For the first time, a clinical study in older men shows that taking NMN increases blood NAD+ levels and improves various indicators of muscle strength and performance.
By Brett J. Weiss
NMN raises blood NAD+ and NAD+ metabolite levels in men over 65.
Supplementing with 250 mg of NMN for 12-weeks enhances muscle function and mobility.
Animal studies have shown that administering the precursor molecule nicotinamide mononucleotide (NMN) elevates nicotinamide adenine dinucleotide (NAD+) levels. Interestingly, age-related NAD+ level reductions have been linked to cardiovascular, neurodegenerative, and metabolic diseases along with reduced muscle function, which NMN supplementation ameliorates – at least in rodents. So, how can we figure out whether NMN supplementation helps with these age-related conditions in humans?
Yamauchi and colleagues from the University of Tokyo released a non-peer reviewed journal article in Research Square showing that orally treating men over age 65 with 250 mg per day of NMN significantly increased their NAD+ levels and improved their muscle performance. Although there were no significant improvements in cognition, NMN supplementation partially improved the auditory capacity of elderly people. Findings from the study add more evidence that NMN’s healthy aging benefits seen in animals like rodents translate to humans.
“We report that supplementation of 250 mg/d NMN for 12 weeks in healthy old men was safe, well tolerated, and significantly increased NAD+ and NAD+ metabolites in whole blood,” said Yamauchi and colleagues. “Additionally, NMN induced improvements in muscle strength and performance. Thus, chronic oral administration of NMN could be an effective strategy for the prevention of age-related muscle disorders.”
Taking NMN for 12-weeks is Well-Tolerated
Before Yamauchi and colleagues tested how effective NMN is at improving muscle function in aged men, the research team wanted to know whether taking it is safe. The research team looked at common blood chemistry measurements indicative of toxicity that included liver enzymes and markers of kidney function after 12 weeks of daily NMN usage. Importantly, the lab results were unaltered in the group of men who took NMN compared to those that did not, indicating that taking NMN is well-tolerated.
Oral NMN Increases NAD+ Levels in People
Since previous research has shown that NMN supplementation increases blood NAD+ levels in aged rodents and that these higher NAD+ levels correlate with improved disease conditions, Yamauchi and colleagues tested whether NMN supplementation increases NAD+ in aged men. They found that the 12-week NMN supplementation substantially increased blood NAD+ levels, providing the first results from any study showing that NMN increases blood NAD+ in humans.
“This is the first study to report that NMN administration significantly increased NAD+ and NAD+ metabolites in the whole blood,” said Yamauchi and colleagues.
Further analyses demonstrated that NMN supplementation improves NAD+ metabolism by promoting NMN’s conversion to NAD+ and the conversion of other NMN metabolites to NAD+ through a separate NAD+ synthesis pathway (the de novo pathway). These findings open up the possibility that NMN drives NAD+ production by activating more than one NAD+ biosynthesis pathway.
(Igarashi et al., 2021 | Research Square) Taking NMN substantially increases blood NMN and NAD+ levels. Following 12 weeks of daily NMN supplementation, blood NMN levels were significantly higher (A), and NAD+ levels were substantially higher (B). These findings are the first to show that long-term NMN administration increases blood NAD+ levels in people.
NMN Enhances Muscle Performance in Men Age 65 and Older
To find out whether these NMN-induced NAD+ level elevations drive improved physical function, Yamauchi and colleagues tested muscle strength and performance. They found that NMN significantly improved several indicators of muscle strength and performance: walking speed, grip strength, and the number of times the participants could stand up from a chair in 30 seconds. Their results demonstrate that oral NMN supplementation for 12 weeks improves muscle strength and performance in healthy, older men.
(Igarashi et al., 2021 | Research Square) Taking NMN daily for 12 weeks significantly improves walking speed, grip strength, and the number of times rising from a chair in 30 seconds. Walking speed (gait speed) in meters per second substantially increased as shown in the upper left quadrant. The lower left quadrant shows that the number of times rising from a chair in 30 seconds (a 30-second chair-stand test) increased significantly after six weeks with NMN supplementation. Left hand grip strength shown in the lower right quadrant also increased significantly with NMN supplementation. These findings indicate that NMN improves muscle motility and function.
“We reported that the chronic oral supplementation of 250 mg NMN per day is safe and a well-tolerated and effective strategy for boosting NAD+ metabolism in healthy elderly men,” stated Yamauchi and colleagues. “Additionally, our exploratory analyses of the effects of NMN supplementation on physiological functions suggest the ability of NMN to improve muscle strength, which is an important clinical indicator of aging.”
How Does NMN Improve Muscle Function?
Although these findings point to long-term NMN supplementation promoting overall muscle health, there’s no evidence as to how this all works. What’s more, the study was performed in a small group of healthy older men. To be more certain of the main conclusions that NMN can boost NAD+ levels and improve muscle strength and performance in people, these studies need to be replicated in a larger group of adults that also includes women. Nevertheless, this is a step in the right direction for NMN to be considered a clinically proven anti-aging agent, as this study is a promising indicator that some of the anti-aging effects of NMN seen in rodents may extend to humans.
What’s more, the 250 mg per day dosage used has been applied in another study showing that NMN improves muscle insulin sensitivity in older women. So, 250 mg per day may give an effective dose in older people, but a study in Japanese men showed that up to 500 mg is well-tolerated. The question, therefore, remains as to whether further benefits could be seen with higher doses that are safely tolerated.
Masaki Igarashi, Masaomi Miura, Yoshiko Nakagawa-Nagahama et al. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle motility in healthy old men, 09 June 2021. DOI: 10.21203/rs.3.rs-455083/v1
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