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NMN vs. NR: The Best Way to Increase NAD+ and Slow Aging

Nicotinamide Mononucleotide (NMN) is one of the most exciting breakthroughs in anti-aging nutrition. NMN is one of six powerful anti-aging ingredients in THRIVE GOLD, which is designed to change the way you age and help you to live vibrantly, longer. 

In numerous rodent studies, NMN administration has been found to literally turn back the clock on age-associated physiological decline by increasing NAD+ levels.

“After 6 days of NMN, 22 month old mice [approx. 95 y.o. humans] had the muscle capacity, endurance and metabolism of 6 month old mice.” (2013 Sinclair)

NMN is both orally bioavailable (unlike NAD+) and highly stable in the body (unlike NR), making it by far the most effective supplement to significantly increase your NAD+ levels. 

NAD+ activates a class of genes (and their associated enzymes) called Sirtuins, which turn off expression of certain genes that promote aging, including genes involved in the regulation of inflammation, fat synthesis and storage and insulin-level management. Read more about NAD+ and aging here.

There are several widely marketed products that feature Nicotinamide Riboside (NR/Niagen) to increase NAD+ levels, which begs the question, which supplement is more effective for boosting NAD+, NMN or NR?

NMN and NR are both special forms of Vitamin B3 and are precursors in the synthesis of NAD+. NMN is an immediate precursor to NAD+ and it readily and directly converts to NAD+  by action of the enzyme NMN adenylyltransferase. 

NR is an indirect precursor to NAD+ and in order to synthesize NAD+ either:

(i) NR must first undergo phosphorylation into NMN, which then converts to NAD+ (the salvage pathway, shown on the right side of the diagram below), or

(ii) NR must travel through a five stage pathway to NAD+ synthesis (NR → Nam → Na → NAMN+ → NAAD+ → NAD+) (the de novo pathway, shown of the left side of the diagram below).

The second stage of the de novo pathway is a conversion from NR to Nicotinic Acid (Na), which is better known as regular Vitamin B3. The de novo pathway is enzymatically rate-limited, which means that you can take all the B3 or Tryptophan you want and it will not raise your NAD+ levels above your baseline.  Supplementation with NMN or NR allows NAD+ synthesis via the salvage pathway, which is effectively a backdoor that allows unrestricted NAD+ synthesis and enables you to raise your NAD+ levels significantly above your baseline.  

Since NR must first convert to NMN before converting to NAD+, it would seem to be common sense that NMN would be the superior supplement to boost NAD+ levels and it turns out that this is mostly true. We’ll get to the scientific research below, but first a brief digression into the realpolitik of the NR vs. NMN debate. 

NR’s current popularity owes largely to the fact that a private company, ChromaDex Corp.,  holds the patent to NR. As the sole supplier, they have invested a lot of resources into both research studies and promotion of NR in order generate massive demand. NMN, by contrast, is not patented and cannot be patented. No private company controls the supply of NMN and therefore no private company has invested significant resources into research studies or promotion of NMN. There is a significant and growing body of research with respect to NMN, but it has been conducted exclusively by universities (particularly Harvard Medical) and government agencies (most publicly, NASA). One of the leaders in NMN research is David Sinclair, professor in the Department of Genetics at Harvard Medical School and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School (links to articles about NMN and his work are at the bottom of this post). Human trials of NMN are well underway, but results have not been published as of the writing of this post. Despite the lack of published human trials, Dr. Sinclair has stated publicly on numerous occasions that he personally supplements with NMN on a daily basis.

There are a number of reasons to conclude that NMN is significantly superior to NR:

  1. In both mice and human studies NR has been shown to be highly unstable and to quickly degrade into regular vitamin B3. NR that degrades into B3 is restricted to the rate-limited de novo pathway and will not raise your NAD+ levels above your baseline. In contrast, NMN is highly stable in the body and thus can more effectively exploit the unrestricted salvage pathway and  raise your NAD+ levels significantly above your baseline.
  2. Unlike NR, which in one rodent study reduced endurance and physical performance by 35%, NMN was shown to increase physical performance, as measured by treadmill run time, by 60% and double exercise endurance. 
  3. In 2 separate studies, NMN was found to improve heart function, NR did not improve heart function.
  4. Alzheimer’s disease is widely believed to be driven by the production and deposition of the Beta-amyloid peptide. NMN decreases Beta-amyloid peptide buildup, while NR does not. 

It has been stated by proponents of NR that NR is superior to NMN, because NR is able to cross cellular membranes, whereas NMN and NAD+ are too large to cross cellular membranes and must therefore first degrade into NR, cross the cellular membranes and then convert back to NMN and NAD+. This is partially true, but only in the liver and not in other tissue. Both NMN and NAD+ have been shown to readily cross cellular membranes in the heart, brain and other tissues. 

Why not take NAD+ directly? NAD+ is not orally bioavailable and must be administered intravenously by IV to be effective. 

There are also a number of companies promoting regular vitamin B3/Niacin as an NAD+ booster. As we explored above, regular vitamin B3/Niacin is a precursor to NAD+ (which makes their claims technically true), but it is only a precursor on the de novo pathway of NAD+ synthesis, which is enzymatically rate-limited and will never increase your NAD+ levels above your baseline. In other words, these B3/Niacin NAD+ boosters are completely ineffective.

Add THRIVE GOLD to your daily regimen today and change the way you live and age.

Read more about NMN and Dr. Sinclair’s work:

https://hms.harvard.edu/news/rewinding-clock

http://time.com/4711023/how-to-keep-your-dna-from-aging/

https://harvardmagazine.com/2017/09/anti-aging-breakthrough

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