Animal data published in the Journal of American College of Cardiology indicated that supplementation with nicotinamide riboside (NR) was associated with stimulation of a cellular response called the “mitochondrial unfolded protein response” (UPRmt) that helps maintain mitochondrial function.
The study, conducted by principal investigators Prof. Ajay Shah and Dr Ioannis Smyrnias at Kings College London, also included a preliminary investigation of human heart tissue samples and found positive correlations between increased UPRmt activation and markers of healthy heart function.
“NR supplementation is a new and exciting intervention that merits testing in the human treatment of heart failure and other cardiac conditions,” said Prof. Shah in a press release. “These study findings showing the potential of NR to activate UPRmt are extremely encouraging and merit further research into the potential for NR to impact human cardiac health.”
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 may increase mitochondrial health and induce the creation of new mitochondria.
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.
As the science develops, more and more companies are launching products containing the ingredient.
Commenting on the new study, Rob Fried, CEO of ChromaDex, said: “There is a significant and fast-growing body of data supporting the health benefits of Niagen and our consumer product Tru Niagen. This important study underscores the role that Niagen may play in human heart health and we look forward to further research.”
Nestlé Health Science has partnered with both ChromaDex and Swiss company Amazentis in recent months to bring consumer products, including dietary supplements, to select markets around the world based on their nicotinamide riboside and urolithin A ingredients, respectively. Both ingredients have the potential to improve mitochondrial function and are supported by growing portfolios of scientific support.
The new study looked at the response of cultured cardiac myocytes to different stresses in vitro, as well as how mice responded to chronic pressure overload, which can lead to heart failure.
Mitochondria play a vital role for heart function by generating ATP to support the contraction and relaxation of the heart muscle. “Mitochondrial dysfunction is a central feature of heart failure by contributing to energetic dysfunction, oxidative stress, calcium dysregulation, and cardiomyocyte death, and is considered a potential therapeutic target,” explained the researchers
The results from the in vitro and mouse studies showed that stress led to a short-lived induction of UPRmt.
By boosting UPRmt with NR “significantly mitigated the reductions in mitochondrial oxygen consumption induced by these stresses”, said the researchers.
“Enhancement of the UPRmt ameliorates mitochondrial and contractile dysfunction, suggesting that it may serve an important protective role in the stressed heart,” concluded the researhcers.
Speaking at the International Conference on the Science of Botanicals at the University of Mississippi this week, Frank Jaksch, co-founder of ChromaDex and executive chairman of the board, explained that TruNiagen is very different to other vitamin B3 forms because of the ribose attachment.
The company is working with over 160 research institutions around the world, which represents over $50 million of research paid for by third parties, he said, and this includes 33 ongoing clinical trials.
Jaksch noted that the ingredient is supported by two successful NDI notifications (NDIN 882 in 2015 and NDIN 1062 in 2018), as well as a successful GRAS notification (GRN 635).
ChromaDex is now pursuing reg approval for Niagen in EU, Australia, Japan, and several other countries, he said.
Source: Journal of American College of Cardiology
Volume 73, Issue 14, April 2019, doi: 10.1016/j.jacc.2018.12.087
“Cardioprotective Effect of the Mitochondrial Unfolded Protein Response During Chronic Pressure Overload”
Authors: I. Smyrnias et al.