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NMN Human Trial Results Published

Researcher suggests clinically but not statistically significant results.

NMN pillsNMN pills
 

The data from a multicenter NMN clinical trial have been published with some very modest but still interesting results [1].

What is NMN?

NMN is short for nicotinamide mononucleotide, a naturally occurring molecule present in all species. It is a precursor of nicotinamide adenine dinucleotide (NAD+), a molecule that may be useful in slowing down some aspects of aging. NAD+ serves many critical functions in our cells, such as electron transport, cell signaling, facilitating cellular energy production, and DNA repair.

A growing amount of evidence suggests that as we age, our levels of NAD+ decline, increasing our risk of age-related diseases. This is why some researchers have proposed that restoring NAD+ levels in older people could help to slow down aging and keep them healthy.

NMN is marketed as a supplement and as a NAD+ booster, even though the data supporting its efficacy in humans was, until now, limited. There have been multiple animal studies suggesting that NMN slows down aging, but the evidence for human use has previously been lacking.

An NMN anti-aging human study

The goal of this study was to determine if NMN has any influence on aging in humans. NAD+ was chosen as its primary endpoint, and its increase was used as an indication of an anti-aging effect.

A higher amount of NAD+ present in cells has been correlated with higher energy levels. This makes sense given that NAD+ helps to produce ATP, which is a universal form of cellular energy.

Higher levels of NAD+ may also convey improved DNA repair, as its presence facilitates that [2]. This could also have an influence over genomic instability, which is thought to be a primary reason we age.

The study also chose the 6m walking test as a secondary endpoint. The researchers believed that NMN would improve energy levels and thus the walking capacity of participants.

The NMN study results

The study involved 66 healthy subjects aged between 40 and 65 years. Participants were given two capsules (containing 150 mg of NMN or starch powder) once a day following breakfast for a period of 60 days.

The primary efficacy parameter, NAD+/NADH levels in the serum, had increased by 11.3% in the active group (Uthever group) at day 30, whereas no change was observed in the placebo group at all. At the end of the study (day 60), the NAD+/NADH levels were increased further by 38% from baseline in the Uthever group, compared to a mere 14.3% rise in the placebo group. The increase in the placebo group may be attributed to the placebo effect in this study. Although the difference between the active and placebo groups is not statistically significant, the results indicate that Uthever does increase the NAD+ levels in the serum after 2 months of duration as well.

This suggests that the NMN is entering the cells to increase energy levels and could be interpreted as an anti-aging effect, albeit it relatively small in this case. That said, the NAD+ levels also increased in placebo participants not taking NMN which needs further investigation.

At the end of the study, the mean HOMA IR Index showed a rise of 0.6% among the NMN group and 30.6% among the Placebo group from baseline.

Homeostatic Model Assessment of Insulin Resistance (HOMA IR) shows how much insulin your pancreas needs to regulate blood sugar levels. Developed in the 1980s, it is an indirect measure that is calculated from fasting glucose and fasting insulin levels. While it does have its limitations, it is widely used in clinical research.

The HOMA score rose in the placebo group given starch powder, while there was little change in the group taking NMN. The researchers suggest that this demonstrates an age-slowing effect and that without NMN, HOMA became worse.

The walking endurance increased by 4.3% in the NMN group and 3.9% in the placebo group on day 30 of the treatment. So no effective difference was seen on day 30 of the treatment for walking endurance. When the same treatment was continued up to day 60, the NMN group showed a rise of 6.5% whereas for the placebo group, it remained the same, i.e., 3.9%.

While this is a small increase, it would be interesting to see if the difference between the placebo and test groups increases with longer-term use.

The analysis of the data obtained in this study did not find any statistically significant changes in efficacy outcomes between the active and placebo groups. However, the increase in NAD+/NADH levels in serum, the improvement in overall health and walking endurance, are clinically significant.

Conclusion

Given the mechanisms by which NAD+ has been shown to work in mice and other animals, there is some reason to believe they may work in a similar way in humans, but so far, conclusive results in people have not been obtained.

This trial was conducted by an employee of Effepharm (Shanghai) Co., Ltd and that the company supplied the NMN. While this does not necessarily mean that the data and their interpretation should be discounted, it should be considered when evaluating the results.

The other caveat is that the size of the trial was only 66 people, which is quite small. The larger the trial, the less prone results are to statistical noise and the more reliable they tend to be.

This study does suggest that NMN may have potential in humans though a longer study, increased dosage, and why the placebo group saw increased NAD+ levels should ideally be explored.

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Literature

[1] Huang, D. A Multicentre, Randomized, 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. Frontiers in Aging, 26.

[2] Li, J., Bonkowski, M. S., Moniot, S., Zhang, D., Hubbard, B. P., Ling, A. J., … & Sinclair, D. A. (2017). A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. Science, 355(6331), 1312-1317.

CategoryNews, Supplements
About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
  1. Jesse C
    June 3, 2022

    The title of this article and some of the content within are inaccurate! There were no significant findings.

    You say: “Human Trial of NMN Suggests Clinically Significant Results” and “The results suggest there is a clear and significant increase of NAD+ levels following the administration of NMN. This would suggest that the NMN is entering the cells to increase energy levels and could be interpreted as an anti-aging effect.”

    However, the article linked actually says: “Although the difference between the active and placebo groups is not statistically significant, the results indicate that Uthever does increase the NAD+ levels in the serum after 2 months of duration as well.”

    And, as for the rest of the trial endpoints:
    -6 Minute Walking Endurance Test: “The findings were not found to be statistically significant.”
    -The SF 36 questionnaire: “The difference in SF-36 scores between the active and placebo groups was not statistically significant…”
    -Blood Pressure: “The findings were not statistically significant.”
    -HOMA IR Index: “The difference in HOMA IR Index between the Uthever and the placebo groups was not found to be statistically significant.”

  2. Jesse C
    June 3, 2022

    Perhaps I am misunderstanding what you meant by “significant”. The linked article does in fact say “The analysis of the data obtained in this study did not find any statistically significant changes in efficacy outcomes between the active and placebo groups. However, the increase in NAD+/NADH levels in serum, the improvement in overall health and walking endurance, are clinically significant.”

    How does one determine clinical significance and is it meaningful even when there is no statistical significance?

    • Steve Hill
      June 3, 2022

      Yes, the use of significant has two meanings here and I probably should not have used that word. Statistically the results are small, but clinically speaking an improvement is good, no matter how small. I am going to reword this to clear up confusion.

      If it helps:

      The main difference between statistical and clinical significance is that the clinical significance observes dissimilarity between the two groups or the two treatment modalities, while statistical significance implies whether there is any mathematical significance to the carried analysis of the results or not.

  3. andrewperks
    June 3, 2022

    I would like to see the study replicated with a higher dose, 1000 mg of NMN.

    • Steve Hill
      June 3, 2022

      Yes I would be interested to see this too and ideally over a longer period that 60 days.

    • bernardrai
      June 4, 2022

      1 gram a day for me is perfect. I’m 72

  4. genesmolko
    June 3, 2022

    This is very confusing. 38% increase in NAD would seem to be very significant but what confuses me more is the 14.8% NAD increase in the placebo group. 14.3% seems like a lot, how could a person mentally will more NAD to be produced? Maybe some other factor led to the increase in NAD, a change in seasons and activity maybe?

    • Steve Hill
      June 3, 2022

      38% is not a bad start I grant you :) But yes, 14.3% is impressive for the placebo.

    • bradou81261
      June 3, 2022

      I don’t understand why Sulforaphane isn’t getting more attention? I think it might have more biologically more activity then any other molecule .

  5. stvhill004
    June 3, 2022

    David Sinclair 1000 mg NMH daily, Harvard, PHD, the expert on aging…

  6. mark4588
    June 4, 2022

    The study is like sending the the greatest quarterback out on the field with the rest of the team. Resveratrol and fats for multiplying factors. How about the coaching team: STOP SUGAR, exercise, etc.

  7. jameschoi
    June 7, 2022

    Who can afford 1000mg of NMN daily. Come on?

    • Steve Hill
      June 7, 2022

      As I have said before in other articles, for an anti-aging therapy to be effective it must 1: Work and 2: Be affordable for the working public. If the pricepoint of NMN does not fall, if it is shown to work, then it will fail as a therapy and the race will be on to achieve the same effects without the cost.

    • rickkaplankipu
      October 11, 2022

      I am positively influenced by David Sinclair so I take 900 mg of NMN and 400 of resveratrol. I have also started intermittent fasting from 8pm to 12pm. I am 71, very active, and I see differences in myself since I started. I take the NMN/resveratrol first thing in the morning (i.e., 5 hours before eating). Does it matter whether it is taken with or without food? Thank you

  8. mark4588
    July 20, 2022

    I stopped taking before I developed a mass on my kidney. Is there any study about this or any other side effect?

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