NMN and NR: How These NAD+ Precursors Measure Up

NR is often thought of as the most efficient precursor to NAD+, but its cousin molecule NMN is raising eyebrows as the new kid https://www.kiva.org/lender/elysiumhealth3 on the block in the field of aging.

Moving into a new home is never easy. Just because a large bed can fit inside a bedroom doesn’t mean it’ll fit through the door of the room. So it’s typical for beds to come in parts that need to be disassembled to make it through a door and then reassembled once inside.

The same can be said for nicotinamide mononucleotide, a molecule called NMN for short. NMN is a precursor to NAD+, or nicotinamide adenine dinucleotide, meaning it becomes NAD+ through a series of chemical transformations. NAD+ is a coenzyme that living things cannot survive without and is critical for everything from energy and metabolism and even sleep, but levels of NAD+ naturally fall with age, making it — and NMN, as a result — crucial to the science of aging.

However, NMN is like a large bed that movers are trying to get through a door: It doesn’t enter the cell easily. One way for NMN to enter the cell is for it to chemically transform into another molecule (called nicotinamide riboside, or NR) before it can enter the cell. NR has earned a name for itself as the ultimate precursor to NAD+ and can enter the cell as is. NMN, meanwhile, sometimes becomes NR before entering the cell, where it chemically transforms back to NMN and then ultimately becomes NAD+.

We've learned that NR leads to NAD+ and that it also has its own pathway that bypasses various steps other NAD+ precursors have to take. In early 2019, though, new research revealed NMN might only have to become NR for certain cell types, as NMN can enter cells in the small intestine of mice. It’s unclear how this will translate to humans, if at all, but it’s teed up NMN as the newer kid on the block of aging research, making many wonder: How does it stack up against NR?

NR vs NMN Molecule

Pitting NR and NMN against each other is, for now, somewhat of a moot point because the two molecules have never been studied side by side in humans. The biggest, and most obvious, difference between NMN and NR is size. NMN is simply larger than NR, meaning it often needs to be broken down to fit into the cell. NR, when compared to other NAD+ precursors (like nicotinic acid or nicotinamide) reigns supreme in efficiency.

Nmn Pathways Graph2

But give NMN a new door, one it can fit through, and it’s a whole new game. This is where cellular transporters come into play. Transporters are proteins that are doors on the cell; they allow molecules to enter the cell without needing to chemically transform.

The latest research from Shin-ichiro Imai, M.D., Ph.D., a professor of developmental biology at Washington University in St. Louis, identified a transporter that allows NMN to get into the cell without converting to NR. The catch? The transporter is only on cells located in the gut of mice and only works in the presence of sodium ions. NR, however, has been shown to enter cells in the liver, muscle, and brain tissue of mouse models. (Additional research is needed to confirm a similar effect in humans.) But again, the two have never been matched up against each other in a way that can truly identify one as superior to the other.

Why We Need NR and NMN

So you might be wondering: Why should I care? What does it matter that these molecules get into the cell a certain way and how they do it? NR and NMN are both beneficial because they elevate levels of NAD+, which decline with age. NAD+ is vital to metabolism, turning nutrients into energy, and it also activates sirtuins, a set of proteins that regulate longevity. We all get NAD+ in our bodies thanks to our diet, by consuming foods with NAD+ precursors in them. While NR and NMN can be found in trace amounts in various foods, though, one can’t eat enough of anything to boost NAD+ levels back to youthful levels. As a result, supplementing with an NAD+ precursor can help mitigate the decline.

Supplementing NR and NMN could provide other myriad benefits as a result of boosting NAD+. NR supplementation in mice, Elysium for example, has proven beneficial for things like mitochondrial function. And NMN supplementation in mice has shown improved blood flow and endurance as well as other age-associated physiological decline like low energy and weight gain. Additional research is needed to confirm similar effects in humans.

At the end of the day, though, what we know is that when compared to other precursors, NR is the most efficient of the bunch. The latest research on NMN could prime it to be the next great vitamin B3, but for now, more research in humans is needed to better understand how beneficial it could be and how it might stack up against NR. One possibility is that each precursor could provide varying benefits depending on the target, especially if transporters, like the recently discovered one in the gut, are only available in specific cells in the body.

For now, there are a lot of unknowns about which doors may open for these precursors in the future, and what they could open up to, which only makes the field of aging research more exciting.