Five Reasons Why NMN Users Should Switch to NR
Updated: Mar 21
Nicotinamide Riboside is likely as good or better than NMN in the following ways:
(4) Availability, and
If you have been told otherwise, you may have been misled. We'll look at all five...
One of the most common half-truths told about NMN is that it is the "most efficient" NAD precursor, because it is just a single biosynthetic step away from becoming NAD. The reason that's half-true is because once you get the NMN inside your cell, it is indeed a single step away from becoming NAD.
The reason that it is nonetheless deceptive is because the NMN in your oral supplement doesn't start inside your cells, it starts outside your cells, and it can't get inside as NMN -- probably not into any cells, and at least not most cells.
NMN can replenish intracellular NAD, but first a circulating enzyme has to degrade the NMN into Nicotinamide or Nicotinamide Riboside by removing a phosphate group. Happily for NMN, there are circulating enzymes that do just that. They are called CD73 and CD57. If you are curious, you can read more here about the various metabolic pathways for NAD biosynthesis.
But that means when you take NMN it first degrades into NR, and then enters some of your trillions of cells and gets built BACK up into NMN and then after that NAD.
So NMN works; that's not the problem. The problem is that it is not actually the shortest, most efficient path to NAD. In fact, it's a longer path than taking NR, because NMN requires the extra step of becoming NR first.
So why did someone tell you that NMN was one step away from NAD, but fail to tell you that the "one step" isn't true if you are taking the NMN as an oral supplement, which is the main reason non-scientists are interested in this?
One possibility is that they might be trying to convince you that NMN is better than NR, but they don't have good reasons, so they rely on half-truths.
If you don't think that you were being influenced by someone with an ulterior motive, it could be because the person who told you that NMN is only one step away from NAD also told you that they aren't selling anything, that they don't have any products, and they are just a scientist who wants you to live longer.
But that could be another half-truth, if the scientist co-founded a company that is itself attempting to patent NMN formulations as a pharmaceutical, and who would like to see aging classified as a disease so that NMN could be prescribed as a pharmaceutical to cure aging. If that were the scenario, then the scientist would be about as disinterested in NMN as an advertisement urging you to ask your doctor if NMN is right for you, because the purpose of the statement could be to build up demand for a future a pharmaceutical.
In fact, a pharmaceutical company that was co-founded by a famous aging scientist and is developing potential pharmaceuticals based on NMN has asked the FDA to only allow NMN to be sold in the United States as a pharmaceutical, not as a health supplement. And the FDA agreed that NMN should not be sold as a health supplement in the US. (You can read more about that here: Is NMN Illegal Now?)
None of that means that NMN doesn't work. In fact, it does work. But the question is whether another NAD precursor works as well or better, and has other advantages, such as effectiveness, safety, availability, reliability, and cost. So let's take a look:
There are four primary NAD precursors, which we will call TRYP, NA, NAM, and NR. The magic of NR is that it bypasses some steps that NA, NAM, and TRYP have to go through. And if those steps are blocked under some circumstances or in some tissues types, then NR can work when the others can't. That's mostly why everyone is talking about NR. (The other reason is because NR seems to have fewer side effects to worry about.)
So NR is kind-of the gold standard. How does NMN stack up compared to NR?
NMN is actually just an NR molecule with a phosphate group added on. In a perfect world, that phosphate group would be a good thing, because phosphates make up part of the NAD molecule that we are targeting.
But health supplements live in the imperfect world of substances that are not already inside your cell. And cell membranes have a "No Phosphates Allowed" sign on the door. So for NMN to get into the cell, it has to lose the phosphate, which it does, becoming just NR, and then it enters the cell as NR.
So now you can see that NMN is actually just a way of delivering NR to cells. Could it be a better way of delivering NR to cells than to simply take the NR? In theory it could be. In theory, maybe the NR doesn't make it to your cells intact, but the NMN gets there intact, then loses the phosphate, and enters as NR.
But there are two reasons why this theory is probably not true. First, the same circulating enzymes that degrade NR can degrade NMN, too, so there is no particular reason to believe that NMN has any advantage at getting to cells. Second, that phosphate group is surprisingly heavy -- about a fourth of the weight of the NMN molecule resides in the phosphate group. That means if you deliver a gram of NMN to your cells, only about three-fourths of a gram of NR actually arrives, whereas if you deliver a gram of NR to your cells, the whole gram is potentially in play. So you would have to take more NMN to get the same effect.
Because NMN works as NR, they are both likely to be equally effective, although I am surprised by studies that show NR to be effective where NMN is not (e.g., "Interestingly, NR but not NMN was efficiently assimilated intact into NAD in the muscle"). Not sure what might cause that, except maybe the NMN not degrading the right way ("CD38 may metabolize NMN, but not NR, into NAM").
The earlier-discovered NAD precursors Niacin (NA) and and Niacinamide (NAM) are generally safe, but at high doses they have some side effects and complications. You can read here about the problems with Niacin and with Niacinamide. The nice thing about NR is that it doesn't seem to have the same, or any, significant negative side effects, and appears to be safe in tests up to 2,000mg per day. (Clinical trials frequently use one or two grams per day.)
From a chemical standpoint, NMN may be just the same as NR. But there are two risks.
First, we just don't know. NMN has not been as thoroughly scrutinized. There are hundreds of studies involving NR, but fewer with NMN. As ChromaDex, the primary manufacturer of NR, says, "Clinical studies, multiple certifications, good manufacturing practices, multiple regulatory approvals and scientific standards have validated Niagen® since its commercialization in 2013." The same cannot be said of NMN.
But there is another risk, too. NMN is chemically different, and may have different effects. First, and simplest, if all of the NMN gets degraded into NR, then there are going to be a lot of phosphates that need to get absorbed or cleared, and we don't know much about how that could go right or wrong.
Second, NMN proponents assert that there is a molecule called slc12a8 that transports NMN directly into cells without having it first degrade into NR. Other scientists disagree, and say that's not what slc12a8 does. I think what everyone does agree on is that slc12a8 is not expressed in every tissue in the body (it is common in the small intestine), and so slc12a8's impact is limited even if it works.
But suppose it does work. Suppose that slc12a8 pours NMN into cells in particular tissues. Well, it turns out that over-accumulations of NMN in cells can be toxic. In neurons, it causes neurodegeneration. So it is not necessarily the case that pumping NMN directly into cells is a great idea, and if in fact slc12a8 allows that to happen, then NMN could have a different safety profile from NR, and potentially worse.
It used to be pretty easy to find both NR and NMN online, but that has changed in the United States. The Food and Drug Administration has declared that NMN may not be sold as a food supplement in the US, and as of March 21, 2023, Amazon seems to have removed most or all NMN products. That's not because NMN is unsafe or ineffective, but because Congress passed a law that allows pharmaceutical companies to have exclusive rights to sell some substances under some circumstances, if the supplement makers do not take steps to show that their ingredient is properly in the food supply before clinical trials begin. ChromaDex did that for NR, and the NMN suppliers did not do that for NMN. So as the FDA decision gets enforced, NR will be easier to come by than NMN, at least in the US.
If you are buying Niagen, then it comes from ChromaDex, and it's manufactured by W.R. Grace in the US, in certified facilities. But it's sometimes difficult to know where NMN is sourced. ChromaDex did a quantitative analysis of twenty-two NMN consumer products and found that most of the products contained little or no NMN, and only about one-in-seven had NMN at or above the label claim. Those are not great odds.
It is difficult to compare the cost of NR and NMN, because NMN comes in so many different sizes and shapes. Historically, NR has retailed for about $1 for a daily dose of 250mg or 300mg, so maybe roughly $4 per gram. That's about how much it might cost today at Amazon or directly from ChromaDex.
NMN used to cost more than that, and was recently being sold as a bulk power for about $1.50 per gram if you buy a hundred grams, or as much as $4/gram in traditional capsule form, which is what Amazon was recommending on the day I checked, back when NMN was still available on Amazon. And maybe some vendors off Amazon are still selling it for similar prices.
If so, then it looks at first like NMN might be less expensive. But there are three reasons to question that. First, some of the NMN formulations actually might contain other stuff, too, like resveratrol or black pepper, which you might not want at all, but at least means some work to calculate exactly how much NMN is actually present in the product. Second, there is a risk that the supplier will turn out to be disreputable, like many that were tested, and include less NMN that stated, which would substantially (or infinitely) increase the per-unit cost compared to what you are expecting. Third, to the extent that NMN is just delivering NR to cells, much of the weight of the NMN molecule consists of a phosphate that will be discarded, so the 1,000mg of NMN is only worth about 764 grams of NR. that's simple math, but the studies support it ("Lower concentrations of NR are required compared to NMN to obtain a similar increase in NAD+").
Even then, there may be places where NR is hard to come by and NMN is cheap and reliable, and might be worth getting instead. But once you bake in the various risks, NR might be a safer bet at most prices.
So should you switch from NMN to NR?
It depends on why you have chosen NMN in the first place. If you chose NMN because that's the one you have heard of, well, now you know about NR and the reasons why NR may be a better choice, so you can switch, or at least try NR to compare.
If you chose NMN because you were misinformed about its relative advantages, then you may have good reasons to revisit your thinking. The supplement industry is filled with confusing half-truths. People advocate gluten-free products because some people have a bad reaction, and then others end up paying more for gluten-free products even though gluten does not cause them a problem.
Similarly, a liposomal or sublingual delivery may be helpful for some nutrients in some instances, but people mistakenly think of it as a universal improvement, when liposomal or sublingual may be completely unnecessary, and possibly even unhelpful, in other circumstances. In the case of NR, liposomal purports to protect against degradation in the stomach or gut, and to improve absorption by cells, but studies show that (1) stomach acid is not a significant problem for NR, (2) delivering NR to the gut actually provides some benefits, and (3) getting NR through the cell wall isn't a problem ("NR does not require conversion to enter the cell, which could partially explain the high level of availability.")
However, if the reason you have preferred NMN is because you live in a place where NR is difficult or very expensive to come by, and reliable NMN can be had for something like half-the-price or better, and the relative risks associated with NMN do not appear to be significant to you, then you might do just fine with NMN -- it does work.