Obesity and aging decrease levels of a metabolic factor found in all living cells and vital in keeping us healthy: nicotinamide adenine dinucleotide (NAD+). The bioavailability of nicotinamide mononucleotide (NMN) is the rate-limiting factor in the production of NAD+.

In a small-scale clinical trial (NCT03151239) and the first clinical trial on NMN, scientists at the Center for Human Nutrition at the Washington University School of Medicine found NMN supplementation enhances the ability of insulin to increase glucose uptake in skeletal muscles and improves expression of genes involved in muscle structure and remodeling in postmenopausal prediabetic women who are overweight or obese.

Glucose uptake by skeletal muscles is often impaired in individuals with obesity, prediabetes or type 2 diabetes. Insulin enhances glucose uptake and storage in muscle, so people who are resistant to insulin are at increased risk for developing type 2 diabetes.

During the 10-week treatment period, 13 women received 250 mg of NMN orally every day and 12 received an inactive placebo every day over the same period.

The findings are reported in an article in the journal Science titled “Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.”

“This is one step toward the development of an anti-aging intervention, though more research is needed to fully understand the cellular mechanisms responsible for the effects observed in skeletal muscle in people,” says co-investigator Shin-ichiro Imai, MD, PhD, professor of developmental biology and medicine.

“Although our study shows a beneficial effect of NMN in skeletal muscle, it is premature to make any clinical recommendations based on the results from our study,” says Samuel Klein, MD, the William H. Danforth Professor of Medicine and Nutritional Science and director of the Center for Human Nutrition and senior investigator on the study. “Normally, when a treatment improves insulin sensitivity in skeletal muscle, as is observed with weight loss or some diabetes medications, there also are related improvements in other markers of metabolic health, which we did not detect in our study participants.”

Earlier studies conducted in mice have shown NMN supplementation slows and ameliorates the effects of age-related decline in levels of NAD, such as insulin resistance and tissue dysfunction.

This randomized, placebo-controlled clinical trial is an attempt to replicate in humans, preclinical rodent results that showed NMN has several benefits, particularly in female mice. This study looks at the metabolic effects of NMN administration and shows that the treatment does not lower blood glucose or blood pressure, improve blood lipid profile, increase insulin sensitivity in the liver, reduce fat in the liver or decrease circulating markers of inflammation, as seen in earlier studies on rodent models.

Based on the benefits of NMN in rodents several companies market NMN as a dietary supplement or a nutraceutical. The U.S. Food and Drug Administration does not review dietary supplement products for safety and effectiveness before they are marketed. The researchers of the study caution that more studies are needed to determine whether NMN has beneficial effects in the prevention or management of prediabetes or diabetes in people.

Klein and Imai are continuing to evaluate NMN in another trial involving women and men.

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