Highlights

  • Rats display no physical abnormalities from consuming 1500 mg/kg/day – the equivalent of 900 mg per day for an average human – for a 90-day period.
  • Rats that consume 1500 mg/kg/day of NMN exhibit increased levels of liver enzymes that may indicate liver damage, an effect not associated with lower NMN doses.
  • Male rats administered this NMN dose have persistent, low grade kidney disease (nephropathy), but males given lower doses don’t have this condition.

Studies using rodent models have demonstrated that supplementing nicotinamide mononucleotide (NMN) mitigates an array of age-related diseases. These conditions range from neurological, cardiovascular, and metabolic disorders. Moreover, human studies suggest that NMN supplementation benefits people by enhancing muscle mobility in aged men and insulin sensitivity in postmenopausal women. However, research has still needed to unravel the maximum doses before which NMN becomes toxic.

Published in Food and Chemical Toxicology, Canault and colleagues from LGD Biotech in France demonstrate that rats may safely consume up to 1500 mg/kg/day over an extended period of 90 days. No observable adverse physical or neurobehavioral effects were seen, suggesting that doses equal to or above this dose may be safely given to rats. Liver enzyme levels that indicate liver damage increase significantly at this dose, but with no discernible liver damage seen, this may be due to a metabolic adjustment to NMN. What’s more, male rats administered 1500 mg/kg/day of NMN exhibit persistent, low grade kidney disease (nephropathy). These findings indicate that liver and kidney health must be closely monitored at doses of 1500 mg/kg/day or higher, equivalent to 900 mg per day for an average adult.

No Adverse Side Effects Were Observed from 1500 mg/kg/day of NMN

To monitor the physical changes that the animals undergo during 90 days of supplementation, Canault and colleagues compared groups administered 375, 750, and 1500 mg/kg/day to those not given NMN. The LGD Biotech team also compared the rats after a 28-day recovery period following supplementation. The research team found that no rats from any of the dosage groups perished during the experiment or during the 28-day follow-up. Moreover, Canault and colleagues found no neurobehavioral abnormalities in any of the groups. Body and organ weight differences and changes between the groups were also negligible, suggesting that doses up to 1500 mg/kg/day may be safely administered to rats.

Since the liver detoxifies metabolites that may come from NMN, the LGD Biotech researchers sought to compare liver health measurements between the three dosage groups and rats not given NMN. They looked at the levels of enzymes that may suggest liver damage. Levels of these enzymes increase significantly at higher doses compared to rats not given NMN. These findings suggest that liver damage may occur at higher NMN doses. However, Canault and colleagues speculate that the higher enzyme levels stem from NMN-driven changes to liver metabolism since no liver disease could be visually detected.

(Cros et al., 2021 | Food and Chemical Toxicology) Levels of enzymes that suggest liver damage significantly increase at higher NMN doses.

Because kidneys filter waste products from the blood that may come from metabolized NMN, Canault and colleagues checked rat kidney health. The LGD Biotech team found that males exhibit persistent, low grade kidney disease (nephropathy). The group of male rats that took 1500 mg/kg/day persistently displayed this condition following the 28-day recovery period. These findings indicate that kidney disease may occur with high doses of NMN over prolonged periods.

“We have established the first safety profile of nicotinamide mononucleotide through in vitro and in vivo studies evaluating the safety parameters of high purity NMN-C®,” said Canault and colleagues. “The results obtained demonstrated that repeated oral administration of NMN-C® at doses up to 1500 mg/kg/d appears to be safe and did not promote toxic effects as seen from bodyweight change, food and water consumption, feed conversion efficiency, biochemical and blood parameters as well as organ toxicity and histological examinations of main organs.”

NMN Doses Less Than Highest Recommended Dose Are Likely Effective

The findings hint that doses up to 900 mg per day for average adults weighing approximately 60 kg, the equivalent of 1500 mg/kg/day in rats, may be safely used without adverse physical effects. Adults who take more than 900 mg per day may consider consulting a physician regarding possible negative effects on the liver or kidneys attributable to these higher doses. Further research is required to find out whether higher NMN doses confer harmful side effects to these organs.

Most human studies showing NMN’s health benefits use doses between 250 and 500 mg per day, well below the possible safety threshold of 900 mg per day. These studies have shown that doses of 250 mg per day effectively boost levels of the essential molecule nicotinamide adenine dinucleotide (NAD+) in the blood. Because researchers believe that NMN provides its beneficial anti-aging effects by increasing NAD+ levels, it is probable that this molecule is effective at doses well below 900 mg per day.