Episode 4: Should You Take a Statin? (Cardiovascular Disease: Part 4)

I’m Dr. Ravi Kumar, a board-certified neurosurgeon. On this show, I question medical dogma, break down bias, and try to bring clarity to complex health topics. My goal is to question everything. It’s something I’ve done throughout my own life, and it’s something I want to share with you—because I genuinely believe that knowledge is power. When it comes to your health, the right information can help you make better choices. It certainly has for me. This is episode 4—and also part 4 of our cardiovascular series. Today, we’re diving into cholesterol-lowering medications, especially statins. These drugs dominate both clinical practice and the medical literature when it comes to managing cardiovascular risk. The information I’ll share today might surprise you, so I hope you’ll stick with me. But before we get started, a quick disclaimer: I am a medical doctor—but I’m not your doctor. This podcast is for informational purposes only. It’s not intended to diagnose or treat any condition. My goal here is to give you clear, honest, and unbiased information. So take what resonates, bring it to your own healthcare provider, and run it through your own common sense algorithms to figure out the best strategy for your health goals. In part one of this cardiovascular series, we talked about saturated fat—how it’s actually one of the most wholesome and healthiest fats we can eat. Yes, it raises cholesterol, but we saw that there’s no solid link between eating saturated fat and developing heart disease. In part two, we covered seed oils—these are highly processed, polyunsaturated fats extracted from seeds we never traditionally used for oil. They’re loaded with linoleic acid, which fills our cholesterol particles with unstable, oxidizable fats. This is something our species has never encountered before in evolutionary history. These seed oils have created an oxidative disaster in the cardiovascular system, contributing to inflammation and the development of heart disease. Then in part three, we focused on LDL. This is the cholesterol that goes up when you eat saturated fat—and it’s often labeled as the “bad cholesterol.” But what LDL actually does is… play a crucial role in the body—delivering cholesterol to nearly every cell, especially when there’s damage, inflammation, or a need for repair. It’s like a first responder. The problem is, in the context of an inflammatory, high-oxidative environment—like the one caused by seed oils, smoking, high blood pressure, diabetes, chronic infections—LDL gets pulled into the damage, tries to help, but ends up entangled. This is what’s known as the injury response hypothesis. Now to be clear, we didn’t dismiss LDL as always harmless. In that episode, I said: yes, in certain cases—especially when there’s ongoing vascular damage and lots of oxidizable fats—LDL can play a pathological role. But the key idea is that this process is modifiable. It’s not just about blocking cholesterol; it’s about addressing the root causes through diet and lifestyle. We’ll revisit this concept later in the podcast. So in this episode, we’re going to talk about cholesterol-lowering medications—namely, statins. These are by far the most widely prescribed, the most well-studied, and the most dominant drugs used to manage cardiovascular risk. The big question is: Should we be using statins to lower LDL cholesterol? And if we do, what are the actual benefits—and what are the risks? Because that’s really what it comes down to anytime you’re considering a medication. You have to ask: What am I getting out of this? And what could it cost me? Once you know those two things, you can make an informed decision about whether or not you want to put this drug in your body. Now, to really understand how we got here, we’ve got to take a step back and look at history. Let’s rewind to the early 1970s. At that time, the United States was in the middle of a full-blown cardiovascular epidemic. Heart attacks were everywhere, and people were desperate for answers. The dominant belief at the time was that cholesterol was the culprit. Cholesterol was clogging our arteries and causing heart attacks. That was the theory. So naturally, researchers started looking for a drug that could block the body from making cholesterol. That made sense—if you accepted the idea that cholesterol was the problem. But here’s the thing. Even from a basic common-sense standpoint, that idea raises questions. Cholesterol is something our bodies make on their own. Why would evolution program us to produce something that’s inherently toxic? But back then, the thinking was: the body was malfunctioning—making too much cholesterol, making bad choices, and flooding our arteries with it. So the solution became: find a way to shut that process down. So in the early 1970s, a Japanese researcher named Akira Endo began searching for compounds that could block cholesterol synthesis. Now, let’s pause for a second and talk about what that actually means—cholesterol synthesis is not some quick, one-step reaction. It’s an incredibly complex process. It involves more than 30 steps and over 20 unique enzymes. Think about that: over 20 highly specialized molecular machines, each built and refined through slow evolutionary trial and error. Each enzyme is a product of countless mutations and natural selection, fine-tuned over thousands—sometimes millions—of years. So if the body goes to that much trouble to make a single molecule, it probably means that molecule is really important. Among those enzymes is one called HMG-CoA reductase—this enzyme controls the rate-limiting step in the entire cholesterol pathway. In other words, it’s the bottleneck. If you slow it down, or block it, the whole process grinds to a halt. So Endo thought, “If we can block this enzyme, we can reduce cholesterol synthesis.” So… Where would he look for this kind of compound? Well.. He decided to look at fungal toxins. Because in nature, microbes are constantly at war with each other—tiny biochemical battles over food, space, and survival. And one of the weapons fungi use in this war is chemistry. Imagine this: a fungal spore lands on a rich source of energy—something full of carbs or fats—and starts growing. But then a worm shows up, also looking to feast. Now the fungus doesn’t want to share. So what does it do? It makes a toxin. A chemical weapon. One that specifically targets the worm by blocking its ability to make cholesterol. Why? Because cholesterol is critical for the worm’s survival. It’s what gives structure to its cell membranes—without it, the worm can’t function. Its cells fall apart, its membranes break down. It either dies, or senses the toxin and avoids the food altogether. Either way, the fungus wins. And remember—a worm is an animal. Just like us, it relies on cholesterol to survive. So Akira Endo knew that fungi could produce toxins capable of blocking cholesterol synthesis. And He began screening a wide range of fungal fermentations, looking for a compound that could inhibit HMG-CoA reductase—the rate-limiting enzyme in cholesterol production. Eventually, he discovered a molecule called mevastatin, produced by a fungus known as Penicillium citrinum. And sure enough, mevastatin turned out to be a powerful inhibitor of HMG-CoA reductase. When given to animals, it dramatically reduced their ability to make cholesterol. But there was a problem: it was too toxic for humans. In early testing, dogs that were given mevastatin got really sick. Still, this discovery sparked a whole new field of drug development—researchers began looking for similar compounds that could safely inhibit cholesterol synthesis in humans. By 1978, another researcher, Alfred Alberts, isolated a related compound called lovastatin from a different fungus: Aspergillus terreus. Lovastatin had the same cholesterol-lowering mechanism, but it was much better tolerated in humans. Now, here’s something to keep in mind about medications: all drugs are, in some way, poisons. That’s not an exaggeration—it’s just biology. The difference between a medicine and a toxin is the dose. If a compound can disrupt a biological process, then at low doses it might have therapeutic effects. At high doses, it might cause harm. That’s the whole idea behind pharmacology. Lovastatin, at controlled doses, significantly lowered LDL cholesterol by blocking that key enzyme in the cholesterol synthesis pathway without killing the patient. And in 1987, it became the first statin approved by the FDA for use in humans. From there, several more statins were developed—both naturally derived and synthetically modified.These include pravastatin, simvastatin, fluvastatin, atorvastatin, and rosuvastatin.You might know them by their brand names: Pravachol, Zocor, Lescol, Lipitor, and Crestor. All of these drugs work by doing the same thing—blocking cholesterol synthesis at that key enzyme, HMG-CoA reductase. Now, cardiovascular disease at this time was the leading cause of death in the United States, responsible for about half of all deaths. It was also a major killer globally. So, naturally, drug companies saw an opportunity. If they could prove that statins reduce cardiovascular risk—they’d have a blockbuster on their hands. And that’s exactly what they set out to do. Whether we like it or not, this is how a lot of medical progress happens in the U.S.—driven by the potential for enormous profits. Statin trials started popping up everywhere. But early on, it was kind of the Wild West. Most of these studies were funded by the drug companies themselves, and they had broad control over how the trials were designed, what outcomes were measured, and how the results were interpreted. It was like letting a four-year-old decide what’s for dinner—there hands were figuratively always in the cookie jar. When the people who stand to make billions are the same ones running the trials to prove that their drugs work, we have to be skeptical about how the evidence was shaped. This went on until around 2004 or 2005, when both the U.S. and Europe stepped in to tighten things up. They introduced formal guidelines to standardize how clinical trials should be conducted—how endpoints were defined, how results were reported, and what counted as meaningful evidence. But by this time, statins started being prescribed to just about everyone. They became ubiquitous. I still remember my first year of medical school in 2006. We were sitting in lecture, and a cardiologist came in to talk to us about cardiovascular disease. He emphasized how essential statins were—that they could lower your risk of heart attacks and save lives. He was so convinced of their importance, he actually said he thought statins should be put in the water supply. I remember sitting there thinking—wait, what? He was essentially suggesting that the government should mass medicate people without their consent, just because the medication was “that important.” And this wasn’t just an offhand comment. He was serious. He compared it to fluoride—something already added to public water to reduce cavities. Fluoride, after all, is a form of medical treatment. It’s intended to be incorporated into your teeth to reduce dental decay. Millions of people around the world drink fluoridated water, whether they know it or not—and whether they want to or not—because it’s considered good for public health. Now, this isn’t me making a statement about fluoride’s effectiveness. It’s just an example of how, even in modern times, mass medication without informed consent does happen. So when that cardiologist said that statins should be added to the water, it made an impression on me. I was just a first-year medical student—I didn’t know any better. I thought, Wow, statins must be incredibly important. Not long after that, I went in for my annual physical with my primary care doctor. My cholesterol came back high—my LDL was around 160. And he said, “You really should be on a statin.” At the time, I was a young man—30 years old. And he told me, “If you want to prevent a heart attack down the line, you should start now.” And I thought, Well, I just heard about this in med school. Seems legit. So I started taking simvastatin—20 milligrams a day. And within just a few days, I started feeling… off. My whole body ached. I had this crushing brain fog like you wouldn’t believe. And remember, I was in the first year of medical school at the time. This is the year where the firehose is wide open—you’re expected to take in massive amounts of information, memorize it all, and then regurgitate it on tests. It’s also the year when most of the students who don’t make it, fail out. I had always been a good student. But now? I couldn’t keep up. Something was wrong. I started feeling anxious and depressed—something that just wasn’t normal for me. So I went to my wife, Chosun. I said, “I don’t know what’s going on. Maybe I have a virus. Maybe it’s something I’m eating. But I have no energy. My whole body aches. I’m not sleeping. I can’t focus in class. I can’t memorize any of these anatomy structures. I feel terrible.” And she looks at me and says, “Didn’t you just start that new medication?” And I said, “Yeah, but no, it’s not that. Believe I’m a medical student. I know this stuff. This drug is important. Statins save lives.” She kind of raised an eyebrow, but let it go. But another few days go by, and I just keep spiraling. It’s hard to describe the feeling, it wasn’t just physical. It was like my entire being wasn’t beginning to fail. It was a feeling I had never experienced before. Finally, Chosun says, “Look. Just stop the statin. If you don’t feel better, fine—you can go back on it. But at least try.” At that point, I thought, Okay. Maybe she’s right. Maybe it’s worth trying. So I stopped it. And within two days, I was back to normal. It was like someone flipped a switch. And I just sat there thinking—Wait a second. I was told this drug was essential. That if I didn’t want to die of a heart attack, I had to be on it. I heard that from my doctor. I heard that in lecture. But when I took it, I had never felt worse in my entire life. And as soon as I stopped, I felt completely fine. That was my first experience with statins. And Even after that first experience, I ended up trying a statin again—about six years later. At that point, I was in my neurosurgery residency. My doctor saw that my LDL was still around 160 and said, “Yeah, you really should be on a statin.” I told him, “I tried simvastatin before, and I felt horrible.” He said, “Okay, but that was simvastatin. Let’s try atorvastatin. You’ll probably tolerate this one better.” So I gave it another shot. And within two days, it was déjà vu. I felt like I was living inside a garbage can again. My body just didn’t work. But this time, I recognized the signs—and I stopped it right away. And again, almost immediately, I felt better. Now, my doctors were sympathetic. They said, “Yeah, some people don’t tolerate statins well. Most people do just fine—you’re just one of the unlucky ones.” But what those experiences really drove home for me is that statins can have serious side effects. And remember what I said at the beginning of this episode—if you’re going to decide whether or not to take a medication, there are two key questions you have to ask: What are the benefits? And what are the risks? So let’s start with the risks. Because once you know the downside, you can better weigh it against the potential benefits. The first—and by far the most common—is myopathy. This means muscle injury. It usually shows up as pain, weakness, or generalized aching. And in some cases, you can actually see signs of muscle breakdown on lab tests. This condition is often referred to as statin-induced myopathy, and it’s not rare. Studies suggest it affects anywhere from 0.9% all the way up to 20% of people who take statins. Now here’s where things get interesting. If you look at the big, drug-company-sponsored clinical trials that test whether statins work—most of them report very low rates of myopathy. And that just doesn’t match what we see in the real world. So what’s going on? Well, it turns out there’s a design trick that can help make a trial look better on paper. It’s called a run-in period. Before the actual trial even starts, researchers will give the drug to a bunch of people as a test run. And if someone reports side effects—like muscle pain—they’re excluded from the main trial. Why? Because those people are more likely to drop out or mess up the results. And remember, even though clinical trials are supposed to follow the scientific method and minimize bias, there’s no such thing as a completely unbiased trial—especially when billions of dollars are on the line. So by the time the trial starts, the people who couldn’t tolerate the drug are already gone. Only the people who had no side effects are left—and of course, that makes the drug look safer and possibly more effective than it really is. Now, contrast that with a study called the PRIMO study—short for Predictor of Muscular Risk in Observational Conditions. This was a large, independent observational study—not funded by pharmaceutical companies—conducted in France. They looked at 7,924 patients who were prescribed statins for high cholesterol. And in that real-world setting, 10.5% of people reported muscle problems. That number feels a lot more accurate. These weren’t cherry-picked patients in a carefully designed trial—these were regular people, just like you and me, being treated for high cholesterol. So that’s problem number one with statins: muscle pain and weakness, affecting roughly 1 in 10 people. Now, this brings us to an important part of the biochemistry behind how statins work—and why they can cause side effects like muscle pain. Remember, statins block the enzyme HMG-CoA reductase, a key step in the cholesterol synthesis pathway. And like we talked about earlier, this is a long, complex pathway—over 30 steps involving more than 20 enzymes. Well, it turns out that cholesterol isn’t the only thing produced in this pathway. There are important spin-off compounds made along the way—molecules the body relies on for other functions. And two of the most critical downstream compounds that also get blocked by statins are Coenzyme Q10 (CoQ10) and heme A. Both of these molecules are essential for energy production inside your cells. Which introduces us to the world of the mitochondria. Now, mitochondria are fascinating little organelles. They’re actually evolutionary remnants of ancient bacteria—specifically alphaproteobacteria—that were engulfed by early animal cells. But instead of digesting them, the host cell basically struck a deal: “I’ll feed and protect you, if you make energy for me?” That’s how we ended up with mitochondria through a process called endosymbiosis—a shared life between two once-separate organisms. And now, every animal cell has mitochondria inside, producing energy in the form of ATP—the fuel that powers nearly everything our body does. The way mitochondria make ATP is through something called the electron transport chain. This system pumps hydrogen atoms and transfers electrons, creating chemical and electrical gradients that ultimately form high-energy bonds. And here’s why I’m telling you this: two of the molecules absolutely essential for this process are CoQ10 and heme A. You can get CoQ10 from your diet—mainly from organ meats and other animal tissues—but not in large amounts unless you’re eating a meat-heavy diet. Heme A, on the other hand, can NOT be obtained from food—you have to make it yourself. So when you take a statin and block HMG-CoA reductase, you’re not just blocking cholesterol production—you’re also cutting off your body’s ability to make CoQ10 and heme A. And that directly impacts mitochondrial energy production. Now think about your muscles—they’re some of the most energy-demanding tissues in your body. They’re what allow you to move, lift, run, and even maintain posture. When you interfere with their ability to make energy, things start to break down. Literally. The mitochondria can’t function properly. The muscle cells can’t sustain themselves. They start to die—and as they die, they break apart and leak their contents into the bloodstream. That’s what causes the aching, the weakness, the soreness. That’s the root of statin-induced myopathy. But that’s not all. Statins also appear to interfere with the metabolism of vitamin K2. Now, vitamin K2 is still relatively new to our understanding of health. You’ve probably heard of vitamin K1—we get it from leafy green plants, and it helps activate clotting factors in the liver. That’s why people on Coumadin (or warfarin) have to watch their vitamin K intake—warfarin blocks the recycling of vitamin K to activate blood clotting. Well, K1 can be converted—in small amounts—to vitamin K2. And vitamin K2 does something entirely different: it activates specials proteins which helps shuttle calcium into your bones and teeth, and out of soft tissues like arteries. So here’s the kicker: Statins can block the conversion of K1 to K2. And if that happens, calcium might not be going where it’s supposed to. Instead of going to bones and teeth, it could be ending up in your arteries, contributing to vascular calcification. Remember when we talked about coronary artery calcium scores? Once calcium starts showing up in your arteries, your cardiovascular risk shoots up. So here’s the question: Could statins actually be increasing coronary artery calcification? That’s actually not a fringe question and its something that deserves further investigation. OK. Lets get back to our list of statin risks. Another serious risk linked to statins is something called statin induced cardiomyopathy. Now, just to back up for a second—your heart is actually a muscle. Its job is to contract and pump blood throughout your body. But when the heart muscle starts to weaken or fail, that’s what we call cardiomyopathy—and it can lead to full-blown heart failure. And here’s the troubling part: statins can cause cardiomyopathy. Why? Because, as we’ve discussed, statins interfere with your body’s ability to make energy at the cellular level by throwing a wrench in the mitochondrial machinery So essentially, you’re poisoning the engine that your heart depends on. In some people, this can lead to weakening of the heart muscle—and that’s cardiomyopathy. There’s a fascinating study that looked at 142 patients who had heart failure and were on statins. The researchers did something simple: They discontinued the statins and started the patients on CoQ10 supplementation. And the results were striking. Patients reported significant improvements in fatigue, muscle pain, weakness—and even memory loss.. But here’s what’s really remarkable: The one-year mortality for those patients was 0% after stopping statins. And the three-year mortality? Just 2.8%. To put that in perspective, patients with this type of cardiomyopathy typically have a mortality rate 10 to 15 times higher at three years. But by simply removing the statin—and giving the body back its ability to produce and use CoQ10—those outcomes dramatically improved. Which strongly suggests that in these cases, statins were damaging the heart. And when the drug was taken away, the heart started to recover. Another big area of concern—one that has mixed data in the literature but is hard to ignore from a common sense standpoint—is how statins affect the brain. And to understand this, there are two important facts you need to know. First, about 20 to 25% of your body’s total cholesterol is found in the brain. That’s incredible, considering the brain is only about the size of a cantaloupe. Meanwhile, your entire body might weigh 100 to 200 pounds—yet a quarter of all your cholesterol is concentrated in this one small, dense, incredibly complex organ. As a neurosurgeon, I operate on the brain all the time. And let me tell you—when you touch brain tissue, it’s soft, gelatinous, and unmistakably fatty. It’s obvious just by handling it: this is a masterpiece of biological engineering where cholesterol plays a central role. Second, cholesterol made by the liver can’t reach the brain. Your liver makes most of the cholesterol in your body and sends it around via LDL particles for delivery. But LDL cholesterol can’t cross the blood-brain barrier—that protective filter that shields your brain from substances in the bloodstream. So the brain has to make all of its own cholesterol—and it does this in specialized brain cells called astrocytes. Now, let’s say you’re taking a fat soluable statin— like atorvastatin, simvastatin, or lovastatin. These drugs can cross the blood-brain barrier and enter the brain. So what happens when you introduce a drug into the brain that blocks the very enzyme responsible for cholesterol synthesis? You have an organ that is dependent on cholesterol… An organ that can’t import it from the outside… And now, you’ve just cut off its ability to make its own cholesterol. From a common sense standpoint, what do you think is going to happen? You’re going to have problems. You’re going to have deterioration in brain function. And while researchers may argue back and forth over conflicting studies, at a certain point, you just have to use some common sense. Now let’s look at some interesting studies. One smaller study examined 18 patients with Alzheimer’s or other forms of dementia who were taking statins. The researchers did a simple thing: They withdrew the statins for six weeks, then reintroduced them for the next six weeks. During this time, they measured cognitive function using Mini-Mental State Exams, which is a standard test for brain performance. What did they find? When the statins were stopped, cognitive scores improved. When the statins were reintroduced, scores worsened. These were patients already struggling with dementia—and they got better just by stopping a medication. Now imagine a drug that improves cognition in people with Alzheimer’s. That would be a blockbuster. But here? Just removing a drug led to measurable improvement. And yet—almost no one talks about this study. It wasn’t repeated. It wasn’t publicized. It was just… ignored. Now, let’s go back to that earlier study we discussed on statin-induced cardiomyopathy. In that same population, researchers also tracked memory loss. At the beginning of the study, 73% of participants had some level of memory loss while on statins. But after discontinuing statins—and giving Coenzyme Q10—the number of people without memory issues dropped to 28%. That’s a 45% absolute reduction in the number of patients with memory loss just by stopping statins and supporting mitochondrial function. That’s not a small effect. That’s a major change. And yet, this too has been largely swept under the rug. Diabetes is another well-documented and measurable complication of taking statins. Some studies have estimated the risk of developing diabetes while on a statin at around 0.4%, while others report it as high as 4%. The true number is probably somewhere in between—but either way, this is a drug that can impair your metabolic health. That’s a risk you have to be willing to take if you’re going to use a statin. Now, the full list of potential complications from statins is long—many of them are rare, but still important to be aware of. We’ve already talked about the major ones—myopathy, cardiomyopathy, cognitive effects, mitochondrial dysfunction, and diabetes. But here are some of the others you should know about: Peripheral neuropathy, Sleep disturbances, Mood changes and depression, Fatigue, Tendinitis and even tendon rupture, Joint pain, Hormonal disruption, Elevated liver enzymes, Pancreatitis, Skin conditions like eczema, Acute kidney injury, Lower testosterone in men, and Exercise intolerance All of these have been reported as potential side effects of statins. And just like I found out the hard way—as a young medical student taking a statin for the first time—Your doctor might be very enthusiastic about these medications. But there are real and significant risks, and I hope I’ve been able to lay those out clearly for you. Interlude Hey guys, I hope you’re enjoying the episode so far. I want to ask you for a quick favor. If you’re finding this valuable—if you believe, like I do, in cutting through bias and misinformation to get to the real truth about health—then help me spread the word. Just take a second to like, subscribe, leave a comment, and share this episode with someone who needs to hear it. The more engagement there is, the more the algorithms will push this out—and the more people we can reach. And again… Thanks so much for joining me on this journey. Okay—so we’ve talked about the risks of taking a statin. Now let’s talk about the benefits. And here’s something important to understand: The risks may apply broadly—but the benefits only apply to certain groups of people. In other words, not everyone benefits equally from statin therapy. So before you can figure out if a statin makes sense for you, you first have to know: What’s your actual risk of having a cardiovascular event—like a heart attack or stroke—over the next 10 years? The most commonly used tool for this is something called the Atherosclerotic Cardiovascular Disease Risk Estimator also called the ASCVD Risk calculator.. I’ll link to the calculator in the show notes, but here’s how it works. You plug in your: Age, Sex, Race, Blood pressure, Total cholesterol, LDL, and HDL, Whether you have diabetes, Whether you smoke (currently, formerly, or never), and Whether you’re on blood pressure meds, statins, or aspirin And based on that information, the calculator gives you a percentage—your estimated risk of having a cardiovascular event in the next 10 years. It’s quick, it’s non-invasive, and it’s the standard tool we use in clinical medicine. That said, it’s not perfect. We talked about another tool in a previous episode—the coronary artery calcium score —which is actually a more accurate way to assess true risk. But that requires a adiological procedure and a small amount of radiation exposure. But back to the ASCVD Risk Estimator for a moment. We use it, but its not perfect. A large study from Kaiser Permanente looked at over 300,000 people. They calculated each person’s 10-year risk using the ASCVD tool, then followed them over time to see who actually had cardiovascular events. And here’s what they found: The calculator significantly overestimated risk—by 2 to 6 times. So if your calculated 10-year risk shows up as, say, 12%… Your real-world risk might actually be more like 2% to 6%. That’s a big difference—especially when you’re deciding whether to take a daily medication that carries real risks. Ok. We have a crude way to measure risk. How do we use it to know if we’ll benefit from a statin? The best study we have to really understand how statins affect outcomes is called the Cholesterol Treatment Trialists’ Collaboration. It was published in 2012, and it analyzed 27 randomized clinical trials looking specifically at statins. Altogether, it included about 134,537 people. This was a meta-analysis, meaning it pooled data from all these trials to try to answer a simple question: How do statins affect cardiovascular disease? Now here’s what the study found— and this is really important. It measure risks based on groups stratifies by their 5 year baseline risk. The ASCVD calculators stratifies risk in 10 year intervals. This study used their own algorithm for determining baseline risk which is not available to us. So I will simply double the baseline cardiovascular risk in this trial to correlate to your 10 year risk on the ASCVD calculator. It might not be exactly what the paper did, but it will give you a rough idea of where you land on in their result groups. You don’t have to worry about this, I’ll call out your ascvd risk and then cross match it to the 5 years risk groups in this study for you. When comparing those who took statins to those who didn’t take statins or took less statins. No matter what your risk level is, statins showed no benefit in non-vascular mortality. So that’s people who die of non cardivascular diseases like cancer. Statins did not improve that metric. Taking a statin won’t reduce your chance of dying from not vascular causes. Now if you have no history of vascular disease, it does not matter what your baseline risk is, this study showed no significant reduction in death from cardiovascular disease. Let me repeat that. If you don’t have vascular disease, statins show no statistically singificant ability to reduce your death from cardiovascular disease. If you do have pre-existing vascular disease, there was an overall absolute risk reduction in your chance of dying of cardiovascular disease of 0.28% per year. And those with baseline 10 year risks of less than 20% showed no significant reduction in cardiovascular death. And to me, that’s the main question. Will this medication help me live longer—or not? And, according to a simple comparison of statin takers versus controls in this massive meta-analysis, the answer is only a little bit and only if you are high risk to begin with. So what about heart attacks? Here’s where things break down further. If your 10-year risk on the ASCVD calculator is between 10 and 20%, statins may reduce your risk of having a heart attack by 0.29% per year. If your risk is below 10%, the benefit drops even further—to just 0.08% reduction in having a heart attack per year. Now let’s look at stroke risk. If your 10-year risk is between 10 and 20%, taking a statin may reduce your stroke risk by 0.09% per year. If your risk is under 10%, that drops to 0.04% per year which is not statistically significant. The reductions in heart attack and stroke risk for those with ASCVD scores less than 20% are so small, in my opinion, they pale in comparison to the risks of taking a statin. We’re talking about a 10% chance of muscle pain, a 1 to 2% chance of developing diabetes, possible fatigue, brain fog, dementia risk, and for some people—like myself—just feeling absolutely horrible. So from my perspective, if my 10-year risk is under 20%, I’m not taking a statin. It just doesn’t make sense, based on the data. Okay, now let’s talk about higher-risk patients. These are people who score higher on the risk calculator—often because they’ve had a prior heart attack or stroke, or they’re smokers. That automatically puts them in a much higher-risk category. So what do the statin trials say about these patients? Well, the Cholesterol Treatment Trialist study breaks them down into three categories—but let’s focus on the highest-risk group. These are people with more than a 60% risk of a cardiovascular event when measure on the ASCVD calculator. This group—the highest-risk patients—did see a 1.13% per year reduction in the risk of having a heart attack while taking a statin. They also saw a 0.23% per year reduction in the risk of having a stroke. And yes—these reductions were statistically significant. And for people at very high risk, those numbers are real. 1 less person in 88 will die per year if they all take a statin. That means if you’re in that high-risk group, statins may give you a measurable, yet modest reduction in heart attack and stroke risk. And while it’s not a massive benefit, it’s not insignificant either. This gives higher-risk patients some actual data—a metric—to help guide their decision. So, I imagine when the Cholesterol Treatment Trialists first saw their numbers—which are right there in their own paper—they were a bit disappointed. Because even though there were some benefits to statin use in high-risk patients, the effect sizes were still fairly small. Yes, they were statistically significant. But they weren’t game-changing. So they decided to take a different approach. They introduced something called a per millimole LDL reduction comparison. Let me explain that with a metaphor. Imagine you have two classrooms—same number of kids, same average intelligence. Each classroom is taught using a different method: one new, one traditional. At the end of the semester, both classes take the same test. The average scores? Roughly the same. So you’d conclude, reasonably, that the new teaching method isn’t any better than the old one. But now imagine the teacher of the new method says, “Hold on. A few of my students did exceptionally well. They studied harder, had better notes, better pencils—and they outperformed the others.” He then uses those students as the example of how great his teaching method is. Even though, on average, it made no difference. That’s essentially what a weighted meta-regression does. It looks at the overall results—then zooms in on subgroups who responded best—and uses that to argue for effectiveness. And that’s what the Cholesterol Treatment Trialists did here. They said, “Okay, our trial didn’t show a significant mortality benefit. And the benefits for heart attacks and strokes were modest—mainly in the highest-risk patients. So let’s try something else.” They looked at per millimole reduction in LDL cholesterol—and measured outcomes based on how much LDL dropped, not just who got the statin or who did not. So now they’re essentially saying, “Let’s take the patients who had the best responses—probably due to genetics or better drug metabolism—and let’s measure the drug’s success based on those groups.” That’s the LDL-weighted meta-regression. And here’s what it showed: In the highest risk group, for every 1 millimole per liter drop in LDL—which is 39 mg/dL in U.S. units—there was a 4.5% reduction in major coronary events over five years, and a 3% reduction in vascular deaths over five years. That works out to: 0.9% reduction per year in major coronary events, and 0.62% reduction per year in vascular deaths, per 39 mg/dL drop in LDL. So, if you had a two mmol drop in LDL or around 80 mg/dL you’d have twice the benefit. That’s basically like 1 less person having a major coronary event out 55 people every year. And that’s where they found their best clinical evidence for statins. Now, I’m not saying this method is invalid. But it does feel like data massaging. Because when we ask questions in medicine, we usually want to know something simple: Did the people who took the drug do better than the people who didn’t? Because when we are prescribed medications, its not based on who the best drug responders will be. And we can really never know this before hand to make a decision anyway. But instead of getting a direct answer, they went down a more complicated path—one that highlights the best responders, and frames the drug in the best possible light. And when you step back and look at the crude analysis, the outcomes just weren’t that impressive. They didn’t make a compelling case that statins were a breakthrough for cardiovascular disease. And it’s important to note that around this same time, other researchers were coming to similar conclusions. In 2003, a group called the Therapeutics Initiative published a report showing that statins didn’t reduce mortality in primary prevention- that’s people who would start a statin but have never had a heart attack or stroke. Then in 2010, a meta-analysis published in JAMA Internal Medicine, came to the same conclusion. No significant mortality benefit from statins in primary prevention—whether patients were low-risk or high-risk. In my opinion, the benefits of statins are frankly unimpressive—even for the highest-risk patients, and even when you massage the data. But there still is an undeniable small benefit to high risk patients. Now, let’s go back to that Cholesterol Treatment Trialists’ meta-analysis— the one that looked at 27 randomized statin trials. I think is something that is important to point out. Guess how many of those trials were funded by pharmaceutical companies? Meaning—they were paid for, or significantly supported, by companies with money on the line. Companies that stood to make a huge profit if the trial went well. Out of the 27 trials, 25 were funded directly by pharmaceutical companies. The remaining 2? Even those were industry-supported—they received free medications and other funding from drug companies. So that’s 25 out of 27 trials directly industry-funded— and the other 2, still tied to industry support. Now let’s be real. This is something people intuitively understand in regular life. If you take your car to a muffler shop, and they tell you, “Hey, you need a new muffler,”— you know there’s an inherent bias there. They make money if you agree. Even if they’re experts—they’re still experts selling mufflers. So what do most people do? They get a second opinion.They ask a friend who knows cars. They find a mechanic who’s not trying to upsell them. Why? Because they want advice that’s unbiased. Well, in this case, the largest meta-analysis we have on statins is riddled with that same kind of incentive bias— a financial interest in a positive outcome. And that’s something we have to take into account. We can’t ignore it. It doesn’t mean the data is worthless— but it does mean we need to view it with a healthy dose of skepticism. So now let’s say—you’re looking at all this data, and you’re wondering what to make of it. The wrong conclusion would be, “Oh, you can’t trust any of this. It’s all garbage.” I don’t think that’s fair. That’s not the right takeaway. What is fair to say, though, is that the benefits of statins were probably overestimated and the risks and side effects of statins were likely underestimated. And given the financial incentives involved— I think that’s a reasonable assumption. Remember, the statin industry is estimated to bring in over $15 billion a year. That’s a massive amount of money.. And we know about— those run-in periods, where they filtered out patients who didn’t tolerate the drug up front. That allowed them to build a cleaner trial population— people who were more likely to respond well. And that skews the results. So when you put all of this together— you’ve got enough information to run through your own common sense filter and make a decision that feels right for you. Another thing we need to talk about here is this idea that lowering cholesterol automatically lowers your risk of cardiovascular disease. That’s the core assumption the statin industry leans on heavily. They want that narrative—lower cholesterol equals lower heart disease risk—to be universally accepted. Simple, clean, straightforward. Something that applies to everyone, everywhere. Because if that belief holds true, then there’s an enormous incentive to keep developing more drugs that lower cholesterol. And cholesterol is a really easy target. It’s involved in a complex synthesis pathway with over 20 enzymes—each of which represents a potential weak point. Plus, there are all kinds of receptors, reuptake pathways, and transport mechanisms tied to cholesterol metabolism. So there are lots of places for drug companies to intervene. If the world buys into the idea that lowering cholesterol leads directly to fewer heart attacks, then that opens the door to a whole range of new drugs—each one potentially profitable. But we have to stop and ask: what if that isn’t entirely true? Or what if it’s only part of the truth? Because if that foundational assumption doesn’t hold up, then we need to take a more rational look at all these cholesterol-lowering drugs that come out—and make our decisions based on real evidence, not just the promise of a simple story. So let’s talk about something I often do when I’m looking at medical claims or widely accepted ideas. Anytime you see a large chorus of scientists or experts all singing the same song in unison, there’s usually a smaller group—the outliers—who are saying the exact opposite. They’re the contrarians. And they’re often completely on the other end of the spectrum, saying that everything the mainstream is promoting is wrong, and that their version is the real truth. Now, they’re usually in the minority—especially when the dominant narrative is loud and unified. But I like to pay attention to these contrarian voices. Not because I always agree with them, and not because I think they’re necessarily right, but because they often raise good questions. Questions that are worth exploring. Points that challenge the status quo and make you think. Even if they’re not entirely correct, they can help you see holes in the mainstream argument—or at least help you get a more balanced view of the topic. Because if you’re only ever hearing one side of the story, you’re not really being informed. You’re just being sold a narrative. To make smart, informed decisions—especially about your health—you’ve got to be willing to hear both sides and weigh the evidence for yourself. One researcher in particular—among several out there—who’s raised strong objections to the mainstream narrative is Dr. Uffe Ravnskov, from Sweden. He’s published extensively on how the statin industry—and the cardiovascular disease research world more broadly—have misled the public on several key issues. In 2018, he published a fascinating critique. In it, he took aim at a consensus statement released by the European Atherosclerosis Society panel. That panel had published data arguing that the more you lower LDL cholesterol, the lower your risk of cardiovascular disease. They included data from 12 clinical trials, showing the five-year risk reduction against the degree of LDL reduction. The data when converted to absolute risk and plotted was a clean visual: a line running from the bottom left to the top right of the graph—suggesting that lowering LDL leads to lower cardiovascular risk. This kind of visualization is called a regression model. Now, let me explain what that means in plain terms. Imagine you’re watching a swarm of bees. They’re flying in all directions, right? They’re buzzing around independently, but as a group, they start forming a cloud— and that cloud drifts steadily across the sky. Each individual bee might be moving randomly, but when you zoom out, you can see the direction of the entire swarm. That overall direction? That’s your regression line. That’s what the researchers did with these 12 trials. They treated each trial like a data point—each bee in the swarm. And when they connected the trend line through those points, it moved up and to the right. So their takeaway was: the more LDL you lower, the more you reduce absolute cardiovascular risk. And if you’re watching this on YouTube, I’ll throw that graph up on the screen. If not, just imagine that upward-sloping line cutting through a cluster of points. But here’s where Dr. Ravnskov raised his hand and said, “Wait a minute. You only included 12 trials in that table. But there are at least 33 trials with this kind of data. Why didn’t you include all of them?” And that’s a valid question. Because if you’re selecting only the data that supports your hypothesis, you’re not testing an idea—you’re confirming a bias. This is exactly what we talked about in Episode One, when we looked at Ancel Keys and the Seven Countries Study. He cherry-picked countries that fit his narrative linking saturated fat to heart disease, rather than objectively testing all available data. Dr. Ravnskov argued that this cholesterol regression model did the same thing. So what did he do? He took the same approach—but he added all 33 available trials, not just the 12 that supported the original conclusion. And when he plotted all the data points? That nice, clean line from the bottom left to the top right disappeared. Instead, the new regression line went straight across the page.What does that mean? It means that when you include all the data,there’s no consistent relationship between lowering LDL cholesterol and reducing absolute cardiovascular risk. In other words, once you look at the full picture, the idea that “lower LDL always equals lower heart disease risk” starts to fall apart. Because of this ongoing, dogmatic focus on lowering LDL to reduce cardiovascular risk, we’ve seen the development of more and more drugs designed specifically to reduce LDL levels. And one of the most effective drugs ever created for that purpose is something called a PCSK9 inhibitor. Here’s how it works. There’s a protein in the body called PCSK9. What it does is bind to LDL receptors in liver cells— those are the receptors responsible for pulling LDL cholesterol out of the bloodstream. Now, normally, after an LDL receptor grabs an LDL particle, it can be recycled—sent back to the cell surface to keep doing its job. But when PCSK9 binds to that receptor, it flags it for destruction. The receptor gets degraded instead of moved back to the cell surface. So the more PCSK9 activity you have, the fewer LDL receptors remain on the surface of liver cells, and that leads to higher LDL levels in the blood—because there are fewer receptors clearing it out. Enter the PCSK9 inhibitor. This is a monoclonal antibody— essentially a custom-built protein that acts like a biological grappling hook. It latches onto the PCSK9 protein and neutralizes it— preventing it from binding to LDL receptors. With PCSK9 blocked, those LDL receptors don’t get destroyed. They stay active, go back to the liver cell surface,and pull even more LDL cholesterol out of the bloodstream. The result? A dramatic drop in LDL levels. One of the biggest clinical trials done on these drugs involved evolocumab, a PCSK9 inhibitor tested in patients who had already had heart attacks and were already on statins. But despite being on statins, their LDL levels were still not dropping below 70 mg/dL—which is often the target for secondary prevention. So here’s what they did: they took these patients and randomized them into two groups. One group received an injection of evolocumab every two weeks— because PCSK9 inhibitors are delivered via injection. The other group got a sham injection— basically a placebo, like saline— but the patients didn’t know whether they were getting the real drug or not. They followed these patients to see who would go on to have another heart attack, and also tracked how their LDL levels responded. And the results were striking. In the evolocumab group, LDL levels dropped all the way to 30 mg/dL. Just think about that for a second. My own LDL is around 160. And when we’ve looked at traditional populations, even the ones with the lowest cholesterol typically have LDL levels around 75 mg/dL. But nowhere in nature—not in traditional cultures, not in ancestral populations—do we see LDL levels naturally dropping to 30 mg/dL. There are rare genetic syndromes where LDL can get that low. And yes, brand-new infants—right after birth and before they start nursing—can sometimes have LDL levels in that range. But as soon as they start breastfeeding, their LDL rises into normal physiological ranges. So driving adults down to 30 mg/dL? That’s far below the physiological range of normal. But that’s what these researchers did. They drove LDL down aggressively— while the control group, who were still on statins, had LDL levels closer to 90 mg/dL. Then what they did was create something called composite endpoints. Now, composite endpoints are used when researchers are looking for meaningful outcomes, but they’re worried there won’t be enough individual events to reach statistical significance. So they bundle several different outcomes together into one combined measurement. In this case, they grouped: cardiovascular death, myocardial infarction, stroke, hospitalization for angina, and coronary revascularization— which includes things like open-heart surgery or stent placement. And they said: “If any one of these happens, we’ll count it as a ‘primary endpoint.’” Then they tracked how often these events occurred in both the placebo group and the PCSK9 inhibitor group. So, they ran the trial. And after 2.2 years, they stopped it early. They said the benefit of the PCSK9 inhibitor was so strong that it was no longer ethical to continue giving a placebo—that it would be wrong to deny patients access to this new treatment. Essentially, they declared victory for the efficacy of PCSK9 inhibitors to fight heart disease. But what were the actual numbers? When they looked at that composite endpoint, 11.3% of people in the placebo group had experienced one of those events. In the PCSK9 inhibitor group, the number was 9.8%. So the absolute difference was 1.5%—over 2.2 years. That works out to a 0.7% per year reduction in the risk of having any of those composite events. And that 0.7% per year reduction in risks was what they considered strong enough evidence to stop the trial and declare that PCSK9 inhibitors were clearly beneficial. And fine—yeah, I get it. I’m a doctor. I don’t want to feel like I’m denying a patient the best care. If I were seeing results that seemed meaningful, I can understand the instinct to stop a trial early. Even though the difference was only 0.7% per year, I can understand the researchers saying, “Okay, we’ve got to stop the trial and give everyone this drug—it’s just too effective.” But when I looked deeper into the data, one thing jumped out at me—and it was hard to ignore. In the PCSK9 inhibitor group, more people had died. Yes—let me say that again. In the group that got the drug, more people died of cardiovascular causes, and more people died overall. Here’s how the numbers broke down: 251 people in the PCSK9 inhibitor group died of cardiovascular causes. 240 people in the placebo group died of cardiovascular causes. So, more deaths in the treatment group. Now, the authors dismissed this. They said it wasn’t statistically significant—so we shouldn’t worry about it. But I’m sorry—this is exactly what we care about. Death is the endpoint that matters most. They stopped the trial early, celebrating a small reduction in a composite endpoint— but at the same time, more people were dying in the treatment group. That’s like playing a 1 on 1 game of basketball to 11. I hit a lucky shot, now I’m up 5 to 4, and I walk away saying, “Okay, game’s over. I win.” And you’d say, “Wait, what? The game’s not over.” And I’d say, “Yeah, but I’ve decided it is. Because I’m just too good.” That’s kind of what this trial felt like. It could have kept going. And sure, I get that there are ethical questions involved. It’s not black and white. But at the end of the day, there were more cardiovascular deaths and all cause deaths in the treatment group. And this was in a group where LDL levels were pushed super low—down to 30 mg/dL. Which, again, is way outside the normal physiological range. And yet—they were dying more often. So now think back to every time you've heard your doctor tell you that heart attacks and strokes are caused by high LDL levels. And then cross reference that with the fact that in this trial, 251 people died from heart attacks and strokes with LDL levels around 30. Is your BS meter going off? Oh—and to top it off, the study was paid for by—guess who? Amgen. The company that makes evolocumab. So now you’ve got a trial that was stopped early, where the absolute benefit was just 0.7% per year on a composite endpoint, in a group with ultra-low LDL levels, and more people in the treatment group still died. It felt like the trial never really reached a clear conclusion— but was declared a win anyway. And it raises this fundamental question: Is lower LDL actually associated with lower cardiovascular risk, especially when you push it to extreme levels? This is where you start to see just how murky things get when you wade into the waters of these major drug trials. Because here’s the reality: Drug companies are heavily invested—financially and emotionally. They’ve poured hundreds of millions of dollars into developing these medications. And they’re banking on big returns. If the trials don’t show success, they’re not just losing development costs— they’re potentially walking away from billions in future profits and seeing their stock price plummet. So yeah—there’s a massive conflict of interest built into the process. And when the sponsor stands to gain that much, it’s hard to ignore how much pressure there is to shape the narrative and claim victory—even when the data is murky. I think another important point to consider is this: Statins, in high-risk patients, have shown a small but real reduction in cardiovascular events. The benefit is modest, but it’s there. But when we look at other cholesterol-lowering drugs— like ezetimibe or PCSK9 inhibitors— they have NOT shown meaningful benefit as solo agents,even though they’re effective at lowering LDL. They’ve only been shown to be effective when used along side a statin. So why is that? Why do statins show some benefit in reducing cardiovascular risk,while other LDL-lowering drugs do not—unless they’re combined with a statin? That’s an important question. All of these drugs lower LDL,but only statins consistently show a benefit when used alone. What makes them different? One interesting explanation is that statins have anti-inflammatory effects— which may play a role in their modest cardiovascular benefit. In the JUPITER trial, researchers enrolled patients who had elevated LDL, but also high CRP— that’s C-reactive protein, a marker of inflammation in the body. They found that rosuvastatin not only lowered LDL, but also lowered CRP levels by 37%. That’s a big drop in inflammation. And it suggests that there may be more to statins’ effects than just cholesterol lowering. As we’ve talked about before, inflammation in the endothelial lining of the arteries plays a central role in atherosclerosis. LDL shows up to help repair that damage— but it also can become involved in the inflammatory process itself. So if statins are reducing inflammation, maybe that’s what’s helping prevent plaque buildup, plaque rupture, and thrombotic events— the things that actually lead to heart attacks and strokes. It’s an interesting possibility— and one that might help explain why statins have a modest benefit, even when other LDL-lowering drugs fall short. Okay, so we’ve now explored statins—their risks, their benefits, and the clinical trials behind them—many of which, as we’ve seen, are often influenced by financial bias. We’ve also looked at PCSK9 inhibitors, which dramatically lower LDL,but whose benefits have been muddled, again, by the same kind of industry entanglement. You now have a lot of information, and ideally, you’re in a better position to make informed decisions. But what actually happens when you go see your doctor? Let’s say your cholesterol is high, and your doctor looks at your numbers and says, “You should really be on a statin. It’ll reduce your risk of a heart attack by 44%.” And now you’re confused. Wait—44%? You’re thinking, “Dr. Kumar didn’t tell me that.” But here’s the thing: that number—44%—comes from the relative risk reduction. And it’s a very misleading way to communicate benefit. Your doctor likely isn’t trying to mislead you. Most of the time, they’re just repeating numbers they’ve seen in studies or heard from pharmaceutical reps—without fully understanding how those numbers are framed. So let’s break this down. When they say 44% risk reduction, or sometimes 25%, or 27%— they’re talking about relative risk. So what does relative risk reduction mean? Let me give you an example. Let’s say I tell you, “If you wear this hat, you’ll have a 100% increased risk of being struck by lightning.” You’d probably panic. That sounds terrifying. But then I tell you— Your normal risk of being struck by lightning is 1 in a million. And if you wear the hat, your risk becomes 2 in a million. So technically, yes—your risk doubled. That’s a 100% increase. But in absolute terms, your risk barely changed at all. The same thing happens in drug trials. Let’s say your baseline risk of a heart attack over a certain period is 2%. And a drug brings that risk down to 1%. You’ve reduced your risk by 1%, in absolute terms. But 1% is half of 2%—so the relative risk reduction is 50%. And that’s the number you’ll hear in the marketing materials: “This drug reduces heart attack risk by 50%!” See how that works? Let’s go back to the JUPITER trial, which looked at rosuvastatin in people with elevated CRP levels. They reported a 44% relative risk reduction in cardiovascular events. Sounds amazing, right? But when you look closer: the actual event rate went from 2.8% to 1.6% over about two years. And 1.6% is 445 lower than 2.8%. But importantly, that’s a 1.2% absolute risk reduction over two years— or about 0.6% per year. So yes, 1.6% is 44% lower than 2.8%. But the real difference in risk—the absolute risk reduction—was just 0.6% per year. And that’s a much less impressive number. So this is how the communication of risk can become deeply misleading. And often, even well-meaning physicians don’t realize how these numbers are framed. It’s not about hiding the data— it’s about how the data is presented. And that difference can completely change how we interpret whether a drug is truly worth taking. Okay, so we’ve talked about the risks and benefits of statins, what the trial data shows, and how LDL lowering might—or might not—relate to cardiovascular disease. And yeah, I’ve probably taken more of a contrarian view here, but that’s largely because the mainstream already dominates the conversation. It’s the prevailing narrative—it has all the ears, all the attention, and it’s what most doctors are trained to follow. So I feel it’s important to balance the scale by giving more weight to the alternative perspective. Because without that, we lose the ability to question, to understand, and to see the bigger picture. That said, I do want to offer some practical advice on how to make sense of dogmatically opposing views—especially when they’re so dug in, so fundamentally at odds. And that is: Don’t pick a team. Because as soon as you do, you’ll be vested in the victory of your team and be blinded to an unbiased view of the truth. For instance, in this debate about LDL and Cardiovascular disease. On one side, you’ve got a camp that sees LDL as a villain. They want it as low as possible—down to 30 mg/dL, which, honestly, is extreme. That’s well below anything we’ve seen in physiologically normal adults. They believe that if we can just get LDL low enough,we can prevent heart disease entirely. On the other side, there’s a camp that says you should never lower LDL—ever. They claim LDL has nothing to do with heart disease, in any context, and sky high LDL cholesterol levels will never cause a problem. These are two extremes—and they’re both dogmatic. And what happens with dogma is this: once someone picks a team, they stop being open to new information. They need their side to be right. And that clouds judgment. But the truth? It’s almost always somewhere in the middle. This isn’t just true in medicine—it’s true in science, in politics, in life. When you look at polarized extremes, the real answer tends to live somewhere in the nuanced intermediate. And that’s exactly what’s going on with LDL. Because here’s what we know: In some situations, LDL can be pathological. We’ve talked about that. When your LDL is loaded with oxidizable fats like linoleic acid, and your arteries are under constant assault—from things like smoking, high blood pressure, diabetes, or chronic inflammation—that’s the perfect storm for LDL to become part of the problem. And the truth is, most of us have ample opportunity to live in that kind of environment. We eat a processed food diet, we’re exposed to pollution, and many of us are dealing with metabolic dysfunction whether we realize it or not. And let’s not forget: the modern food supply is flooded with linoleic acid,an omega-6 fat that turns LDL into a highly oxidizable particles. That’s when LDL stops being helpful—and starts becoming dangerous. But in other situations, LDL is exactly what it was designed to be. It’s a healing molecule. A repair tool. A survival mechanism that helps patch damage, deliver cholesterol and essential fatty acids where they’re needed, and support the body’s natural resilience. So for people who aren’t constantly inflamed, who eat a cleaner diet, who have healthier metabolic function— even LDL levels above 190 might not be a problem. And we’ve seen that play out in studies involving coronary artery calcium scans. So what we’re really dealing with here is a duality. LDL’s role is context-dependent. It can be helpful or harmful, depending on the environment it’s operating in. And I think that’s one of the main reasons why the data on statins and LDL feels so conflicting— because we’re trying to apply one-size-fits-all answers to something that depends heavily on individual context. But here’s the thing: even brilliant scientists are prone to oversimplifying complex systems. They want to reduce a messy, multifactorial issue into something clean and easy to communicate. “High LDL = heart disease.” “High saturated fat = heart disease.” These are tidy soundbites. But they leave out the nuance— and the nuance is where the truth lives. Understanding the full picture means wading through uncomfortable gray areas, and not clinging to convenient absolutes. So this brings us back to the original question: Should you take a statin—or any cholesterol-lowering medication—to prevent heart disease? I’ve given you a lot of information. We’ve looked at trial data, the risks, the modest benefits, and the broader context of LDL. Now it’s up to you to run that data through your own common sense filter and decide what feels right. I’m not your doctor, so I can’t give you personal medical advice— but I can tell you what I would do for my own health. Right now, I’m in a healthy state. I avoid seed oils, I don’t smoke, I don’t have high blood pressure. Even though my LDL is relatively high, I’m not living in the kind of inflammatory environment that would make it dangerous. So personally, I don’t take a statin. There’s no common sense indication for it in my case, and I already know how strongly I react to statins—I’ve tried them twice. The side effects were debilitating. But what if I were in a different situation? Let’s say I smoked. Or had diabetes. Or uncontrolled high blood pressure and I fell into a high-risk category on the ASCVD risk calculator, here’s what I would do: First, I’d get a coronary artery calcium scan. I think it’s a more accurate assessment than the traditional calculators. If I had calcium—if there were visible plaque in my arteries— then yes, I’d seriously consider going on a cholesterol-lowering medication, at least temporarily. Now, given how poorly I tolerated statins, I’d likely choose bempedoic acid instead. It’s more expensive, yes. But it works two steps further down the cholesterol synthesis pathway—meaning it doesn’t block coenzyme Q10 and heme A production, which is crucial for mitochondrial energy production. That may be why I felt so awful on statins. And importantly, bempedoic acid doesn’t impair cholesterol production in muscle or brain tissue. Plus, it’s one of the few non-statin drugs that has shown some cardiovascular benefit when used alone. So I’d start there. But if I hadn’t had issues with statins, I’d probably go with one—because they’re cheap, accessible, and modestly effective in high risk individuals. But I’d always pair it with coenzyme Q10 and vitamin K2 supplements. No one should be on a statin without taking those two nutrients. Still, in either case—whether it’s statins or bempedoic acid—my intention would be to use the medication temporarily, while I work on reversing the root causes of the problem. If I smoked, I’d quit. If I had high blood pressure, I’d work hard to lower it. If I had diabetes, I’d remove refined carbs from my diet, likely adopting a low-carbohydrate approach. I’d also eliminate seed oils completely and shift to more stable fats—like monounsaturated fats and healthy saturated fats. And of course, I’d clean up the rest of my lifestyle— with strategies I’ll go into more detail on in our next episode. So, again—I’d use a medication only as a bridge, until I could address the real issue: ongoing damage to the endothelium and the oxidizability of my LDL particles. As for PCSK9 inhibitors—yes, they’re an option. But they lower cholesterol so dramatically that it honestly concerns me. Especially when we’ve seen research showing that ultra-low cholesterol is associated with increased all-cause mortality and reduced survival after heart attacks. I just don’t believe there’s any situation where LDL levels that low—like 30 mg/dL—are beneficial in the long term. So yes—this was a lot. We’ve covered a mountain of data on statins and cardiovascular disease. And what we’ve seen is that in certain high-risk groups, statins can offer modest benefit. Not impressive, but real. But what if I told you that those benefits could be dwarfed—absolutely blown away—by lifestyle changes? I mean it. The kinds of benefits we’re talking about through non-pharmaceutical approaches make statin effects look tiny in comparison. And that’s what we’re going to dive into in the next and final episode of this cardiovascular disease series. You do not want to miss it. Because some of the data I’m going to share might just blow your mind— and make you wonder why you’d ever rely on medication when you could take back control with simple, powerful changes to how you live. So, thank you again for joining me on this journey of discovery. I’ll see you in the next episode. Cheers.