Article Summary: Evaluating the Safety of Nicotinamide Mononucleotide (NMN) in Healthy Adults
Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme involved in various metabolic activities. Decreased levels of NAD+ have been associated with age-related diseases and metabolic abnormalities. Previous studies have shown that supplementing with nicotinamide mononucleotide (NMN), a precursor of NAD+, can alleviate these conditions. However, the safety of NMN intake at high doses has not been thoroughly studied in humans.
The findings of a study aimed to evaluate the safety of orally administering 1250 mg of β-NMN once daily for up to 4 weeks in healthy adult men and women aged 20-65 were as follows:
- Oral administration of β-NMN did not result in significant changes in clinical parameters.
- No severe adverse events were observed.
These results indicate that β-NMN is safe and well-tolerated in healthy adults at a dose of 1250 mg once daily for up to 4 weeks.
Role of NAD+ and NMN
NAD+ is involved in various redox reactions in energy-generating pathways and plays a role in DNA repair, gene regulation, protein modifications, and circadian rhythms. Age-related decline in NAD+ levels is associated with diseases such as Cockayne syndrome. Maintaining intracellular NAD+ levels may prevent and treat these diseases. However, direct administration of NAD+ does not efficiently increase intracellular levels, so precursors like NMN and NR are used instead. NMN and NR supplementation have shown efficacy in increasing NAD+ levels and improving lifespan and age-related decline in various organisms, including rodents, nematodes, and fruit flies. They also have potential therapeutic effects in the treatment of COVID-19.
NMN Safety in Human Clinical Trials
Human clinical trials have reported the safety and efficacy of NMN in improving glucose metabolism and aerobic exercise capacity. However, the safety of repeated daily oral administration of ≥1000 mg of NMN has not been studied. This study aimed to fill that gap by evaluating the safety of administering 1250 mg of NMN once daily for up to 4 weeks in healthy adults.
Study Design and Participants
The study design was randomized, double-blind, placebo-controlled, and parallel-group. The participants included 31 healthy adult men and women aged 20-65 years. The participants were randomly assigned to either the placebo or NMN group. Compliance with the study instructions was high, and the consumption rate of the test foods was nearly 99% in both groups. The study conducted various hematological, clinical biochemical, body composition and vital sign, and urinalysis tests to assess safety parameters. Adverse events were monitored throughout the study period.
The study found that oral administration of 1250 mg of NMN did not result in significant changes in the measured clinical parameters, and no severe adverse events were observed. The Ames test showed that NMN did not induce mutagenicity. The study concluded that NMN intake at a dose of 1250 mg once daily for up to 4 weeks is safe and well-tolerated in healthy adults. These findings are consistent with previous studies that have demonstrated the safety of NMN in human subjects.
In conclusion, NMN supplementation appears to be a safe option for maintaining NAD+ levels in healthy adults. Oral administration of NMN at doses up to 1250 mg once daily for 4 weeks did not have adverse effects on body composition or renal function. However, further studies are needed to confirm the bioavailability and disposition of NMN metabolites and to conduct more comprehensive safety assessments.
Title of paper: Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women
Author(s): Fukamizu Y, Uchida Y, Shigekawa A, Sato T, Kosaka H, Sakurai T.
Year published: 2022
Published in: Sci Rep
Original article can be found here.