Scientists generally agree that a high NAD level is desirable in humans, as it can improve the lifespan and plays an important role in disease prevention. Thus, anti-aging researchers constantly look for new ways to elevate NAD levels as we age.
One such way may be NMN supplementation. This is a naturally occurring molecule converted to NAD in our body. Many studies have found a correlation between NMN intake and elevated NAD levels. Of course, correlation does not equal causation.
Only animal studies have shown that NMN supplementation increases NAD concentrations throughout the body…until now, that is!
This study may be a game-changer
Researchers from the US, China, Netherlands, and India have joined forces to conduct a human clinical trial on the efficacy of nmn, the results of which have been published in the GeroScience Journal (A journal by the American Aging Association) in December 2022.
The study was titled: 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
This trial had multiple goals:
- Check how different dosages of NMN supplementation affect the NAD concentration
- Assess the tolerability and safety of supplementing NMN
- Evaluating clinical efficacy using various assays and assessments
Study design for NMN efficacy and safety
This was a randomized, double-blind, placebo-controlled, parallel-group, dose-dependent, multicenter clinical trial. This is considered the gold standard in terms of study design for medical research.
In addition, the sample size was also fairly large, with 80 middle-aged (between 40 and 65 years old) healthy adults serving as test subjects. These participants were randomly assigned to 4 different groups. 3 experimental groups and 1 placebo control group. The experimental groups supplemented either 300, 600, or 900 mg NMN via oral ingestion once daily.
Here is a better overview of the 4 groups consisting of 20 participants each:
Placebo Group (n=20)
300 mg Experimental Group 1 (n=20)
600 mg Experimental Group 2 (n=20)
900 mg Experimental Group 3 (n=20)
NMN supplemented per day
2 x 150 mg (n=7)
4 x 150 mg (n=7)
6 x 150 mg (n=6)
2 x 150 mg
4 x 150 mg
6 x 150 mg
The trial lasted for 60 days. None of the 80 participants had to drop out during this time.
Assessments and tests conducted
On day 0 of the study, the participants were randomly assigned to one of the four groups, and a baseline assessment was conducted to determine their normal values before the ingestion of any NMN supplement. On day 30, efficacy, safety, and dosing compliance assessments were conducted. At the last day of the study (day 60) an end-of-trial assessment was completed. Let’s take a close look at these assessments:
Safety and tolerability of NMN supplementation
One of the secondary goals of this trial was to assess whether NMN was safe to supplement or whether any adverse events could occur. Blood and urinary tests, as well as physical examinations, were conducted. The tolerability could be evaluated by comparing the dropout rate of the experimental groups to the dropout rate of the placebo group.
NAD concentration in the blood
The central question of this trial was whether the NAD concentration could be increased. A colorimetric NAD test kit was used, which measures the concentrations of both NADH and NAD+ in the blood serum.
6-minute walking test
This test was designed to measure endurance and energy level . It was conducted on day 0, day 30, and day 60. Participants walked on a treadmill, which recorded the total walking distance. Another study on nmn and endurance can be found here.
The “biological age”
The so-called Aging.Ai 3.0 calculator is a formula based on 19 different laboratory test parameters (amongst others, triglycerides, red blood cells, LDL cholesterol, and calcium). This formula is meant to determine the “biological age” of the participants.
This is the value that is particularly meaningful in terms of insulin resistance. It represents the extent to which insulin can still work in your body. Values between 0.8 and 1.4 are desirable. Diabetes begins at a value of about 2.5.
This questionnaire was designed to assess a participant’s quality of life and general health status.
Efficacy of the placebo and three NMN-treated groups, comparisons of the three treated groups vs. placebo, 600 mg vs. 300 mg, and 900 mg vs. 600 mg on the changes of efficacy (Δmean ± SEM) from baseline to day 30 and/or day 60. Image source from Springer.
Based on the assessments outlined above, the clinical trial was able to determine how various NMN supplementation dosages:
- …affect NAD concentration in the blood.
- …are tolerated by the human body.
- …affect physical endurance.
- …alter our biological age.
- …affect our insulin resistance.
- …affect our perceived quality of life and general health.
Here’s what we learned!
Takeaway 1: NMN supplementation seems safe and relatively tolerable
No abnormality in any of the clinical lab parameters was found in any of the 80 participants 9 adverse events were reported, but none were deemed serious, and 6 of these were reported in participants taking the placebo. No adverse events were related to the NMN. There was also not a single dropout during the trial, which is quite rare.
Takeaway 2: The NAD concentration was statistically significantly elevated.
Compared to the placebo group, the blood NAD concentrations were statistically significantly increased in all three experimental groups. The difference in NAD concentration between the 600 mg and 900 mg groups was minuscule.
Takeaway 3: Walking distances improved in the experimental groups
The walking performance did not change significantly in the placebo group. But compared to the placebo group, all 3 NMN groups had significantly better results on days 30 and 60. The walking distance of the 600 mg group was even significantly better than the 300 mg group. But just again, there was no statistically significant difference between the 600 mg and 900 mg groups. Study: NMN may improve muscle function.
Takeaway 4: The blood biological age was reduced
In all three experimental groups, the biological age was statistically significantly reduced on day 60 compared to baseline. Meanwhile, the placebo group's biological age significantly increased.
Takeaway 5: Better perceived quality of life and general health
The SF-36 scores were significantly improved in all 3 experimental groups on day 60. They did not significantly differ from one another. Meanwhile, SF-36 scores did not increase significantly in the placebo group.
It seems as if various parameters related to general health, well-being, aging, and endurance can be improved through daily NMN supplementation. The difference nmn efficacy between a 300 mg and a 600 mg daily dosage was significant, whereas a 900 mg dosage did not provide much additional benefit compared to the 600 mg daily dose.