NMN vs NR
Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are biosynthetic precursors to an essential molecule for metabolism– nicotinamide adenine dinucleotide (NAD+). Numerous studies indicate NAD+ levels decrease significantly during aging, with restoration of NAD+ levels in aged animals extending lifespan and promoting health. Research on the two molecules indicates supplementation with either increases NAD+ levels during aging.
The Chemistry ---NMN vs NR
Dr. Sinclair understands the structure and behavior of the molecules involved in the process of creating and increasing levels of NAD. There are four molecules which are important in this process:
NAM – also known as Nicotinamide or niacin C6H6N2O
NR – Nicotinamide riboside C11H15N2O5+
NMN – Nicotinamide mononucleotide C11H15N2O8P
NAD – Nicotinamide adenine dinucleotide C21H27N7O14P2
You don't have to be a chemist to look at the chemical formulae for these molecules and recognize that they become increasingly more complex, beginning with NAM, and up the chain to NAD. NR and NMN are very similar, with one important exception: NMN and NAD both contain phosphorus (P); whereas, NAM and NR do not. Another simple observation is that NAD is almost exactly twice the size of NMN. If you put two NMN molecules together, it's not hard to envision them joining to become an NAD molecule. NMN, in this context, becomes a 'precursor' to NAD.
Precursors are compounds that participate in chemical reactions, resulting in the creation of another compound. In human biochemistry, foods and herbs act as precursors to hormones, proteins, and other vital biochemicals. For example, certain foods, like soy and fenugreek, are known as phytoestrogens, meaning that they are precursors to the production of estrogen. The amino acid, L dopa, is a precursor to the hormone dopamine.
The presence of phosphorus in the NMN and NAD molecules is important when evaluating NMN and NR side-by-side. Even though phosphorus is abundant in the human body, it has a unique characteristic, which is that the phosphorus atom does not appear in nature by itself. It only appears combined with other atoms in molecular structures.
In the NMN and NAD molecules, phosphorus bonds with oxygen. So, any precursor to NAD needs phosphorus, but it can only use phosphorus that is already bonded with oxygen. This adds a layer of complexity to the process when considering NR as your chosen NAD precursor, because NR needs to find a form of compatible phosphorus to complete the process of transformation to NAD, whereas NMN already contains phosphorus.
Early studies using rat intestines concluded that NAM, NR, and NMN were all viable precursors to NAD, but NR and NMN had to be first broken down into NAM and other simpler components in order to be fully digested and assimilated into an animal's body. Once inside the body, these individual components reassembled, first into NR and NMN, and then subsequently converted into NAD. The reason for this is that the small intestine sometimes has difficulty assimilating more complex molecules, and therefore they must be broken down into simpler components first. This is true with animals and also, to a lesser extent, humans.
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. Some scientists believe NMN is too large to cross cellular membranes and must convert to NR before entering cells, where NAD+ biosynthesis occurs. Otherwise, NMN would need to get transported into cells by a transporter specific for NMN, such as Slc12a8.
Once inside cells, NR gets converted to NMN via enzymes called ‘NRKs.’ Once NMN has been synthesized, the molecules enter the ‘nicotinamide core recycling pathway.’
In the ‘nicotinamide core recycling pathway,’ the enzyme, NMNAT, converts NMN to NAD+. Proteins called ‘sirtuins’ utilize NAD+ to maintain cellular health and turn NAD+ to nicotinamide (NAM). NAM then converts to NMN via the enzyme NAMPT.
Foods from a standard diet contain B3 vitamins, which are nicotinamide (NAM), nicotinic acid (NA), and nicotinamide riboside (NR). NAD+ gets synthesized from B3 vitamins or tryptophan from the diet. Humans cannot synthesize NAD+ without B3 vitamins or tryptophan from the diet or NMN supplements.
A study from 2007 demonstrates NR substantially raises NAD+ levels in yeast. Further studies on the topic reveal NR increases NAD+ in mammalian cells up to 270%. These studies imply a special role for the salvage pathway of NAD+ biosynthesis involving NR and NMN in increasing NAD+ levels. The actual mechanism through which this happens remains unclear.
Scientists continue to debate which of the two biosynthetic precursors, NMN or NR, is superior regarding safety and efficacy. Due to the size of NMN, some scientists believe it must convert to NR before crossing the cell membrane to enter cells. Once inside cells, NR would convert to NMN. If this scenario provides the full story, the more efficient precursor would be NR.
Scientists from Washington University School of Medicine in St. Louis recently provide compelling evidence for the existence of a specific transporter for NMN in the gut of mice called Slc12a8. A transporter is a protein which allows the smooth passage of a molecule across a cellular barrier, such as a cell membrane.
Genomics data, which analyzes entire gene sets of humans, indicate the gene encoding this transporter exists in humans. The question is whether the transporter gets expressed in humans similar to mice, thus allowing NMN transport across the cell membrane. According to a genomics database, which examines entire gene sets of humans, SLC12A8 is expressed in humans “…with highest levels in small intestine, stomach, testis, thyroid, and colon.” Thus, the possibility exists this NMN-specific transporter is expressed similarly in the gut of humans and has a similar role in NMN absorption as well.
Confirming this NMN-specific transporter’s expression pattern in the gut of humans will require further research. If studies confirm a similar expression pattern of this transporter for NMN between mice and humans, the possibility remains NMN constitutes the more efficient and effective precursor compared to NR.
NMN vs NR - The Research
To date, more human research has been completed to date on NR than on NMN. This is primarily due to the fact that some of the companies who market NR are financed by investors who have funded the research. The results of these studies are promising. They show that NR can double the levels of NAD in humans by oral consumption . These studies also report other benefits, including the growth of blood vessels (vascular endothelial function) and the reduction of inflammation .
There are currently at least three major studies of NMN underway involving human subjects. Two include one conducted by the Washington School of Medicine in St. Louis, and the second by Keio University Medical School in Tokyo, in conjunction with Washington School of Medicine. The third study, and perhaps the most important one, is being conducted by Brigham and Women's hospital in Boston, under the watchful eyes of Harvard longevity scientists. The results of these trials should be published soon.
Animal studies with NMN and NR appear to be more-or-less comparable, showing promising possibilities for increases in lifespan and enhanced healthspan. So, if there is more completed human research on NR, and both NR and NMN appear to be effective in increasing NAD levels, why does Dr. David Sinclair, and thousands of others, take NMN, and not NR?
Where to Buy Nicotinamide Mononucleotide(NMN) Powder in Bulk?
If you are looking to buy Nicotinamide Mononucleotide(NMN) powder in bulk, the best place to buy NMN powder is cofttek.com. Cofttek is a high-tech pharmaceutical enterprise that has been providing innovative and high-quality products since 2008. The company boasts of an impressive R&D team with experienced individuals committed to the development of competitive products. Cofttek has partners and supplies its products to pharmaceutical companies in China, Europe, India, and North America. The β-Nicotinamide Mononucleotide supplied by Cofttek is of very high-quality and completely safe for human consumption. More importantly, the company supplies this powder in bulk, i.e. in units of 25kgs. Thus, if you are looking to buy this powder in bulk, Cofttek is the company you should contact — they are the best Nicotinamide Mononucleotide (NMN) powder supplier in the market.
References
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5. Assiri M. A., Ali H. R., Marentette J. O., Yun Y., Liu J., Hirschey M. D., et al. (2019). Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease. Hum. Genomics 13:65. 10.1186/s40246-019-0251-1