How Can NMN Boost Your NAD+ Levels

How Can NMN Boost Your NAD+ Levels

Felix Krengel

You have probably heard about ATP (adenosine triphosphate) being the energy currency of the cell and how this molecule plays an essential role in virtually all life processes. While there’s nothing wrong with this metaphor, neither currency units nor ATP appear out of nowhere. Just as coinage relies on the disposability of materials, tools, and labor, so ATP production depends on specific precursors, enzymes, and a continuing electron flow. 

This is where NAD (nicotinamide adenine dinucleotide) comes in. In a way, this cofactor resembles the spark that lights the fire required to heat the coinsmith’s cauldron. It does so by serving as an intermediary between the citric acid cycle and the electron transport chain, accepting two electrons from the former and donating them to the latter, thus contributing to the creation of a proton gradient that eventually results in the production of ATP by the enzyme ATP-synthase. 

When molecules gain or loose electrons, there are said to undergo reduction or oxidation, respectively. In its reduced state, NAD actually forms NADH (the molecule gains two electrons and one proton), whereas the denomination NAD+ is commonly used to refer to the cofactor’s oxidized state (by losing two electrons, the molecule acquires a positive charge, as indicated by the plus sign). Because the reduction of an electron acceptor necessarily implies the oxidation of an electron donor, this kind of chemical process is called a redox reaction (Stein & Imai, 2012).

In addition to its importance for energy production, NAD is also involved in many other life-sustaining processes, such as the regulation of gene expression and immune responses, as well as DNA repair, amongst others. In line with these facts, current research findings suggest that human health and even lifespan could benefit greatly from maintaining appropriate and well-balanced levels of NADH/NAD+, particularly because the latter tend to decline with age. 

Can Supplemental NAD+ Work?

Naturally, the question that comes to mind at this point is: Can you boost these levels by taking certain supplements? The short answer is yes. NMN (nicotinamide mononucleotide), for instance, is a precursor of NAD that can be found in a variety of foods derived from both animals and plants. Administering NMN exogenously in concentrated form has proved to be a viable strategy for raising deficient NAD levels and even influence the development of related diseases positively (Braidy & Liu, 2020; Hong et al., 2020). 

In order to understand the logic behind these causal relations, we have to consider the biosynthesis of NAD in mammals. Although the cofactor can be produced by three different pathways, one provides considerably greater amounts of NAD than the other two. In this so-called salvage pathway, intracellular NAD is enzymatically degraded into NAM (nicotinamide), which in turn is converted into NMN. At the same time, extracellular NR (nicotinamide riboside) enters the cell and is transformed into NMN, too. The latter eventually originates NAD, thus closing the cycle. To complicate things further, the structural difference between NMN and NR mainly consists in the presence of a phosphate group, making the first molecule larger than the second. 

It was therefore long thought that extracellular NMN had to be degraded into NR in order to make its way across the cell membrane to the other, i.e., intracellular side. Notwithstanding, recently published experiments imply the existence of membrane transport proteins that bind extracellular NMN and release it into the cell. In any case, NAD biosynthesis is driven by enzyme activity, and corresponding age-dependent alterations are probably the main culprits behind decreasing levels of this cofactor over time. 

Aging inevitably implies a growing exposure to oxidative stress, inflammation, and DNA damaging agents. In consequence, the expression and activity of NAD-producing enzymes like NAMPT (nicotinamide phophoribosyltransferase), responsible for converting NAM to NMN, can gradually decline, while NAD+-consuming enzymes may be incrementally activated. Hence, there are two hypothetical options to prevent NAD deficiency: Either you raise NAMPT levels and reduce NAD+-consuming enzyme activity or you supply precursors like NMN. Although physical exercise appears to have beneficial effects on NAMPT expression to some degree, the second approach is much easier to comply with. All you have to do is to take an appropriately formulated  supplement (Hong et al., 2020).

So now that you understand the biological importance of adequate NADH/NAD+ levels in the body, why they decline with age, and what can be done against this time-dependent development, should you just get yourself a decent supply of chemically pure NMN and start enjoying the pleasures of rejuvenation?  

NMN Is Safe

What can be said at this moment is that NMN seems to be generally safe in humans. Moreover, the results obtained so far leave little room for doubt that ingesting the compound can actually cause NAD levels to increase, especially with regard to age- or disease-related NAD deficiency. Restoring these levels may not only delay general aging processes by improving mitochondrial function, as well as mitigating the deleterious effects of oxidative stress and inflammation. Beyond that, continuous NMN use may ultimately prevent or even reverse some of the worst scourges of humanity, particularly cardiovascular and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease.  

In addition, NMN has shown to positively influence the development of several metabolic disorders, e.g. diabetes and obesity. Notwithstanding the compound’s great therapeutic potential, an universally accepted dose range has yet to be established based on solid clinical research. The optimal dose likely depends on a variety of highly individual factors and is therefore supposed to differ significantly from person to person (Braidy & Liu, 2020; Hong et al., 2020).

 

About Felix Krengel

Felix is a researcher and scientific writer who loves and lives to explore the intersections of biology, chemistry, and medicine. His line of research focuses on the biosynthesis and pharmacognosy of antiaddictive alkaloids from tropical plants, but his work as a freelance author has allowed him to venture into many corners of the realm of knowledge. After earning a PhD in biological sciences and publishing a series of peer-reviewed papers, he has been dedicating himself to the difficult task of
maximising the real-world impact of academic activities and findings.

 

References

Braidy, N., & Liu, Y. (2020). NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Experimental gerontology, 132, 110831. https://doi.org/10.1016/j.exger.2020.110831

Hong, W., Mo, F., Zhang, Z., Huang, M., & Wei, X. (2020). Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Frontiers in cell and developmental biology, 8, 246. https://doi.org/10.3389/fcell.2020.00246

Stein, L. R., & Imai, S. (2012). The dynamic regulation of NAD metabolism in mitochondria. Trends in endocrinology and metabolism: TEM, 23(9), 420–428.  https://doi.org/10.1016/j.tem.2012.06.005

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