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Summary of recent NMN human clinical trials (1)

武本 重毅

カテゴリー: 

Alleviation of arteriosclerosis

Increased walking distance

Suppression of biological aging

Increased insulin sensitivity

 

β-Nicotinamide Mononucleotide (NMN) is

an anti-aging supplement

that has been gaining a lot of attention in recent years.

 

Until now,

NMN has been gaining attention

due to its anti-aging effects such as animal tests.

However, there are many uncertainties

as to whether this is possible for humans

with significantly different Life Spans.

 

In the past few years,

data from human clinical trials,

such as efficacy, safety, and kinetics,

have begun to be reported.

So let’s take a look at some of the published papers.

 

Nicotinamide after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial
Scientific Reports 2023;13:2786

Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) prevents the reduction of NAD+ levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports of NMN supplementation in humans. Thus, this study aimed to investigate the influence of a 12-week NMN oral supplementation on biochemical and metabolic health parameters. A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness.

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.

In animal studies, β-nicotinamide mononucleotide (NMN) supplementation increases nicotinamide adenine dinucleotide (NAD) concentrations and improves healthspan and lifespan with great safety. However, it is unclear if these effects can be transferred to humans. This randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial included 80 middle-aged healthy adults being randomized for a 60-day clinical trial with once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN. The primary objective was to evaluate blood NAD concentration with dose-dependent regimens. The secondary objectives were to assess the safety and tolerability of NMN supplementation, next to the evaluation of clinical efficacy by measuring physical performance (six-minute walking test), blood biological age (Aging.Ai 3.0 calculator), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and subjective general health assessment [36-Item Short Form Survey Instrument (SF-36)]. Statistical analysis was performed using the Per Protocol analysis with significant level set at p = 0.05. All 80 participants completed the trial without trial protocol violation. 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 (all p ≤ 0.001). Blood NAD concentrations were highest in the groups taking 600 mg and 900 mg NMN. No safety issues, based on monitoring adverse events (AEs), laboratory and clinical measures, were found, and NMN supplementation was well tolerated. 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 (all p < 0.01), with longest walking distances measured in the 600 mg and 900 mg groups. The 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 (all p < 0.05). The HOMA-IR showed no statistically significant differences for all NMN-treated groups as compared to placebo at day 60. The change of SF-36 scores at day 30 and day 60 indicated statistically significantly better health of all three treated groups when compared to the placebo group (p < 0.05), except for the SF-36 score change in the 300 mg group at day 30. NMN supplementation increases blood NAD concentrations and is safe and well tolerated with oral dosing up to 900 mg NMN daily. Clinical efficacy expressed by blood NAD concentration and physical performance reaches highest at a dose of 600 mg daily oral intake. 

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 May 5;3:851698.

Objective: The purpose of the study was to evaluate the anti-aging effect of NMN and its safety in a double-blind, parallel, randomised controlled clinical trial. Methods: The study was carried out on 66 healthy subjects between the ages of 40 and65 years, instructed to take two capsules (each containing 150 mg. of NMN or starch powder) once a day after breakfast for 60 days. 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. In the case of SF 36, at day 60, the Uthever group showed a rise of 6.5%, whereas the placebo group was merely raised by 3.4%. At the end of the study, the mean HOMA IR Index showed a rise of 0.6% among the Uthever group and 30.6% among the Placebo group from baseline. Conclusion: The rise in the levels of NAD+/NADH at day 30 and day 60 illustrated the potential of Uthever to raise the levels of NAD+ in the cells, which is linked to higher energy levels and an anti-aging effect. Increased sensitivity to insulin has also been linked to anti-aging. There was no noteworthy change in HOMA score, in the Uthever group whereas there was a noteworthy rise in the placebo group, demonstrating the anti-aging effect of Uthever as in its absence, the parameters worsened.

 

 

Author:

武本 重毅

聚楽内科クリニックの院長、医学博士。