So far, human trials have demonstrated the safety of nicotinamide mononucleotide (NMN), as well as its enhanced performance and insulin sensitivity.
NMN is a precursor to the essential, longevity-beneficial molecule nicotinamide adenine dinucleotide (NAD+) and has been under FDA review since November 2022. Following these lines, the FDA concluded that "NMN is authorized for study as a new drug (before it can be legally marketed in supplements) and is the subject of a large number of clinical studies that have been established and made public." Therefore, the finding excludes the marketing of NMN as a dietary supplement. Even so, sales of NMN continued, and the FDA did not enforce their decision. Those who continue to buy and consume NMN despite the FDA's ruling, or others who are waiting for a prescription for NMN, may be wondering what published NMN trials say about its safety and efficacy as an anti-aging supplement.
Published in Advances in Nutrition, Yang from Hangzhou Normal University and colleagues at the University of China reviewed the currently published NMN human trials, taking a closer look at the safety and efficacy of its physiological deterioration during aging. Based on human trials, NMN appears to confer physical and metabolic benefits on older adults. Even so, the researchers found that it is unclear whether many of the benefits of NMN can combat organ degeneration in older rodents and apply to aging humans. Analysis of available data from human trials of NMN suggests that NMN is expected to be an anti-aging force**, but suggests that human trial studies still have a long way to go before conclusions can be drawn on whether the excessive benefits of NMN for aging are translated from rodents to humans.
"Existing human clinical trials have shown that oral administration of NMN is generally safe, and although only a limited number of indicators have been studied, the results suggest that NMN has the potential to act as an anti-aging agent," Yang and colleagues said.As NAD+ levels decline with age, researchers hypothesize that increasing its levels with precursors such as NMN can protect against age-related organ degeneration. As a result, a large number of people have started to replenish NMN, and this number is expected to grow in the next few years, and the global NMN market will grow from 2$52.7 billion raised by 2020 is expected to reach $3 by 2027$85.7 billion. Having a large population consuming NMN, perhaps the most important aspect of the phenomenon is the security of NMN.
The first study to evaluate the safety of NMN came from Keio University in Japan in 2016. The short-term study consisted of male participants ingesting either morning or 500 mg of NMN. They were monitored by the investigators over the next five hours. The results of the study showed no harm to blood pressure, heart rate, oxygen saturation or body temperature. Based on their results, researchers at Keio University concluded that up to 500 mg of NMN is safe and well tolerated.
Since the 2016 Keio University study, seven other human trials have been conducted, testing safety parameters at different doses. In a Harvard study, NMN was given the highest oral dose, 1,000 mg twice daily for 14 days, with no adverse effects*** These studies showed that NMN was safe, well tolerated, and did not induce cancer.
Rodent studies testing the benefits of NMN on aging have given some positive findings related to bodily functions, brain function and metabolism, and other physiological parameters. In light of such positive findings in rodents, researchers have recently expanded their human trials to test whether NMN can improve age-related physical decline. Along those lines, Igarashi and colleagues found that NMN improved muscle movement, walking speed, left-handed grip strength and frequency of standing and sitting in chairs in the second period of 30 older adults. The data from the study suggests that NMN improves physical performance in older adults.
Another measure of NMN on physical performance came from Liao and colleagues, who measured its effects on trained runners. NMN significantly improves aerobic capacity in runners, as measured by blood oxygen consumption – the amount of oxygen the body uses to produce energy. In addition, researchers from Huang and colleagues showed that NMN promoted sustained improvement at ages 40 to 40 to 65 years, as measured by a 6-minute walking endurance test. These findings suggest that NMN can enhance exercise capacity in middle-aged and older adults.
One study noted the effects of NMN on prediabetes in postmenopausal women who were overweight or obese. According to the results of the study, NMN increased the participants' intramuscular insulin sensitivity by about 25% while improving insulin signaling. These results suggest that NMN has metabolic benefits, especially for people with prediabetes.
More evidence from human trials suggests that NMN improves age-related hearing loss. Along these lines, Igarashi and colleagues found that supplementing with NMN 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 NMN per day nearly doubled the telomere length in blood cells (peripheral blood mononuclear cells) for 90 days after 90 days in men aged 40 to 60 years**. These results suggest that NMN supplementation at the molecular level has an anti-aging effect.
Human trial results have shown that NMN is safe and has benefits for bodily function, insulin sensitivity, telomere length, and possibly hearing during aging.
Many rodent studies have shown that NMN improves brain, respiratory, liver, heart, immune, and reproductive function, but it remains to be determined whether these benefits translate to humans. Essentially, more human trials are needed to determine whether NMN has the same benefits for humans as for rodents.
Human trials of NMN have shown that the NAD+ precursor NMN improves physical function, metabolism, telomere length, and may have hearing abilities during aging. Research to date has also shown that the use of NMN is safe. The biggest question that remains has to do with whether NMN has the same benefits for multiple organ systems during the aging process in humans as it does in rodents. In addition, the length of the studies, none of which was durable for more than three months, may not be sufficient for NMN to provide its beneficial maximum effect. Due to the short duration of these studies, it is also difficult to tell if NMN supplements are *** long-term. These questions deserve to be studied in human trials 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 have shown that it has some anti-aging benefits. In addition, the fact that NMN is being studied as a new drug supports its potential as an anti-aging molecule. In addition, there has been a significant increase in the number of issues surrounding the sale and consumption of NMN as a supplement and its potential to alleviate age-related physiological decline in the wake of a ban on access to it.