Nicotinamide mononucleotide (“NMN” and “β-NMN”) is a nucleotide derived from ribose and nicotinamide. Niacinamide (nicotinamide,) is a derivative of vitamin B3, also known as niacin.) As a biochemical precursor of NAD+, it may be useful in the prevention of pellagra.
Its precursor, niacin, is found in a variety of nutritional sources: peanuts, mushrooms (portobello, grilled), avocados, green peas (fresh), and certain fish and animal meats.
In studies on mice, NMN has shown to reverse age-related arterial dysfunction by decreasing oxidative stress. A long-term study indicates that NMN can slow down the physiologic decline in ageing mice. As a result, the older mice in the study have metabolism and energy levels resembling those of younger mice, with extended life spans. However, NMN did not show similar beneficial effects in young mice.
The anti-aging properties is being tested on humans in Japan.
The researchers found a variety of beneficial effects of NMN supplementation, including in skeletal muscle, liver function, bone density, eye function, insulin sensitivity, immune function, body weight and physical activity levels. But these benefits were seen exclusively in older mice.
“When we give NMN to the young mice, they do not become healthier young mice,” Yoshino said. “NMN supplementation has no effect in the young mice because they are still making plenty of their own NMN. We suspect that the increase in inflammation that happens with aging reduces the body’s ability to make NMN and, by extension, NAD.”
In skeletal muscle, the investigators — including the study’s first author, Kathryn Mills, the research supervisor in Imai’s lab — found that NMN administration helps energy metabolism by improving the function of mitochondria, which operate as cellular power plants. They also found that mice given NMN gained less weight with aging even as they consumed more food, likely because their boosted metabolism generated more energy for physical activity. The researchers also found better function of the mouse retina with NMN supplementation, as well as increased tear production, which is often lost with aging. They also found improved insulin sensitivity in the older mice receiving NMN, and this difference remained significant even when they corrected for differences in body weight.
In a paper published earlier this year in Cell Reports, Yoshino and his colleagues revealed more details of how NAD works in influencing glucose metabolism and the body’s fat tissue. In that study, the mice had a defect in the ability to manufacture NAD only in the body’s fat tissue. The rest of their tissues and organs were normal.
“Even though NAD synthesis was stopped only in the fat tissue, we saw metabolic dysfunction throughout the body, including the skeletal muscle, the heart muscle, the liver and in measures of the blood lipids,” Yoshino said. “When we gave NMN to these mice, these dysfunctions were reversed. That means NAD in adipose tissue is a critical regulator of whole body metabolism.”
Added Imai, “This is important because Jun showed that if you mess up NAD synthesis only in fat tissue, you see insulin resistance everywhere. Adipose tissue must be doing something remarkable to control whole body insulin sensitivity.”
During the long-term NMN study in healthy mice, Imai also said they monitored the animals for any potential increase in cancer development as a result of NMN administration.
“Some tumor cells are known to have a higher capability to synthesize NAD, so we were concerned that giving NMN might increase cancer incidence,” Imai said. “But we have not seen any differences in cancer rates between the groups.”
The phase 1 trial in Japan is using NMN manufactured by Oriental Yeast Co., which also provided the NMN used in these mouse studies. Outside of this clinical trial, high-grade NMN for human consumption is not commercially available. But there’s always broccoli.