For the first time, these researchers, in collaboration with a team from the National Institute on Aging (NIA/NIH) confirm that this natural dietary supplement, NR can enter the brain. The discovery was made by Christopher Martens, professor of kinesiology and physiology at the Delaware Center for Cognitive Aging Research, and NIA researcher Dr. Dimitrios Kapogiannis. NR, by reaching the brain, could thus modify the metabolism of the relevant biological pathways involved in neurodegenerative diseases such as Alzheimer’s disease.
NR, NAD+ and cellular and DNA repair
The researchers explain that when consumed, NR is rapidly converted to nicotinamide adenine dinucleotide (NAD+), a compound essential for cell repair and the repair of damaged DNA. We therefore find here the benefits already documented in regenerative medicine with a “boost” effect on stem cells.
NR counters an aging effect while with age, NAD+ is gradually lost, as well as in case of chronic diseases. Loss of NAD+ is also linked to obesity and other negative lifestyle factors, including smoking. Thus, higher levels of NAD+ would be required to counteract these negative consequences of aging. The same team also demonstrated that NAD+ levels can be increased by supplementation with NR. However, until then it was unknown that the compound could reach all tissues, including brain tissue, with a real therapeutic effect.
Measure the level of NAD+ in the brain in humans is a challenge. There are emerging techniques involving MRI, but they only provide an indirect measurement and are expensive and difficult to implement. The team therefore measured NAD+ directly in tiny particles called extracellular vesicles originating from neurons and circulating in the blood. These extracellular vesicles can provide advanced blood biomarkers for brain disorders and serve as a “liquid biopsy” of neurons, giving researchers insight into the molecules they contain.
- Especially since each vesicle has a unique molecular signature on its surface, including proteins that provide clues to its origin. The researchers therefore selected vesicles that carried markers characteristic of neurons, measured the NAD+ in these specific vesicles in order to obtain an evaluation, by extension, of the levels of NAD+ in the brain.
In elderly participants, the researchers note that:
- NAD+ levels gradually increase in these vesicles after 6 weeks, suggesting an association with some of the biomarkers of neurodegenerative disease;
- in participants in whom this increase in NAD+ is the most marked, changes are also observed in biomarkers such as beta-amyloid and tau protein, hallmarks of Alzheimer’s disease;
- when the NAD + increases sharply, the change in some of the biomarkers of the disease is also greater;
Taken together, these observations suggest that NAD+ not only enters the brain, but likely also has an effect on its metabolism and its multiple interrelated pathways.
Is NAD+ depletion a direct cause of Alzheimer’s disease and other neurodegenerative diseases? A study on NR in elderly people with mild cognitive impairment is underway, which should validate the benefit of increased consumption of NR in this group of patients.
While the drugs available to patients with Alzheimer’s disease have only a modest effect on symptoms and no curative effect, the authors hope for an effect of NR in maintaining cognitive function and slowing down its decline with age.
