A human trial of NMN has recently concluded, and the results are not impressive at all; however, this is perfectly fine because that was not the purpose of the study, and, despite the lackluster results, the study was a success!
This might sound strange, but perhaps the words of the study authors may make it a bit clearer why this is absolutely no cause for alarm.
We, therefore, conducted a clinical trial to investigate the safety of single NMN administration in 10 healthy men.
The reason we should not be concerned with the results of this small human trial of NMN is because it achieved what it set out to establish: to demonstrate that the drug is safe and well tolerated at the dosage used.
The trial did not set out to demonstrate efficacy of NMN, and given the small number of trial participants, the single dose, and the short study time, it was never going to do more than establish that the drug is safe for human use.
The study at the Clinical Trial Unit, Keio University School of Medicine, Japan included a total of 10 healthy men aged between 40 and 60 years old and observed them to ensure that there were no adverse side effects.
During the study, the researchers observed various biomarkers, and no significant changes were evident following the single dose of NMN. This is hardly surprising, as the dosage range used of 100, 250, and 500 mg is also fairly low. The only notable result was that bilirubin levels rose by 51.3% and glucose fell by 11.7% following dosage. However, those two changes are most likely associated with the overnight fast prior to taking NMN and the five-hour fast following dosage.
The researchers also could not detect NMN in the blood samples taken in the study, but this is likely due to them being frozen before extraction, which degraded the NMN. This is unfortunate, but it serves as a useful cautionary tale for future studies to hopefully learn from.
Recent studies have revealed that decline in cellular nicotinamide adenine dinucleotide (NAD+) levels causes aging-related disorders and therapeutic approaches increasing cellular NAD+ prevent these disorders in animal models. The administration of nicotinamide mononucleotide (NMN) has been shown to mitigate aging-related dysfunctions. However, the safety of NMN in humans have remained unclear. We, therefore, conducted a clinical trial to investigate the safety of single NMN administration in 10 healthy men. A single-arm non-randomized intervention was conducted by single oral administration of 100, 250, and 500 mg NMN. Clinical findings and parameters, and the pharmacokinetics of NMN metabolites were investigated for 5 h after each intervention. Ophthalmic examination and sleep quality assessment were also conducted before and after the intervention. 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. 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. Results of ophthalmic examination and sleep quality score showed no differences before and after the intervention. Plasma concentrations of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-5-carboxamide were significantly increased dose-dependently by NMN administration. 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.
There have been a plethora of mouse studies; however, the safety and efficacy of NMN in humans was unclear, and this trial helps to confirm that, in general, the drug is safe and well tolerated; to that end, the trial can be considered a success.
The next step for researchers will be to investigate the efficacy of NMN, and a suitable dosage and frequency would then be established as part of that process. Of course, it is certainly possible that NMN may fail during efficacy testing in humans, but this initial safety study has no bearing on that potential outcome whatsoever.
There is currently an ongoing human trial for NMN at Brigham and Women’s Hospital in Boston from which efficacy data should be forthcoming, and until that data is in, no conclusion beyond NMN being safe can really be drawn.
Irie, J., Inagaki, E., Fujita, M., Nakaya, H., Mitsuishi, M., Yamaguchi, S., … & Okano, H. (2019). Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine journal, EJ19-0313.