebo group had shown no change at all. At the end of the study, i.e., day 60, the NAD+/NADH levels were increased further by 38% compared to baseline, against a mere 14.3% in the placebo group.
The 6-minute walking endurance increased by 4.3% in the Uthever NMN group and 3.9% in the placebo group on day 30, however by day 60 the NMN group showed a rise of 6.5% compared to 3.9% for the placebo group.

6 – Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women

Summary: “A human clinical trial shows that nicotinamide mononucleotide (NMN) improves metabolism in aged women with prediabetes.” (6a)

Date: April 2022
Model: prediabetic women between the ages of 55 and 75 who were overweight
Type: randomized, placebo-controlled, double-blind trial
Duration: 10 weeks
Dosage: 250 mg capsules/day of oral NMN
Results:

“This clinical study is the first to report the effectiveness of NMN on human health.” (6a)

“NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling.” (6a)

“The researchers show that NMN increases blood cell NAD+ levels and improves muscle insulin sensitivity and structure in aged, prediabetic women.” (6a)

5 – Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects

Summary: “A recently-published University of Toyama study from Japan reveals that a daily intake of 250 mg of nicotinamide mononucleotide (NMN) significantly raises blood NAD+.” (5a)

Date: April 2022
Participants: thirty healthy subjects
Type: placebo-controlled, randomized, double blind, parallel-group trial
Duration: 12 weeks
Dosage: 250 mg/day of NMN (n = 15) or placebo (n = 15)
Results:

“Healthy human subjects who took two 125 mg doses of NMN per day for 12 weeks nearly doubled their whole blood nicotinamide adenine dinucleotide (NAD) levels” (5a)

“No adverse physiological side effects, such as altered body weight or elevated blood pressure, were observed following NMN supplementation.” (5a)

“Whole blood NAD+ levels plateaued after four weeks of NMN usage and persisted for the 12-week duration of the study.” (5a)

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

Summary: A clinical study shows that 12 weeks of supplementation with the immediate NAD+ precursor NMN enhances sleep quality and lower limb function to potentially benefit physical and mental health.

Date: Feb 2022
Participants: 108 participants divided into four groups (NMN_AM; antemeridian, NMN_PM; post meridian, Placebo_AM, Placebo_PM)
Type: Randomized, double-blind placebo-controlled study
Duration: 12 weeks
Dosage: 250mg/day or placebo
Results:

NMN supplementation improves sleep quality to reduce drowsiness in adults over 65 years old.
Better sleep has been shown to improve cognition and physical performance, which may improve aged adults’ outlook on life and the overall number of healthy years people live.

3 – 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

Summary: “A study published by a research team from Metro International Biotech and Harvard Medical School shows that a pharmaceutical-grade preparation of NMN known as MIB-626 increases blood levels of NAD+ in one week in middle-aged and older adults.” (3a)

Date: Feb 2022
Participants: 32 overweight or obese adults, 55-80 years
Type: double-blind, placebo-controlled study
Duration: 14 days
Dosage: 1000-mg MIB-626 NMN once daily, twice daily, or placebo
Results:

“MIB-626 is a pharmaceutical-grade tablet of NMN from Metro International Biotech.” (3a)

“This study evaluated the ability of varying oral MIB-626 doses to raise intracellular NAD+ levels.” (3a)

“Two 500 mg MIB-626 tablets taken once or twice daily for two weeks doubled NAD+ blood levels in the participants middle-aged and older adults.” (3a)

2 – Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study

Summary: “Together with exercise training, NMN supplementation increases the endurance performance of middle-aged athletes by improving aerobic capacity.” (2a)

Date: July 2021
Participants: 48 young and middle-aged recreationally trained runners
Type: Randomized, double-blind placebo-controlled four-arm clinical trial
Duration: 6 weeks
Dosage: participants were randomized into four groups: the low dosage group (300 mg/day NMN), the medium dosage group (600 mg/day NMN), the high dosage group (1200 mg/day NMN), and the control group (placebo)
Results:

“In middle-aged runners, supplementing 600 to 1200 mg/day of NMN for six weeks increases the aerobic capacity of humans during exercise training, and the improvement is likely the result of enhanced O2 utilization of the skeletal muscle.” (2a)

“The muscle oxygen utilization improvements increased with higher NMN doses during endurance exercise.” (2a)

“No adverse health effects while taking up to 1200 mg/day of NMN for six weeks were reported.” (2a)

1 – Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men

Summary: “Scientists from Keio University School of Medicine in Japan publish first study evaluating safety of nicotinamide mononucleotide (NMN) administration in humans, showing no adverse health concerns.” (1a)

Date: Feb 2020
Participants: 10 healthy men
Type: single-arm non-randomized
Duration: 5 hours
Dosage: single oral administration of 100, 250, and 500 mg NMN
Results:

The single oral administrations of NMN did not cause any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature. (1)
Laboratory analysis results did not show significant changes, except for increases in serum bilirubin levels and decreases in serum creatinine, chloride, and blood glucose levels within the normal ranges, independent of the dose of NMN. (1)
Results of ophthalmic examination and sleep quality score showed no differences before and after the intervention. (1)
Plasma concentrations of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-5-carboxamide were significantly increased dose-dependently by NMN administration. (1)
The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects. Thus, the oral administration of NMN was found to be feasible, implicating a potential therapeutic strategy to mitigate aging-related disorders in humans. (1)

References:

1 – Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men

1a – Clinical Trial Shows Safety of NMN in Humans

2 – Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study

2a – Human Trial Shows NMN Enhances Exercise Endurance in Runners

3a – Metro Biotech Publishes MIB-626 NMN Human Data

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

5 – Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects

5a – Clinical Study Indicates that NMN Efficaciously Increases Blood NAD+ in Humans

6 – Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women

6a – Metabolic Benefits of NMN Shown for First Time in Humans

8 – Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men