Muscle for Life with Mike Matthews - What Are NMN Supplements and Do They Really Work?

Episode Date: February 21, 2024

Nicotinamide mononucleotide (NMN) is often touted as the frontier of anti-aging supplements, promising not just more years of life, but better quality ones.  With bold claims of enhancing lifespan and slowing down aging, to improving physical performance, body composition, and brain health, NMN has captured the attention of both consumers and scientists. But how much truth is there to these claims?  In this episode, I’ll explore the molecule NMN, its benefits, the research supporting it, and whether or not it stands up to the hype.  Whether you're a skeptic or a hopeful believer in the search for the fountain of youth, listen to this podcast to learn about the potential of NMN supplements. Timestamps: 0:00 - Please leave a review of the show wherever you listen to podcasts and make sure to subscribe! 2:19 - What is NMN and Why Is It Important? 5:31 - What Does Current Research Say About NMN? 9:52 - Can NMN Really Improve Your Physical Performance and Body Composition? 12:12 - Legion One-on-One Coaching: https://www.muscleforlife.show/vip 13:53 - Is NMN Anti-Aging? Can NMN Supplements Stop or Reverse Aging? 16:57 - Do NMN Supplements Improve Cognition and Brain Health? 21:15 - Are NMN Supplements Worth the Hype? Mentioned on the Show: Legion One-on-One Coaching: https://www.muscleforlife.show/vip

Hello, hello. This is Muscle for Life, and I'm Mike Matthews. Thank you for joining me today for a new episode on a popular supplement that I'm asked frequently about, especially over my Q&As that I do on Instagram that I then bring over here to the podcast. In just about every one, someone asks about NMN, which is nicotinamide mononucleotide. It's a molecule found naturally in our bodies and various foods. And according to some of its more ardent advocates, often people who are part of companies that sell NMN, are part of companies that sell NMN, this supplement is the new frontier in anti-aging because by swallowing a pill or two a day of it, the story goes, you can dramatically enhance your lifespan and slow down the various negative processes associated with aging. So not only can you live longer,

but you can enjoy those years more fully. Now on the face of it, such claims sound at least dubious, if not absurd. However, there is a fair amount of evidence that purportedly supports these claims. And you can find some very credentialed people who make these claims and who point to that evidence and interpret it in such a way that indicates that NMN is shaping up

to be a breakthrough in health and longevity, something that everyone should be taking, maybe comparable to creatine, which at this point is a supplement that everyone should be taking, even people who are not doing any sort of resistance training or strength training, which they should be. But even if they are not, even if all they do is maybe some cardio or maybe they don't exercise at all, they still should be taking creatine for its various benefits related to heart health and related to brain health. And so, of course, the questions I'm going to be answering in today's podcast are, how true are these claims regarding NMN and should you consider taking it? Okay, so let's start this discussion with a quick explanation of what NMN is. So it stands for

nicotinamide mononucleotide, and this is a molecule that's found naturally in our bodies and in various foods. And it is a precursor, which is a substance that something else is formed from to something else in the body called nicotinamide adenine dinucleotide or NAD+, as it is generally referred to. Now, this NAD plus molecule is important for our health because it is a coenzyme, which is a substance that's required by various enzymes for their activity. And enzymes are just chemicals in the body that bring about specific chemical reactions. And so this NAD plus assists various important enzymes in the body that relate to all kinds of cellular processes like energy metabolism, DNA repair and gene expression. Now, research shows that our body's NAD plus levels decline as we get older, and that in turn causes various problems.

It limits our body's ability to generate energy at a cellular level. It limits our body's ability to repair DNA. It limits genomic signaling, which in simple terms is just the system whereby a cell translates genetic information that is encoded in the DNA into action. And so when you think about many of the negative effects that people generally associate with aging, a lot of them relate to energy levels, function of various organs and risk of disease. And so when scientists discovered the importance of NAD plus in aging and the connection between NAD plus levels and energy production and DNA repair and genomic

signaling, they naturally began to wonder if we could somehow increase NAD levels as we get older. And if we could, if that would mitigate or maybe even eliminate some of the negative effects associated with aging. And that brings us to NMN, which is a derivative of vitamin B3 of niacin, which has been shown in previous research to increase NAD plus levels in the body. And according to proponents of NMN, it is superior to niacin, both flush and non-flush niacin for the purpose of increasing NAD plus levels, usually for two reasons. One, they will say that it is simply more effective in most people at increasing NAD plus levels. And two, it has fewer side effects like the flushing, for example, that I personally enjoy. I take niacin

every day, not only for its effects on NAD plus levels for reasons that I will get into in this podcast, but also and more importantly for its cardioprotective effects, its effects on cholesterol levels. So niacin is an effective supplement for raising HDL cholesterol levels and lowering LDL cholesterol levels. And that is good if you want to have a healthy heart. Now, the key question, what does the research say about NMN and about increasing NAD plus levels in general? Can this supplement NMN and can this mechanism of action increasing NAD plus levels, can it improve cardio metabolic health? Can it improve physical performance? Can it improve cognitive performance? Those are the three main benefits that I've seen claimed for NMN. And I suppose you could say for increasing NAD plus levels in general, which would

also apply to niacin, but niacin is cheap and unsexy. So NMN is the supplement of choice. That one is special. That one is exotic. That one is expensive. Well, let's start with cardio, metabolic health, and with animal research, initial research done on NMN that was positive, that got a lot of people excited. There were several studies that were published in the journals Aging Cell and Cell that found that NMN restored NAD plus levels in older mice and that that in turn enhanced their cardiovascular health. And it also reversed some age related reductions in blood flow and capillary density. There was another study conducted by scientists at Washington University School of

Medicine that found that NMN replenished NAD plus levels in diabetic mice and that that in turn improved their insulin sensitivity and improved their blood lipid profile. It restored gene expression related to circadian rhythm, inflammation, oxidative stress, all very exciting, very promising. But then the human research came and so far it is less exciting. For example, in a 2021 study published in Science, researchers gave postmenopausal women with prediabetes 250 milligrams of NMN or a placebo every day for 10 weeks. And the results were NMN did cause blood NAD plus levels to rise. However, muscle NAD plus levels remained the same. And that is a finding that was echoed in previous research on a very similar molecule, which is nicotinamide riboside, otherwise known as non-flush niacin.

So that molecule is almost identical to the NMN molecule. And so this is a problem with NMN. If the body is not absorbing it into the skeletal muscle, that's probably going to limit its benefits. I mean, I'm not a scientist, but I have a hunch. And just as a quick note, because you may be wondering, flush niacin has been shown to effectively increase NAD plus levels in muscle tissue. For example, in one study, flush niacin increased muscle NAD plus levels by 1.3 times at four months and 2.3 times at 10 months. Anyway, coming back to this study with postmenopausal women, they did not experience any changes

in body composition. They did not experience any changes in blood glucose and insulin levels or blood pressure, but they did see a 25% increase in their muscle insulin sensitivity, which is interesting given that NAD plus levels did not rise in the muscle tissue, but is obviously due to another mechanism. So that's one human study that I would say constitutes a strike against NMN, at least how it is generally promoted. If we look at another that was published in Scientific Reports, we find that 12 weeks of NMN supplementation did not improve arterial health, which is specifically what the researchers were looking to investigate. And then we have two

other human trials related to cardiometabolic health that found that taking NMN failed to improve blood levels of glucose, insulin, and cholesterol. And in fact, in one of those studies, the NMN increased blood insulin levels after eating, which could have negative health consequences, at least over the long term. And so if we look at the current weight of the evidence, there is no compelling reason to believe that taking NMN is going to improve your cardio metabolic health. Now, what about physical performance and body composition? Can NMN improve either of these things? These are two major claims often made to sell these supplements. And let's start with a study that was conducted by scientists at Guangzhou University. In this study, runners, they took 300 to 1200 milligrams of NMN every day for six weeks,

and that failed to improve several markers of physical performance and cardiovascular fitness that researchers were measuring. And as for body composition, researchers looked at that too, and the runners experienced no meaningful change in body weight, muscle looked at that too, and the runners experienced no meaningful change in body weight, muscle mass, BMI, or body fat percentage, and they didn't perform better in grip strength, push-up, or sit-and-reach tests than the placebo group. So in this study, NMN was a complete flop. Now, if we look at a few similar studies, like one conducted by researchers at Osaka University, another one at the University

of Tsukuba, we see that NMN does indeed raise blood NAD plus levels. That is established, but it did not have a significant effect on walking endurance, walking speed, grip strength, insulin sensitivity, general well-being, sleep quality, fatigue, also mostly a flop. However, there are two studies that suggest that NMN may indeed benefit physical performance. The first was published in NPGA Aging, and it found that taking NMN nominally increased walking speed and grip strength, but had no effect on body composition, hearing, blood pressure, vascular health, or cognitive function. And by the way, the reason I emphasized nominally is the effects were pretty small. And in the case of grip strength,

did not reach statistical significance. So are questionable as to whether it was caused by the supplement or it was just random. So in the case of gait speed, for example, after 12 weeks of supplementation, the gait speed went from an average of 1.3 meters per second to 1.6 meters per second. And in the case of the grip strength, after 12 weeks, it went from an average of 34.1 kilograms to 37.4 kilograms. But again, this did not reach statistical significance. So you have to put less weight on it. Do you want to transform your body, but you just can't seem to break out of the rut? Have you read books and articles,

watched videos, listened to podcasts, but still just aren't sure exactly how to put all the pieces together for you? Or maybe you know what to do, but you're still struggling to stay motivated and on track and do the things that you know you should do. Well, if you are nodding your head, I understand. Getting into great shape is pretty straightforward when you know what to do, but it's not easy. It takes time. It takes effort. It takes grit. And that's why I created my VIP one-on-one coaching service. We take people by the hand and we give them everything they need to build their best body ever. We give them a custom diet plan, training plan,

thing they need to build their best body ever. We give them a custom diet plan, training plan, supplementation plan. If they want supplements, you don't have to take supplements. We coach them on how to do every exercise correctly. We give them emotional encouragement and support, accountability, and the rest of it. And we are pretty good at it too. We have worked with thousands of men and women of all ages and abilities and lifestyles and help them build a body they can be proud of. And guess what? We can probably do the same for you. If there's a fit, head over to buylegion.com slash VIP. That's buylegion.com slash VIP and book your free consultation call now. Now, there's another study I want to talk about in the context of physical performance because it made for some rather striking headlines that claimed that it was evidence that taking NMN could effectively halt aging. So this study was published in Geroscience, and it claims that NMN

supplementation significantly improved six-minute walking distances. It also significantly improved health scores based on a 36-question survey that asks things about energy and fatigue and emotional well-being and social functioning and pain and general health and other things. And the clincher that generated a lot of headlines that blood biological age increased less with NMN compared to a placebo. Hence, the exaggerated lines about halting aging. That said, if we take the data from this study at face value, that would be a pretty big arrow into NMN's quiver. The study was short. Certain aspects of how it was conducted were questionable. For example, it put a lot of weight on an AI-driven model to determine the blood biological age. So that component of the study was according to AI. And subsequently, other experts

have criticized that model as inaccurate. For example, according to this model, in the 60 days that this study was conducted, the placebo group had aged more than five years. So when that's your placebo group, it's not hard to show a quote unquote improvement in your supplement group. Also, the study's participants were very slow, suspiciously slow for supposedly healthy 50 year olds, slow, suspiciously slow for supposedly healthy 50-year-olds, some of them walking just over 300 meters in six minutes. And just so you understand the discrepancy here, I have a six-year-old daughter and six-year-olds typically walk about one and a half meters per second. So she would cover 300 meters in three to four minutes. My six-year-old? We're supposed to believe that on average, she walks twice as fast as a healthy 50-year-old? Hmm. Now, what could possibly account for these

anomalies? Well, maybe it has something to do with money. Of course, money. Where did the research money come from? It came from a supplement company that sells NMN and of course has a vested interest in the outcome, duly noted. And so to wrap up on this physical performance and body composition, there is currently very weak evidence if we consider the overall weight of the evidence that NMN is going to improve physical performance or body composition, especially if you are a young-ish, let's just say anywhere from 30 to 60 years old, healthy person who exercises regularly. Okay, now what about cognition, brain health, brain function, another major area of benefit that is used to sell these supplements. Well, the strongest evidence for these types of claims, unfortunately, is animal research.

Several trials have shown that NMN improves cognitive function in older animals. But as is always the case, it is a mistake or it is simply dishonest to extrapolate animal research to humans to say, hey, look at what it's doing in animals. It certainly, almost certainly, even probably will do the same thing in humans. That's not how it works. So many times that fails for so many different reasons. And so then what does the human evidence have to say on the matter, NMN and cognitive function? Meh. Because there's just very little to go on. One study, for example, reported mixed results on fatigue. Interesting. Another study suggested that NMN could improve cognitive function as we get older because there's a relationship between muscle health and brain health and that NMN supplementation

may improve muscle function. Yeah, a lot of contingency. And so it's too early to rule out the possibility that NMN can improve cognitive function, but it's also too early to claim that it does. It is currently a theory that needs more investigation. And the same goes for other potential benefits often used to sell NMN, like protecting against DNA damage, improving reproductive health, bone health, kidney health, eye health, all things that have been shown in mice, but not yet in humans. Now, if you are still listening and you've understood everything that we've just gone through and you figure that you're just going to include NMN in your regimen in case it pans out, if we fast forward 10 years, a lot more research is done, and it actually does have some pretty significant

benefits that are just not clear right now. That is a reasonable position because it's not going to hurt you. It's well tolerated. It causes no adverse effects, even with long-term use. So it's safe. However, you should know that many NMN supplements on the market are frauds. And we can see this in an analysis that was conducted by a supplement manufacturer, a company called Chromadex. They make a niacin product, an NAD plus product, and they analyzed the 22 most popular NMN brands in these products. So top 22, 14% met or exceeded the NMN amount on the label. Just 14% met or exceeded label claims. 23% fell slightly short. So they contained 88 to 99% of the stated amount and 88% is sloppy manufacturing. Anything between let's say 95

and 100% or let's just say 95 and 105% is more acceptable. You are not going to get to 100% on the mark in every pill or in every serving or every powder. It's actually just physically impossible. And so even legally you're allowed a little bit of variability, but it shouldn't be in the 80s. And it definitely should not be in the 70s or lower. 64% of the 22 most popular brands on Amazon contained less than 1% of the amount of NMN claimed on the label. So basically none. And 14% contained actually none. No detectable amount of NMN. And together, that's 78% of the top 22 brands contained less than 1% down to 0%. And if you want to check this white paper, I guess we can call it out for yourself. You can just find it online. Search for quantitative analysis of 22 NMN consumer products.

And if you're going to buy NMN, make sure that you are buying from a company that actually is providing NMN. All right. So where does all this leave us? Well, we've learned that NMN is not the anti-aging panacea that some of its more credentialed champions claim, or at least that the evidence for such claims is weak to non-existent currently. But do you know what can support such claims? Do you know what has been shown repeatedly in human research, well-designed, well-executed to dramatically improve the various processes that are negatively impacted by aging? You probably guessed it. It's regular exercise

and particularly regular cardiovascular exercise. Strength training is very important as well, but you want to do both. If you want to maximize health and longevity, you really, really want to do both. A couple of hours of strength training per week, a couple of hours of endurance exercise per week is a very effective regimen. More exercise is generally better. Of course, you can take that too far, but it is difficult to take too far. If you are exercising 20 plus hours per week, you probably are taking it too far unless you are extremely conditioned and you've worked up to that over the course of many years and you are getting blood work done and you know that your health is in a good place and you don't have an

eating disorder and, and, and. But for most of us, just four or five hours of exercise per week split about equally between strength training and cardiovascular training is going to provide the vast majority of exercise related benefits to aging and everything else. Now, if you're doing that and you're open to some speculative supplementation advice that won't harm you, but may or may not make a meaningful difference, I would recommend flush niacin over NMN because the research I would say actually is more positive at this point on flush niacin taken on the whole, because again, as I mentioned earlier, it has been shown to increase NAD plus levels in skeletal muscle. And we know that it can dramatically improve

our cholesterol profile. And as for dosing, if you look at studies on flush niacin, the dosing ranges from a few hundred milligrams per day to three grams per day. I take one gram per day. I could probably argue that two grams per day is significantly better, is meaningfully better at least than one gram per day. And as I say that, maybe it will work up to two grams per day. But currently, I take one gram per day. If you want to start taking flush niacin, do not go from zero to one gram or even 500 milligrams per day, or you are going to get a rather unpleasant reaction. You want to work up to a larger dose. You're going to want to start probably at 50 milligrams, certainly no higher than 100 milligrams.

Just look online for a standard dosing protocol for flush niacin. How do you go from zero to one to two grams per day without blowing yourself up? Well, I hope you liked this episode. I hope you found it helpful. And if you did, subscribe to the show because it makes sure that you don't miss new episodes. And it also helps me because it increases the rankings of the show a little bit, which of course then makes it a little bit more easily found by other people who may like it just as much as you. And if you didn't like something about this episode or about the show in general, or if you have ideas or suggestions or just feedback to share, shoot me an email, mike at muscleforlife.com, muscleforlife.com,

and let me know what I could do better or just what your thoughts are about maybe what you'd like to see me do in the future. I read everything myself. I'm always looking for new ideas and constructive feedback. So thanks again for listening to this episode and I hope to hear from you soon.