May 11, 2021

Supplement improves glucose metabolism in women’s muscle

At a Glance

  • In a small trial, the muscles of women who took a supplement called nicotinamide mononucleotide for 10 weeks had improvements in their ability to process sugar.
  • More research is needed to see if the supplement can help prevent or manage diabetes in people.
Older woman using weights with a physical therapist A supplement improved insulin sensitivity in muscle and is now being tested in a larger trial. PeopleImages / E+ via Getty Images

People with diabetes have blood sugar (glucose) levels that are too high. Over time, high levels of blood glucose can damage many organs in the body. In type 2 diabetes—the most common type—the body has problems making or using the hormone insulin. The body’s ability to use insulin properly and control blood sugar levels is called insulin sensitivity.

About 13% of adults in the U.S. have diabetes. And more than 1 in 3 have prediabetes. That’s when blood sugar levels are higher than normal, but not high enough to be diagnosed as type 2 diabetes. New treatments to prevent and treat diabetes are urgently needed.

A compound in the body called nicotinamide adenine dinucleotide (NAD+), which declines with aging and obesity, is thought to play a role in healthy glucose metabolism. Another compound, nicotinamide mononucleotide (NMN), is required for the production of NAD+.

Studies have found that NMN could improve the ability of obese mice to process sugar and increase insulin sensitivity. NMN is currently marketed in the U.S. as a dietary supplement. However, no studies have tested whether it improves metabolism in people.

To fill this gap, researchers led by Dr. Samuel Klein from Washington University in St. Louis enrolled 25 postmenopausal women with prediabetes in a randomized clinical trial. Thirteen women received daily NMN supplements for 10 weeks, and 12 received placebo pills. The researchers analyzed glucose metabolism in muscles and took other measurements before and after supplementation.

The study was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute on Aging (NIA). Results were published on April 22, 2021, in Science.

After 10 weeks of treatment, NAD+ levels increased in the blood cells of women who had received NMN, but not those who took the placebo. Extra NAD+ wasn’t found in muscles after NMN treatment. However, changes in certain proteins indicated that the muscles in women who took NMN produced and used more NAD+ than those in women who took the placebo.

The ability of the muscles to use glucose in response to insulin increased by about 25% in the women who took NMN. This improvement in insulin sensitivity is similar to that seen after people lose about 10% of their body weight. No such improvement was seen in women who took the placebo.

NMN specifically affected insulin sensitivity in muscle. Other measures related to the development of diabetes remained unchanged. These included body fat, blood pressure, sugar or insulin in the bloodstream, blood lipids such as cholesterol, and insulin sensitivity of the liver.

More trials are needed to see whether NMN can help prevent or manage diabetes in people. The team is currently testing the compound in a larger trial with both women and men.

“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,” Klein says. “Normally, when a treatment improves insulin sensitivity in skeletal muscle...there also are related improvements in other markers of metabolic health, which we did not detect in our study participants.”

—by Sharon Reynolds

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References: Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Yoshino M, Yoshino J, Kayser BD, Patti G, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Science. 2021 Apr 22:eabe9985. doi: 10.1126/science.abe9985. Online ahead of print. PMID: 33888596.

Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute on Aging (NIA); Tanaka Fund; Foundation for Barnes-Jewish Hospital.