Highlights: 

  • 1000 mg/kg of NMN (Restorin) for female rats and 500 mg/kg for male rats is well-tolerated over the course of ninety-one days.
  • Major side effects include weight loss and decreased food consumption.

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in a myriad of cellular processes that keep our cells functioning and alive. However, NAD+ levels progressively decline with age, which is associated with age-related diseases. Our cells synthesize NAD+ primarily through its precursor nicotinamide adenine dinucleotide (NMN). NMN supports increased NAD+ levels, which mitigates age-related diseases in animals. Still, there is a lack of studies demonstrating that NMN is safe.

Researchers from Nucro-Technics, a third-party pharmaceutical diagnostics contractor, report in Frontiers of Pharmacology results for their safety evaluation of Restorin, a high-purity synthetic form of NMN. Turner and colleagues find that while higher doses of Restorin present some adverse effects in rats, lower doses lead to limited adverse effects, including weight loss and reduced food consumption. Overall, 1000 mg/kg of Restorin in females and 500 mg/kg in males is well tolerated.

Restorin Is Well Tolerated in Rats

To evaluate the safety of Restorin NMN, Turner and colleagues administered Restorin to male and female rats orally for fourteen days. The maximum dose assessed was 5,000 mg/kg, which led to decreased body weight and reduced food consumption. A few animals had adverse side effects, such as dehydration and weakness. Additionally, the weight of several organs was altered and showed signs of dysfunction within the 3,000 mg/kg to 5,000 mg/kg dosage range. No adverse effects were found with 500 mg/kg and 1000 mg/kg doses. 

After finding that 3,000 mg/kg and 5,000 mg/kg of Restorin may lead to adverse side effects, Turner and colleagues focused on 500 mg/kg, 1,000 mg/kg, and 2,000 mg/kg doses administered daily for ninety-one days. The effects of Restorin NMN were compared to another NAD+ precursor called nicotinamide riboside chloride (NRC). All doses of NMN led to a reduction in body weight, with higher doses leading to more weight loss. All doses also led to an increase in urine acidification which could be due to excretion of the drug, and do not necessarily indicate kidney damage.

At 2,000 mg/kg of Restorin, many of the changes observed with NMN were similar to the changes observed with NRC administration, including increased hemoglobin levels and higher white blood cell counts. Most other measurements were not considered physiologically significant. Effects like skin lesions were observed in both treated and untreated animals, indicating that the lesions were not due to the treatment. Finally, some of the chemical changes observed, such as those seen in the kidneys of male rats, are specific to rodents and do not occur in humans.

Is NMN Safe for Humans?

While there have not yet been clinical trials evaluating the safety of Restorin in humans, there are a few trials that have tested the safety of other NMN products. One such study showed that single oral administration of 100, 250, and 500 mg of NMN is safe for healthy men. Another clinical study showed that a daily dose of 300, 600, and 1,200 mg of NMN for six weeks in healthy amateur runners led to no obvious adverse symptoms. In a 10-week clinical trial, it was demonstrated that 250 mg of NMN increased muscle insulin sensitivity in women with prediabetes. So, is NMN safe? It seems, in the short-term, yes. However, long-term clinical trials testing the effects of NMN have not been completed, so we do not know if NMN causes adverse effects if taken over the course of months and years.