New NR Research: How Does it Compare to NMN?

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NMN and NR are precursors to the coenzyme NAD+.

A recently published study looked at the impacts of supplementing overweight or obese adults with nicotinamide riboside (NR). Although the research resulted in a few interesting conclusions about NR, there are some missed opportunities involving NMN, also known as nicotinamide mononucleotide.

Just how does NR compare to NMN? This article will describe the objectives and outcomes of the recent study, as well as some points about what was missed. 

An Overview of NAD+, NR, and NMN

NAD+ is a crucial coenzyme necessary for metabolizing food into fuel, repairing damaged DNA, and maintaining a healthy aging process. However, it is known that NAD+ levels decline with age. 

One of the ways that NAD+ promotes longevity is through its ability to activate sirtuins, which are a family of proteins that play a key role in the aging process. Maintaining adequate NAD+ levels with age can slow down cellular aging and reduce the risk of developing chronic diseases.

Two of the primary precursors to NAD+ are NR and NMN. It was previously thought that only NR could directly enter cells and convert into NAD+; NMN was thought to require conversion into NR first. But recent research has found that NMN can also directly enter cells through a specific NMN transporter, which will be discussed in more detail later on in the article.

What Was The Study About? 

The April 2020 study was published in the American Journal of Clinical Nutrition, with the title:

“Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans.” 

This study was a controlled cross-over trial involving 13 overweight or obese adults, who were randomized to receive either 1000 mg per day of NR or a placebo for six weeks. 

Their primary outcome measures were insulin sensitivity, mitochondrial function, and metabolic markers. They also looked at blood pressure, body composition, and skeletal muscle NAD+ metabolites. 

What Did They Find?

Their results did not find any significant changes with their primary outcomes, as the group supplemented with NR did not have improvements in insulin sensitivity or skeletal muscle mitochondrial function. 

The researchers also report that the NR supplementation did not increase NAD+ levels in the skeletal muscle. Rather, NR increased two NAD+ metabolites (NAAD and MeNAM), but there was no increase in total NAD+ content. 

However, what they did find is that NR supplementation improved body composition, sleeping metabolic rate, and skeletal muscle acetylcarnitine concentrations.

Key Points About NMN That Were Missed

There are also some key factors regarding NMN that should be mentioned in any study that assesses the precursors to NAD+.

1. NMN has been shown to be safe in humans. 

One thing to note is that the NR supplements in the study, which were the brand Niagen, were provided by Niagen’s manufacturer, ChromaDex.  

In a recent interview about the research, ChromaDex’s CEO Rob Fried was quoted as saying:

“As the scientific potential of NAD+ has grown, so too has the number of unproven claims and popularity of untested precursors on the market, like NMN, that have not been shown in human clinicals to safely and effectively increase NAD+ levels.”

While it’s true that there are not completed clinical trials assessing NMN’s conversion into NAD+ in humans, you can visit ClinialTrials.gov and view the ones that are in the works. Additionally, a clinical trial published in February 2020 in Endocrine Journal suggests that NMN supplementation in doses ranging from 100 mg to 500 mg is considered “safe” for human use without harmful side effects. 

Nicotinamide mononucleotide (NMN) is safe for human use and has been shown to improve health outcomes in animal studies.

2. NMN is able to increase NAD+ levels effectively and has improved many health outcomes in animal studies.

A December 2016 study published in Cell Metabolism found that mice who had their chow supplemented with NMN for 12 months had increased NAD+ levels in tissues. Not only that, but the NMN-supplemented mice had several improvements in typical age-related symptoms, including improved energy metabolism, eye function, insulin sensitivity, lipid profiles, and suppression of age-associated weight gain. 

These results are interesting, as NMN was able to improve one of the primary outcomes — insulin sensitivity — that NR was not shown to do in the recently published American Journal of Clinical Nutrition study.

Another study, published in June 2019 in Redox Biology, found that supplemental NMN improves the brain health of aging mice. In the two-week study, older mice who received NMN had improved neurovascular health, spatial working memory, and gait coordination. 

The researchers, including David Sinclair, PhD, conclude that NMN reduces oxidative stress and improves the brain's microvascular function, both of which are compromised in cognitive decline and neurodegenerative diseases.

3. NMN has a specific transporter, making it similar to NR in how it enters cells and increases NAD+ in tissues.

Recent research has shown that there is a transporter specific to NMN that transports the molecule across cell membranes to be directly converted into NAD+. The transporter, Slc12a8, enables NMN to bypass its intermediary conversion into NR, which was previously thought to be the only way NMN acted as a precursor to NAD+.

But after the research on the NMN transporter was published, a piece published in the Matters Arising section of Nature Communications claims that there is an absence of evidence that this transporter exists. It’s worth mentioning, however, that one of the authors of this rebuttal owns stock in and is the chief scientific adviser to ChromaDex, the supplier of NR in the primary study.

Key Takeaway

There is still undoubtedly a lot to be learned about NMN and how it functions in the human body. However, there are plenty of animal studies that show how NMN can ameliorate the aging process and support overall health and longevity. 

While it’s true that more research on NMN, especially in human clinical trials, is needed, the small body of evidence that we do have on the benefits of NMN thus far shouldn’t be ignored. 

Although NR is also a suitable precursor to NAD+, it can’t be known which one is “better” unless they are tested against each other in a human clinical trial.

Show references

Irie J, Inagaki E, Fujita M, et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocr J. 2020;67(2):153‐160. doi:10.1507/endocrj.EJ19-0313

Mills KF, Yoshida S, Stein LR, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016;24(6):795‐806. doi:10.1016/j.cmet.2016.09.013

Remie CME, Roumans KHM, Moonen MPB, et al. Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans [published online ahead of print, 2020 Apr 22] . Am J Clin Nutr. 2020. doi:10.1093/ajcn/nqaa072

Schmidt, M.S., Brenner, C. Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter. Nat Metab 1, 660–661 (2019). doi:10.1038/s42255-019-0085-0

Tarantini S, Valcarcel-Ares MN, Toth P, et al. Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biol. 2019;24:101192. doi:10.1016/j.redox.2019.101192
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