[Oct. 31, 2023: Marina Affo, University of Delaware]
Christopher Martens, director of the Delaware Center for Cognitive Aging Research, is leading a study into whether nicotinamide riboside (NR) improves memory and brain blood flow in older adults with mild cognitive impairment. (CREDIT: University of Delaware)
For the first time, a researcher at the University of Delaware College of Health Sciences in collaboration with a team at the National Institute on Aging, a division of the National Institutes of Health, has determined that the naturally occurring dietary supplement, nicotinamide riboside (NR), can enter the brain.
The discovery was made by Christopher Martens, assistant professor of kinesiology and applied physiology and director of the Delaware Center for Cognitive Aging Research, and Dr. Dimitrios Kapogiannis, a senior investigator at the National Institute on Aging. The finding is significant because it supports the idea that NR, upon reaching the brain, can alter the metabolism of relevant biological pathways involved in neurodegenerative diseases like Alzheimer’s. Their work, supported by an NIH grant, and in part by the Intramural Research Program of the NIH National Institute on Aging, was recently published in the journal Aging Cell.
“NAD+ is gradually lost as we get older or develop chronic diseases. Loss of NAD+ is linked to obesity and other negative lifestyle habits like smoking,” Martens said. “Because more NAD+ is needed to counteract those negative consequences, it’s more likely to be depleted in the face of negative lifestyle habits.”
Martens has been studying the compound since he was a postdoctoral fellow at the University of Colorado Boulder. In an initial study, he found that levels of NAD+ could be boosted in the blood if people ingested NR, but it was not clear if it could reach other tissues in the body.
“We had some preliminary signs of efficacy, including lower blood pressure in people who had high blood pressure to begin with,” he said. “But until now, it was unknown whether NR reached targeted organs like the brain to have a real therapeutic effect.”
Christopher Martens, assistant professor of kinesiology and applied physiology and director of the Delaware Center for Cognitive Aging Research, works with blood samples as part of his groundbreaking Alzheimer’s research. (CREDIT: University of Delaware)
“Each vesicle has a unique molecular signature on its surface, including proteins that give you clues about its origin,” Martens said. “In our case, we selected vesicles that carry markers that are characteristic of neurons, and so we have confidence that the NAD+ we measured in them reflects what happens in the neurons, and by extension the brain.”
NAD+ and NADH concentrations in NEVs and change–change correlations with insulin signaling proteins. (a) Concentration of NAD+ after 6 weeks of oral nicotinamide riboside (NR) supplementation was significantly higher in NEVs when compared to placebo. (CREDIT: Aging Cell)
“When NAD+ goes up in these vesicles, we see an association with some of the biomarkers of neurodegenerative disease,” Martens said. “Particularly, in people where we saw an increase in NAD+, we also saw changes in biomarkers like amyloid beta and tau, which are both related to Alzheimer’s disease,” Martens said.
Martens and Kapogiannis also found a correlation between these neurodegenerative biomarkers and change in NAD+.
Some of these blood-based biomarkers could be used down the road to determine if NAD+ depletion is a cause of Alzheimer’s and other neurodegenerative diseases. It is even possible that these types of tests could become more accessible to the population for more routine testing.
NEV biomarkers in response to oral nicotinamide riboside supplementation. (a) Alzheimer's disease biomarkers. (b) Canonical insulin/Akt signaling mediators. (CREDIT: Aging Cell)
Martens is leading a 12-week study involving NR in older adults with mild cognitive impairment. The study is supported by the Delaware Center for Cognitive Aging Research and the National Institute on Aging and is actively seeking more participants.
“They’re coming in with cognitive deficits, and as a result, are more likely to have an accumulation of some of these biomarkers in their brain, so there’s a chance we’ll see bigger reductions in these biomarkers because they have more of them in their cells,” Martens said.
Nearly all drugs on the market for patients with Alzheimer’s have only a modest effect on the symptoms but do not significantly stop the underlying progression of the disease.
“In our ongoing trial, we’re measuring markers of cognitive function and other things related to functional independence and quality of life, but we’re also hoping to gain some insight on the underlying disease process,” Martens said. “We’re hoping that the people who take the NR might have preserved function.”
After proving its efficacy, Martens and Kapogiannis will test whether increased use of NR improves cognition, and ultimately, whether it can be used to slow neurodegenerative disease progression.