By Kathleen Berger, Executive Producer for Science & Technology
Anti-aging therapies, procedures and products are trending. But Shin-ichiro Imai, MD, PhD, professor of developmental biology and medicine at Washington University School of Medicine in St. Louis, will tell anyone that just because something is trending, doesn’t mean it works or is worth the money.
However, Imai is investigating one aging intervention treatment based on a natural compound called NMN, nicotinamide mononucleotide.
Years ago, Imai was first to prove the success of an NMN nutraceutical in mice, as it worked safely to “slow down” signs of aging, as well as boost energy and rejuvenate metabolism.
“There are a wide variety of anti-aging effects on tissue functions and we need to figure out how many and how much can be really translated to humans,” said Imai.
Having a lab focused on basic mechanisms of aging and longevity, Imai is a leader in NMN research.
“NMN is remarkable because it really increases this essential compound NAD, nicotinamide adenine dinucleotide. And this compound NAD is required to maintain our energy and our metabolism,” said Imai. “Regulating NAD Is very important to activate enzymes called sirtuins. And sirtuins absolutely require this NAD compound for their enzymatic activities and then regulate metabolism and eventually the process of aging and longevity.”
The remarkable beneficial effects of NMN in rodents have led several companies in Japan, China and in the U.S. to market the compound as a dietary supplement or a neutraceutical. The U.S. Food and Drug Administration is not authorized to review dietary supplement products for safety and effectiveness before they are marketed, and many people in the U.S. and around the world now take NMN despite the lack of evidence to show clinical benefits in people.
Imai is continuing his studies to determine whether a particular NMN nutraceutical tablet may one day offer a range of health benefits to the aging population. He cautions many NMN products on the market may not be safe and effective. However, Imai said there is one worth investigating.
“The company originally contacted me back in 2008,” said Imai. “And my lab and this company started collaborating together to develop the methodology to make a high quality NMN. Our lab also tested the quality and efficacy of this particular NMN in mouse models.”
Imai won’t name the company because he said he cannot endorse a company or product. But after successful animal studies, Imai is putting the product to the test in human clinical trials.
In order to investigate safety and efficacy in humans, Imai teamed up with senior investigator Samuel Klein, MD, the William H. Danforth Professor of Medicine and Nutritional Science anddirector of the Center for Human Nutrition at Washington University School of Medicine.
“We received NMN kindly from a company in Japan that we know makes a very pure form of this product. And so we know that there is very few little impurities. It’s really a pure NMN form and it’s of the highest quality of NMN.” said Klein. “This is the same NMN that Dr. Imai has used in rodent models demonstrating profound benefits in terms of therapeutic effects on health, longevity and multiple organ system functions. But it has never been tested in humans before this trial.”
So the team created a small human clinical trial with 25 postmenopausal women who had prediabetes, meaning they had higher than normal blood sugar levels, but the levels were not high enough to be diagnosed as having diabetes. Women were enrolled in this trial because mouse studies showed NMN had the greatest effects in female mice.
“In this study, we particularly selected participants who were postmenopausal women with prediabetes. Because studies on rodents have shown that female mice have a better response to NMN therapy than do male mice. In addition, people with prediabetes have some significant metabolic abnormalities that could potentially be ameliorated by treatment with NMN as shown in rodent models. And so this particular group we thought was ideal to test the potential metabolic benefits of NMN therapy in the first randomized clinical trial in people,” said Klein. “This was a double-blind randomized-control trial in which the participants received either placebo therapy or 250mg of NMN daily for 10 weeks and were studied before and after the intervention.”
From the study, the researchers discovered NMN improves muscle glucose metabolism.
“Improved insulin sensitivity and muscle in our participants. And what that means is that it improved the ability of insulin to stimulate glucose uptake in muscle tissue,’ said Klein. “A defect in insulin action in muscle is an important metabolic complication that’s associated with obesity that’s involved in causing prediabetes and type 2 diabetes.”
Klein says it’s encouraging how NMN improves the ability of insulin to increase glucose uptake in skeletal muscles.
“The ability of muscle to respond to insulin by enhancing its glucose uptake could improve glycemic control, meaning improving the control of blood sugar in the body. This is one early study and so these early findings support that potential concept of NMN improving blood glucose control, but we really need more and more definitive studies in the future to fully evaluate this potential.”
Ongoing research exploring anti-aging benefits of NMN is now supported by a $3.8 million grant from the U.S. Department of Defense. Imai explained how the funding is supporting a second human clinical trial. In the second trial, they increased the NMN dosage and duration. The trial has an enrollment of 60 people – 30 men and 30 women -between the ages of 50 and 75.
“A little bit higher dose and a little bit longer duration and what happens to people? That’s exactly what we are now assessing in the second clinical study,” Imai explained.
Imai said the findings from the first clinical trial give him reason to believe that NMN may one day offer clinical benefits to boost what he calls “productive aging”.
“If our second clinical trial suggest more beneficial effects of NMN in humans, then maybe it might be an interesting idea to take NMN for a longer time and see what happens to our metabolism particularly in older individuals,” said Imai.
Imai wants to find out if the daily intake of NMN could provide a person with a metabolism that’s many years younger. The idea is to increase the quality of life as people get older by providing aging intervention.
“We cannot make any clinical recommendations for people,” warned Klein. “And so this is like many things. We really need more studies in human subjects to identify the potential of NMN as a therapeutic agent both improving health, energy, metabolic function and longevity. Only time will tell.”