Transcription
Excuse me, but what? Why did nobody tell me about this?
This pivotal study [music] from 20 years ago shows you can lower your cholesterol, but without prescription drugs and without even changing [music] your diet. It's something simple, something natural. And the mechanism blew my [music] mind. It's something totally different from frontline cholesterol-lowering therapy, statins. And it changed fundamentally [music] how I think about cholesterol, LDL, apple manipulation. And it all comes down to a simple plant compound, bourberine.
In this video, I'm going to break down how statins really work and how bourberine is the same, but actually totally different. And if you stick around to the end, I promise I'll even reveal a little secret, a new tool that I have that I want to share with you and a brand new experiment I'm going to conduct on myself. It's a big one. So, let's go.
Statins can decrease GLP1, cause insulin resistance, risk for type 2 diabetes. But bourberine doesn't do that. Distinct. Totally distinct from statins. That's the paradox. That's the puzzle. Giving the cell more time to produce the LDL receptor protein. This hit me hard. LDL cholesterol dropped by 20%. There were basically no side effects. Improved markers of liver function. It excites me.
Okay, 20 seconds of your time before we begin. First of all, always more details in the newsletter below. Second of all, in this video, we delve deep into mechanisms and I get really enthusiastic about the science, but I want you to see this not as a prescription, not as a pivot, but a call for unity around excitement for understanding how our bodies work and being able to leverage that for better health.
With that, let's get to the road map. So, I've broken this into six chapters. How statins work, the Bourberine paradox, the Bourberine randomized control trial, Bourberine versus Statins, my next big experiment, and why I wasn't told about this. Each chapter does build on the others. So, I hope you have the endurance to stick around, but I did want to give you a road map. And yes, that endurance thing was a challenge. So, let's see how many of you can stick around. But, let's begin.
Chapter one, how statins really work. Before we get to bourberine, I really do want to start with this statins and mechanism. This is the standard of care for cholesterol lowering. And I'm guessing your doctor has never explained to you the biochemistry. Maybe they don't know how these drugs fundamentally work. And understanding this will be critical in appreciating how bourberine is totally different. So hang in there. Or if you really don't want to biochemistry lesson, you can skip ahead to the next chapter. But that would make me sad. And I know you don't want to make me sad. So let's go.
Statins. They inhibit this enzyme called HMG COA reductase. This is the key enzyme in cholesterol synthesis, the rate limiting enzyme. And this inhibition, it happens in many cells in the body, muscles, brain, elsewhere, but especially in the liver, which is the major site of cholesterol production for the body. So by blocking this enzyme HMG reductase, statins cause a cholesterol starvation inside the liver cells. They deplete the intracellular cholesterol pool. Now the liver has a sensor in it that detects this drop in internal cholesterol. And when it senses this relative cholesterol depletion, it activates something called brace for jargon stero regulatory element binding proteins or sbps which are held outside the cell's nucleus like a dog on a leash. And once activated, these SRBps move into the nucleus, bind DNA, and turn on genes, including the gene for the LDL receptor. So the gene is turned into an mRNA transcript. This is the blueprint for making the LDL protein, which then goes to the surface of the cell and grabs LDL particles containing cholesterol from the bloodstream to pull them into the liver to compensate for that cholesterol starvation caused by the statin in the first place.
So, let's pause. I know I threw a lot at you, but this one sentence explains how statins actually work. Statins inhibit an enzyme leading to the depletion of the pool of cholesterol in the liver, forcing an adaptation to increase the LDL receptor that pulls cholesterol containing particles into the liver which lowers your LDL cholesterol. Maybe that was more than one sentence or if it was a sentence, it was totally a run-on. But if you understand that, you're going to understand how bourberine is totally different.
But first to double click on statins. This mechanism it's effective at lowering LDL and apple B. But it has downsides because by inhibiting this enzyme HMG quo reductase statins also block the production of downstream products that are important for metabolism like co-enzyme Q which is crucial for mitochondrial function. So this can lead to mitochondrial and muscle disruption. And statins can also increase markers of liver damage like A and ALT. We'll get back to those because bourberine again is totally different. Statins can decrease GLP-1, cause insulin resistance, risk for type two diabetes. All these are really well codified in the human literature, and I'll link to more details below.
But I do want to get on to bourberine, the star of today's show. So, chapter 2, the bourberine paradox. The researchers first conducted a screening of natural compounds with longstanding safety profiles, and bourberine stood out. What is bourberine, though? Bourberine is a natural compound derived from the plant genus burbaris from which it gets its name obviously. So quickly by way of beautiful illustration, this selandine, I think that's how you pronounce it. This selonine yellow poppy actually gets its yellow hue from bourberine. That's the yellow color. Anyway, when the researchers tested in this study bourberine, it had a strong activity for boosting levels of the LDL receptor mRNA, the transcript, the blueprint for making the LDL receptor, just like with statins. And yes, in humans and in animals, this translated to a substantial reduction in total and LDL cholesterol. But more on that in a moment, the human data.
First, I want to go over how bourberine works because it's very unusual and completely mind-blowing. Recall how statins work. They create this internal state of cholesterol starvation in the liver which triggers an adaptation the release of these sterile regulatory element binding proteins these sbps that then go to the nucleus and turn on the genes that code for the LDL receptor but bourberine, it doesn't do that. It doesn't deplete the liver's cholesterol pool and it doesn't impact srbp processing. In fact, the authors of the study make this point very clearly. To quote them, the lack of any sterile regulatory effect through the SRBP pathway suggests that bourberine increases LDL receptor expression by a mechanism distinct, totally distinct from statins.
So what the heck is bourberine doing? Let's back up. To increase levels of the LDL receptor, the gene first needs to be switched on, which produces the mRNA transcript, that intermediate blueprint for making the LDL receptor protein. But surprisingly, bourberine did not increase LDL receptor gene expression in the traditional sense. I won't bore you with the methodology, although you can find more details in the newsletters linked below. Anyway, bourberine did increase levels of the LDL transcript, that blueprint, that mRNA, and ultimately led to increased levels of LDL receptor protein. So, how, how can you not increase expression of the LDL receptor gene, but you still get more LDL receptor transcript? That's the paradox. That's the puzzle.
So, pause the video here and see if you can solve the puzzle before I reveal the answer. Drop your hypothesis in the comments. Here's the twist. Here's the answer. Bourberine stabilized the transcript. It stabilized the blueprint. So quoting the authors, Bourberine prolonged the turnover rate of the LDL receptor transcript by approximately three-fold from 64 minutes to 198 minutes. So over 3 hours. Think about it like this if it hasn't landed yet. Normally these instructions for making proteins the LDL receptor are shredded up by the cell after about an hour. But bourberine lets the instructions stick around for over 3 hours, giving the cell more time to produce the LDL receptor protein. And this process is completely independent of intracellular cholesterol starvation. Yet, it still leads to more LDL receptors on the liver cells and therefore more LDL being pulled from the bloodstream.
Now, this hit me hard. I spent years studying medicine and physiology and I had no idea about this pathway. Now later in this video, I'll show you how exactly I'm testing this on myself and a tool I'm using to understand how this could reshape my own LDL cholesterol management. But first, let's look at how this actually did in real human patients, not me. A human randomized control trial.
So, chapter 3, bourberine randomized control trial. The researchers then ran a randomized placeboc controlled randomized control trial. Sorry I'm saying that a lot with 91 patients. Each patient received 500 mg of bourberine twice per day. So 1 g per day for 3 months or a placebo control. And the results were striking. LDL cholesterol dropped by 20%, triglycerides dropped by 28% and HDL cholesterol remained unchanged as compared to the placebo. And among patients not taking other lipid lowering medications. So if you kind of stratify out people on statins and other drugs, the effects were even more pronounced. So LDL dropped by 25%. 31 milligs per deciliter. That was the absolute drop. Triglycerides fell by 35% almost 70 milligs per deciliter for an absolute drop. And again HDL cholesterol was not harmed. And even more interestingly, bourberine improved markers of liver function, liver damage markers ALT and A and GGT. This might be due to a reduction in liver fat caused by the bourberine and is totally different than statins which can increase the liver damage markers.
So to summarize, bourberine reduces LDL cholesterol and presumably apple as well and triglycerides. It does so through a totally novel mechanism by stabilizing the LDL receptor transcript, the mRNA, the instructions to make the protein so you can make more protein. And it does this without depleting intracellular cholesterol pools and with minimal side effects. In fact, in this pioneering human trial, there were basically no side effects. Just one participant exhibited mild constipation which was resolved when the dose was decreased from 500 milligrams B that means twice per day to 250 milligrams B. Pretty cool right?
And that brings us to chapter 4. I want to give a concise comparison between bourberine and statins mechanisms benefits side effects. So statins starting with statin mechanisms statins inhibit HMG KO reductase the key enzyme in making cholesterol in the liver. This depletes cholesterol levels in the liver cells leading to activation of the SRBP pathway to compensate. This increases the LDL receptor gene expression ultimately leading to more LDL receptor protein and this lowers LDL. But side effects can be many, including muscle pain and muscle damage, mitochondrial disruption via depleting co-enzyme Q and other mechanisms, decreasing GLP-1 hormone, increasing insulin resistance, increasing diabetes risk, and potentially increasing liver damage markers, the ALT, AAS, among other side effects. That said, just to give credit where it's due, statins can also increase vasoddilation, venitric oxide, and potentially can decrease inflammation if you have high baseline inflammation.
And now on to bourberine. remember mechanism totally different. It stabilizes the LDL receptor mRNA transfer with the blueprint for making the protein. So then you make more LDL receptor protein and this ends up pulling LDL particles out of the bloodstream. The side effects are less minimal overall occasional mild constipation that's dose dependent and can be resolved by just reducing the dose and improves glycemic control potentially lowers waist circumference and improves liver damage markers which is opposite to statins.
And finally just to make this point and broaden the discussion these findings aren't a oneoff. This was a landmark seminal paper. But since then, many randomized control trials have consistently demonstrated that bourberine lowers LDL cholesterol and apple without reducing HDL cholesterol. And it also has neutral to beneficial effects on triglycerides, overall metabolic health, waist circumference, visceral atyposity, body mass index, and so on. In fact, I'd probably argue that bourberine's cardiovascular benefits are driven largely by mechanisms beyond LDL cholesterol and apple bee reduction. But that's beyond the scope of this video. This video I really wanted to bring you this fascinating mechanism cuz it blew my mind. I was excited about it. And if you have further questions about bourberine, I'll make more content on it. So drop your comments and questions in the video notes or at the newsletter.
But now, as I promised, I wanted to share what I'm currently working on. That brings us to chapter five, my next big experiment. For those who are new here, I have unusually high cholesterol. My total cholesterol is over 700 and my LDL is in the 500s. But I don't have a genetic defect. I don't have familial hyper cholesterolmia, but rather a phenotype known as the lean mass hyper respponder. Basically, when I restrict carbohydrates, my body compensates by increasing fat fuel trafficking via cholesterol containing particles. It's kind of this energy trafficking system. If you want more details, you can read the paper I'm going to link below. Anyway, the clinical implications of my profile this mechanism are unclear. On the one hand, when I get cardiac scans, highresolution coronary CT angography, my heart is completely clean to date, which is reassuring. On the other hand, I still want to take responsible steps to ensure I'm managing my risk thoughtfully. And at present, I'm not taking any medications. I'm not taking statins or conventional lipid lowering therapy for a variety of reasons, which I've reviewed previously. However, I'm actively exploring. I'm always exploring new options and self-experimenting with protocols to help me better understand what works in my body.
So, I'm going to be launching an N equals 1 crossover experiment. In this study, I'm going to be comparing different interventions on myself, including bambidoic acid, a PCSK9 inhibitor, a zettobe, and bourberine. Now, I want to do this properly, which means this approach will include wash out periods, and I'll be working with lipidology consultants, cardiology experts to ensure clinical rigor. The experiment could take a year or longer.
But moving on, one of the reasons I'm moving forward with this now is because I've accepted a new role as a senior scientific adviser at 100 health, an AI based support tool for metabolic health, unlike anything I've encountered. When I was talking with them, I wasn't prepared to be as impressed as I was. And yes, prepare for a plug now. Although really, it's just an honest disclosure about a very exciting tool that I'm helping to build. So this app, this 100 health app, it personalizes treatments and interventions based on your health goals and your background. It draws directly from over 400 electronical medical records, includes over a 100 biomarkers just in the baseline package, and then it uses state-of-the-art AI in an independent review of the literature. We're not talking about chat GTP pulling hallucinations here. We're talking about something totally different to produce a personalized metabolic health protocol that exceeds anything else on the market. This is really incredible. In fact, to give credit where it's due, it was my very own 100 health personalized protocol that got me to this Burberry Nature Medicine paper that we just talked about. And if you're interested, I'm going to drop way more information and the signup link below. I'm really all in on this one because this team is unbelievable, driven by altruistic purpose. So motivated and frankly the reason I joined is because I believe it's going to be a huge disruptive force for N equals 1 medicine and healthcare overall and I wanted to be on the ground floor of that. So that's my disclosure.
And as I run this N equals1 trial that I just described to you on myself, I'll be using 100 health, not just to track my lipid markers, but to assess the much broader metabolic health outcomes in me across all the interventions. The platform gives me a level of granularity and integration I haven't seen anywhere before in my self-tracking. So, if you have questions, drop them below. I'm committed to being transparent throughout this process and I'll share my data and insights as they come to me. Let's see what we can learn together.
But finally wrapping up, chapter 6, why I wasn't told. Here we have a decades old discovery published in a major journal when I was 9 years old, offering a radically different way to lower LDL and apple B with fewer side effects and potentially other benefits. So I asked myself, why wasn't I told? Why didn't I learn about this in my training? And here's my answer. Conventional medicine cares more about outcomes than mechanisms. And at face value, that's totally reasonable, right? Of course, we care about patient outcomes first. But there's a catch. If we only focus on particular mechanisms, we lose the sense of the bigger picture. So if our sole focus is on LDL and apple reduction, we're going to gravitate to the interventions that move that number the most, potentially missing broader implications. Mechanisms aren't just academic curiosities. Mechanisms give us insight into tradeoffs, downstream effects, and areas where clinical data may not have arrived or may never arrive. So even after years of conventional training, I still lean heavily on mechanisms when navigating my personal health decision. And this mechanism on bourberine, it excites me. It makes biological sense. And frankly, it gives me more confidence than the mechanisms behind other standard treatments like statins which we reviewed.
So that's why I'm diving in head first into this my N equals 1 journey because I'm well, you know what I am. It is what we are. I am curious. Thank you for joining me. I really appreciate you being part of the Stay Curious community. Stay curious and I hope you learned something valuable. [music] >> [music]