Medical Mystery: The Man Who Got Weaker When He Started Training

18:29Dr. Austin Baraki:If he's approaching the diabetes diagnosis, he can go on lipid lowering therapy, things like that, as well as ideally, if you're lucky, get some counseling for the lifestyle related changes. Maybe if you're even luckier, have access to getting referred to a, you know, a registered dietitian or something like that. I would say that the more kind of modern, the big brain paradigm that should preferably be applied these days would be attacking the problem at its source. And the source here is the adiposity, likely the excess abdominal body fat, the fat that is likely infiltrating this individual's liver if we can attack that.

19:04Dr. Austin Baraki:And the way to most potently go about doing that is going to be through a combination of the lifestyle interventions, which we're happy to go over. We've been talking about this for a better part of a decade or more at this point, but we can certainly do that again, as well as medical therapy, medical intervention on top of the lifestyle things up front, just because look, I'm trying to prevent all these complications and help you live longer. And I'm like less biased in terms of how exactly we go about it compared with what you'll hear a lot of folks talking about on the internet where it has to be lifestyle or nothing.

19:35Dr. Austin Baraki:And so maybe this person should be initiated on something like an anti-obesity medication, like a GLP-1 receptor agonist like terzepatide, for example. And then the other kind of escalatory line of therapy, which absent any intervention is not the first thing that I'm going to jump to, but rather thinking about, is this person somebody who may be a candidate for consideration of metabolic bariatric surgery? Again, not something that is like on day one that I meet this person going to be immediately making happen, but is in the back of my mind as, yeah, it's an option. He may well meet criteria for eligibility for that sort of thing.

20:11Dr. Austin Baraki:And so, This is the more modern paradigm because instead of kind of trying to cut the individual heads off the hydra of your blood pressure and your blood sugar and your blood cholesterol and treating the complications, treating the quote unquote root cause, which is the smart way to go about this, addressing the obesity itself through lifestyle medications, potentially surgery, is the way to fix all of those other things. And so that would be my approach here. And so that may involve starting a GLP-1 receptor agonist. It may still also involve starting some lipid lowering therapy. As I said, I would not be initiating a fibrate in this situation.

20:43Dr. Austin Baraki:I do not tend to use vibrates very often at all. It's pretty uncommon that I end up prescribing them to patients outside of very extreme situations. But most of the time, it's going to be a relatively potent statin for some of these individuals. And then other interventions, there are a lot of really potent lifestyle strategies to manage triglyceride levels, as well as prescription fish oil, omega-3 derivatives, and things like that that can also be useful in that situation that I might look at for somebody like this as well.

21:11Dr. Jordan Feigenbaum:Yeah, yeah. I mean, that's what I'm hearing from you is that the whole point of treating this guy aggressively is that his cardiac risk is real and not just his cardiovascular risk, but also the risk to his kidneys, the risk to his liver, this CKM sort of situation. And so rather than just doing one thing at a time, seeing how the person responds, we want to get all of these variables quote optimized as quickly as possible because effectively the risk from these things is worse over time, the longer you let them kind of persist. And the exercise piece is supposed to help with all of it. We know that.

21:43Dr. Jordan Feigenbaum:And he's doing it. He's taking his medications. He's open to quitting smoking. He's getting off the couch, which is what makes the next part of this case so important because something in that picture, maybe that combination of doing all the right things actually goes sideways. And the question is whether anyone catches it in time and whether this guy ends up trusting the medical system enough to keep using it going forward. That's coming up next. So we've got the history. We've got the med list. Now let's see the labs because there's a number on this panel that probably is going to change where your brain is going.

22:12Dr. Jordan Feigenbaum:So his lipid panel, he's got a second one here. His total cholesterol is 250. His triglycerides are 154, both down significantly from where he started, which was a cholesterol of 278 and triglycerides of 48. The medications are doing their job on the lipid side. And then there's the CK. A quick definition for anyone who hasn't heard this term, we've talked about it a lot on the podcast, but if you're new to the podcast, CK stands for creatine kinase. It's an enzyme that lives inside the muscle cells, and when the muscle cells get damaged, CK leaks into the blood. The more damage, the higher the number, and a normal CK is somewhere under 170 or so, depending on the lab.

22:45Dr. Jordan Feigenbaum:This patient's CK came back at 18 ,979. That's over 150 times the upper limit of normal. He came back into the office, though, so he's sitting right in front of you. He says he feels fine, maybe a little sore, but what's going through your mind?

22:58Dr. Austin Baraki:Yeah, this is basically what I expected, especially when you told me that on our physical exam, his muscles, he had seemingly like muscular tenderness and maybe even some swelling there, which is again, disproportionate for somebody with his level of fitness who is doing not a terribly crazy home exercise program. And so I was concerned that he had a muscle kind of centric problem here, maybe some form of myopathy or myositis. That presentation can also fit with what exertional rhabdomyolysis looks like. And so that's where I would go back and say, Can you tell me again exactly what your home exercise program has looked like and how it's been feeling?

23:38Dr. Jordan Feigenbaum:Well, so, Dr. Baraki, fine. You know, you're pressing me on this. I didn't want to mention it because I don't want to complain. You know, I'm just trying to do my best here. But when I first started working out with the dumbbells, I had a lot of soreness everywhere. Chest, arms, legs. My legs felt heavy and stiff. And then I had some weird stuff when I went to the bathroom. I don't know. It was a little dark colored. But it went away after two days. and so I didn't think anything of it and just kept going. I feel fine today, so. Yeah, yeah, so we're at a point

24:08Dr. Austin Baraki:where we have definitively localized the problem to the muscles. The question is, what is the nature of that problem? What are the precipitating, provoking factors and what is the likely, we'll call it natural history? What is the likely prognosis of this going forward if we don't do anything about it? Or is there something that we have to do to intervene? That's kind of like where my mind is at right now. So what could be going on? he could have i'll put this under the gigantic umbrella of like a muscle disease we'll call it a myopathy of some kind that can be due to inflammation like my like myositis which is often involves the involvement of the like immune system there are autoimmune conditions where your body can attack its own muscles in again extremely rare cases there are autoimmune forms of myositis that can be triggered by the use of statins very very rare but i've seen it a handful of times over the years.

24:59Dr. Austin Baraki:Or he might not have an inflammatory myositis, but he might have a myopathy related to his exertion itself, the rhabdomyolysis, which can be exertional. And then lastly, he can also have rhabdomyolysis that is not necessarily exclusively exertional, but the exertion didn't necessarily help things. And what I mean is something that kind of set him up to have more vulnerable muscles. And one of my concerns there is the combination of statin and fibrate that in some situations can interact to increase the risk of a myopathy that in the setting of maybe more modest exercise than somebody might expect can trigger this sort of thing.

25:38Dr. Austin Baraki:So at this point in time, any of these are really possible. And to add one little layer of, I don't know, caveat to what you said about the CK, while a quote unquote normal CK level might really be that low of what you were describing, like 100 or something like that, there's a normal, you know, physiologically reasonable expected trajectory of CK that'll increase after exercise that wouldn't necessarily alarm me. If I had a trainee who, you know, did a hard workout and their CK level came back at 800 or 1000 or something, that wouldn't really faze me. 18 ,000 is much more elevated. And especially when it's in the context of him having symptoms, muscular tenderness, swelling, telling me I maybe had this episode of like dark urination, things like that.

26:20Dr. Austin Baraki:This much more fits the picture of somebody with rhabdomyolysis. And what I'm trying to get to the bottom of is, is this purely exertional? Is there something he's not telling me about like really how hard he exercised? Is he embarrassed to tell me that maybe he's not as fit as he thought and he went too hard too soon? Or is it a combination thing where it was the exertion in the setting of being on the medications? Or lastly, the no miss sort of thing that would definitely require intervention. Is this truly like an inflammatory or an autoimmune kind of muscle problem that really needs medical intervention to address.

26:51Dr. Austin Baraki:And I've seen all of these things happen in practice before. One of the more memorable cases that I can think of from several years back was this little old lady who actually came in and she was in frank rhabdomyolysis. And we asked her about her exertion and she was like, I was just doing my normal like house cleaning, like nothing out of the ordinary. And she ended up having polymyositis, which is an autoimmune inflammatory myositis, but her like a normal habitual level of exertion in the context of that condition that she had developed became too much. And she ended up coming in with symptoms and was in rhabdo and we had to do both.

27:23Dr. Austin Baraki:We had to treat the rhabdo and also suppress her immune system from attacking her own muscles. So that's kind of where I'm at in this case. You told me his lipids, you told me his CK. What I need to know is what does his urine look like? Not just visually, but a urinalysis. What does his kidney function look like? This guy should probably go to an emergency department and get some of those tests done relatively quickly. He may need some fluids, and we need to see what his CK trend looks like. The possible ways this plays out is with that type of management, his CK gradually comes back down, never comes back up.

27:53Dr. Austin Baraki:He never has any problems again. We like recondition him a little bit more gradually to exercise. I would stop his vibrate. I would probably even hold his statin for the short time, for the time being. The other way this plays out is he gets treated. His CK either never comes all the way down or just like plateaus at that level, which would make me much more concerned that he has like an ongoing kind of myositis type issue that would need some additional blood testing, potentially a muscle biopsy to sort out.

28:19Dr. Jordan Feigenbaum:Yeah, yeah. Just for our audience, we've talked about rhabdomyolysis in detail on this podcast a number of times before, but just as a reminder, this is what happens when the muscle breaks down fast enough that the contents of the cells dump into the bloodstream in a large quantity. And one of those contents that's normally within the muscle cell is myoglobin, carries oxygen around. And when it hits the kidneys in high enough concentrations, it can clog things up and cause acute kidney injury. That's one of the things that makes rhabdomyolysis so dangerous, along with electrolyte disturbances that can possibly cause heart arrhythmia.

28:50Dr. Jordan Feigenbaum:The muscles can also swell too much, causing compartment syndrome, which we've talked about, and there are other sort of risks as well. So identifying rhabdomyolysis isn't more of like, hey, cool, you got rhabdo, and you got, you know, give yourself a high five for that. It's more like, do you need to go to the hospital or can we, you know, monitor you at home? And a distinction that we've also made before that's relevant here, and you've alluded to this, is the difference between having just a high CK creatine kinase and actual rhabdomyolysis. Now, there's a fancy term for CK that's about five times the upper limit of normal.

29:22Dr. Jordan Feigenbaum:Sometimes it's called hyper-CKemia. And people have this all the time, particularly athletes. There are people who just, in response to exercise, their CK goes through the roof, but they're otherwise fine. And it happens no matter how trained they get or whatever. They just have a high CK level. These are hyper-CKemia-ers. if you will. But this like 19 ,000 CK level is a different story. That's much higher than that. And to your point, it impressed you enough where you're like, this guy probably needs to go to the hospital to suss this out. And because it's more likely to be rhabdomyolysis at that level, we need to be concerned about the myoglobin.

29:58Dr. Jordan Feigenbaum:We need to be concerned, you know, what's going on with his urine to assess that as well as electrolytes and things of that nature. So we're going to call this rhabdomyolysis. So he was sent to the emergency room. Both of his medications were stopped, the statin and the fibrate. They started IV fluids for his kidneys. On admission, his liver associated enzymes were also elevated. His ALT was 132. His AST was 248. Those are likely from muscle damage. I think you'd agree rather than the liver, but we don't know for sure. We did a whole episode on this. You can check out our last mystery case. Over the next several days, his CK came down first to 5 ,134 and then to 1 ,823.

30:38Dr. Jordan Feigenbaum:And his transaminases or liver associated enzymes also started dropping. His kidney function was normal throughout and he was discharged after two days. So I've got another set of questions for you here, Dr. Baraki. First, what's your final diagnosis?

30:52Dr. Austin Baraki:Yeah, so it sounds like he responded kind of appropriately in terms of what I would expect for somebody with a kind of more routine or run-of-the-mill case of rhabdomyolysis. rhabdomyolysis. In fact, once his CK got down to 5 ,000, I would have just discharged him from there. He didn't necessarily need to stay in the hospital too much longer. The risk of kidney problems once you're down at that level is actually low enough that you can safely go home. They probably kept him in there a little bit longer than he needed to, but that's okay. And so glad he didn't have any kidney complications or anything like that.

31:20Dr. Austin Baraki:So this was clearly a case of rhabdomyolysis. And I think that what we can likely conclude is that it was at least exertional rhabdomyolysis. and he may have had an additional predisposing contribution from the medications that he was taking and especially taking those in combination. And so this is not to say that he can never take any form of lipid-lowering therapy again, but rather that particular combination and that combination in the context of that exercise program probably not the move for him. What I would do with somebody like this in practice is, again, I would return to, I'm wanting to make sure that I'm treating the quote-unquote root cause of his issue addressing the obesity.

31:59Dr. Austin Baraki:There are probably honestly some pretty straightforward in dietary modifications that can relatively robustly improve those triglycerides. Like that's something that tends to be pretty responsive to dietary changes in a lot of people. There are some genetic conditions that can lead to, you know, persistent high triglycerides, but things like high intake of alcohol, as well as a lot of refined carbohydrate intake can really lead to persistent elevations in triglycerides. And so swapping those things out can lead to substantial improvements in a lot of people. And then as far as lipid lowering therapy goes, nowadays, we have lots of options.

32:33Dr. Austin Baraki:He still may well tolerate a statin just fine. He may not even need the 20 milligrams of atorvastatin. He may do just fine on like five milligrams of rosuvastatin. Or sometimes when I have patients who are a little bit more sensitive to statins, I might suggest to them trying a different one that is a little bit less well recognized called pitavastatin that has a lot of interesting kind of unique aspects to it and can be better tolerated by some patients. So whether something like five or 10 of rosuvastatin, a couple milligrams of pitavastatin may be an option for him, or if he doesn't want to use a statin at all, I still would not put him on a fibrate and we could go in an entirely different direction with other meds.

33:08Dr. Austin Baraki:But addressing the obesity is going to be the main thing. So the combination of lifestyle and if he's a candidate or qualifies or could end up on something like terzapatide would be an excellent move from a medical management standpoint of this patient's risk.

33:21Dr. Jordan Feigenbaum:Yeah. Say for those medication changes. If you were this patient's doctor at the time, he said he wanted to start exercising. Would you have done anything differently?

33:32Dr. Austin Baraki:Aside from not ever having put him on the fibrate in the first place and just probably the statin that he was on, although I tend to use rosuvastatin more than a torvastatin, I think that his exercise program, the way he went about it, if he felt comfortable, confident initiating a home exercise program with dumbbells, I think that that's completely fine. So I actually don't fault him for that. Again, I didn't get specific details of like, where did he find this program? What exactly was he doing? Sets reps. If he jumped into something that was clearly way too much too soon for him, then that's something else that we would have a conversation about.

34:03Dr. Austin Baraki:I see a lot of rhabdo in the hospital. And so this is something that I always also have this conversation when I'm getting people ready to discharge. Because a lot of times, either they themselves are apprehensive, or sometimes it's like their partner, their girlfriend, their mom might be in the room, and they're like, you know, oh, you need to be, you You know, obviously they're like traumatized by having been hospitalized for this thing. And they're like, can he ever exercise again? So I'm like abundantly, explicitly clear. You absolutely can exercise again. You should exercise again. But the way we go about it might need to be smarter.

34:33Dr. Austin Baraki:We need to get you, you know, it's almost like I have that conversation about when we talk about youth athletic development, like training to train. We need to get you fit enough to be able to train. And it seems that whatever you did before this, you were not ready to handle that. you were not sufficiently fit to tolerate the training that you tried to do. And so setting you up more successfully for that would be the goal over time in the ensuing weeks after hospitalization.

34:58Dr. Jordan Feigenbaum:Yeah. You also kind of alluded to the idea that combining the statin and the fibrate together, perhaps not these two particular ones, although generally speaking, might have led or exacerbated or made his muscles more vulnerable. So the two medications seems to matter. And the question I have for you is, is there any way to really tell the difference between maybe a drug side effect and then the expected CK bump that you'd see in somebody new to exercise? Because, you know, you kind of not hand waved away, but you dismiss like, look, your CK bumps to a thousand. You just started working out. Yeah.

35:33Dr. Jordan Feigenbaum:Not really impressed. But now that you got two medications on board that could potentially make somebody more vulnerable, are you more vigilant to the rise in CK? Are you more permissive of a CK rise, something like that?

35:45Dr. Austin Baraki:I don't really think so absent the person's like clinical syndrome. In other words, just because I put somebody on medicines like this. And so to be clear, you know, when I think of medicines that are more prone, more problematic in this context, that can be things like high doses of Simvastatin, which fortunately like nobody should be using anymore, or Gemfibrozil, I think among the Fibrates is one that might be a little bit higher risk than Fentafibrate as the more preferred one if somebody needs to be on a Fibrate these days. And there are other drug interactions that can happen. whether between statins or even non-statin medicines that can impact the muscles.

36:18Dr. Austin Baraki:I won't go down that pharmacology kind of rabbit hole here today. But these things can happen. But that doesn't mean that you're routinely monitoring somebody's CK just for the sake of it in most situations. Even though there's some exceptions, but I'll leave those aside. And so I am not aware of like strong evidence in this space. I don't know if you found something where there is clearly like a different tier of expected or acceptable CK deviations in somebody on certain medicines compared with not. I'm much more concerned about their subjective symptom experience because that frames my interpretation of these lab results.

36:53Dr. Austin Baraki:Somebody who trains, they're performing well, they're feeling well, they have no complaints. They're like, yeah, everything is going awesome. And somebody just happened to pull a CK and it's like 2 ,500 or something. I'm still like, that gets a shrug from me. Again, when I'm approaching like 20 ,000, there are very few situations that I can think of where somebody is at those levels and has no symptoms. But at the same time, I would be curious after somebody does, I don't know, their first high rocks or like an ultra marathon or something like that. Like we're not routinely testing those if somebody has no symptoms.

37:24Dr. Austin Baraki:Maybe people do routinely get to those levels and I just don't know it. So what do you think?

37:28Dr. Jordan Feigenbaum:Well, there is some data showing that CK bumps are kind of expected on certainly statins. There's some really good evidence here. We'll talk about the STOMP trial later where they actually had people take either high-dose atorvastatin, 80 milligrams, versus placebo and add them to exercise. That's a lot of milligrams. That's right. But their CK on average went up about 21 units, for example. Yeah. Which both were elevated after exercise, just was higher in the statin group. Another study on lovastatin, which we'll also talk about, the CK levels were 75 % higher on average, which, you know, depending on what was going on is interesting.

38:03Dr. Jordan Feigenbaum:But I think this actually dovetails nicely into the new guidelines. As we're aware, the 2026 ACC and AHA lipid management guidelines just came out to replace the ones from 2018, first update in eight years. And for the first time, the new guideline explicitly lists vigorous exercise as a risk factor for statin-associated muscle symptoms, kind of this acronym called SAMS. We won't name that later, but if you see that, S-A-M-S, that's what it means. That's new. It wasn't in the 2018 version. and the entire section on managing statin muscle symptoms is new, which I think was pretty good. But at the same time, that same guideline says that routine CK monitoring in people taking statins who don't have symptoms is not recommended.

38:44Dr. Jordan Feigenbaum:Now, this patient had a CK of nearly 19 ,000 and was basically asymptomatic at the time of the lab draw. So under the current protocol, that number wouldn't have gotten caught unless somebody happened to order a CK for another reason, which is exactly what happened here. He had these other symptoms and they were like, hey, we got to get a CK just to check. So the guideline acknowledges the risk, but also says don't go looking for it. It's not necessarily a contradiction, particularly in this patient. But, you know, there could be false positives, unnecessary cost, unnecessary anxiety. This case does show you what could slip through that gap, though maybe he would be fine.

39:17Dr. Jordan Feigenbaum:So maybe the more interesting question for this particular segment, do you think this patient should have been sent to the ER? Like he was asymptomatic, but his CK was high. Do you think that automatically buys him a trip to the ER?

39:29Dr. Austin Baraki:Yeah, I disagree that he was asymptomatic. He was telling you that he's having muscular weakness, exertional intolerance, and then he had muscle tenderness and swelling on exam. So I don't agree with the premise that he was asymptomatic. And so having symptoms in the context of an 18, 19 ,000 CK, yeah, I concur. I stand by the management in this case.

39:47Dr. Jordan Feigenbaum:Yeah, had he come in and he had no soreness, but just historical, like a remote history of soreness and whatever, and his urine looked fine, you know, as far as it wasn't dark. You don't, you don't, you didn't test for it.

39:57Dr. Austin Baraki:Yeah, that's a slightly more nuanced situation, I would say. If that was all you got from him, then probably no, I wouldn't have routinely tested for it. However, if I did still have that history where he said, look, I'm doing this exercise and I noticed that I'm not progressing, I'm actually regressing, and I feel myself weaker than usual for a couple days after exercise, I still would have checked to CK in that situation. Not necessarily because the statin is the only thing on my mind, But because that is how myopathies can present is like this disproportionate or unexplained weakness or fatigability, things like that.

40:32Dr. Austin Baraki:That would have been my approach to the case. So I would have found it in that situation anyway with that background history.

40:38Dr. Jordan Feigenbaum:All right. I like that. All right. Well, so look, the medications were stopped and he recovered. Now, the question is what was actually happening at the level of his muscle cells? Because understanding the mechanism here changes the differential. If it were too much exercise itself, you'd expect the symptoms to scale with the training. Too much volume and intensity, not enough recovery, the muscle can't keep up. And so if you dial it back, you recover, the person's fine. The muscle itself is healthy, you just ask too much of it. But what's different with this sort of statin-induced or medication-induced myopathy is that the drug changes the muscle's tolerance for work.

41:11Dr. Jordan Feigenbaum:The training load this guy took on, some dumbbell exercises at home, should have been completely manageable. but it wasn't because the drug had exposed a vulnerability in the muscle that was already there or created that vulnerability before he ever picked up weight. When we come back from the break, we'll get into the mechanism of how statins affect muscles, including whether or not they affect performance. If you listen to our podcast on nutrition for a while, you know that what I'm about to tell you is no surprise. Eating well is not a willpower problem. It is a setup problem. When there is something healthy and ready to go in my fridge, I'm going to eat it.

41:42Dr. Jordan Feigenbaum:And when there's not, I end up staring at a cast iron skillet at 8 p.m. and just not doing that. Now, that's where factor comes in. These are fully prepared meals designed by dieticians and crafted by chefs, and they're delivered right to your door. I've been leaning on the MusclePro collection because the macros line up well with my training, but they have meals built around whatever your goals are, whether it's weight loss, overall nutrition, more protein, and even GLP-1 support. And the quality is actually there, too. We're talking about lean proteins, colorful vegetables, whole foods, and healthy fats.

42:09Dr. Jordan Feigenbaum:It's just nutrient-dense food, and it's always fresh, it's never frozen, with over 100 rotating options so that you're not eating the same thing every week. And they're also ready in about two minutes. To get set up and to make sure that your fridge doesn't look like a barren wasteland, head over to factormeals.com slash bbm50off and use code bbm50off to get 50 % off and a free daily greens box, if that's something you're into. New subscribers only, while supplies last. See website for more details. That's factormeals.com slash bbm50off. We talk a lot about high yield strategies in the gym, and I think that same logic should apply to your closet, especially this time of year when the weather starts to shift and you realize half of what you own doesn't work anymore.

42:46Dr. Jordan Feigenbaum:Last time I mentioned quints, I was talking about their overshirts and their Pima cotton tees. But now that San Diego has been heating up, I've been reaching for their linen pieces instead. They've got men's linen pants and shirts made with 100 % European linen and they're lightweight, they're breathable, and they hit that sweet spot between laid back and put together. I look like I care without looking like I'm trying too hard. They also have a line called Flow Knit for active wear. They're moisture wicking, anti-odor, soft enough that you actually want to wear it all day. And I've been using it for training sometimes and just general running around town.

43:14Dr. Jordan Feigenbaum:Now, the reason the prices are 50 to 60 % less than what you would see at a high-end mall is that Quince works directly with ethical factories and cuts out the middlemen. You're paying for the materials and not the brand markup. Everything they make is designed to last, and they're rated between 4.5 and 5 stars by thousands of people online. Refresh your wardrobe with Quince. Go to quince.com slash bbm for free shipping and 365 day returns. They're now available in Canada too. Go to quince.com slash bbm for free shipping and 365 day returns. That's quince.com slash bbm. At Barbell Medicine, you know that we take our recommendations very seriously here.

43:49Dr. Jordan Feigenbaum:We don't recommend things just because they have a popular logo or they have a big ad budget. We look at the evidence and we look at what works. And the evidence on standard issue hospital scrubs? Not very good. You're basically wearing something that fits like a repurposed parachute and feels about as pleasant as sandpaper. And that's why we've been partnering with FIGS. For those of us working in healthcare, FIGS makes scrubs and apparel that are actually designed for what we do. They're comfortable, they're lightweight, and they're durable enough for long days and endless wash cycles. They're also antimicrobial, which, given the environments that we work in, is not a small thing.

44:18Dr. Jordan Feigenbaum:And they finally fixed the fit. No more boxy, scratchy scrubs that make you look like you're walking around in a cardboard box. FIGS rethought the tailoring completely with tons of styles and colors to choose from. They've also teamed up with New Balance on supportive sneakers. They also make compression socks for those 14-hour shifts where your legs start to feel like lead weights. They also have outerwear for when the hospital decides to turn the ICU into a walk-in freezer. If you want to check them out, Figs is offering 15 % off your first purchase. Just go to wearfigs.com and use the code FIGSRX at checkout.

44:46Dr. Jordan Feigenbaum:That's wearfigs.com, code FIGSRX at checkout for 15 % off. All right, we're back here in the Barbell Medicine podcast. Now, before the break, we were walking through a mystery case where a 43-year-old man ended up in the emergency room with rhabdomyolysis after starting a home dumbbell program. But it was really the combination of medications he was on, particularly the statins and fibrates, mixed together, not necessarily as training. So let's get into the mechanism here, specifically on statins and how they affect your muscles and whether they affect your training outcomes at all. Statins work by blocking an enzyme called HMG-CoA reductase.

45:21Dr. Jordan Feigenbaum:You don't need to remember that name. What matters is what the enzyme does. You can think of it as a factory inside your cells, the main product being cholesterol. If you block this enzyme, the factory slows down, cholesterol production drops, and the liver compensates by pulling more LDL out of the blood and circulating LDL subsequently falls. That's the intended effect and that's why statins work. The problem is that the factory doesn't only make cholesterol, it also makes a handful of other molecules that the muscle cells depend on. And when you slow the whole factory down, you reduce all of them.

45:50Dr. Jordan Feigenbaum:So the first mechanism here is that the cell's energy supply gets squeezed. One of the products of the factory is CoQ10, coenzyme Q10. It works inside the mitochondria, the part of the cell that converts food into usable energy, which we call ATP. That's the fuel that your muscles run on. When statin use reduces CoQ10 levels, the cells become less efficient at making energy, and muscle is one of the most energy-hungry tissues in the body. During a hard workout, ATP demand spikes, And if a muscle cell starts with a lower energy ceiling because of reduced CoQ10, the gap between what the cell needs and what it can produce gets wider the harder you push.

46:27Dr. Jordan Feigenbaum:Now, patients ask about CoQ10 supplements all the time, and the logic makes sense. If the statin depletes it, just take more. But the clinical trials don't really back that up. The evidence doesn't show that supplementing CoQ10 reliably improves statin-related muscle symptoms. And the 2026 guidelines specifically note it's not recommended for this purpose. So I pose the question to you, Dr. Baraki. You get patients asking about CoQ10 for statin side effects probably all the time or in your DMs. The mechanism sounds plausible, but the trial data isn't really there yet. What's your take on CoQ10?

46:56Dr. Austin Baraki:Yeah, I just don't really care that much if somebody wants to try taking it. As long as I trust that the supplement they're using is not contaminated, if it has the appropriate labeling on it, it's purified, that's the only ingredient, say it's CGMP certified, you know, it's like I find it plausible enough. and so if somebody wants to try taking it and if it helps them be more adherent to the therapy that is more likely to benefit them, who am I to just like tell them, no, don't take it, but then they're gonna either lose trust in me or stop taking the medicine that I think is helping them. And so if somebody wants to try taking some coenzyme Q10 and it's from a trusted or it's like a high quality sort of thing, fine.

47:35Dr. Austin Baraki:I'm not routinely recommending that everyone who takes a statin use it because in fact, most people do fine, especially people who don't know about this as a potential side effect. Most of them do fine and don't end up reporting any of these side effects. The reporting of side effects tends to increase. There's definitely a component of nocebo there. It is not 100 % nocebo, but there's a substantial component of that. If somebody wants to try taking those things, fine. I've seen mechanistic hypothesizing. I've seen anecdotal reports. I've seen things where people say either coenzyme Q10 or vitamin D levels that normalizing vitamin D levels can help this.

48:12Dr. Austin Baraki:Again, it gets a shrug for me. If you want to try it, go for it. I would also make sure that the person doesn't have another reason for myopathy. So for example, like thyroid function, making sure their TSH is okay because hypothyroidism can also contribute to muscle issues that might be also like compounding when we're using multiple things. So, you know, those are some other things that I'd be thinking about in these situations. You know what I'd like to see? despite our, you know, shoulder shrug nature regarding this particular supplement.

48:40Dr. Jordan Feigenbaum:Creatine. Look, if intracellular energy is the real limiting factor here.

48:44Dr. Austin Baraki:Yeah. And, you know, another way to think about this is like, I wonder, you know, if people do have some of these statin-associated muscle symptoms, I find it very plausible that different people can end up having those symptoms by way of different mechanisms, right? And if you lump all of these people with the same nonspecific symptom into a study, and you put them all on coenzyme Q10, is it not plausible that that effect, if it is present for some of those, that it might wash out in the overall? It's like, I find that to be a plausible kind of explanation.

49:15Dr. Jordan Feigenbaum:The second mechanism here is that the muscle cell's outer membrane gets fragile. The same factory that makes cholesterol also makes structural molecules. You might hear them called isoprenoids in the literature. Think of them like rebar and concrete. They help hold the cell together. Now, when statin use reduces them, the outer membrane of the muscle cell, the sarcolemma, appears to become more vulnerable to mechanical stress. So during the lowering phase of a lift, the eccentric phase as it were, where the muscle is producing force while lengthening, the membrane is under a lot of mechanical load.

49:44Dr. Jordan Feigenbaum:In a healthy cell, it handles that stress and repairs normally, but in a cell whose structural molecules have been depleted, the same load may cause disproportionate damage. Now this is largely derived from animal and cell culture work, but it does fit the clinical pattern. And it helps explain something important. Statin myopathy appears to depend not just on the drug's dose, but also on the training load. Two patients on the same statin at the same dose can have very different outcomes depending on how hard they're training. The third mechanism, and this is a newer piece of the puzzle because it required some new imaging techniques called cryo-electron microscopy.

50:17Dr. Jordan Feigenbaum:That recently showed that statins can bind directly to a calcium release channel in the skeletal muscle that's called the ryanodine receptor. Now here's a short version. Muscle cells keep calcium locked away in a sort of storage compartment and then releases it in a controlled way to trigger muscular contractions. The ryanidine receptor is that gate. When statins bind to it, the gate becomes leaky, and calcium seeps into the cell when it shouldn't. Now, excess calcium inside a muscle cell is a problem. It activates enzymes that break down proteins. It generates damaging molecules called reactive oxygen species, or ROS.

50:49Dr. Jordan Feigenbaum:And if the cell can't pump the calcium back out fast enough, which requires energy it may already be short on, the damage can compound. So the patient is sort of in this tug of war. Training is trying to build muscle, but the drug is accelerating muscle protein breakdown. The net effect can be that the strength goes down, muscle damage increases, and so does the CK. It goes up. Now, if these mechanisms affect everyone on a statin, why doesn't everyone get myopathy? And that's an interesting question. These biochemical changes, some degree of CoQ10 reduction, some degree of membrane vulnerability, probably do happen in most people taking statins.

51:23Dr. Jordan Feigenbaum:But for the vast majority, the body compensates. They back up energy pathways, back up repair mechanisms, and the magnitude of effect at a typical dose just isn't enough to cause symptoms. What does tip people over the edge is the combination of factors. Genetics, for example. Some people carry variants that make the ryanodine receptor more prone to leaking. There's a liver transporter gene that reduces how efficiently the body clears the statin, so you get higher levels of statin in the blood. Older age, female sex, kidney disease, thyroid problems, drug-drug interactions, and relevant to our patient, exercise.

51:55Dr. Jordan Feigenbaum:All piled on top of that genetic baseline. So the short answer here, the mechanism is probably always running at a low level, but it takes a specific combination of dose, genetics, and stress to push it past the threshold where it causes real damage. One more quick little factoid on this, and I think it's a good one for the nocebo conversation you alluded to. You've referenced this before, this 2018 study that looked at the number of websites in different countries that discussed statin side effects and compared that to the reported statin intolerance rate. The correlation was super strong. Countries with more online content about side effects had a higher reported intolerance to statins.

52:32Dr. Jordan Feigenbaum:And in the ASCOT trial, muscle symptoms occurred at the same rate on statins versus placebo during the blinded phase of the study. It was only during the open label extension when patients knew that they were taking a statin that reports jumped by about 41%, which to me is wild. There's an even more elegant trial called SAMSON, where 60 patients who previously quit statins because of side effects were given 12 months of randomized blinded treatment. During four months, they got a statin. Another four months, they got placebo. And four months of nothing. They tracked symptoms daily on a phone app.

53:05Dr. Jordan Feigenbaum:The result? About 90 % of the symptom burden people attributed to statins occurred equally when they were taking the placebo. Statin months and placebo months were virtually identical. but both were no worse than the no tablet months where they weren't telling whether they were taking nothing and that tells you that the act of taking a pill any pill was driving most of the symptoms and here's the kicker at least to me after seeing their own data half of these patients who'd sworn off statins successfully restarted them yeah none of this means the statin myopathy isn't real it does appear to be a real thing that people experience but we just spent the last 10 minutes explaining the mechanisms and there's something there the point is that the reported rates are inflated by expectation or at least influenced by expectation and the true pharmacological rate meaning the excess above what placebo causes is estimated to be between one to five percent in control trials pretty low uh but you might see other numbers if you do your own research and i think that has to do with terminology we've kind of used a number of terms uh interchangeably but they're not and this is problematic also in the research so myalgia for example is just muscle pain, but no real CK elevation.

54:11Dr. Jordan Feigenbaum:Myositis is muscle pain with a CK elevation, meaning that there's measurable muscle damage. And myopathy is a broader umbrella term that covers the whole spectrum with rhabdomyolysis is being on the severe end where CK is extremely elevated and the kidneys are at risk, the heart's at risk, your risk of compartment syndrome goes up, etc. But these terms again get used interchangeably. We've been lazy about it here. We should we should do better. Our call to action is to do better maybe. But if you define the outcome as any muscle symptom at all, including like a vague aching with no ck elevation you might get a rate as high as 25 percent with relationship to using statins but if you restrict it to objectively confirmed muscle damage with ck elevation the number drops to below five percent and if you're just looking at rhabdomyolysis alone with kidney involvement it's less than 0.1 percent so austin how much detail about myositis myalgia and rhabdomyolysis risk you go to uh into with patients who may be starting a statin or even combination therapy?

55:08Dr. Austin Baraki:Yeah, certainly not into great detail with those most rare scenarios of like a much less than 0.1 % level risk. Because presumably, as part of their comprehensive assessment, their cardiovascular risk is likely to be much, much higher than that. And so that's a situation where that potential benefit versus that potential risk is clearly favorable. As far as the other symptoms go, it kind of is something that at this point in my career, when I'm doing this, I'm kind of feeling out the person as part of our conversation. What's the level of comfort versus apprehension with these medicines? Sometimes they might ask about the risk of certain side effects, and then that'll just kind of evolve into a conversation somewhat more naturally.

55:51Dr. Austin Baraki:Sometimes I'll even explain that the more side effects that people tend to get warned about, the more they are likely to experience them. And so sometimes if the person is apprehensive about that, I might say, how about, you know, if you're willing to give this a try for a couple weeks, then you can let me know if you experience anything. But a lot of times people have already done some degree of research or reading, or they might already be familiar with some of those side effects and they ask me specifically about them. In which case I'll have a conversation, kind of a simplified version of a lot of the discussion that we just had.

56:18Dr. Austin Baraki:And then also I point out that, look, I tend to be, unless we're in an ultra high risk situation, I tend to be pretty conservative in terms of using low dose combination therapy much more often, like the suvastatin 5 or 10 combined with an azetamide 10. And as an example, compared with cranking people up to maximum doses of single agents, just because I know that, hey, we're getting the biggest bang for our buck in terms of benefits and mitigating the risk of side effects in that situation to make it feel like I'm on their side, because I am. In this journey, we're trying to find a workable solution for them.

56:51Dr. Austin Baraki:And it's interesting, you know, you laid out a lot of these mechanisms, and there's truly a lot of variability in what people experience. But that's kind of the case for every medicine, right? You put 10 people on a blood pressure medicine, you're going to get 10 different degrees of blood pressure lowering. I put hundreds of people on GLP-1 receptor agonists, and I see some people with a lot more nausea, some people with less, some people with more reflux, some people with less constipation, more or less, some none. Some go in the other direction and have some diarrhea. Again, most have none.

57:17Dr. Austin Baraki:I think that there's just such complexity and variability, and our tools, as advanced as they are these days, it still is a relatively crude option just to put a large group of biologically variable organisms on this one thing, and then you're going to see some divergent responses. I wonder, and maybe this is a premature hot take, but I think it would be great one day once we have cheap generic$5 oral PCSK9 inhibitors instead of statins because they work via such a fundamentally different mechanism. PCSK9 inhibitors accelerate clearance of LDL particles from the blood, whereas statins interfere more with the production side of things in the liver, leading to then subsequent clearance.

57:58Dr. Austin Baraki:And so I think that it seems to me that we observe less of these kind of off-target effects. There's not really any of this kind of muscular phenomenon that we observe on PCSK9 inhibitors. And so just purely acting on the clearance side of the equation seems to me the more sensible way to go. It's just that access to those medicines is a lot tougher still at this point in time, even as prices gradually come down. So I wonder if, you know, fast forward to the distant future, if we have those options and they're much more prevalent, and then maybe gradually statins will start to actually decline in use.

58:28Dr. Austin Baraki:They're here to stay for a long time because they're cheap, generic, and effective for their intended use in the vast majority of situations. But I do think that this is going to be an evolving space in the coming, I'll call it, decades.

58:41Dr. Jordan Feigenbaum:Yeah, yeah, watch this space. One thing I wanted to investigate, which I hadn't seen adequately addressed anywhere else, was the effect of statins on training outcomes. Like, has anybody run a trial? like you get a placebo, you get a statin, let's have you guys both train and see what happens. Turns out there's been a few studies, more admittedly when it comes to aerobic exercise, endurance exercise compared to resistance training, which is the case, unfortunately in America. That's for everything. Dr. Cooper, just like you, we'll get to that. But anyway, so this comes up a lot. The best data we have is from the STOMP trial, great acronym, the effect of statins on skeletal muscle function and performance.

59:24Dr. Jordan Feigenbaum:stomp we love it they took 420 healthy statin naive people and randomized them to get either high dose atorvastatin 80 milligrams verse placebo for six months on a standardized resistance training program there was no significant difference in the amount of muscular strength they gained both groups got stronger or muscle size or exercise capacity between the two groups ck creatine kinase did go up on average about 21 units more in the group that was getting atorvastatin but honestly for that dose that's pretty impressive i would have expected more you know if any finding at all but yeah that was pretty pretty uh reasonable to me um additional data shows that statins uh amplify the ck response to exercise potentially even higher lovastatin we talked about uh had an average of a 75 percent increase higher ck level at 24 and 48 hours after resistance training compared to placebo so that could be a signal there if you're starting somebody on that at a high dose.

1:00:21Dr. Jordan Feigenbaum:Now, again, I alluded to this, but there's more data on endurance. And this is where things get genuinely interesting to me. We could have had a whole podcast on just like what the heck is going on with statins and, you know, gaining cardiorespiratory fitness. However, here's my take on it. We have limited evidence that statins, especially at higher doses, may reduce baseline muscle oxidative capacity and potentially blunt or reduce the aerobic fitness gains that people get from training. There's one study from 2013 in particular that showed this, whereas some other studies that tried to replicate that didn't find that.

1:00:56Dr. Jordan Feigenbaum:So the data is mixed, does appear to be dose dependent. And again, all from mostly small studies, unfortunately. What we do know from meta analyses and larger studies is that the combination of statin therapy and exercise produces better survival than either alone. and cardiorespiratory fitness still improves. So it's not like it's blunting it entirely if it has any effect at all. So to me, the clinical takeaway here hasn't changed. You should train, take a medication if it's indicated and work with your doctor to find the lowest dose that gets you to target here. But it is worth knowing that the interaction exists because it's another reason to optimize dosing rather than just defaulting to the maximum.

1:01:35Dr. Jordan Feigenbaum:So the picture that's emerging here is that statins don't meaningfully impair training in the average user, but in the subset of susceptible people, and our patient was clearly in that subset, the combination of drug exposure, genetics, and in this case, training stress crossed a threshold where the damage was real and measurable. Since we're talking about muscles, medications, and metabolic syndrome, three of my favorite M's, there's one more thing to watch in the space, and it is terzepatide. You mentioned this earlier. This is that dual GIP-GLP1 receptor agonist that most people know as either Manjaro or Zeppon, it's generating some interesting cardiovascular data.

1:02:14Dr. Jordan Feigenbaum:So in addition to its metabolic effects, clinical trials have shown that it can lower triglycerides by about 25 to 30 percent and reduce apolipoprotein B, ApoB, which is the protein that rides around on cholesterol particles and builds plaque. ApoB reduction is a meaningful signal because it tracks closely with cardiovascular risk. A trial called T-Plaq is currently looking at whether terzepatide directly slows coronary plaque progression and the early results are promising. The 2026 guidelines mentioned terzepatide and semaglutide in the context of weight management with secondary lipid benefits.

1:02:48Dr. Jordan Feigenbaum:So like use it to lose weight or as you mentioned, reduce this sort of address the root cause of what's going on here. But also you get these lipid benefits on top of that. But they're not yet positioned as a sort of primary lipid-lowering drugs like statins, for example. But for patients who have overlapping metabolic, cardiovascular, and kidney risk, what the guidelines now call CKM syndrome, cardiovascular kidney metabolic syndrome, this drug class may eventually become another tool. So Austin, I think I know the answer to this already, but I want you to drive it home. What do you think about combining GLP-1s with statins and lifestyle interventions to optimize someone's health relating to CKM syndrome?

1:03:27Dr. Jordan Feigenbaum:I think it is an ultra-potent strategy.

1:03:29Dr. Austin Baraki:and so it is very strongly recommended for you know when used appropriately and in the right patient it's honestly a pretty remarkable time to be alive with these conditions and certainly if you're trying to to prevent them if you're you're eligible or if you have access to these medicines the use of trisepatide and certainly you know the the ones that we're expecting to to come down the pipe in the in the coming year or two that are there actually one literally just got approved within the past couple days the next oral agent terrible name by the way yeah I agree. And then as I mentioned, the use of statins judiciously and dosed properly and when appropriate, or if somebody has access to the more potent therapies like a PCSK9 inhibitor also when appropriate, or certainly just when they become more accessible in the future might even augment things further.

1:04:18Dr. Austin Baraki:So I think the incentives are there for these companies to generate effective treatments, right? So cardiovascular disease, leading cause of death in the world, obesity and its downstream complications, super prevalent. They're clearly figuring these pathways out. They are competing with one another to generate ever more potent, more effective, safer, more well-tolerated agents. And that's just, I think, I guess if you want to complain about capitalism, you certainly have a lot of reasons that you could. But this seems to be one of the more favorable results that is emerging from that system of competition.

1:04:51Dr. Jordan Feigenbaum:Yeah, I agree. All right. Well, we've laid out the mechanism. now who's most at risk and what's the one test that separates a drug problem from a programming problem so statin related muscle problems can sit on spectrum we talked about this at the mild end it's myalgia this sort of aching and soreness without any creatine kinase or ck elevation in the middle would be myositis pain in the muscles with a measurable muscle damage as that means that ck is elevated and at the severe end we got rhabdomyolysis you know massive ck A spike, potential kidney injury, potential arrhythmias, things like that.

1:05:24Dr. Jordan Feigenbaum:So the early stages look identical for people who are new to exercise. You know, just delayed onset muscle soreness or is it something else here? And we need to keep making this point. Real drug-caused statin myopathy is incredibly uncommon, all things considered. In controlled trials where patients don't know whether they were on a drug or placebo, the excess rate of muscle symptoms, like we said, is roughly 1 % to 5%. A meaningful portion of what patients report appears to be driven by expectation, the nocebo effect that we've talked about yeah to your point for the better part of a decade but uncommon doesn't mean zero and in certain subgroups the risk is meaningfully higher again the 2026 guidelines list vigorous exercise as a risk factor for statin related muscle symptoms to my knowledge this is the first time it's ever appeared as a risk factor on any of these guidelines which i think is look if they're going to put it as a risk factor i have high hopes that when the American Heart Association's newest guidelines on resistance training after, you know, acute coronary syndrome or with heart disease or whatever, they're going to take some steps here and put more stuff about exercise in there.

1:06:27Dr. Jordan Feigenbaum:That might turn out to be unfounded, but we'll see. But here are the other risk factors that the guidelines call out. First is drug combinations. So in this case, statin plus a fibrate, which is exactly what our patient was on. You'd mentioned that Gemfibrozyl carries the highest risk, mainly because of how it directly competes with statin metabolism in the liver so statin levels in the blood become much much higher so phenofibrate would be preferred if you need both but it's still not risk-free a statin type you've talked about this a bunch fat soluble statins like a torvistatin and simvastatin tend to cause more muscle problems than the water soluble ones like pravastatin or rosuvastatin in one review simvastatin accounted for 55 of 112 rhabdomyolysis cases

1:07:12Dr. Austin Baraki:though you see why i had that hot take of nobody should be on simvastatin on earth anymore i just

1:07:18Dr. Jordan Feigenbaum:know that somebody's listening to this who has been on simvastatin for like 20 years and they're like what do you mean you're just calling my doctor an idiot i'm like well no just they're busy and you know if you're doing fine you're doing fine but and they're probably old it's like when i see anybody on simvastatin and atenolol i'm like your doctor's old oh yeah yeah yeah that's that's true that is hot take all right uh other drug interactions like antibiotics antifungals calcium channel blockers and even grapefruit juice can all raise circulating statin levels by interfering with the enzyme that clears the drug from the body and the liver uh demographics are contributory here older age particularly over the age of 65 female sex both appear to increase risk based on observational data although it is interesting rhabdomyolysis cases just generally speaking uh much more prevalent in men and i it's not all men but it's always a man like just maybe in this particular setting got a bench you know yeah do got a bench um genetics talked about this oh i did put this in my notes the liver transporter gene that i was trying to recall is slco 1b1 did you ever hear about that uh probably come across it at some point but i don't quote a lot of genetics in my day-to-day practice yeah a twud uh that is a specific variant that reduces statin clearance and raises blood levels it's like i guess constantly drinking grapefruit juice or something like that.

1:08:35Dr. Jordan Feigenbaum:You can get genetic testing for this, but it's quite expensive as I apparently looked up earlier. Other medical conditions, hypothyroidism, kidney disease, liver disease, and both very high and very low BMI are all listed. There's also this very rare autoimmune variant that you had talked about twice now. In rare cases, statins can actually trigger the immune system to produce antibodies against the enzyme that the statin targets. At that point, the immune system is attacking the muscle independently of the drug. And a 2024 case report describes a patient whose CK was over 80 ,000. And it didn't come down after stopping the statin.

1:09:13Dr. Jordan Feigenbaum:It only improved after IV steroids. If CK stays elevated after the drug is stopped, this would be something that would be on your radar, which would have changed your differential, I think. Exactly.

1:09:22Dr. Austin Baraki:Yeah, that was one of the things I mentioned, is if this patient's CK did not improve all the way back down to normal, then I'd be much more concerned for some sort of immune inflammatory process. And yeah, I've seen this very infrequently. This is known as the statin-induced or autoimmune necrotizing myopathy. And the more interesting thing you did, you said it was antibodies against that HMG-CoA reductase. It is actually not true that it can only be triggered by statins. There are some very, very, very, very unlucky people who will spontaneously develop antibodies against that enzyme and they will develop this condition even having never taken a statin.

1:09:55Dr. Austin Baraki:So it's just like the worst luck on earth. Are you sure it's not seed oils or the soy? Yeah, so it's rough. Very, very terrible condition if somebody develops it. Although, again, it is quite uncommon and requires long-term immunosuppression, unfortunately.

1:10:11Dr. Jordan Feigenbaum:All right. All right. Well, Dr. Baraki, here's what I want to get your take on. Given everything that we've talked about so far, if a patient on a statin comes to you and says, look, my strength is going down, got persistent soreness, what do you do?

1:10:24Dr. Austin Baraki:Yeah, I'm going to take a kind of a thorough history as we did in this case, review the rest of their medicines, review the rest of their supplements, get a sense of which statin they're on and the dose, how strongly I feel that they need to be on that particular statin at that particular dose, potentially do some dose adjustments. If I'm concerned that there are drug interactions, address those, potentially switch them to a different statin or, again, low-dose combination, and talk about other strategies for mitigating their cardiovascular risk as well as assessing their training. and is it a good fit for their level of fitness?

1:10:54Dr. Austin Baraki:Those would be some of the places where I would start. If they felt strongly and they wanted to try things like we mentioned, if they wanted to try taking coenzyme Q or if they wanted to try taking vitamin D, I'm not gonna stop them, although those aren't necessarily like the first line things that I'm immediately jumping to in these situations.

1:11:10Dr. Jordan Feigenbaum:I noticed you didn't immediately say, stop the statin for sure, stop exercising for sure. It's more about, let's see if we can suss this out.

1:11:18Dr. Austin Baraki:Yeah, yeah, exactly. yeah neither neither of those are appropriate immediate first steps unless somebody is again in actual rhabdomyolysis and in the er then you're generally going to be okay to continue in some form of treatment and continue activity in some form it might just need to be a dose

1:11:35Dr. Jordan Feigenbaum:adjusted on both fronts yeah well said all right well let's close this out with what happened to the patient and what to do if this is you after discharge the statin fibrate combination was off the table going forward he was put on um a health promoting diet because and referred to our how to eat healthy article and also fish oil and continued on a statin but no fibrate um quick aside on the fish oil because we've done a full episode on this fish oil specifically the omega-3 fatty acids epa and dha do lower triglycerides by roughly 15 at the standard supplement doses now whether that's useful to you or not and where that 15 comes from is depending on how high your triglycerides were in the first place.

1:12:14Dr. Jordan Feigenbaum:That's helpful, but for patients who need serious triglyceride reduction, like the patient discussed here, over-the-counter official usually isn't enough. And so I refer you to the REDUCE-IT trial. They used a high-dose prescription form, which is this sort of synthetic version of official that seems to work a little bit better. And at four grams a day, they saw a 25 % reduction in cardiovascular events. The synthetic purified EPA forms are what the data supports most strongly for cardiovascular outcomes also they tend to be the purest form as it were standard fish oil supplementation while it does lower triglycerides modestly hasn't shown the same robust benefit for reducing heart attacks and strokes in people who don't already have a high cardiovascular disease risk so we still recommend trying to eat fish at least once to twice a week for the overall package of benefits from the food the sort of food matrix effect if you're eating more fish, you're eating less of whatever else it's displacing.

1:13:09Dr. Jordan Feigenbaum:And honestly, the people who do eat fish on a regular basis tend to have a healthier dietary pattern overall. But if you need to take something like fish oil, probably the prescription one would be the one we'd recommend over something over the counter. And for this particular patient, at the two-day follow-up, after he was discharged, his CK and liver-associated enzymes were still elevated but trending in the right direction. One month later, his CK and transaminases were normal. Lipids were also improved. His total cholesterol was 238. Triglycerides were 216. So still above target, but moving.

1:13:43Dr. Jordan Feigenbaum:He was asymptomatic at this time, exercising regularly with no reoccurrence, and he'd quit smoking. The formal diagnosis here was drug-induced myositis, meaning that the medication tended to be the primary cause of the muscle damage. So what are the 2026 guidelines change for a patient like this. So for a patient who develops statin related muscle problems that can't reach their LDL target on a tolerable statin dose, the guidelines do lay out a clear escalation. Hopefully that tool that you'd mentioned is updated soon. First line options include reducing the statin dose, like you'd mentioned, and adding a non-statin drug like bempidoic acid, azetimibe, or a PCSK9 inhibitor.

1:14:23Dr. Jordan Feigenbaum:Do you use the bempidoic acid frequently or no?

1:14:26Dr. Austin Baraki:I've not had a need to use it just yet. I am open to those opportunities should they arise, but I've had other ways to achieve the targets for patients without having to go to that just yet.

1:14:37Dr. Jordan Feigenbaum:okay uh well it does work and it blocks a different enzyme in the same cholesterol production pathway but it's upstream of where statins work the key difference here is that it's a it's called a pro drug which means that it's inactive when you swallow it and only gets activated by an enzyme in the liver and the muscle cells don't have that activating enzyme so the drug doesn't really turn on there and in trials bemphidoic acid is shown to significantly lower the rates of muscle side effects compared to statins which could be useful for a patient like this. This plus azetamide might be a plan for this guy without the same muscle risk.

1:15:12Dr. Jordan Feigenbaum:The guidelines also recommend measuring something called LP little a, which we've talked about for how many years ago was that now? Almost three. I think that you first brought this up and we actually did a podcast episode on it and an article. We ahead of the curve or is it just that the Europeans were ahead and then we were subsequently ahead of the American guidelines?

1:15:30Dr. Austin Baraki:Yeah. I mean, it seems like we've been ahead of the guidelines for a little while now, so glad they're coming around.

1:15:34Dr. Jordan Feigenbaum:Yeah. Yes. So again, the goal is the LDL target. There are other options. Like we said, pempadoic acid, azetamide, PCSK9 inhibitors, a newer injectable called incliceran. The specific drug is negotiable, but again, the LDL target is what it is. So for physicians, when you prescribe a statin and you counsel folks on exercise, those two prescriptions can interact at the level of the muscle. Most patients tolerate both just fine. All right, Austin, I'm going to suggest something here. I think maybe we should be getting a baseline CK on patients who exercise regularly before they start on a statin.

1:16:09Dr. Jordan Feigenbaum:Now, I know the guidelines say don't do routine CK monitoring, and I do get that for people who aren't exercising. But for somebody who actively trains, I might want to know where their CK normally runs, like in between training sessions. Obviously, it's going to vary. But that way, if they come back with symptoms, I actually have something to compare it against. Does that strike you as totally unreasonable? Am I crazy here?

1:16:30Dr. Austin Baraki:I don't think it's totally unreasonable. I think that one of the things that's cool about being a doctor is you can do stuff if you feel like it is appropriate and so like in your clinic if you wanted to do that with your patients prior to initiating them you could I in mine do not routinely do that and and part of the reason why is just because I have somebody who is habitually exercising does not necessarily mean that if I draw a CK on them that it is going to be a quote-unquote baseline just because it's always going to be fluctuating. Not unlike checking somebody's testosterone level, it is always either on the way up or on the way down, depending on the time of day, it's not a steady state thing.

1:17:07Dr. Austin Baraki:So most people even who are physically active do not just live with Oh, this person just lives at a CK of 800 all the time. It's probably relative to their last workout, either again, on the way up or on the way down. And I don't really know what to what to make of that. And so I don't I don't routinely do it if you felt like it was helpful for your decision making and you know, go for it.

1:17:28Dr. Jordan Feigenbaum:Yeah. All right. Now for patients and lifters listening to this podcast, if you're on a statin and you train, none of what we've discussed here is a reason to stop doing either one, especially without talking to your doctor. Statins reduce cardiovascular events, exercise reduces all cause mortality and benefits basically every organ system in the body. Both are worth keeping. But if you develop muscle pain, weakness, or dark urine, that doesn't really track with your training. Or even if it does track with your training and you've got dark urine, talk to your doctor urgently in that case. And if it turns out that you do have a statin intolerance, that is not the end of the road.

1:18:00Dr. Jordan Feigenbaum:The goal is the LDL target, not necessarily the specific drug, and there are more ways to get there now more than there have ever been.

1:18:06Dr. Austin Baraki:Yeah, I think it's fair if you don't know how to interpret your own urine situation, which I feel, you know, grateful that I can do that for myself. But if I didn't have that training, yeah, I'd be seeking out some help. All right, five takeaways here.

1:18:18Dr. Jordan Feigenbaum:One, statomyopathy is real but relatively uncommon. The excess symptom rate above placebo in controlled trials is roughly 1-5%, but in exercising patients, especially those on combination therapy, the risk can be higher. Two, there are three proposed mechanisms. One has to do with reduced energy production from CoQ10 depletion. Two has to do with compromised muscle cell membranes from loss of structural molecules. And three, there can be some accelerated protein breakdown. Exercise also amplifies all three, though the vast majority of people can compensate for these changes. Of note, CoQ10 supplementation gets a shoulder shrug from us.

1:18:52Dr. Jordan Feigenbaum:Three, if you're on a statin and your strength is going down, talk to your doctor before stopping the medication or changing your training. You can get more testing, like a CK test, which could be helpful at separating a drug problem from a programming problem. Four, the 2026 guidelines list vigorous exercise as a risk factor for statin-associated muscle symptoms for the first time. They also give statin-intolerant patients a clear escalation pathway, Bempinoic acid, ezetimibe, PCSK9 inhibitors, and so on. There are options here. Five, lower is better for LDL. There's a 33 % relative reduction in cardiovascular events at less than 55 versus 70 in the latest trial.

1:19:30Dr. Jordan Feigenbaum:Again, lower for longer is better. Healthy lifestyle changes and getting on effective lipid-lowering therapy, if needed, are some of the best things you can do for cardiovascular risk. All right, that's a wrap. Leave us a five-star rating and a review. it's the best thing you can do so we can keep bringing you all the latest nuance in health and fitness. I'm Dr. Jordan Feigenbaum. That's Dr. Austin Baraki. We'll catch you next week right here on the Barbell Medicine Podcast.

1:20:07Dr. Jordan Feigenbaum:I'm here on the job site with Dale, who's a framing contractor. Hey, good morning. They all traded up to Geico Commercial Auto Insurance for all his business vehicles. We're here where he needs us most. Yep, they sure are. We make it easy for him

1:20:19Dr. Austin Baraki:to save on all his insurance needs, all in one place, with coverage that fits his business and

1:20:23Dr. Jordan Feigenbaum:bottom line. Oh, I shouldn't have looked down. It's all right. We're so far up here. Look at me, take a deep breath. I'm good. So good. Get a commercial auto insurance quote today at geico.com and see how much you could save. It feels good to Geico.