Before we can talk about NR and NMN we must understand the molecule that they affect – NAD+.
NAD+ or nicotinamide adenine dinucleotide is a critical molecule. It is one of the most abundant and essential components of our biology. Water happens to be the most abundant molecule in our bodies.
Its main functions are:
- Converting food into energy
- Maintaining the integrity of our DNA
- Ensuring our ‘longevity’ genes remain operational (to fight aging-related illness)
Without NAD+ we would die in the time it takes to boil a kettle!
It is obvious why this molecule is important, however, this molecule sadly does not ‘age’ well in our bodies. It’s been anecdotally mentioned that by the time you are 20 you have lost half of your NAD+ levels and when you’re 40 you may be down to just 25% of your original NAD+ levels.
Lower NAD+ levels correlate to many health problems including:
- Weakened immune system
- Increased feelings of fatigue
- Skin aging
- Weight gain
Aging and decreased NAD+ levels are very highly correlated which is why a lot of important research has gone into finding ways to increase NAD+ levels. This is where NMN & NR come into play.
NMN & NR – The NAD+ Boosters
Research has proven time and again that NMN & NR can effectively increase NAD+ levels. “NAD+ levels can be increased … by supplementing with NAD precursors, including nicotinamide riboside(NR) and nicotinamide mononucleotide (NMN).”(Shade et al 2020).
So NMN and NR are both NAD precursors, meaning that supplementation of them increases levels of NAD+ in the body.
Remember more NAD+ is a very good thing.
So if they both ensure the same outcome (increased levels of NAD+) how do we determine which is better?
This article will examine NMN & NR in 4 areas.
- Effectiveness – Which supplement produces more NAD+.
- Safety – How safe are they over long-term use.
- Price – How cost-effective are they.
- Other – Are there any other separating factors?
NMN vs NR – Which boosts NAD+ best?
It is difficult to ascertain exactly which supplement is most effective in boosting NAD+ levels. One study on NR found that it increased NAD+ levels in mammalian cells by up to 260%.
Dellinger et al 2017 looked at high doses of NR combined with pterostilbene. He found that NR was well tolerated in humans and boosted NAD+ levels by up to 90% over 4 weeks. What made this study more interesting was that the NAD+ increases were dose-dependent which gave us a look into the metrics of NAD+ boosting. “NAD+ levels increased by approximately 40% in the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks”. NR clearly has a lot of research backing up its NAD+ boosting prowess.
NMN has also been proven to show it can boost NAD+ effectively.
For example Igarashi et al 2021.
Their examination of older men taking NMN found that doses of just 250mg increased NAD+ quite dramatically. You can see that NAD+ levels roughly doubled in their participants.
Igarashi et al 2021
There are however many factors that determine which precursor is the most effective at boosting NAD+.
For a start, NMN is bigger than NR which some would argue makes NMN more difficult to get where it needs to in the body. Precursors need to get through the cell barriers to affect the cell. In general, a bigger molecule will have a harder time getting through a cell barrier than a smaller one.
On the other hand, NMN (unlike NR) is an immediate precursor to NAD+. This means that when NMN enters the body it can be immediately converted into NAD+. NR on the other hand must be phosphorylated to create NMN before being converted into NAD+. This means it is likely easier for the body to convert NMN into NAD+.
Recent research in 2019 found that mice had a dedicated NMN transporter called Slc12a8. This was found to be an effective ‘key’ in allowing NMN to enter the cell barrier. The fact that this was found to be an effective transporter in mice was exciting, but genomics data also found that this transporter existed in human DNA. The evidence is still unclear as to whether this transporter is consistently found (expressed) in the human body but if it is expressed it would strongly suggest that NMN was the more efficient NAD+ booster.
While the evidence isn’t crystal clear on which is more efficient at boosting NAD+ levels, evidence points to NMN being positioned to be the better of the two.
Safety of NMN vs NR
Let's start by establishing that both of these supplements have been very well tolerated and deemed to be safe in animal and human studies. Many studies have found NMN and NR to be well tolerated even at larger doses. For example, a proprietary form of NR developed by Chromadex was found to be safe by the FDA.
NMN has also been proven to be safe in numerous studies. One study looked at NMN supplementation among Japanese males. They found orally ingested doses of up to 500mg safe; “The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects.” (Irie et al, 2020).
Similarly, a recent study in Japan conducted by Igarashi et al 2021 observed the changes in older men (65+) on muscle performance after 6 – 12 weeks of long-term NMN supplementation. They found that NMN was not only safe but also had a positive impact on muscular performance.
So both precursors are safe but there are some differences in how they work in the body.
NR is less stable than NMN in the body: “NR is not stable in circulation, and its utilization is rate-limited by the expression of nicotinamide riboside kinases”( Giroud-Gerbetant et al, 2020). Furthermore, while NR does increase NAD+ levels its conversion does come at a cost. This article shows that NR supplementation led to increased NAM levels in the blood of mice. NAM(nicotinamide) can inhibit the function of SIRT’s which is not good for us. Studies suggest that NR does not convert into NAD as effectively as NMN. This leads to by-products such as NAM being left in the body. While evidence suggests that both precursors are extremely safe - because NMN is more easily converted it is arguably the ‘cleaner’ or safer of the two.
NMN vs NR which is cheaper?
Prices of these supplements vary wildly. This is largely due to the quality and purity of the product you buy. Some less than reputable suppliers sell these supplements without the correct certificates of authenticity or correct storage procedures.
When you purchase these precursors make sure your product comes with a certificate of authenticity and that it has been correctly handled.
With all that being said NMN tends to be cheaper than NR when comparing like for like products.
Winner – Dependent on the supplier.
Other Differences between NMN & NR
NMN has been linked to a wide range of health benefits. NR has similarly shared in these. It is not clear if these benefits all come from the boosting of NAD+ or if the precursors have inherent benefits as well. It is hard to determine non-NAD+ boosting benefits of these supplements but we can look at the studies that examine NR and NMN’s effect on different biological factors.
Evidence suggests that NMN can improve various aging symptoms and diseases while NR is not able to do the same. For example, NMN has been shown to increase endurance and exercise capacity while NR hasn’t quite documented the same success.
One study found NMN could improve athletic performance in older males.
Furthermore, when studying a mitochondrial disease model (Friedreich’s ataxia), NMN was found to be able to treat various symptoms (Martin et al, 2017), while NR could not. Some anti-aging experts predict that Mitochondrial treatments are the biggest key in unlocking our longevity potential. Treating Mitochondrial dysfunction will go a long way to optimising our biology.
NMN+ to boost Fertility?
It’s no secret that global fertility rates are dropping. Environmental factors such as pollution and trends in modern populations to have babies later in life are contributing to this. But could NMN reverse infertility?
A fascinating study looking into modern trends in fertility rates decided to test whether NMN boosted NAD+ levels could increase fertility.
They found “NAD+ repletion using NMN restores oocyte quality and enhances ovulation rate and fertility”(Bertoldo et al, 2020). Much more research should go into this area as current treatments for infertility are very expensive and not as efficacious as desired. While a boost in NAD+ may improve fertility regardless of precursor, the current literature has mainly focused on NMN.
NR vs NMN to extend the lifespan
NMN has been proven to extend healthy lifespans of living organisms such as mice. Multiple studies show NMN can extend lifespans such as Gomes et al. 2013, “[NMN Supplementation] demonstrated a robust correction in age-associated metabolic dysfunction and restored muscle mitochondrial function in old mice to levels seen in younger control mice.” NR on the other hand hasn’t had such stellar success in these areas. (Harrison et al 2021). While lifespan studies have generally been conducted on mice and animals it is important to note NMN has shown promise in its ability to reverse age-related damage to many cellular organisms.
NR vs NMN - Diabetes
Dollerup et al, 2018, found no significant benefit to insulin sensitivity when supplementing with NR.
NMN on the other hand has shown promise in tackling symptoms of Diabetes. For instance, Yoshino et al, 2021, found NMN supplementation made an “improvement in muscle insulin sensitivity … similar to the improvement observed after ~10% weight loss...”.
With Diabetes rates growing yearly around the world NMN could help in the fight against it.
Anecdotally you can find many reviews of NMN being more effective than NR – from Amazon to YouTube. David Sinclair – one of the leading scientists of anti-aging research, summarises a rodent study stating that “NMN increased endurance… [but NR did not]”. In his summary of a mitochondrial disease intervention in animals, he also stated that NMN was more effective than NR. Most important of all to note is that this expert in the antiaging field takes NMN and does not take NR. This is all largely anecdotal, but it does point to NMN being the stronger of the two.
NMN research has found a plethora of diverse benefits associated with its intake that NR hasn’t always mirrored. As a result for all of this miscellaneous battle, we give the nod to NMN.
NMN vs NR - which is best?:
NMN is a bigger but more easily converted NAD+ precursor. It has shown promise in studies ranging from cardiovascular performance to insulin sensitivity. NR has also demonstrated efficaciousness in these areas but not always to the extent of NMN. NMN has been proven to be safe with little to no side effects. NR is also safe but the process by which it converts into NAD+ has led to findings of increased NAM, which is not always desirable. By and large, the research currently suggests that NMN is more effective than NR but more studies are required.
- Shade C. The Science Behind NMN-A Stable, Reliable NAD+Activator and Anti-Aging Molecule. Integr Med (Encinitas). 2020;19(1):12-14.
- Yang T, Chan NY, Sauve AA. Syntheses of nicotinamide riboside and derivatives: effective agents for increasing nicotinamide adenine dinucleotide concentrations in mammalian cells. J Med Chem. 2007 Dec 27;50(26):6458-61. doi: 10.1021/jm701001c. Epub 2007 Dec 6. PMID: 18052316.
- Dellinger, R.W., Santos, S.R., Morris, M. et al. Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. npj Aging Mech Dis 3, 17 (2017). https://doi.org/10.1038/s41514-017-0016-9
- Irie J, Inagaki E, Fujita M, et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocr J. 2020;67(2):153-160. doi:10.1507/endocrj.EJ19-0313
- Martin, Angelical S et al. “Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich's ataxia cardiomyopathy model.” JCI insight 2,14 e93885. 20 Jul. 2017, doi:10.1172/jci.insight.93885
- Grozio A, Mills KF, Yoshino J, et al. Slc12a8 is a nicotinamide mononucleotide transporter [published correction appears in Nat Metab. 2019 Jul;1(7):743]. Nat Metab. 2019;1(1):47-57. doi:10.1038/s42255-018-0009-4
- Judith Giroud-Gerbetant, Magali Joffraud, Maria Pilar Giner, Angelique Cercillieux, Simona Bartova, Mikhail V. Makarov, Rubén Zapata-Pérez, José L. Sánchez-García, Riekelt H. Houtkooper, Marie E. Migaud, Sofia Moco, Carles Canto,
- A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor, Molecular Metabolism, Volume 30, 2019, Pages 192-202, ISSN 2212-8778, https://doi.org/10.1016/j.molmet.2019.09.013.)
- 17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex
- A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects
- Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle motility in healthy old men