Data from the study, performed in the laboratory of Dr Charles Brenner at the University of Iowa, also supported the safety profile of the ingredient, which is a no-flush version of niacin (vitamin B3).
“The results of this study constitute a significant milestone in the translation of NR technologies as it is first time an increase in NAD+ in humans has been demonstrated through NR supplementation,” said Dr Brenner. “As noted in numerous scientific studies, the potential health and therapeutic benefits of NR as a precursor to NAD+ are significant. The results of this clinical study should encourage more studies and research regarding the possible health benefits of NR in humans.”
The new human data was called a “landmark result” by Frank Jaksch, CEO of ChromaDex, and a “significant bridge between the numerous animal studies previously conducted that have demonstrated not only an increase in NAD+, but also a broad range of therapeutic benefits.
“Dysfunctional cellular energy metabolism in mitochondria is increasingly implicated in diseases of aging, autoimmune diseases, muscle wasting, neuropathies and other conditions, and this study opens the door to the development of both consumer products and pharmaceuticals addressing these conditions.”
Nobel Laureate Dr. Roger Kornberg, who chairs ChromaDex’s Scientific Advisory Board, commented, “Demonstrating that NR is an effective precursor to increase NAD+ in humans has significant positive implications and may be a cornerstone to developing solutions to delay or reverse the effects of aging, obesity and disease.”
NAD+, mitochondria and aging
It’s already well known that the function of mitochondria declines with age, while aging is a known risk factor for a number of common age-related and neurodegenerative disorders. This led to the proposition that secondary mitochondrial dysfunction may lead to degenerative diseases.
A role for oxidative stress has been proposed to promote mitochondrial dysfunction, leading some researchers to examine if antioxidants such as CoQ10, and vitamins C and E may play a role.
Another approach has been to raise levels of co-enzyme nicotinamide adenine dinucleotide (NAD+) in the mitochondria, which is an important cellular co-factor for improvement of mitochondrial performance and energy metabolism.
David Sinclair from Harvard University, who did so much to boost the anti-aging potential of resveratrol into the mainstream, recently published data from a mouse study in Cell (2013, Vol. 155, pp. 1625-1638, doi: 10.1016/j.cell.2013.11.037), which concluded that, “raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner”. SIRT1 is a cellular protein that plays a major role in mitochondrial biogenesis, glucose regulation and protection against age-related disease.
This has led scientists to look at ways to boost NAD+. NAD+ can be made from tryptophan in a biological process that involves about eight steps. However, NR is a precursor to NAD+ in the mitochondria of animals via a two-step process, making for a more efficient and potent NAD+ source.
Results of a mouse study conducted by the National Institutes of Health (NIH) in collaboration with ChromaDex indicated that (NR) was effective at restoring NAD+ levels in mitochondria and rescuing phenotypes associated with a devastating accelerated aging disease known as Cockayne Syndrome (Cell Metabolism , Nov 2014, Vol. 20, pp. 840-855) The researchers concluded that NR showed promise as a potential therapy for the disease, as well as for other age-related neurodegenerative conditions.
The study also established an effective dose range for NR in humans, said ChromaDex in a statement. “We got statistically significant results for the two lowest doses used in the study, which was great news for us as it supports the dose range of the products in the market,” Jaksch told NutraIngredients-USA.
The full results of the study will be submitted for peer review in the scientific literature, said the company.
In the supplement space, nicotinamide riboside is commercialized by ChromaDex, which has been accumulating the IP surrounding the ingredient for a couple of years, having licensed patents from Cornell University, Dartmouth College, and Washington University in St Louis.
The Irvine, CA-based company has signed deals with a number of supplement manufacturers to get its Niagen-branded ingredient into finished products, including High Performance Nutrition’s (HPN) N(R) product to support neuroprotection in contact sports, Thorne Research for the healthcare-practitioner channel, and 5LINX for the use of Niagen in dietary supplements exclusively in the network marketing sales channel in the United States, Canada and Philippines.
Numerous academic institutions are researching the potential health benefits of the ingredient, including Scripps, the Mayo Clinic, ULB Brussels, Queen’s University Belfast, Cornell, Harvard, MIT, and Iowa, with the company in discussions with more.
Source: Cell Metabolism
Volume 20, Issue 5, Pages 840-855, doi: 10.1016/j.cmet.2014.10.005
“A High-Fat Diet and NAD+ Activate Sirt1 to Rescue Premature Aging in Cockayne Syndrome”
Authors: M. Scheibye-Knudsen, S.J. Mitchell, E.F. Fang, et al.