Various NMN clinical trials have recently been conducted to evaluate NMN efficacy in humans. Both in vivo and in vitro studies showed that increasing NAD+ levels with NMN ingredient, the most efficient precursor, can prevent and manage many age-related diseases. Numerous age-related illnesses and metabolic disorders are followed by NAD+ decline. NAD+ takes part in glycolysis, the TCA cycle, redox reactions, DNA repair, and other biological processes in the body, all requiring NAD+ as a substrate. Therefore, alleviating age-related symptoms and preserving healthy levels of this coenzyme may enhance healthy aging.
The key finding
Nicotinamide adenine dinucleotide (NAD) is a crucial cofactor that regulates a number of redox processes by allowing the transfer of electrons between NADH and NAD+. Despite being a well-studied metabolite discovered more than a century ago, NAD+ has recently gained attention because of its anti-aging properties. Oral administration of NAD+ precursors, such as nicotinamide mononucleotide (NMN), improves aging-related conditions and restores NAD+ levels.
Therefore, this study focuses on the oral administration of NMN in healthy humans. This study is a randomized, double-blind investigation that includes 31 healthy adult men and women aged 20–65. Several parameters were measured before administration, after 2 weeks, after 4 weeks, and after information was obtained to evaluate the impact of oral NMN administration. People with tumors, disorders, taking medication, allergic to certain medications, and pregnant were excluded from this study.
Before participating, they shouldn’t change their lifestyle, medication, excessive eating and drinking, drinking alcohol, etc. They should avoid drinking or eating 6 hours before the blood collection. During the study medications for colds and headaches were allowed and written down in the medication column in the diary.
The participants were randomly divided into NMN and placebo groups, all with different men/women ratios. They were given oral NMN at different concentrations, including 313, 625, 1250, 2500, and 5000 µg/plate. The results were obtained according to their evaluation from clinical, biochemical tests, hematological tests, urinalysis, body composition, vital signs, and adverse effects.
Fukamizu, Y., Uchida, Y., Shigekawa, A., Sato, T., Kosaka, H., & Sakurai, T. (2022). Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Scientific Reports, 12. https://doi.org/10.1038/s41598-022-18272-y
(The phases that both groups undergo.)
According to the hematologic tests done, there were no significant differences between the both NMN and placebo groups. All results were within the reference range. The results from the clinical, biochemical tests show some changes within the groups. The sodium levels in the placebo group declined when measured at week 2, while the NMN group was significantly low at week 0. The LDH levels in the NMN group increased at week 0. The same results were for total protein levels compared to the placebo group. All the obtained results were within the reference ranges.
Fukamizu, Y., Uchida, Y., Shigekawa, A., Sato, T., Kosaka, H., & Sakurai, T. (2022). Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Scientific Reports, 12. https://doi.org/10.1038/s41598-022-18272-y
(The sodium and LDH levels during the observation.)
The body composition and vital signs showed no changes between both groups. However, the results of some parameters from the urinalysis were changed. The urobilinogen levels at week 2 were changed only in the placebo group. Urine occult blood was obtained at week 2 and week 6 in the placebo group. The placebo group also changed urine glucose at week 0 and urine ketone bodies at weeks 2 and 4. The results from the other parameters, such as pH level, specific gravity, and bilirubin, were within the reference values in both groups.
Fukamizu, Y., Uchida, Y., Shigekawa, A., Sato, T., Kosaka, H., & Sakurai, T. (2022). Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Scientific Reports, 12. https://doi.org/10.1038/s41598-022-18272-y
(The results from the parameters of urinalysis.)
Five side effects were recorded during the study but were not linked with the administration of the test food.
Safety of oral NMN administration
According to this study and the results obtained, investigators found that the 1250 mg oral NMN administration is safe for healthy women and men. They administrated NMN once daily for 4 weeks which was well-tolerated without any adverse effects.
Previous clinical studies observed the safety of oral NMN administration up to 500 mg as a single dose. The results showed that NMN administration of 100 mg, 250 mg, and 500 mg was safe to use among healthy males. Compared to the previous study, this study showed safety NMN administration of very high doses of up to 1250 mg daily for 4 weeks.
Also, the total bilirubin levels were increased, while there were no significant changes in this study. Furthermore, the glucose blood and chloride levels with oral NMN administration significantly decreased within the reference laboratory range in the previous study. In contrast, in this study, no changes were observed.
The only change observed was at 1350 mg of NMN oral administration. This high dose has slightly increased the blood creatinine levels in beagle dogs, which indicates renal dysfunction. Despite this research, in both studies, low and high concentrations of oral NMN did not observe any changes in the blood creatinine levels.
Considering all results and studies, oral NMN administration is safe to use in humans and is well-tolerated without signs of any possible adverse effects.
Limitations
There were several limitations linked to this study. The NMN metabolites in the urine and blood samples were not obtained during the study period. Also, the metabolomic analysis of NMN, which can show the bioavailability and disposition of NMN, was not measured. In addition to the analysis obtained, clinical physiological tests such as MRI, ECG, and EEG were not performed and used as criteria for safety. Further study for long-term administration is needed, and more participants should be included.
To sum up
Many previous studies claimed oral NMN administration is safe for postmenopausal women and patients with obesity and other diseases. Together with this study, the conclusion is clear. Oral NMN administration is safe to use in healthy humans and patients with glucose metabolism diseases, and other conditions, up to 1250 mg. A higher concentration of NMN is non-toxic, with no adverse effects shown.
References:
- Fukamizu, Y., Uchida, Y., Shigekawa, A., Sato, T., Kosaka, H., & Sakurai, T. (2022). Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Scientific Reports, 12. https://doi.org/10.1038/s41598-022-18272-y
