NMN vs NR - Which is the Best Longevity Supplement?

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NMN vs NR - Which is best?

NMN vs NR: both are precursors to NAD, one of nature's most essential molecules for human life, well-being and longevity. It's great that we have such precursors to NAD, because the levels of this essential coenzyme steadily declines as we age. In fact, anti-aging expert Dr. David Sinclair says that by age 50, your NAD levels are about half what they were when you were 20, and without it, you'd be dead in about 30 seconds.

NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) are both available for sale as food supplements. But which is the better choice, NMN or NR?

To say that NMN and NR are "precursors" to NAD means that, through a series of chemical actions that happen in your body, they act as building blocks for NAD: NMN and NR are transformed into NAD. Nicotinamide, more commonly known as niacin and Vitamin B3, also acts as a precursor to NAD.

The deterioration and depletion of NAD has been linked by researchers to the aging syndrome, and numerous age-related pathologies [1] . Scientists now believe that by increasing our levels of NAD, we can forestall the aging process, and also mitigate many age-related diseases at the same time. This belief is based largely on the promising outcomes of the large body of animal studies [2] . However, there have also been some promising human studies conducted, which have explored the effectiveness of NMN and NR as NAD precursors, and a number of other important human studies are ongoing. Verifying the link between NAD and human longevity with controlled studies using human subjects will ultimately provide the final evidence sought by longevity researchers.

NMN vs NR – What Does Dr. Sinclair Know?

In order to properly consider the question, "Which is the best longevity supplement", we should look at a combination of scientifically-based evidence combined with anecdotal evidence. Let's start with a piece of anecdotal evidence.

Do the experts prefer NMN or NR?

One of the world's leading authorities on longevity and the science behind NNM, NR, and NAD is Harvard scientist, Dr. David Sinclair. Dr. Sinclair has authored over 140 published scientific research papers on the subject of longevity, many of which address NAD, NMN, and/or NR. Dr. Sinclair is among just a few scientists credited with demonstrating the role that NMN and NR play in elevating NAD levels in animals and humans.

Dr. Sinclair has a personal health regimen which involves various factors, including diet, exercise, medications, and supplementation. His research indicates that resveratrol, a super-antioxidant derived from flavonoids found in fruits and vegetables, and NMN have a big role in upregulating so-called "longevity genes" called sirtuins. Unsurprisingly, Dr. Sinclair supplements with resveratrol and NMN every day, but not NR [3] . He could easily take both NMN and NR, but chooses only NMN. Why? My guess is that given Dr. Sinclair is a scientist who understands NMN and NR intimately on a scientific level, he selects NMN because the science suggests it's the better NAD precursor.

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 [4] [5] . These studies also report other benefits, including the growth of blood vessels (vascular endothelial function) and the reduction of inflammation [6] [7] .

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 [8] . 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?

NMN vs NR - The Chemistry

Is the answer to the 'NMN vs NR' question to be found in the science?

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:

  1. NAM – also known as Nicotinamide or niacin C6H6N2O
  2. NR – Nicotinamide riboside C11H15N2O5+
  3. NMN – Nicotinamide mononucleotide C11H15N2O8P
  4. 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.

Scientists have for many years assumed that this necessity of breaking NMN and NR down to facilitate assimilation discovered in animal tests was probably also applicable to humans. However, more recent research, published in 'Nature' in January 2019, has demonstrated that NMN (the whole molecule) can make it through the digestion process intact with the help of a gene 'transporter', known as 'Slc12a8'. [9]

The study's abstract states:

"Nicotinamide mononucleotide (NMN) is a biosynthetic precursor of nicotinamide adenine dinucleotide (NAD+), known to promote cellular NAD+ production and counteract age-associated pathologies associated with a decline in tissue NAD+ levels... Here we show that the Slc12a8 gene encodes a specific NMN transporter... We further show that Slc12a8 specifically transports NMN, but not nicotinamide riboside... Our work identifies a specific NMN transporter and demonstrates that Slc12a8 has a critical role in regulating intestinal NAD+ metabolism."

What we now know, as a result of this study's findings, is that NMN does not need to be broken down into its constituent parts, and then reassembled back into NMN and then NAD. The NMN molecule is assimilated intact, thereby making the process of increasing NAD levels faster, more assured, and more efficient [10] . The study also concluded that NR is not benefited by this same transporter, but instead must go through the process of breaking all the way down and then, reassembling; first as NMN, and then NAD.

Presumably, the fact that NMN can pass through the digestion/assimilation process intact is one of the reasons that David Sinclair takes NMN and not NR. He also understands that the NMN molecule and the NAD+ molecules are nearly identical, so the conversion of NMN into NAD+ is a fairly simple process by comparison.

NMN vs NR – The Anecdotal Evidence

Even though the observations and conclusions made by users of supplements and medicines are not considered to be valid scientific evidence, they are still important in day-to-day healthcare management. When your health care professional recommends a medicine or supplement, the next time he sees you, he asks, "What happened?" He's asking for anecdotal evidence.

NMN is preferred over NR by people who have used both.

NMN and NR have been sold as supplements for a few years now, and thousands of people have taken one, the other, or both. Customer reviews of these products offer some valuable insights into the reactions of people who have used both NMN and NR. The following reviews represent a sampling of these reactions which have been obtained from purchase-verified reviews on Amazon.

Duwayne Howe - (alertness, energy) - I've been taking NR for almost a year now, and recently tried NMN. Hands down, NMN has noticeably outperformed the NR. My afternoon deliveries would be scary sometimes because I would be fighting back the sleepiness. Your NMN product has solved that problem for me. That's one noticeable area where it clearly does the job for me.

gn - (energy) - I can feel the increase of energy and am more alive after taking it. NMN is much better than NR.

Craig R Martin - (energy, focus) - We switched from NR to NMN several months ago and the results were significantly better than those we received using Niagen--for both of us. NMN is the real thing, and we are thrilled to have discovered it. We both have a greater boost in energy, cognitive function, and endurance than we did with Niagen-nicotinamide riboside.

Taab Siddiqi - (blood sugar, sleep) - I used NR ( TRUGEN ) for a month, again at 150 mg twice a day. The TRUGEN gave somewhat enhanced sleep but did not in my case deliver any other benefits which could be measured or experienced. THE BIGGEST DIFFERENCE IN MY INDIVIDUAL CASE was that the TRUGEN had no effect on my diabetes. I have no relationship whatsoever to either company and am an independent individual who wants to share the benefits experienced and a comparison of NMN with NR. The objective is to share findings with the larger user community and also present a comparison of the two forms of NAD precursors as they worked in my individual case. I have given it a four star due to its strong anti diabetes effectsI hope this is useful as a guide for other users.

Healthy Chris - (energy) - NMN is a great supplement that shows a lot of promise. I've had conversations with biochemists who are researching NMN & NR, and they have said that NMN performance at least as well and sometimes better than NR in every study (not all have been published). Decent price. Take it sublingually for better absorption.

Frodizzle – (energy) - I have used it and I found it to be much better than NR niagen. I was using resveratrol and it didn't seem to be working until I paired it with nmn.

Nils – (energy) - It's surprising to me that NMN would have such a potent effect, considering that I felt terrible... I felt like death warmed over... when I was taking the NR. I tried two different brands of NR, TruNiagen and Life Extension. Most of them made me feel dizzy, weak, and sick; I needed to take several naps just to get through the day when taking NR, and still felt exhausted when I woke up. I tried NR for two weeks, thinking my body might need some time to adjust to it, then gave up on it. By contrast, taking NMN is totally energizing, at least so far.

Conclusion

It appears that NMN works on genetic and cellular levels without targeting any particular tissue, organ, or health complaint. Therefore, anyone taking NMN should do so objectively, and assess the benefits, if any, on an individual basis.

As for the debate regarding NMN vs NR -- at this point it appears that NMN has a clear edge over its smaller cousin.

This article has not been evaluated by the Food and Drug Administration. Its purpose is to provide information and is not intended to diagnose, treat, cure, or prevent any disease.

Show references
  1. https://www.ncbi.nlm.nih.gov/pubmed/28649105
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477631/
  3. https://lifespanbook.com/nad-boosters/
  4. https://www.ncbi.nlm.nih.gov/pubmed/27721479
  5. https://www.ncbi.nlm.nih.gov/pubmed/29211728
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389020/
  7. https://lifespanbook.com/nad-boosters/
  8. https://www.prohealthlongevity.com/blogs/control-how-you-age/nmn-is-safe-for-humans
  9. https://www.nature.com/articles/s42255-018-0009-4
  10. https://www.prohealthlongevity.com/blogs/control-how-you-age/slc12a8-newly-discovered-nmn-specific-transporter
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