Science 101

What Is Nicotinamide Riboside?

This form of Vitamin B could be the key to helping you live healthier for longer — here’s why.

Nr 1500X1000 V7

When you’re on your way to a new destination and you open up your phone’s GPS, a few options pop up. There are routes that avoid highways, traffic, walking, and train transfers. But there’s always the one route that reigns supreme, that gets you to your destination and makes the best use of your time and energy. It’s nonsensical to go out of your way. The same goes for your health.

Enter nicotinamide riboside, a form of Vitamin B that is the most efficient route to NAD+, or nicotinamide adenine dinucleotide, a coenzyme so crucial to energy, metabolism, mitochondrial function, and the nervous system that living things cannot survive without it. Levels of NAD+ naturally fall as we get older, and researchers now suspect that this decrease may contribute to deteriorating health with age, says Joseph A. Baur, PhD, an associate professor of physiology at the University of Pennsylvania Perelman School of Medicine, who studies the basic mechanisms that lead to aging.

Nicotinamide riboside is often called NR for short, and it’s a precursor to NAD+, meaning it's the raw material from which your body makes NAD+ through a series of chemical transformations.  But not much was known about exactly what NR did in the body until 2004, when scientists discovered that, not only is NR a precursor to NAD+ production in the body, it’s even more efficient than other NAD+ precursors.

A more efficient way to make the very molecule that keeps you healthier for longer prompted scientists to research NR more carefully and, specifically, to see how we could get more of it.

How Nicotinamide Riboside Works

NR is a vitamin, an organic compound that our bodies need to complete biological functions but that we must get through diet. There are eight kinds of Vitamin Bs, and NR is a Vitamin B3 found in small amounts in foods like dairy products. NR is one of a few variations of B3; others include nicotinamide and nicotinic acid (also called niacin).

These forms of Vitamin B3 might sound familiar. You may even recognize the word ‘niacin’ from packaged foods or flours. That’s because B3 is so important to human health that governments mandate it’s in our food. In 1940, the U.S. recommended the fortification of foods with a form of B3 in order to stave off a fatal disease called pellagra. Now, there’s international legislation for similar fortification in rice and flours.  

“Nicotinamide or other vitamin B3 forms can go through multiple well-characterized reactions to get to NAD+, but what changed was that, in the early 2000s, it was recognized that an alternative route for nicotinamide riboside route existed that is less energetically costly,” Baur says.

This route essentially allows NR to become NAD+ by bypassing a step other precursors must go through. As the science world was learning about NR’s efficiencies, aging researchers were starting to identify low levels of NAD+ as a factor in the aging process. These two notions triggered the idea of NR supplementation.

“In terms of timing, it was kind of a happy coincidence that the ability of NR to serve as a precursor was being recognized at the same time that people were realizing that boosting  NAD+ might be a good idea,” Baur says.

Nr Celldiagrams

Nicotinamide Riboside for Health and Aging

We know that NAD+ levels decline with age, but it’s not clear exactly why NAD+ declines, though some scientists hypothesize it could be related to the overactivity of the NAD+-consuming enzyme CD38.

Still, it’s yet to be known whether NR yields more NAD+ or even if it becomes NAD+ faster than other precursors. However, it is thought to be the most efficient precursor, using less energy in the body, and giving the body more energy to use elsewhere.

Mmn Nadlevels Wrap

“There's also a theoretical argument that with nicotinamide riboside, you can boost NAD+ levels higher than would be possible starting from nicotinamide or other precursors,” Baur says. “This is because the enzyme that NR bypasses—called nicotinamide phosphoribosyltransferase—is subject to inhibition by NAD+. This inherently limits how much NAD+ can be made from nicotinamide, but using NR bypasses the inhibited step.”

2016 study compared NR, nicotinamide, and nicotinic acid supplementation in mice, with NR elevating NAD+ “distinctly with respect to other vitamins….indicating that NR drives greater NAD+-consuming activities.” And a 2018 study found similar results from NR supplementation.  

The initial approach with NR supplementation was to boost NAD+ levels in aging and diseased states, when NAD+ levels are known to be lower. But it has proven to be even more promising.

“The thought was that you could supplement with NAD+ precursors as a sort of rescue,” Baur says. “But the series of successes over the last few years have just been showing that in animal models, NR really does seem to have a therapeutic effect when NAD+ is deficient, and in some cases, even in animal models where there’s not really an obvious NAD+ deficiency,” Baur says.

For example, a 2014 study on mice with mitochondrial myopathy showed how NR supplementation works to increase NAD+ levels, even on younger mice without an NAD+ decificit.

The field is keeping a close eye on the vitamin, with human clinical trials for NR supplementation for NAD+ in the works for health conditions like mitochondrial disease and congestive heart failure.

“I think it’s a very exciting time for the field as human studies are in progress in the hopes of providing more concrete support for some of the benefits that have been seen in animal models,” Baur says. He’s hopeful it won’t be long either, with many human trials expected to report in the coming year.

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