I Tried Statins — Here’s What Happened | Dr Nick Norwitz MD PhD

I have high cholesterol, and like many people with high cholesterol, I was prescribed a statin. The statins. Statins. Statins. Statins. Now, as an MD-PhD myself, I'm pretty well informed on this topic, and I had my concerns, but I'm also open-minded, so I decided I'd try it. Just collect data on myself, right? See what would happen. Well, like so many people who try statins, I started experiencing side effects. In my case, muscle pains. We call these myalgias, and this occurred with an increase and a muscle damage marker in my blood. But this isn't actually what concerned me. What concerned me is what it might represent. Because we also know statins can impact the heart of our metabolism, the mitochondria, the powerhouse of the cell, not just in our muscles, but throughout our body, including in our brain. Now I want to be clear, this isn't about scaremongering. This is about talking about underappreciated truths about one of the most prescribed and most profitable drugs in history. Not telling you do or do not, but giving you the information you need to make an informed choice. So let's get in to what the data actually say. Most doctors aren't being educated on these data. And what they found was striking. You can have a trial with 5 million people that's worse than useless. It's all about context. Statins impaired a functional metric of muscle metabolism. What you do with that knowledge is up to you and between you and your doctor. Sleep and exercise. Statins aren't the only option. Why wasn't this headline news? In today's video though, I'm going to first cover striking human data, a study that shows how statins can harm mitochondria in humans even at very low concentrations. Then I'm going to talk about targeted support, specific supplements and lifestyle strategies you can use to protect and enhance your mitochondrial health. I'm also going to then move on to my response, specifically thoughts on feedback on another popular study on statins. You can see this video for more if you want to see that one first. And then finally, I'm going to talk about systems-level failures in medicine—why research like this, including human randomized controlled trials we've talked about previously on this channel about side effects of statins, often fail to reach your doctor's ear and the doctor's office. But first, I'll hit some feedback right off the bat. A caveat. I know the immediate pushback will be, "But statins reduce cardiovascular events, particularly in patients with established disease when used as part of a secondary prevention strategy." Again, for patients with pre-existing disease. But here's the point: the right tools are needed for the right job. You don't use a chainsaw to drive a nail, you use a hammer. And you don't fell a tree with a hammer either. It's all about context. That is a theme here on this channel. The right tool for the right task. Context, context, context. I am different than you. In the same way, you want to use the right medication for the right patient. Just because statins may reduce mortality in a patient with obesity and preexisting cardiovascular disease does not mean a statin will benefit an otherwise healthy person who happens to have high cholesterol. In fact, in that context, the potential for long-term harm may outweigh the benefit. That should not be a controversial statement. It is all about risk-benefit analysis in a given individual. But with that preamble over, let's get on to the study at hand, which was published last year in the Journal of Clinical Investigations. In this study, the researchers enrolled an equal number of men and women with overweight or obesity and treated them with atorvastatin 80mg daily for 56 days. And one of the key outcome metrics they assessed in this study was muscle oxygen consumption, specifically how quickly muscles recovered after exercise. This recovery rate, known as MV02, is a direct indicator of muscle's aerobic capacity, and what they found was striking. There was a 23% reduction in the rate constant of muscle recovery. To quote the authors so you can hear it from their mouth, "This indicates a decrease in muscle oxidative capacity." Or, in simpler terms, statins impaired a functional metric of muscle metabolism. Now, what might be causing this? I already alluded to it— mitochondria. Since mitochondria are the metabolic engines of the cell, it's reasonable to suspect that the root cause of the muscle problem might derive from mitochondrial damage. So, to explore this possibility, the researchers performed a series of mitochondrial assays. Taken from muscle biopsies after an overnight fast. And across these analyses, a consistent pattern emerged: statins progressively reduced mitochondrial function. One of the most affected components was complex IV of the mitochondrial electron transport chain. Even at very low concentrations, as little as 10 nanomolar, atorvastatin inhibited complex IV activity by greater than 50%. Again, quoting directly from this clinical study, "The magnitude at which mitochondrial respiratory capacity in skeletal muscles decreased in response to 8 weeks of high-intensity atorvastatin treatment was striking." Again, that is a direct quote. So, I want to raise an open-ended question, and I will emphasize this is an open-ended question, only one you can answer. I'm not answering it for you. How does any given medication, statin or otherwise, weigh out in your own personalized risk-benefit analysis, taking into account all the outcomes that matter to you—not just heart health, but also brain function, muscle integrity, and overall well-being. Again, that is not a question anyone can answer for you, but it's one worth asking yourself. With that in mind, I want to offer a few practical thoughts on mitochondrial health and some tips. First, if you are exploring lipid-lowering therapies for yourself, I'm not recommending this or otherwise, but you should know statins aren't the only option. There are other medications worth knowing about. I'll give two examples. One alternative is called ezetimibe. Ezetimibe reduces cholesterol absorption in the intestines. Specifically, it blocks something called the Niemann-Pick C1-like 1 protein, a key transporter on the surface of intestinal cells.. And by blocking this transporter, ezetimibe prevents dietary and biliary cholesterol from being absorbed back into the body. And this reduces the absorption of cholesterol, leading to a decrease in the liver's cholesterol stores. Then, as a compensatory response, what the liver does is it increases the number of LDL receptors on its surface, and this pulls more LDL particles out of the bloodstream. This medication, in my opinion, based on the physiological mechanisms, is less likely to harm your mitochondria. It's more gut-specific. And then another is called bempedoic acid. It works more specifically in the liver and may avoid the muscle-related side effects associated with statins. Specifically, bempedoic acid is a prodrug—it's a precursor molecule that is converted into its active form once in the liver. And it works a bit differently than statins by blocking a different enzyme called adenosine triphosphate citrate lyase, You don't really need to know that term, but that's the enzyme's name. And this liver-specific action of bempedoic acid means that unlike statins, it does not accumulate in muscle tissue, which may reduce the risk of muscle-related side effects and mitochondrial harm in muscles and elsewhere. I might also add that the structure of this molecule is— a bit ironic. Anyway, the point is the landscape of lipid-modifying drugs is expanding. A sort of therapeutic buffet. And to be clear, I'm not telling you you should take these alternatives if you have high cholesterol. I'm not. I'm simply saying they exist, and they should be mentioned. What you do with that knowledge is up to you and between you and your doctor. And beyond pharmaceuticals, there are also supplements and lifestyle strategies that can support mitochondrial health. And yes, this is particularly relevant if you're concerned about the potential statin-related side effects on cellular energy and mitochondrial health. So, let's talk about the big one. You might have heard of it, but I'm going to tell you something different about it: Coenzyme Q. So, statins interfere with the body's synthesis of Coenzyme Q, which is an essential electron transporter in the mitochondrial electron chain. Mitochondria use this chain to produce energy. And Coenzyme Q, what it does is it shuttles electrons between complexes, specifically between complexes I and III and II and III. Now, To make this simple, disrupting this process is like tackling a runner just as they're about to pass the baton in a relay race. The handoff fails and energy production stalls. Fortunately, you can supplement with Coenzyme Q. Though, and here's the point, not all forms are as effective at getting the Coenzyme Q where it matters most: into mitochondria. So I went a little bit deeper into the research and I found a product that contains what's known as Coenzyme Q Phytosome Phospholipid Complex. I know, L. A lot of words. Basically, this is a formulation where Coenzyme Q is complexed with phospholipids. This improves its absorption and bioavailability. Phospholipids are what are called amphipathic molecules, so basically they're lipid and water soluble. Or, this is basically nerd speak for they're biomolecular stealth ninjas that help get the Coenzyme Q to penetrate cell membranes and get it where you want it to go. So take a look at this graph. This shows that phytosome formulation, the red, increases bioavailability of the Coenzyme Q at least threefold compared to standard Coenzyme Q, and it leads to consistently more elevated levels. So in brief, this phytosome delivery vehicle, the mitochondrial stealth protection ninjas, this system enhances Coenzyme Q's ability to provide its core benefits, including enhancing cellular energy production at the mitochondrial level and also antioxidant protection. But of course there are other interventions that support mitochondrial function that may seem less exciting but they're no less essential, namely sleep and exercise. If you want more details on sleep and mitochondria, see this video covering a new Nature paper that absolutely blew my mind. And if you want the straightforward answer to the question, "What's the best exercise for mitochondria?" I'd argue that at least some high-intensity work, ideally twice per week or more, is critical for optimizing mitochondrial function. At a high level, I want you to think about it this way: exercise training works on the principle of progressive overload. You go to the gym and you persistently push yourself beyond what's comfortable in order to evolve. And this isn't just happening at the gross whole muscle level, it's happening first and foremost at the level of mitochondria, at the metabolic level. So consider hill sprints, jumping alternating lunges, and muscle-ups, if you can do them, your mitochondrial friends. Now I want to shift gears in this video and respond to some common pieces of feedback I received on a prior newsletter and video I did about statins. And this applies equally to the current discussion and current paper reviewed. So in that earlier video, I walked through a human randomized controlled trial published in the prestigious journal Cell Metabolism that showed statins can promote insulin resistance, increase average blood sugar , and reduce levels of the hormone GLP-1, an important hormone involved in metabolic regulation and the basis for drugs like Ozempic and Wegovy. Now, the most frequent question I got asked was this: "Isn't this just a small study with only 40 patients? How important can it really be?" And here's my answer to that question: that is exactly the point. First, let's be clear, sample size does not determine the rigor or value of a study. You can have a trial with 5 million people that's worse than useless. On the other hand, you can have a carefully controlled study with just a handful of participants, or even one, that can reveal something profoundly important. So the fact that the Statins Reduced GLP-1 trial had 40 participants does not diminish its validity or the clarity of its findings. And those findings were robust. Statins cut GLP levels in half in humans, with a consistent downtrend largely by disrupting the gut microbiome. You can see the full details in that prior content. But the broader issue is this: when high-quality data are published in a top scientific journal showing that a widely prescribed medication— actually the most profitable medication class in history— may have a significant downside on human metabolism, and there may be a potential solution— again, see that video— the lack of follow-up is concerning. That raises two critical questions: Why wasn't this headline news? And why has no large-scale follow-up study been done? The answer, unfortunately, is quite simple: There's no financial incentive. Who is going to fund that follow-up study that questions the blockbuster drug or suggests off-patent solutions? Who stands to profit from digging deeper into side effects when the existing narrative works so well for the market? And to be crystal clear, this isn't about accusing individual individuals of wrongdoing. It's about recognizing a structural truth. Medicine is not governed solely by patient well-being. It's governed by economics. It's a business. That's not cynicism. It's gross reality. So yes, the small size of a trial matters, but not in the way critics think. It highlights how even when rigorous, peer-reviewed evidence in a human randomized controlled trial shows a clear risk, and suggests a way to mitigate it, the healthcare system fails to act. That should all give us pause to think. I'll also point out that while most of the feedback I received was overwhelmingly positive, all of the critical responses, 100% of 'em, that I observed failed to engage with the actual data at hand. Instead, they were vague dismissals, offhand remarks, and attempts to undermine the messenger, but not actually addressing the message. I think that's telling. What do you think? Really, one of the biggest problems in today's health and nutrition discourse, especially on social media, is that we don't engage with what people are actually saying. This is a pet peeve and frustration of mine, getting people to hear what I'm actually saying, not what they think I'm going to say. So I challenge you to listen closely to the arguments, mine and others. Not just the ones you assume are going to be made. This applies to the statin mitochondria study we just discussed here as well. Yes, it was a small study. Yes, it has limitations. All studies have limitations. But the results were striking, showing that statins impaired mitochondrial function in humans, even at very, very low concentrations, and even without symptoms. That should spark serious questions about what the long-term side effects and consequences might be across different patient populations. The way we do studies now is we group a heterogeneous mass of people and then try to generalize back out. To individuals. Oh, and for one quippy but true remark: if you conduct the smallest possible trial on yourself, an n=1 experiment, and the results are bad, in fact horrible, do you respond, "Well, it's just a small study. It's an n=1. Don't worry about it." Didn't think so. But wrapping up, these conversations should not be limited to niche corners of metabolic health Twitter or obscure YouTube channels. They should be happening in medical schools and in your doctor's office. Here's the uncomfortable truth though: most doctors aren't being educated on these data. And it's not because they're lazy or inattentive or don't want these data in hand. In fact, many do and are appreciative when they get it. But it's because the system does not prioritize this sort of evidence. And that's a systems-level failure, not a personal one. So the goal here, the true goal here, it's not to provoke fear or advocate against statins outright, but rather to bring awareness to the full picture, the known benefits, the potential trade-offs in the broader physiological context so you can make an informed choice. I really don't see what's wrong with that. Stay curious, stay informed, drop your comments. I know this is going to be controversial, but I'm happy to be out here speaking about it because quite honestly, the conversation is important and provocatively reasonable. Hope you agree. Have a good one.