NMN is a Vitamin B3 Derivative that is intermediary in the biosynthesis of NAD. The administration of NMN has been proven in numerous preclinical Studies have shown that NMN has a beneficial effect on various age-related diseases. The work of a team of French researchers led by Cecile Cros now addressed the question of the safety of NMN. The study was within the framework of the OECD guidelines carried out with the aim of assessing mutagenicity and genotoxicity, acute oral and subchronic oral toxicity. The test product is NMN-C®, a highly pure form of NMN.
Methodology
The toxicity experiments (acute and subchronic) were conducted on Sprague-Dawley rats – an outbred albino rat strain. Because of their “good nature and easy handling” they are used primarily in the fields of toxicology, pharmacology, reproduction and behavioral research (according to EMF Portal).
The research approach to assess the safety profile of NMN included four test conditions:
- Ames Test for the evaluation of Mutagenicity
- vitro Micronucleus assay on Chinese hamster ovary cells to investigate the Genotoxicity
- acute toxicity (14 days, rats)
- subchronic toxicity (90 days administration period, rats)
As part of the study of acute toxicity, the researchers administered a single NMN dose of 2666mg/kg body weight. Over the next 14 days, they checked their health status daily.
In the study of subchronic toxicity, male and female Sprague-Dawley rats were given NMN at a dose of 375, 750 or 1500 mg/kg for 90 days, followed by a 28-day recovery period. There was also a control group that was given only a placebo. The researchers used NMN-C® with a verified Purity of 99,03%.
Results
Ames test: Overall, NMN-C® is considered non-mutagenic and non-promutagenic under the experimental conditions tested.
In vitro micronucleus assay: NMN-C® did not cause chromosomal damage or changes in chromosome number in Chinese hamster ovary cells at the doses tested. Ergo, no genotoxicity was found.
acute toxicity: No abnormal weight changes, increased mortality, clinical signs or gross pathological lesions were observed during the 14-day follow-up period. A single high-dose NMN administration of 2666 mg/kg did not cause any discomfort or increased animal mortality.
Chronic toxicity: The results suggest that regular oral administration of NMN-C® at a dose of up to 1500mg/kg/day appears to be safe. The research team found that no toxic effects were promoted. This was demonstrated by monitoring body weight, food and water consumption, biochemical and blood parameters, as well as organ toxicity and histological examinations of the major organs.
Discussion
In the discussion, the study authors emphasize that this is the first safety evaluation of NMN within the framework of the OECD guidelines. The researchers estimated or determined the NOAEL (No-Observable Adverse Effect Level) over the 90-day treatment period to ≥ 1500 mg / kg / day. NOAEL is an endpoint parameter in toxicity studies. It "corresponds to the highest dose or exposure concentration of a substance in subchronic or chronic studies at which no significantly increased adverse treatment-related findings in morphology, function, growth, development or lifespan are observed"
The study on the safety of NMN was published in February 2021 in the journal Food and Chemical Toxicology.
Sources
Books
Safety evaluation after acute and sub-chronic oral administration of high purity nicotinamide mononucleotide (NMN-C®) in Sprague-Dawley rats.
https://doi.org/10.1016/j.fct.2021.112060
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