Highlights

  • Throughout NMN human trials from the past three years, the NAD+ precursor hasn’t triggered any adverse physiological effects, confirming its safety.
  • Human trials show NMN’s beneficial effects of enhancing insulin sensitivity and increasing physical capacity in aged adults.

NMN is a precursor for the essential, pro-longevity molecule nicotinamide adenine dinucleotide (NAD+) and has come under FDA scrutiny as of November 2022. Along those lines, the FDA concluded that “NMN was authorized for investigation as a new drug (before being lawfully marketed in supplements) and was the subject of substantial clinical investigations that were instituted and made public.” As such, the finding excludes NMN’s sale as a dietary supplement. Even so, NMN sales continue without the FDA’s enforcement of their decision. Those who continue to buy and consume NMN despite the FDA’s ruling or others waiting for a prescription for NMN may wonder what published NMN trials have to say about its safety and efficacy as an anti-aging supplement.

Published in Advances in Nutrition, Yang and colleagues from Hangzhou Normal University in China review the currently published NMN human trials, taking a closer look at its safety and effectiveness against physiological deterioration during aging. According to human trials, NMN seems to confer physical and metabolic benefits in aged adults. Even so, the researchers find that it’s still unknown whether many of NMN’s benefits against organ deterioration in aged rodents apply to aging humans. Analyzing the currently available data from NMN human trials reveals NMN’s promise as an anti-aging therapeutic but suggests human trial research has a long way to go before concluding whether the plethora of NMN’s benefits against aging in rodents translates to humans.

“Existing human clinical trials suggest that oral NMN administration is generally safe, and although only a limited number of indicators were studied, the results suggest that NMN has potential as an anti-ageing agent,” said Yang and colleagues.

NMN Is Safe and Enhances Aged Adult Physical Function and Metabolism

As NAD+ levels decline with age, researchers have postulated that increasing its levels with precursors like NMN can protect adults against age-related organ deterioration. As a result, a large number of people have begun supplementing with NMN, and that number is expected to grow in the coming years raising the global NMN market from $252.7 million in 2020 to a predicted $385.7 million in 2027. With a vast swath of the population consuming NMN, perhaps the most important aspect of this phenomenon is NMN’s safety.

The first study evaluating NMN’s safety came from Keio University in Japan in 2016. The short-term study encompassed male participants consuming 100, 250, or 500 mg of NMN in the morning. Researchers monitored them for five subsequent hours. The study’s results showed no harmful effects or changes in blood pressure, heart rate, blood oxygen saturation, or body temperature. Following 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 other human trials testing safety parameters with varying doses have been conducted. The highest NMN oral dose was administered in a Harvard study using 1,000 mg twice daily for 14 days with no adverse side effects. These studies suggest that NMN is safe, well-tolerated, and doesn’t induce cancer.

(Song et al., 2023 | Advances in Nutrition) Youthful individuals have optimal NAD+ levels, which decline as they grow older, yet supplementing with the NAD+ precursor NMN has been shown to increase blood NAD+ levels.

Rodent studies testing NMN’s benefits against aging have given a number of positive findings related to physical performance, brain function, and metabolism, among other physiological parameters. Given such positive findings in rodents, researchers have recently expanded their human trials to test whether NMN improves age-related physical decline. Along those lines, Igarashi and colleagues found that NMN improves muscle motility, walking speed, left-handed grip strength and the frequency of standing and sitting down on a chair in a 30 second period in aged individuals. The study’s data suggest that NMN improves physical performance in older people.

Another study measuring NMN’s effects on physical performance came from Liao and colleagues who measured its effects on trained runners. NMN significantly improved aerobic capacity in the runners as measured by blood oxygen consumption — the amount of oxygen the body uses for energy production. Additionally, a study from Huang and colleagues showed that NMN promoted a sustained improvement in walking endurance in adults aged 40 to 65 years as measured with a six-minute walking endurance test. These findings suggest that NMN enhances exercise capacity in middle aged and older adults.

One study pointed to NMN’s benefits against prediabetes in postmenopausal women who were overweight or obese. According to the study’s findings, NMN increased the participants’ muscle insulin sensitivity by about 25% along with improvements in insulin signaling. These results suggest NMN confers metabolic benefits, especially in women with prediabetes.

More evidence from human trials suggests that NMN improves age-related hearing loss. Along those lines, Igarashi and colleagues found that supplementing with NMN improves hearing capabilities in the right ear of older men. These findings suggest that NMN may restore hearing in aged individuals.

The ends of chromosomes (telomeres) shorten with age, and this shortening serves as a biological marker of aging. As such, Niu and colleagues showed that supplementing with 300 mg of NMN per day nearly doubled telomere lengths in blood cells (peripheral blood mononuclear cells) within 90 days of treatment in men aged 40 to 60 years. These results suggest an anti-aging effect from supplementing NMN at the molecular level.

(Song et al., 2023 | Advances in Nutrition) Human trial results show NMN is safe and confers benefits to physical function, insulin sensitivity, telomere length, and possibly hearing during aging.

A number of rodent studies have shown that NMN improves brain, respiratory system, liver, heart, immune, and reproductive function, yet whether these benefits translate to humans remains to be determined. Essentially, more human trials are needed to find whether NMN confers the same benefits in humans as it does in rodents.

Finding Whether NMN Beneficially Affects Multiple Human Organ Systems During Aging

Human trials with NMN have shown that the NAD+ precursor NMN improves physical function, metabolism, telomere length, and possibly hearing capabilities during aging. Studies to date have also shown that using NMN is safe. The biggest questions that remain relate to whether NMN confers the same benefits on multiple organ systems during aging in humans as it does in rodents. Moreover, the lengths of the studies, with none lasting more than three months, may not suffice for NMN to provide its beneficial effects to the maximum extent. Due to the short durations of these studies, it’s also difficult to tell whether NMN supplementation has side effects in the long term. These issues warrant continued NMN human trial research.

Although the FDA has excluded the sale of NMN as a supplement, it doesn’t appear that the molecule poses any safety risks, and human trials to date suggest it confers some anti-aging benefits. What’s more, the fact that NMN is under investigation as a new drug supports its potential as an anti-aging molecule. Additionally, the controversy surrounding the sale and consumption of NMN as a supplement along with its potential to alleviate age-related physiological decline draw questions of the motives behind suppressing access to it.