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, recently reported in the June 2012 issue of the journal, Cell Metabolism, reveal
that high doses of the vitamin precursor, nicotinamide
riboside (NR) — a cousin of niacin — prevent obesity in mice that are fed a
fatty diet, and also increase muscle performance, improve energy expenditure
and prevent diabetes development, all without side effects.
The
Swiss researchers, led by Dr. Johan Auwerx, performed the mouse experiments,
while the ability to give the animals sufficient doses of NR was made possible
by Weill Cornell Medical College researchers, who played key roles in
uncovering the biological story of NR.
"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 Medical College.
Dr.
Sauve is the pharmacologist and organic chemist who has invented a simple
method for efficiently synthesizing NR in large scale. He was first to show
that NR increases nicotinamide adenine dinucleotide (NAD) levels in mammalian
cells. NAD is a central player in energy metabolism. He has pioneered research
into the compound, and he is a leader in investigating how NAD can signal
adaptation in cells and in physiology.
"The
research also suggests that the effects of NR could be even broader," Dr.
Sauve says. "The bottom line is that NR improves the function of
mitochondria, the cell's energy factories. Mitochondrial decline is the
hallmark of many diseases associated with aging, such as cancer and
neurodegeneration, and NR supplementation boosts mitochondrial
functioning."
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 a Stanford researcher and 1959 Nobel Laureate, Arthur
Kornberg. 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
allows sugars, fats, and proteins to be converted into energy. Dr. Sauve's
research provided the first evidence that NR enhances NAD levels in the
mitochondria in mammalian cells in culture. These findings are published in the
current study. These cell-based observations 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.
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," he says. His laboratory is also widely
recognized for developing an expertise in the measurement of NAD metabolism in
cell tissues.
With
this compound, the Swiss researchers found that mice on a high-fat diet
supplemented with NR gained significantly less weight (60 percent) than mice
fed the same diet without NR, even though the mice supplemented with NR ate the
same amount of food as mice on the high fat diet not treated with NR. They had
improved energy. They were in better shape than the untreated mice, with
significantly better endurance and stronger muscles.
Additionally,
none of the treated mice developed diabetes, as seen in the untreated mice on
the high fat diet. And when fed a normal diet, NR treated mice had improved
sensitivity to insulin. The NR treated mice also showed lower cholesterol
levels. All of these benefits came without toxicity.
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," he says.
Provided
by New
York- Presbyterian Hospital
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