The study, which used ChromaDex’s Niagen branded form of NR, was conducted on mice that were altered to mimic the effect of aging. NR has been shown to be a precursor of NAD+ (nicotinamide adenine dinucleotide), which is a key component of the cellular energy pathway. Researchers at the University of Pennsylvania said that lower levels of NAD are postulated as one of the consequences of aging, and can make aged mice more susceptible to frailty and metabolic diseases. Less NAD+ in the tissues detracts from essential functions such as metabolism and DNA repair.
“We know that the amount of NAD+ in muscles declines as we age. But what was completely unknown before this study was whether that decline had any functional consequences,” said lead author David W Frederick of Penn. The researchers concluded that the level of NAD+ in muscle cells is important to muscle function, and that it may be possible to restore muscle function lost due to aging by replenishing NAD+ levels.
NR restores muscle function
To test NR’s effect on this process, the researchers at Penn’s Perelman School of Medicine, together with collaborators at Princeton University and Queens University, Belfast, bred a line of mice that had less of an enzyme important in the NAD synthesis pathway. The researchers found they when they depressed NAD+ levels to about 15% of normal baseline, the mice were still functional, which points to the metabolic flexibility of skeletal muscle. But over time, the mice showed decreased muscle strength and decreased endurance on a treadmill test. The test was important in establishing the lower limit of NAD+ that must be present for normal muscle function, Frederick said.
Once loss of lean mass and endurance was apparent in the knockout mice, the NAD+ levels were then replenished by feeding water enriched with NR, an NAD+ precursor (or booster). After just one week, the knockout mice experienced a complete restoration of exercise capacity.
Frank Jaksch, CEO of ChromaDex, said the study builds upon work the company has already done on the ingredient and feeds into clinical trials that are ongoing. While this result is in only one type of mouse, Jaksch said he’s confident that it will be borne out in later human trials.
“The animal studies should be predictive because energy metabolism in lower mammals is pretty analogous to humans,” Jaksch told NutraIngredients-USA.
The human study that is closest to being finished focuses on the similar endpoints in humans, Jaksch said (without the deliberate depression of the NAD+ pathway enzyme, of course).
“We’re focusing on a pharmacodynamic study,” he said. “We’re testing different dosages, 100mg, 300mg and one gram, and we’re monitoring the effect on NAD+ over a three week period,” he said.
NR’s effect on NAD+ was part of the story from the start of ChromaDex’s involvement, as it started acquiring patent rights to the ingredients in 2012. As evidence for the ingredient continues to come in, Jaksch said the view of the ingredient has expanded beyond a simple anti aging message.
“When we started the licensing process we had our own list of why we felt this ingredient was important. Our main focus was why it was effective on maintaing NAD+ levels. But then a cardiovascular study started up at the University of Washington. And there have been cognitive related studies, that are helping to establish the link between certain neurodegenerative diseases and low NAD+ levels. If you could repair NAD+ function, you could potentially move the needle on some of those,” Jaksch said.
Source: Cell Metabolism
2016 Aug 9;24(2):269-282. doi: 10.1016/j.cmet.2016.07.005
“Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle”
Authors: Frederick, DW et al