Does the World’s Most Profitable Drug Damage Muscle?

Muscle loss, the impact of drugs. Get this, a doctor friend of mine recently texted me, "I'm stopping my statin." Rather than jumping in with my own opinion, I responded with curiosity. Interesting, what compelled you to make that decision and why now? He replied, "Haven't you seen this new paper? It scared the sarcomeres out of me." Let me know if you get that joke. He then texted me the new paper analyzing data from 300,000 participants with some followed over a decade and it concluded Foods. Continuous statin use is associated with a decline in muscle function and mass over time, with as much as a 73% decrease in lean mass compared to non-statin users. Now here's why that matters. Statins are one of the most prescribed drugs on Earth, and muscle loss is one of the strongest predictors of disability and mortality. But we don't stop at the headlines now, do we? So let's dip in. Oh, I sat on my phone. Continuous statin use was significantly associated with accelerated declining grip strength and declining lean mass. Even stronger people declining faster, so they become the weaker people. When I first saw this graph, I actually thought there was a mistake because there's something extremely odd. The opposite was true. I'm going to test this on myself. This is one of those results where you should stop the video and re-listen. So what's the takeaway? What's the summary? Here's a tip that's not so obvious. As you can see in the intro, I actually did break my phone. Unfortunate. Well, hopefully it's a good video. Now after watching this video, if you want more information, check out the associated Stay Curious Metabolism newsletters below, including one covering the paper we're going to discuss, but also a bunch of other letters covering statins and other lipid-lowering medications. They're all grounded in data, not dogma. But with that, on to the roadmap for this video. I've broken this video into 5 chapters. Chapter 1, we're going to go over the study design and main findings. Then in Chapter 2, we're going to cover some unexpected results, with the most surprising finding in those who exercise the most. In Chapter 3, we're going to go over biological mechanisms—my favorite—how statins impair muscle mass and function biochemically. Chapter 4, we're going to take a balanced approach, going over the pros and cons of statins. And then in Chapter 5, I'm going to talk about protective strategies, supplements to help preserve muscle health with age, whether or not you're on a statin. And before we begin, if you think you know where this video is going, you're probably wrong. But with that, Chapter 1: Study Design and Main Findings. We'll break this up by discussing two separate analyses: the cross-sectional analysis—that's a single time point—and then the longitudinal analysis—when you follow people over time. So to start with the single time point, the cross-sectional, how did statin users compare to non-statin users? Well, in the fully adjusted model, adjusting for age, sex, education, smoking, BMI, activity score, diet quality, high blood pressure, diabetes, and so on, statin use was associated with lower grip strength and lower what's called appendicular lean mass—basically the arms and legs. You can look at the statistics if you want for yourself, but they did perform multiple analyses in this study to stress test the robustness of their findings, and across all approaches, the inverse association between statin use and grip strength and lean mass remained consistent. More statins, lower grip strength, less lean mass. But building on this, and this is what's more interesting I think, they wanted to actually follow people over time to get a trajectory. So they followed a subset of the participants for a decade on average. And echoing the prior analyses, continuous statin use was significantly associated with accelerated declining grip strength and declining lean mass. Basically, on this graph, the steeper the slope means the faster the decline. Or if you want the pithy punchy version, statin use is linked to faster muscle decline. But, when I first saw this graph, I actually thought there was a mistake because there's something extremely odd, something that appears to contradict what I just said. Can you see it? Well, that brings us to Chapter 2: Unexpected Results. There were actually at least two really confusing patterns. First, if you look at the graph for grip strength and the graph for lean mass over time in the longitudinal cohort, the one followed over time, interestingly the statin users start with higher lean mass and grip strength. This is weird, right? Because I said in the cross-sectional analysis, which one can take to mean the beginning of the study, a single time point, statin users were generally weaker with less lean mass. Is there a contradiction here? Are you confused? Good, I was too. Let's unconfuse us. First, please note that the group followed over time, the longitudinal cohort, was a smaller group, 35,557 people of the original about 300,000. So this is a select smaller group compared to the larger cohort. Of course this makes sense because you're just not going to be able to follow up everybody over a decade. Not everybody has two time points. But let's make sense of the pattern. A higher proportion of the statin users in the longitudinal analysis were men as compared to women. And men, of course, exhibit greater strength and muscle mass in general, so it makes sense that at baseline, the statin group enriched in men would have more strength and muscle mass. However, over time, you see this cross point where the continuous statin use group because they were declining so much more quickly, ended up with less muscle mass and less strength. So what's the takeaway? What's the summary? Well, I guess don't ask grandpa to open the pickle jar. You might wanna ask grandma. Anyway, there are other possible reasons that I discuss in the letter, but the point is simply that the pattern doesn't contradict the main findings, but actually strengthens it. It's not just about weak people getting progressively weaker, but even stronger people declining faster so they become the weaker people. And another really interesting element occurred when they looked at the interaction between statin use and its impact on lean mass, grouping people into their physical activity groups—high activity versus low activity. And whereas you might think highly active users of statins would have a lesser decline than less active users of statins, the opposite was true. Highly active statin users exhibited a much faster decline in lean mass over time. And this really caught me off guard. This is one of those results where you should stop the video and re-listen to that last bit. Highly active statin users exhibited a much faster decline in lean mass over time. It suggests that the more you exercise, the more activity you do, it could actually accelerate the negative impacts of statins on lean mass if we assume some element of causality. We'll get into that assumption in a minute. Now why this would be is not entirely clear. If we assume some element of causality, it could be indirect because statins cause symptoms that could lead to impaired function or intensity of exercise, or it could be direct where there are actually metabolic challenges of statins—we're going to talk about a few in a minute—and these compound with exercise to exacerbate muscular decline. Basically, you're overstressing your muscles, leading to degradation rather than building them up. So I've been reading through all the comments on the posts around this paper people saying statins annihilated my workouts, it lowered gym time. Now obviously these are anecdotes, and the data we're reviewing in this paper, they're not our RCT, they can't prove causation. But that gave me an idea. I'm going to test this on myself in a blinded randomized controlled trial comparing 80mg of atorvastatin to a placebo control. What are your hypotheses? And more information below. That brings us to Chapter 3. Let's talk about the biologically plausible mechanisms by which statins could harm muscle function and potentially muscle mass. The first you might have heard of, CoQ10. Coenzyme Q10 is vital for mitochondrial energy production and statins can inhibit CoQ10 synthesis. Two, mitochondrial metabolism more directly. Statins have been linked to mitochondrial dysfunction, particularly inhibiting complex IV of the electron transport chain in mitochondria. They can also disrupt intracellular, within the cell calcium metabolism. Both of these are critical to healthy muscle physiology. 3. Statins can cause some degree of myotoxicity, or muscle fiber damage, which may explain the muscle pain and elevated biomarkers, ones called creatine kinase, seen in some statin users. This actually happened to me when I tried rosuvastatin. I had muscle pain and my muscle damage marker creatine kinase went up. 4. Insulin resistance. Over long-term use, say a decade of continuous use, statins can worsen insulin resistance and can increase diabetes risk, and this can have further indirect effects, negative effects on muscle function. I looked a lot more details in deep deep dive letters linked below, but that's your starter list. But with that, let's get to Chapter 4. I want to give a balanced perspective—pros and cons of statins. And again, I want to be clear, these data that we just reviewed, they're not definitive. They're worth attention, but they're correlative. That said, a caveat on the caveat, even if this study doesn't prove causation beyond a shadow of a doubt, ignoring correlative data combined with biologically plausible mechanisms is how we miss slow harms. But again, let's step back and highlight pros and cons as clearly as I can in a bulleted list. Pros: statins can lower LDL and ApoB, which can reduce risk in some patients. They also reduce inflammation and improve endothelial function and vascular health. Cons though: statins can impair muscle function and mass, decrease coenzyme Q synthesis, lower GLP-1 levels, an important hormone in metabolism, increase insulin resistance, raise diabetes risk, and cross the blood-brain barrier with variable effects. And of course, they can harm mitochondria. So there's your list, marinate on it, but if you or a loved one are taking a statin, that's part of your medication regime, it's not going to change, there are things you can consider to potentially offset the negative side effects. That brings us to Chapter 5. One example is a compound called TU-DC-A. I discussed this in a prior video and a newsletter. It may help actually mitigate statin-induced decreases on GLP-1, insulin sensitivity, and diabetes risk. It also has direct anti-inflammatory effects on blood vessels which could improve cardiovascular outcomes. It's actually quite astonishing how well it works at least in preclinical models, with randomized controlled trials outstanding—more discussed below. There are also general supplements that can support with muscle growth, maintenance, and function, especially as we age. Top of this list probably is creatine monohydrate. Old or young, And beyond just drawing water into muscles, creatine is really important for muscle function. When combined with resistance training, it can help to activate muscle stem cells to support muscle growth. A few moments later. To support muscle growth. I don't know why that was hard to say. Anyway, the data are, like you after taking creatine, very strong. I recommend taking at least 5 grams with meals, and if you want more on creatine protocols, you know where to look. Moving on. Urolithin A. Urolithin A is very interesting. It's a postbiotic compound produced by the gut or supplemented. It can be produced by the gut from ellagitannins. So if you're looking for food sources naturally rich in ellagitannins that your gut may be able to turn into urolithin A, pomegranates, especially the white part that most people throw out, and walnuts. But again, urolithin A can be supplemented and it's known to enhance mitochondrial health and muscle function and performance. 4, sarcosine. This is an oddball misunderstood amino acid or amino acid derivative involved in methylation and glycine metabolism. And some really interesting recent evidence suggests it might help fight age-related muscle loss. See this video for more, which includes me doing push-ups with my mom. "Papa, wow, you really can do this." That brings us to 5: Coenzyme Q10. Obvious, but no less important. But here's a tip that's not so obvious. If you're looking for the most bioavailable form of coenzyme Q10, the one that gets into the mitochondria the best, choose one that's called a phytosome phospholipid complex coenzyme Q10. So there's a tip for you. It's also worth noting that there are other pharmacological options for lowering cholesterol that have far less impact on muscle. If you want to learn more about these, I have a whole concise masterclass which you can check out here covering how they work, their pros and cons. I built this to be a resource for you and your doctor, so print it out Bring it to your doctor, hopefully it's valuable to you. Anyway, let's wrap up. The goal here is not to vilify statins, but to examine the emerging data with nuance, especially as it relates to long-term muscle health. What is clear is that statins, sometimes presented as God's gift to medicine, are not benign medications. That's not just opinion, that is fact. But on opinions, my opinion remains that there is a strong bias towards highlighting the potential benefits of pharmacotherapy statins and other drugs to patients while sweeping the side effects under the rug. And honestly, my purpose here is to humbly rebalance the conversation, give you data you need to make an informed choice. So the real question isn't whether statins are good or bad, it's whether we're honest enough to talk about tradeoffs. Are we?