Tiny Vitamin In Milk Makes For Mightier Mice

Date: Jun-19-2012A new study reveals that giving mice high doses of a tiny, newly-found relative of vitamin B3 that is present naturally in milk makes them leaner, faster
and stronger and less prone to chronic illnesses like obesity and diabetes, even when fed on a high-fat diet. However, the researchers cautioned this does
not mean it would do the same for humans: only further studies would show if this was the case.

The researchers found that high doses of nicotinamide riboside (NR), which is related to niacin and other common forms of vitaim B3, stopped mice on a high
fat diet from becoming obese. It also increased muscle performance, improved energy expenditure and stopped them developing diabetes, without side
effects.

The team, from New York's Weill Cornell Medical College in the US, and École Polytechnique Fédérale de Lausanne in Switzerland, write about their findings in
the 6 June issue of the journal Cell Metabolism.

Anthony Sauve, associate professor of Pharmacology, led the Weill Cornell Medical College team. He said the study was important because:

"It shows that in animals, the use of NR offers the health benefits of a low-calorie diet and exercise - without doing either one."

Sauve said their findings also suggest that NR could have an even broader effect.

"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."

Johan Auwerx led the Swiss side of the study. He told the press that NR, which the team likens to a new vitamin, "is present in what we've all been eating since
day one".

Auwerx's team discovered NR as they were looking for new ways to boost SIRT1, a gene that is well-known for its effects on metabolism and longevity. One way
is to target the gene directly, as particular doses of the red wine ingredient resveratol appear to do.

They proposed there was a simpler way to do this: and that is to boost a co-factor of the SIRT1 protein called nicotinamide adenine dinucleotide (NAD+), which
plays a central role in energy metabolism. It allows sugars, fats, and proteins to be converted into energy.

And this is where the Weill Cornell team comes in, because Sauve had already pioneered the discovery that NR increases levels of NAD+ in mammalian cells and
is a world authority on how NAD+ can signal adaptation in cells and in phyisiology.
Studying the Effect of Nicotinamide Riboside (NR) on Nicotinamide Adenine Dinucleotide (NAD+)
In the current study, Sauve's team offers the first evidence that in cultured mamalian cells, NR enhances NAD+ levels in the mitochondria.

The cell-based observations were key to showing that NR could stimulate NAD+ in animals. And they already knew that NAD+ stimulates sirtuins, the proteins
coded by SIRT1, which help organisms adapt to low-calorie diets that can prolong lifespan in many.

Another crucial contribution Sauve made to the study was that he had already developed a simple way of synthesizing NR on a large scale, big enough to produce
the quantities researchers require to investigate its effects on health.

His lab has also developed methods to determine levels of NAD+ in cells, tissue and organelles, measures of which were a key part of the study's results.
Testing Effect of NR In Mice
With readily available doses of NR in concentrations higher than found naturally in milk, the Swiss team could then go ahead with tests in mice.

They found that mice fed on a high-fat diet supplemented with NR put on significantly less weight (60% less) than mice fed on the same diet but without the NR
supplement. This was despite the fact both sets of mice ate the same amount of food.

The researchers also found that the NR-supplemented mice had improved energy use and were in better shape that the untreated mice: they had better
endurance and stronger muscles.

Also, none of the treated mice developed diabetes, while some of the treated mice did. The NR-supplemented mice also showed lower levels of cholesterol and
there were no toxic side effects.

How Might NR Affect Humans?
Sauve warned that while this study shows high doses of NR can largely prevent the negative health consequences of a poor diet in mice, and the general
implications are encouraging:

"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."

There is "much more work to do," he added.

Auwerx added that it wouldn't be easy to get the results they saw in the mice from drinking milk. He said it was more likely, subject to human trials to replicate the
effect and sort out the details, that NR would serve as a kind of metabolism-boosting supplement.

On the other hand, he said, this milk compound ultimately offers the same benefits attributed to resveratrol, but in a different way, and conjectured  there may be many
such ingredients in our diets, that help us keep our waistlines slim, and live longer lives.

Written by Catharine Paddock PhD

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