Scientists from the Ecole Polytechnique Federale de Lausanne in Switzerland noted that people with mild cognitive impairment and Alzheimer’s disease have characteristic changes in their brain mitochondria, and that mitochondrial energy output is reduced as the disease develops.
This led the researchers to investigate if NR could exert beneficial effects. NR is found naturally in trace amounts in milk and other foods, and is a more potent, no-flush version of niacin (vitamin B3). Published research has shown that NR is a potent precursor to NAD+ in the mitochondria of animals. NAD+ is an important cellular co-factor for improvement of mitochondrial performance and energy metabolism.
As organisms age, NAD+ levels drop, which leads to a decrease in mitochondrial health; this in turn leads to age-related health issues. Low NAD+ levels limit activity of a group of enzymes called sirtuins, which are believed to play a key role in longevity. NAD+ levels also can be depleted by lifestyle choices such as overeating and lack of exercise. By boosting NAD+, NR can increase mitochondrial health and induce creation of new mitochondria.
Writing in the prestigious journal Nature, the Lausanne-based scientists showed that Alzheimer’s disease (AD) mice treated with NR had lower degrees of amyloid deposits, improved mitochondrial energy production and improved memory.
“NR robustly reduced [amyloid-beta] deposits in cortex tissues of the mice with AD [… and] also increased context-dependent memory in the […] mice with AD, which was impaired compared to wild-type mice, as assessed by contextual fear conditioning, suggesting a potential positive impact on cognitive function,” wrote the researchers.
“We therefore propose that restoring or increasing mitochondrial function and proteostasis induces a conserved repair mechanism, in worms and mice, that leads to decreased [amyloid-beta] proteotoxicity and improves health- and lifespan.”
NR as a neuroprotective agent in people
Irvine, CA-based ChromaDex has been accumulating the IP surrounding NR for a couple of years, having licensed patents from Cornell University, Dartmouth College, and Washington University in St Louis.
Dr Charles Brenner, the Roy J. Carver Chair and Head of Biochemistry at the University of Iowa and the Chief Scientific Advisor of ChromaDex, is credited with discovering NR. Commenting on the new research Dr Brenner said: “Given the preclinical data and the human safety data that are coming out, we’re thrilled to have additional well vetted applications where we can test NR to improve the human condition.
“By combining novel imaging modalities with NAD metabolomics, we expect to see multiple opportunities to test NR as a neuroprotective agent in people in coming years.”
Dr. Rudolph Tanzi, the Vice-Chair of Neurology and Director of the Genetics and Aging Research Unit at Massachusetts General Hospital, the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School, and a member of the Scientific Advisory Board of ChromaDex, added: “We’ve long been fascinated by mitochondrial changes in AD pathology and have been intrigued with the possibility of a bioenergetic deficit in AD. Work published today clearly justifies testing NR in the context of mild cognitive impairment.”
Published online, doi:10.1038/nature25143
“Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity”
Authors: V. Sorrentino et al.