NMN and NR: How These NAD+ Precursors Measure Up

Nicotinamide riboside (NR) is often regarded as a highly efficient precursor to NAD+, but its cousin molecule nicotinamide mononucleotide (NMN), an ingredient in our metabolic health product Signal, is raising eyebrows as the new kid on the block.

 

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

NMN and NR are structurally very similar except for a phosphate group on NMN which makes this precursor larger than NR (see figure below). Historically, researchers believed that because of its size, NMN first had to transform into NR before it could enter cells. However, new research in mice now shows that certain tissues express a transporter called Slc12a8 that helps NMN (but not NR) enter the cells intact where it can then be converted to NAD+. The results from this study suggest that different tissues (or parts of your body) may have a preference for NMN or NR.

Once inside the cell, NMN is actually one step closer than NR to becoming NAD+. NR first needs to be converted to NMN before it can be converted to NAD+. In contrast, NMN is the immediate precursor to NAD+, requiring only one conversion step to become NAD+ (see figure below of the NAD+ biosynthesis pathways).

All of this may lead you to wonder: How does NMN stack up against NR?

NR vs NMN Molecule

Comparing the efficacy of NR and NMN is, for now, somewhat of a moot point because the two molecules have never been studied side by side in humans. To date, both have been shown to effectively increase NAD+ levels in humans and are safe for consumption. There is a growing number of completed and ongoing human clinical trials studying the effects of NR or NMN on specific aspects of human physiology or performance. For example, NMN supplementation appeared to support healthy insulin sensitivity in muscle and improve aerobic capacity in two different studies. NR supplementation has recently been shown to increase NAD+ levels in the brain and decrease levels of inflammatory cytokines in the central nervous system. These studies are based on varying dosages and are limited to specific cohort types and therefore need confirmation in larger, broader trials. However, these initial findings provide compelling evidence for various health benefits of NAD+ precursor supplementation. More studies will be needed to determine if their benefits differ by tissue type.

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 do they do it? NR and NMN are both beneficial because they elevate levels of NAD+, which decline with age. NAD+ is vital to cellular metabolism (turning nutrients into cellular energy) maintaining DNA health, activating sirtuins, and hundreds of other metabolic processes. 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 significantly boost NAD+ levels. As a result, supplementing with an NAD+ precursor can help mitigate the decline. Studies in both humans and animal models provide evidence for various health benefits of supplementation with NR or NMN.

What can you do with this information today? We know from human studies, including our own clinical trial, that it’s possible to increase NAD+ levels by up to 40 percent, safely and sustainably, with NR or NMN. We also know that a clear association exists between NAD+ abundance and healthy aging. In a paper published in the journal Nature Aging, Janssens and colleagues profiled metabolites in the muscle tissue of younger and older adults and found that NAD+ was one of the most depleted metabolites in older adults—in line with results from preclinical studies. Remarkably, the lower NAD+ level was even more pronounced in physically impaired older individuals, while NAD+ levels in exercise-trained older adults were closer to those of young adults. These results confirm that there is not only a correlation between NAD+ levels and age, but that elevated levels of NAD+ are linked to healthier aging. Our products Basis and Signal each contain an NAD+ precursor combined with key ingredients designed to activate distinct sirtuins and target different aspects of aging. 

Basis contains NR and pterostilbene, which work together to support cellular aging and healthy DNA by increasing NAD+ levels and activating SIRT1. Signal contains NMN, honokiol, and viniferin. These ingredients work synergistically to support metabolic aging and mitochondrial function by increasing NAD+ and activating SIRT3. Visit our Signal and Basis pages to learn more about each product.

As for the debate about which NAD+ precursor reigns supreme? We believe NR and NMN both have important functions that only time and good research will reveal. Stay tuned for more information as the science of NR and NMN continues to unfold.

 

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