Transcription
With unmedicated cholesterol of this high level, should be dead. I should be dead. All right, I hope you're ready for this one because I don't even know if I am. But I want to start by talking about my cholesterol. My cholesterol is so high, it's a number most doctors never see in their entire careers. It's over 700 with an LDL bag cholesterol of 574. Now, to give this some context, most people get flagged as high around 130. 190 is when doctors start to get concerned about a genetic condition. 300 is oh no territory. 500 is immediate action. Take a pill, please. Here are some statins or you're shopping for a casket. So, a total cholesterol over 700 with an LDL near 600, that is medical case report level. In fact, there are not one but several case reports on me. And the first time my doctors saw these numbers, they thought the lab made a typo, but they didn't.
And here is where things get controversial. For nearly 7 years, I have declined, refused medication. I've tried a few for experimental purposes here and there, but never for more than 6 weeks, and sometimes with really unpleasant side effects, as in the case of statins.
"But I just feel terrible. Just feels."
And I have been ruthlessly chastised for being reckless. One of my peers at Harvard Medical School even once told me I was being dumber than riding a motorcycle drunk without a helmet. Now, if you go by the dogma in the textbooks, they'd be right. A 30-year-old with unmedicated cholesterol of this high level should be dead. I should be dead.
Now, to be honest, and rewind a bit, when I first saw these numbers in myself, I was terrified. I genuinely thought I was on my way to an early grave. But I was also intensely curious. Why? Why did my levels go so high? What did it actually mean? What was going on inside me? And in this video, I will answer those questions. But here's the big point. After years of public scrutiny, after being chastised by colleagues, fired by doctors, and mocked for refusing statins, I'm finally changing my tone in a big way. I'm starting not just one but two cholesterol-lowering medications. Now, if you know me, that might be a big shock. And I promise you, I promise you this is not a shallow stunt. I wouldn't do that to you and I wouldn't do that to myself. But I'm not doing it for the reason you think. And if you can believe it, we're not done with epic plot twists because this isn't about heart health at all. It's actually about brain health. Now, let's get into it. Literally.
All right. I hope you're excited. I want to give you a road map for this video. First, there's going to be four chapters. Chapter one, 700 cholesterol and not a lab error. I'll walk you through my initial reaction to discovering I had shockingly high cholesterol. Then, in chapter 2, I'm going to go over why I refused medications for 7 years. I'll explain why I remained unmedicated until now, which brings us to chapter 3, the plot twist. I'll get to our big reveal, our plot twist, what changed, and why I'm finally reconsidering. All right, so some exciting news for you. I've decided to update this video because in actuality, I realized there isn't just one plot twist, there are three. The first is that I've decided to take cholesterol-lowering medications. Ooh. The second is why, which isn't necessarily clear-cut. And the third, you're going to have to wait and see. And then in chapter four, I'm going to go over how to think when the guidelines don't fit. I'm going to zoom out and discuss what this means for you. Because this isn't just my story. It's not just a cathartic vent to you. It's a case study in making really difficult medical decisions. I'm going to give you a transparent lens into my mind how I think, which is a little bit crazy admittedly, but hopefully it will help you think through your own hard medical choices with rigor, nuance, and of course, curiosity.
So, that brings us to the beginning of our story, chapter 1, cholesterol 700, and not a lab error. The date was June 1st, 2019. This was the day when I first adopted the ketogenic diet. And for me, it was a life-saving moment. To frame this up a bit with my own story, I'd been dealing with debilitating inflammatory bowel disease, ulcerative colitis. To paint a somewhat graphic picture, it was taking every part of my life. It took my body, my social life, my career, my mental health. And at the beginning, very few knew how bad it was. It took a long time for me to come out and actually talk about it. Let me just give you one illustrative example. In the days leading up to my college graduation, I didn't eat a thing. Why? Well, I was giving the validatory address to 11,000 people.
"Even a bad decision can be a good decision so long as you learn from it."
It was quite the honor and I even got to stand at the same stump as Roger Federer. But I was literally scaredless that I was going to poop blood on stage on camera in front of 11,000 people. So, I didn't eat. I even gave myself a dining hall coffee enema for good measure. And that day, I was wrecked with anxiety through what should have been a happy day of celebration with my friends and family. And it even got worse to the point that when I started my PhD in Oxford, England, I was literally dying. I was in and out of intensive care. But then going on a ketogenic diet dramatically improved my symptoms. It put me into biopsy proven remission. But it came with medical baggage. You already know this part. My once normal cholesterol levels exploded. I'm talking numbers that rival those seen in textbooks describing a 1 in 1 million genetic condition, homozygous familial hypercholesterolemia, a deadly genetic condition. My cholesterol levels peaked over 700. And coming from a medical background, both my parents were MDPhDs. I knew what this meant. I was terrified. My family was terrified. My doctors were terrified. They looked at those numbers once they realized they were real, like I'd just been diagnosed with ALS or Huntington's disease. Cholesterol that high is presumed to be a death sentence if you don't act.
But mixed in with my fear, my bone chilling fear was intense curiosity. Because here's the thing, I don't have a genetic condition. Most of my life, my cholesterol levels have been normal until I restricted carbs. So the question became, why? Why this massive shift and what did it mean? The answer in short form is something modern medicine doesn't yet fully recognize. A mechanism my colleagues and I have actually been studying called the lipid energy model. You can read more about it if you're interested in this paper we published in 2022. But here's the very short version. In people like me who are lean, insulin sensitive, and eating a low carb diet like a ketogenic diet, the body ramps up fat metabolism. This means a massive shift, a massive increase in fat-based fuel transport through my bloodstream and as a byproduct, a sharp increase in cholesterol levels. The leaner I am, the more active I am, the higher my cholesterol goes. It's not necessarily pathological. It's dynamic. It's an adaptive system responding to the metabolic demands of my personal dietary shifts and my lifestyle. When I'm not sick, at least I'm known to be a rather high energy person, maybe as you're gathering.
But that leads to the next question. If the mechanism behind my high cholesterol is totally different, does that mean my risk profile, my heart health risk is different, too? I think it's plausible, probably even likely, because in biology, cause matters. Here's a quick analogy for you. It's like being tall, which I admittedly not, but let's go with the analogy. It's like being tall. You can be tall because your parents are tall or you can be tall for other reasons like a brain tumor secreting growth hormone. Same height potentially but very different ultimate outcomes. That's the big idea.
So now let's move on to chapter two and the harder question. Why I refuse medications for 7 years? Here's the deal. When you're faced with a biological outlier or you are the biological outlier, medicine doesn't always have a clear answer. So what do you do? Let's be honest. It's possible that staying unmedicated, I'm taking a massive risk, that I could have a heart attack and die by age 30. Luckily, I didn't, but I was gambling. Many cardiologists told me by now I'd be dead. But medicating for life has risks, too. Take statins, the standard of care in the drug I made a mess with in the intro.
"Please, here are some statins."
They can impair mitochondrial function, worsen insulin resistance, increase diabetes risk, slash GLP-1 levels, and potentially lead to long-term muscle damage or loss. In fact, when experimenting with statins myself, I even found they dramatically impaired my exercise performance and randomized crossover trial I performed on myself.
"And I'm gassed. I'm having these pains in my legs, but I just feel terrible. Just feels."
Which had a meaningful impact on my quality of life in a negative way. So yes, doctors will often say the preponderance of evidence, meaning the overall body of published literature, supports statins is safe and effective. But here's the problem. The entire body of evidence showing any benefit comes from metabolically unhealthy patients. When you start filtering out people who are even moderately healthy, the benefits of these drugs shrink for heart health. We'll double-click on heart health in a moment. So extend that reasoning to someone like me. Near optimal metabolic health. No signs of metabolic dysfunction. What can we conclude? Well, honestly, we have no data to say that statins or other drugs will help my heart health. Those data are non-existent as pertains to people like me. But the risks, those are still very real. So now I'm faced with a medical conundrum. The benefits are uncertain. Some risks are known, but many are also uncertain. So what do you do? What should I do? Because here's the truth. No decision is still a decision. This is a fork in the road. I have to choose. I have to make that choice. And to do that, I rely on my background in biochemistry and medicine. I dive deep into the research, study the mechanisms, and try to build the most holistic risk-benefit picture I can for me. And so far, up until this date, I have not been convinced that any medication would help me more than harm me. Obviously until now, which is why I'm making this video.
That brings us to chapter three. The big plot twist in what's changed. Now, there's something else I haven't told you yet. We're going to go on a tangent. Something that I consider even more concerning in my cholesterol levels. I carry not one but two copies of the ApoE4 gene variant, the highest known genetic risk factor for Alzheimer's disease. This puts me at a 10 to 15-fold increased risk of Alzheimer's. So naturally, I pay very close attention to any interventions that might reduce my Alzheimer's risk. And recently, two cholesterol-lowering drugs, not statins, ezetimibe and bempedoic acid, have caught my attention, not because of their effect on cholesterol, but because of their potential neuroprotective benefits. That is the twist. These drugs appear independent of cholesterol lowering to potentially help the brain. This isn't a cholesterol story. It's a cholesterol coincidence.
"It's now time to slide in to another clarification. Sorry, my child sometimes keeps me out."
So, plot twist one was that I'm taking cholesterol-lowering medications. Plot twist two was why, for my brain? And let me emphasize, at no point am I saying it is the cholesterol-lowering that is mediating the brain benefits. Rather, that's just a side effect, if you will. Medicine has labeled these cholesterol-lowering medications based on where it's shown the spotlight, but it has nothing to do with the inherent nature of these molecules. They do what they do. So, you can think of the cholesterol-lowering is just kind of like a side piece for the bigger story here. That's what I mean by cholesterol coincidence. I also want to provide a little proof that I'm actually doing this, not just blowing smoke. So, this is what happened to my LDL and this is what happened to my ApoB after just a few weeks of monotherapy. 56% reductions, which is pretty impressive. I'll explain why below. It's not a matter of just being a hyper absorber. It's a little bit more complicated than that. And um, let's get back to your main narrative. And at just a big level, molecules, whether natural or synthetic, they don't respect the categories we humans like to put them in. Just because we call something a cholesterol-lowering drug, doesn't mean it only or even primarily has that function. Let me explain each in turn. And just be warned, this does get technical, but I believe you can handle it. I have respect for your intelligence, and I'll link more deep dives below if you want to go down the rabbit hole. Let's start with a brand name Zedia. It's commonly known to block cholesterol absorption in the gut. That's how it lowers LDL cholesterol. But what most don't know is ezetimibe can cross into the brain where in this case, it does something good. It blocks an interaction between two proteins 14-3-3 and hexokinase. And this action helps reduce protein misfolding, reduce amyloid buildup, reduce tau aggregation which are hallmarks of Alzheimer's disease. And it even improves autophagy, cellular recycling in the brain by as much as 40% at least in cell culture models. The pre-clinical data are interesting if not compelling. And in a human data set, people taking ezetimibe were found to have an eightfold lower risk of Alzheimer's disease. Now admittedly, are these randomized control trial data? Are they perfect data? No, absolutely not. They are early data. But is it enough for me to consider seriously given my genetics and my personal concerns? Absolutely. But now let's shift gears and show how lightning can strike twice. Then there's bempedoic acid, brand name Nexletol. I've actually tried it before and it lowered my LDL by 28% as part of an experiment. Now, it's a prodrug, meaning it's only activated in specific organs. Here, the liver, which is what made it appealing to me because there should be less systemic whole body exposure and fewer side effects as compared to statins. That's why I wanted to try it. But now, medicine gets humbled again. A new study going to print in May 2026 in Cell Metabolism shows that even the inactive prodrug form is actually active. It has biological activity. Specifically, bempedoic acid binds directly to and activates a transcription factor known as PPAR alpha. What's exciting is that PPAR alpha regulates amyloid processing in the brain, shifting the processing of what's known as amyloid precursor protein away from the toxic amyloidogenic pathway and towards a neuroprotective anti-amyloidogenic pathway. So, here's another case where a cholesterol drug might help, but it has nothing to do with cholesterol. Again, it's a cholesterol coincidence. Let me hammer this home with an analogy. Imagine you've grown up your whole life seeing a spoon as a pea catapult. Everybody had always told you this is a pea catapult and that's what it's used for. That is its purpose.
"Okay, in the spirit of stay curious, how far do you think that I can catapult this little pea with this spoon? Let's find out. I'm guessing 12 ft. All right, moment of truth. All right, just under 15 ft, about 14' 9"."
Can you beat that? And then when you're 30 or 40 or 50, you find out to your surprise you can use a spoon to eat soup. What a revelation. I know it's a goofy analogy, but it achieves the point. This is all about taking a different lens on things that we categorize in specific buckets. But achieving this insight requires an authentically open mind and a willingness to resist the narrow categories into which we put things, be those things drugs or people. Now, for those of you who've been following me for a while, this is where I want to pat myself on the back. Forgive me just for a moment. Then you can decide whether or not my self-celebration is warranted. But the truth is, I genuinely agonize over these concepts. The groundwork for this video wasn't laid overnight. It's been built over dozens of prior letters, actually hundreds, literally hundreds of hours, combing through scientific literature, a privilege most physicians simply don't have or don't have time for. What I'm trying to communicate here by sharing all this is something simple and honest. This is hard. It takes time. Just because of a few diplomas and letters after my name doesn't make it easy. It doesn't mean I inherently know what's right and wrong. I still spend time wrestling with the same questions that you do. What is most likely true? What am I missing? What questions do I need to ask to get better answers and better questions? This process will never stop being difficult, nor should it. The trick is not to make it easy, but to learn to enjoy it. So, I hope you can take solace in two things. First, knowing you're not alone. And second, knowing that my goal here is not to hand you all the answers. It's humbler than that. It's to share and show that the time I spend wrestling with these complexities might at least help accelerate your path, if not make it easy, and to reassure you that someone else is walking this path with you, too. That is why I'm here, not to make this easy for you, but just to make it less hard and hopefully a little more enjoyable along the way.
But that brings us to chapter 4. How to think when the guidelines don't fit. Here's the part where I want to zoom out and hand the mic to you. Because while this has been my story, the real point is this. Sound bites won't save you. I was raised to trust institutions and experts. Not blindly, but because I had some appreciation. Being the son of two MD PhDs, I appreciated what goes into being in academic medicine. It's like respecting an elite athlete or fighter. There's an art. There's a craft to be admired. But then I became one. I became an MD/PhD. I went through the rigors of a role and I ran into a situation where I had to make a decision where the guidelines and taught rules didn't fit my body, my metabolism, my story. And that is when I realized you don't need advice from trained experts. You need the motivation and drive and internal permission to think even and especially when you are not the leading expert. That's not arrogance. That's courage in taking responsibility for your own health. That's what I want for you. We live in a world that rewards certainty, but medicine lives and thrives in uncertainty, especially when it comes to complex lifelong trade-offs like heart health and brain health. And the deeper truth is no one is coming to make the perfect decision for you. Not your doctor, not the headlines, not a family member, not even me. That's why you need a framework. Not for what to think, but how to think. Start with mechanisms. Ask why a marker is elevated, not just noticing that it is. We need to understand that somebody's health risk can't be summed up in one number and treated as one number. It's all about interactions between the diets we eat, the lifestyles we live, who we are as human beings. It's all about context. Your context, my context, our context. So, be rigorous, but stay open because the evidence evolves. And above all, and probably this is the most important point I'll make in this video, don't confuse lack of certainty for lack of responsibility. My challenge to you and the challenge that makes our community so intellectually unique and why I'm so excited to be here is I want you to see lack of certainty and not be intimidated, but stay curious. That moment I had at the beginning of our story where I was terrified that I was dying, scared to my bones because I didn't know what was happening to me, but at the same time was fiercely curious to know why. That feeling is what I want for you. I want not to talk down to you, but to elevate you to a level where you can unlock that curiosity with that ferocity because that is a superpower. That is why I'm here. That is why I want you with me. That is why stay curious.
So, I know you've been waiting for it, the epic plot twist 3, and here's what it's going to be. Um, yes, I've updated my decision based on new data, but the whole theme here is open-mindedness, assessing your individual context holistically. And here there were new variables at play that had to do with my brain health. But the fact of the matter is I've been running a natural experiment on myself for 7 years where I've had a total cholesterol about 700 and LDLs in the 500 with ApoBs that are off the charts. All the textbooks say my heart should be clogged with plaque. So plot twist three is we're going to find out whether my high cholesterol was actually killing me or whether the textbooks are wrong. I'm getting an advanced coronary CT and angiography scan of my heart with expert guided reads, objective plus AI guided quantification, quantifying the plaque in my heart down to the nearest millimeter cubed and we'll find out if I am an idiot and I'm actually already partly dead or if the textbooks were wrong. So, you're going to have to stay tuned for that. Come back and we'll find out together.