NMN vs NR: Best Way to Increase Your NAD+ Levels (2023)

Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are both precursors to an essential molecule for metabolism– nicotinamide adenine dinucleotide (NAD+). NAD+ is a very important substance in the cells. It provides energy for cells and is also a cofactor for proteins that repair and maintain our epigenome and our DNA.

During aging, the epigenome becomes more and more dysregulated. The older we get, the less NAD+ is present in our cells. Supplementing with NAD precursors has been identified to increase NAD+ levels.

NMN and NR are both NAD precursors and are often mixed up and confused by most consumers. We will cover the essentials and explain about each of these two related compounds.
Source: Therapeutic Potential of NAD+-Boosting Molecules: The In Vivo Evidence. Cell Metabolism. Luis Rajman, etc al.

What is NMN?

NMN stands for nicotinamide mononucleotide, a molecule naturally occurring in all life forms. NMN is the direct precursor of the essential molecule nicotinamide adenine dinucleotide (NAD+) and is considered a key component to increase NAD+ levels in cells.

NMN is a precursor to NAD+, or nicotinamide adenine dinucleotide, meaning it becomes NAD+ through a series of chemical transformations. NAD+ is a critical found in every cell of your body, but levels of NAD+ naturally fall with age, making it — and NMN, as a result — crucial.

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 a highly efficient 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 whether or how this will translate to humans, if at all, but it’s teed up NMN as the newer kid on the block, making many wonder: How does it stack up against NR?

What Foods Contain NMN? NMN can be found naturally in broccoli, cabbage, cucumber, edamame and avocado.

What is NR?

Of all the NAD+ boosters - compounds which either convert directly into, or contribute in some way to the process of creating NAD+, nicotinamide riboside (NR) has been the most extensively studied - mostly in animals.

In rodent studies NR has been shown to have a variety of different effects desirable for different people looking for different things. In one study, mice who were fed a diet high in both sugar and fat in order to quickly create obesity, gained less body fat and demonstrated increased insulin sensitivity when taking an orally-administered dose of NR.

Mice receiving the same size dose of NR as the obesity study (400mg per kilo of bodyweight) were also found in another study to have reversed mitochondrial damage and increased mitochondrial biogenesis, the process through which mitochondria are created.

Finally, neurological benefits from NR supplementation were also confirmed in rodents, including neurogenesis, synaptic plasticity, and reduced beta-amyloid build up in the brain, a strong indicator of Alzheimer’s risk.

“Whether taking nicotinamide riboside will have the same effects on delaying aging or improving mitochondrial function in humans as it does in animals is unknown,”writes famed longevity expert Dr. Rhonda Patrick on her blog.

“However, when people with type 2 diabetes took a nicotinic acid derivative (an NAD+ precursor), they exhibited improvements in mitochondrial function in their skeletal muscle as well as increased NAD+ levels in their muscles”.

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. 

The molecular structures of NMN and NR are roughly the same, except NMN has an added phosphate group. This added phosphate group makes NMN a larger molecule than NR, meaning it often needs to be broken down to fit into the cell. 

NMN converts to NAD+ whereas NR must first be converted into NMN before it can be converted into NAD+.

NMN and NR Studies

Well, we know that NAD boosters have shown efficacy in plenty of cell cultures and in mouse models of human diseases. Both NR and NMN have been shown to benefit the health of elderly mice, and neither of these treatments show negative health effects, even in long-term mouse experiments—not in inflammation, senescence, or cancer models.

The side effect in a mouse? Slightly longer life, and even that’s debated.

In humans, research into the effects of NR and NMN is still gaining traction — with a few small-scale registered clinical trials completed and multiple others underway. Ultimately, no mouse study is proof these molecules will work or will fail in humans to treat a disease or affect the lace of aging. We have to test them in people, in rigorous and independent scientific studies.

Most of what has been completed in humans so far helps us better understand NR.

For example:

1. A randomized, double-blind, three-arm crossover pharmacokinetic study in 12 human subjects showed that NR raises NAD+ by as much as 2.7-fold in human blood with a single oral dose of 1000 mg.

2. Researchers at the University of Washington have completed a clinical trial with 140 participants showing that orally administered NR gives a dose dependent increase in NAD+ from 250-1000 mg/d plateauing at a 2-fold increase in NAD+ at day nine.

3. Researchers have also reported positive effects of NR on vascular endothelial function in healthy middle-aged and older adults, with further investigations of motor and cognitive changes to come.

4. Recently, researchers have found that a resveratrol analog called pterostilbene combined with NR seemed to help ALS/Lou Gehrig’s patients.*

5. Most recently, a placebo-controlled study assessing 500 mg of NR, taken twice daily by 70- to 80-year olds, showed increases in NAD+ in blood (but not muscle.) Inflammation fell and, unexpectedly, mitochondrial activity did too.

6. Multiple other studies are now underway assessing the effects of NR on muscle mitochondrial function, cognition, immune function, kidney function, traumatic brain injury, brown fat activity, lipid accumulation, energy metabolism, cardiovascular risk, body composition, and acetylcarnitine levels.

When will we have human trial results for NMN? Likely very soon. Right now, for instance, we know that:

An international collaborative team including researchers from Keio University in Tokyo and Washington University School of Medicine in St. Louis is running a Phase I human clinical study of NMN in Japan.

Clinical trials examining the safety and efficacy of NMN are also currently being run at Washington University, investigating the effect on insulin sensitivity, endothelial function, lipids, body and liver fat and markers of cardiovascular and metabolic health.

According to David Sinclair

"The bottom line, for now, is that the science is a bit further along when it comes to NR, but it is far too early to say which is better for humans. This is not a race. Science isn’t a contest between two competitors."

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. To date there is not yet evidence that these mouse studies can be extrapolated to 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.

As research grows, it is likely to become clearer that NMN and NR may have differing benefits depending on the part of the body and their use. Where NMN transporters are found, they could make one more preferable over the other. NMN has also been found to improve insulin activity and production which could help to accelerate metabolisms and make the body more glucose tolerant.

Credit: Lifespanbook.com

NR (Nicotinamide Riboside) vs NMN

While most anti-aging products try to reverse signs of aging on your skin, nicotinamide riboside — also called niagen — aims to reverse signs of aging from inside your body.

There are multiple precursors to NAD+, each with its own physiologic effects. Nicotinamide riboside (NR) is a popular one with several notable benefits over other precursors like niacin (NA) and niacinamide (NAM). NA, for instance, may induce uncomfortable flushing, while NAM may inhibit sirtuin at high doses, both undesirable effects.

Because of its unique profile of benefits and low risks, NR has emerged as a popular choice, especially by its discoverer, biochemist Charles Brenner, among the NAD+ precursors. In Scientific Reports, researchers noted:

“Because NR does not cause flushing or inhibit sirtuins and the genes (NRK1 and NRK2) required for the metabolism of NR to NAD+ are upregulated in conditions of metabolic stress, NR has a particularly strong potential as a distinct vitamin B3 to support human wellness during metabolic stress and aging.”

“Therefore, administration of niacin or niacinamide is unlikely to be widely adopted for maintaining health and function with aging,” researchers wrote in Nature Communications.

Within your body, nicotinamide riboside is converted into NAD+, a helper molecule that exists inside each of your cells and supports many aspects of healthy aging.

Like other forms of vitamin B3, nicotinamide riboside is converted by your body into nicotinamide adenine dinucleotide (NAD+), a coenzyme or helper molecule.

Nicotinamide riboside supplements — such as niagen — have quickly become popular because they appear to be especially effective at raising NAD+ levels (Trusted Source). Nicotinamide riboside is also found in trace amounts in cows’ milk, yeast and beer (Trusted Source).

NR used to be considered superior because no NMN transporter — required to get it into cells — had been detected. We now know there is such a transporter, which gives NMN the advantage as it’s also a more direct NAD+ precursor.

Most of the NAD+ precursor research is done with NR. However, as you can see from the image above, NMN converts to NAD+ whereas NR must first be converted into NMN before it can be converted into NAD+, so it makes more sense to use NMN for NAD+ augmentation.

The image above also shows how niacin (NA) also finds its way to become NAD+. Niacin is also a useful supplement to use in increasing NAD+ levels. You just need to limit the dose to about 25 mg, which most is a dose low enough not to cause any flushing. Higher doses are not likely as effective as NMN and exercise in producing NAD+.

NMN vs NR: Dr David Sinclair

There has been few, if any, head to head research published comparing Nicotinamide MonoNucleotide (NMN) and Nicotinamide Riboside (NR).

However, Dr. Sinclair recently said he takes NMN instead of NR based on a head to head research he did that found NR did not work at all, while NMN increased the endurance in older mice such that they were able to run twice as far as those on placebo.

NAD is a big molecule relative to vitamin B3. It's got those phosphates on there. It's got a sugar. It's got the vitamin B attached. So you've got all these components that come together to make this very complicated molecule called NAD. And when you give NMN, it contains all three components that the body needs to make NAD. If you give NR or just vitamin B3, which is an even smaller molecule, the body has to find these other components from somewhere else. So where do you get phosphate? Well, body needs it for DNA, needs it for bones. So high doses of something that requires additional phosphate makes me a little concerned...

David Sinclair was referencing this research, but unfortunately, they did not publish the results they found with NR.

NMN has much stronger record of benefit to humans in clinical studies

  • NMN has much stronger record of benefit to humans in clinical studies
  • NMN treatment increased muscle insulin sensitivity
  • NR did not improve insulin sensitivity in trials

Bioavailability Issues with NR and NMN

Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR) both have very poor bioavailability and if not improved, a tiny fraction is able to make it to the bloodstream and reach tissues throughout the body.

Delivery methods that improve the bioavailability are far more important than which molecule is used.

Now, both NMN and NR are available in Liposomes, which protect them from digestion even more than sublingual delivery. Liposomes release the payload in the bloodstream slowly over 24 hours, greatly minimizing the surge in NAM that is known to cause problems with standard NMN and NR capsules.

Clinical Studies

Corporate backing of NR by Chromadex has been a factor in encouraging more clinical studies but NR has failed to achieve notable success in any of their 11 studies, and did not improve insulin sensitivity in 3 trials while NMN was successful in their clinical studies published to date.

Dr. David Sinclair: The Biology of Slowing & Reversing Aging (Podcast)



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