So far, human trials have demonstrated the safety of nicotinamide mononucleotide (NMN), as well as its enhancement of physical function and insulin sensitivity.
NMN, a precursor to the essential, longevity-promoting molecule nicotinamide adenine dinucleotide (NAD+), has been under FDA review since November 2022.
Along these lines, the FDA concluded that “NMN was authorized for investigational use as a new drug (before it was legally marketed in supplements) and was the subject of numerous established and published clinical studies. Therefore, this finding excludes nicotinamide mononucleotide as a dietary supplement promotion of.
Even so, sales of NMN continued, and the FDA did not implement their decision. Those who continue to purchase and consume nicotinamide mononucleotide despite the FDA’s ruling, or others who are awaiting a prescription for NMN, may be wondering what published trials of nicotinamide mononucleotide say about its safety and effectiveness as an anti-aging supplement.
Published in Advances in Nutrition, Yang and colleagues from Hangzhou Normal University in China reviewed the currently published human trials of NMN, taking a closer look at its safety and efficacy against physiological deterioration during aging.
NMN is safe and can enhance the physical fitness, function and metabolism of the elderly
Based on human trials, nicotinamide mononucleotide appears to confer physical and metabolic benefits in older adults. Even so, the researchers found that it’s unclear whether many of NMN’s benefits against organ degeneration in older rodents apply to aging humans.
Analysis of existing data from human trials of nicotinamide mononucleotide shows promise as an anti-aging treatment, but suggests human trial studies have a long way to go before concluding whether NMN’s plethora of benefits on aging translate to humans in rodents.
“Existing human clinical trials indicate that oral administration of NMN is generally safe, and although only a limited number of indicators have been studied, the results suggest that nicotinamide mononucleotide has potential as an anti-aging agent,” Yang and colleagues said.
As NAD+ levels decline with age, researchers hypothesized that increasing its levels with precursors such as NMN could protect adults against age-related organ degeneration.
As a result, a large number of people have started supplementing nicotinamide mononucleotide and this number is expected to grow in the coming years, with the global NMN market expected to reach US$385.7 million by 2027, up from US$252.7 million in 2020.
With a large population consuming nicotinamide mononucleotide, perhaps the most important aspect of this phenomenon is the safety of NMN.
The first study to evaluate the safety of NMN came from Keio University in Japan in 2016.
The short-term study included male participants who consumed 100, 250 or 500 mg of nicotinamide mononucleotide in the morning. The researchers monitored them for the next five hours.
The findings showed no harm in blood pressure, heart rate, oxygen saturation or body temperature. Based on their results, the Keio University researchers concluded that up to 500 mg of NMN is safe and well-tolerated.
Since the 2016 Keio University study, seven additional human trials have been conducted testing safety parameters at different doses. In a Harvard study, the highest oral dose of nicotinamide mononucleotide, 1,000 mg twice daily for 14 days, had no adverse side effects.
These studies indicate that NMN is safe, well-tolerated and does not induce cancer.
Rodent studies testing the aging benefits of NMN have given some positive findings related to body function, brain function and metabolism, as well as other physiological parameters.
In light of such positive findings in rodents, the researchers recently expanded their human trials to test whether NMN can improve age-related physical decline.
Along those same lines, Igarashi and colleagues found that nicotinamide mononucleotide improved muscle motility, walking speed, left-handed grip strength and frequency of standing and sitting in a chair in 30 older adults over the second period. Data from this study suggest that nicotinamide mononucleotide improves physical performance in older adults.
Another measure of NMN’s effect on physical performance comes from Liao and colleagues, who measured its effects in trained runners.
NMN significantly increases aerobic capacity in runners, as measured by blood oxygen consumption—the amount of oxygen the body uses to produce energy.
Additionally, research from Huang and colleagues showed that nicotinamide mononucleotide promoted sustained improvements from 40 to 65 years of age, as measured by a 6-minute walking endurance test.
These findings suggest that NMN can enhance the exercise ability of middle-aged and elderly people.
One study noted the effects of nicotinamide mononucleotide on prediabetes in overweight or obese postmenopausal women.
According to study results, NMN increased participants’ muscle insulin sensitivity by approximately 25% while improving insulin signaling.
These results suggest that nicotinamide mononucleotide has metabolic benefits, especially in people with prediabetes.
More evidence from human trials suggests that NMN can improve age-related hearing loss. Along these lines, Igarashi and colleagues found that nicotinamide mononucleotide supplementation improved hearing in the right ear of older men. These findings suggest that NMN can restore hearing in older adults.
The ends of chromosomes (telomeres) shorten with age, and this shortening is a biomarker of aging.
Thus, Niu and colleagues showed that supplementation with 300 mg of nicotinamide mononucleotide per day nearly doubled the length of telomeres in blood cells (peripheral blood mononuclear cells) for 90 days after treatment in men aged 40 to 60 years. These results indicate that NMN supplementation has anti-aging effects at the molecular level.
Human trial results show that NMN is safe and has benefits for physical function, insulin sensitivity, telomere length, and possibly hearing during aging.
Discover whether NMN beneficially affects multiple human organ systems during aging
Many rodent studies have shown that NMN improves brain, respiratory, liver, cardiac, immune, and reproductive function, but whether these benefits translate to humans remains to be determined.
Essentially, more human trials are needed to determine whether nicotinamide mononucleotide has the same benefits in humans as it does in rodents.
Human trials of NMN suggest that the NAD+ precursor nicotinamide mononucleotide improves physical performance, metabolism, telomere length and possibly hearing ability during aging.
Research to date also shows that using NMN is safe. The biggest remaining question concerns whether NMN has the same benefits across multiple organ systems during aging in humans that it does in rodents.
Additionally, the length of the studies, none of which lasted longer than three months, may not be long enough for nicotinamide mononucleotide to provide the fullest extent of its beneficial effects. Because the duration of these studies was so short, it’s also difficult to tell whether NMN supplements have side effects long-term. These issues warrant continued human trial research on NMN.
Although the FDA has ruled out the sale of NMN as a supplement, the molecule does not appear to pose any safety risks, and human trials to date suggest it has some anti-aging benefits.
What is In addition, the fact that NMN is being studied as a new drug supports its potential as an anti-aging molecule.
Additionally, concerns surrounding the sale and consumption of NMN as a supplement and its potential to alleviate age-related physiological decline have triggered engine problems following a ban on access to it.
