"The bottom line is that nicotinamide riboside improves the function of mitochondria, the cell's energy factories."
A novel form of vitamin B3 found in milk in small quantities produces remarkable health benefits in mice when high doses are administered, according to a new study conducted by researchers at Weill Cornell Medical College and the Polytechnic School in Lausanne, Switzerland.
The findings, published June 6 by Cell Metabolism, reveal that high doses of the vitamin precursor, nicotinamide riboside (NR) – a cousin of niacin:
• Prevented obesity in mice that are fed a fatty diet (reduced weight gain 60% vs those not supplemented with NR), while controlling cholesterol levels, and also
• Increased muscle performance/strength,
• Improved energy expenditure and endurance,
• Prevented the development of diabetes seen in the unsupplemented mice, and improved insulin sensitivity when the mice were fed a normal diet,
• All without side effects or toxicity.
"This study is very important. It shows that in animals, the use of NR offers the health benefits of a low-calorie diet and exercise – without doing either one," says Dr. Anthony Sauve, associate professor of Pharmacology at Weill Cornell.
The animal studies were led by Drs. Carles Canto and Johan Auwerx, at Ecole Polytechnique de Lausanne’s energy metabolism lab, and it was Dr. Sauve who invented a simple method for efficiently synthesizing NR in large scale.
• Dr. Sauve was also first to show that NR increases nicotinamide adenine dinucleotide (NAD) levels in mammalian cells. NAD is a central player in energy metabolism.
• He is a leader in investigating how NAD can signal adaptation in cells and in physiology.
• And he believes the research suggests the effects of NR can be even broader.
"The bottom line is that NR improves the function of mitochondria, the cell's energy factories,” Dr. Sauve says.
“Mitochondrial decline is the hallmark of many diseases associated with aging, such as cancer and neurodegeneration, and NR supplementation boosts mitochondrial functioning," he adds.
Trace Amounts of NR Possible in Other Foods
The Swiss researchers call NR a "hidden vitamin" that is believed to also be present in many other foods, although levels are low and difficult to measure.
Nevertheless, the effects of NR on metabolism "are nothing short of astonishing."
Got Nicotinamide Riboside?
The study depended on a series of crucial discoveries by Dr. Sauve and his laboratory colleagues.
NR, related to niacin and other common forms of vitamin B3, was first investigated more than 60 years ago by Stanford researcher Arthur Kornberg, who won a Nobel Prize in 1959 for his discovery of how DNA is assembled.
But little more was known about its effects in mammals until Dr. Sauve discovered the effect NR had in stimulating levels of NAD in mammalian cells – work he published in 2007. NAD (nicotinamide adenine dinucleotide) is a coenzyme found in all living cells that plays a key role in the energy generating citric acid cycle.
NAD allows sugars, fats, and proteins to be converted into energy. (The secret of calorie restriction’s life-extending effects?)
Dr. Sauve's research provided the first evidence that NR enhances NAD levels in the mitochondria in mammalian cells in culture. These cell-based findings, published in the current study, were key to the demonstration:
• That NR could stimulate tissue NAD levels in animals,
• And that it could stimulate NAD-dependent sirtuins, which adapt physiology to the low calorie diets that are known to extend the lifespan of many organisms.
Large-Scale Synthesizing Method Now Patented
Dr. Sauve invented a relatively simple method for efficiently synthesizing NR in large scale so that its health benefits can be studied. This methodology, which makes it possible to make NR commercially available, was patented by Cornell's Center for Technology Enterprise and Commercialization and subsequently licensed to ChromaDex Corporation.
The development of a means to synthesize NR in adequate quantities was crucial to the current research, and the Sauve lab provided methods and NR to make the study possible. In addition, the biological observations on the effects of NR on NAD levels in cells and on mitochondria were key to the study.
Finally, the Sauve laboratory has developed state of the art analytical methods to determine NAD levels in cells, tissues and organelles, and the laboratory provided several key metabolic measurements highlighted in the study.
"Our published scientific work has verified that NR is perhaps the most potent NAD enhancing agent ever identified," Dr. Sauve says.
While the new study demonstrates that high doses of NR can largely prevent the negative health consequences of a poor diet in mice, Dr. Sauve stresses that the effects of high doses of the vitamin in humans have not been evaluated. "It is important to keep in mind that the amount of NR in milk and other foods appears to be small. We don't know what effects NR would have in humans at relatively high doses," he says.
"Still, we have very encouraging evidence of benefits of NR and NAD augmentation in general from this animal study – and much more work to do."
Source: Based on Weill Cornell Medical College news release, Jun 14, 2012