“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.”
the reason for the uncertainty is that it is difficult to measure nad+ levels in the brain. new mri techniques provide useful information but are expensive and offer only indirect measurements. instead, the team measured nad+ by looking at extracellular vesicles — tiny particles in the blood that originated from neurons. by using these vesicles as a new form of blood-based biomarker for brain disorders, the team could essentially view a “liquid biopsy” of the brain’s neurons.
“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.”
using samples from their first initial clinical trial, they discovered that levels of nad+ increased in vesicles roughly six weeks after ingesting nr. “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.”
they also found a correlation between these neurodegenerative biomarkers and changes in nad+. “if nad+ went up a lot, there was typically a larger change in some of the disease biomarkers,” martens said. “that tells us the nad+ is not only getting into the brain but it’s likely also having some effect on its metabolism and multiple interrelated pathways.”