Latest / Common Sense Health / ApoB: The Truth
Transcript
- Stephen Thomas BSc. Hons: Hello, let's talk about ApoB, which is the new cardiovascular marker that's been sitting on the shelf since 1990, admittedly. And why do we suddenly care about it now? There must be a good reason. Now, a quick note before I dive in. I did write and speak about this topic a few months ago, and I used the sort of style of a medical mystery story, sort of all dramatic reveals and suspenseful timing and... Many of the comments just asked me to cover it again, but this time I get crystal clear what I'm actually talking about from the start. So fair enough, I am trying different stories, always try to do it unedited. So here it goes. Let's have a straightforward look at ApoB, Apolipoprotein B and LDLC and why ApoB has suddenly become the cardiologists new favorite number and how the timing of this enthusiasm has rather a lot to do with pharmaceutical profit margins. and a lot less to do with clinical breakthroughs. So let's get into it. So the new kid on the block has actually been around for 34 years. Apo B is being talked about as though it's some sort of revolutionary new discovery in cardiovascular medicine. What doctors are ordering now, cardiologists are writing guidelines around it. The medical establishment is acting like they've just unearthed some long lost treasure that's going to change everything. Well, here's the thing. App OB has been measurable in clinical labs since the early 1990s. So not last year, not five years ago, but since 1990. That's three decades. So this test has been sitting on the lab menus like, you know, like that gym membership you keep paying for, but you never go to the gym. It's been available. It's affordable, but it's really largely ignored. And then suddenly, right around 2015 to 2020, cardiologists across the world had a collective epiphany. You know what? We should really be measuring APO-B. It's so much better than LDLC. Why haven't we been doing this all along? They asked. Why indeed? Shall I give you a spoiler alert? The answer involves approximately $5 billion in annual pharmaceutical revenue. So yeah, follow the money. And it's a rather inconvenient thing called a patent cliff. Now, what actually is APO-B? Let's do that first. because people seem to like the science. So before we get into the financial shenanigans, this bit helps. So ApoB is a protein that sits on the surface of every lipoprotein particle that carries fats and cholesterol through your bloodstream. And that's the elegant bit. There's exactly one ApoB molecule per particle. No more, no less, just one particle, one protein. Always very simple. Well, what this means then is when you measure ApoB, you're essentially counting the total number of lipoprotein particles floating around in your blood. All of them LDL particles, VLDL particles, IDL, the lot. One number total particle count. Sounds good, doesn't it? Now compare that to LDL-C, which has been cardiology's obsession for the past 30 years. LDL-C measures the amount of cholesterol inside LDL particles specifically, not the number of particles, just the cholesterol content. And there's other things in there as well, but anyway. just cholesterol. So think of it like this. LDRC tells you how much cargo is loaded into one specific type of lorry. APOB tells you the total number of vehicles on the road. Lorries, vans, cars, all of them. So in metabolically healthy people, these two numbers track together pretty closely. But in people with problems around the insulin or metabolic syndrome, type 2 diabetes, which, let's be honest, describes a significant chunk of the population, You can have a relatively normal LDLC but an elevated APO-B. Well, why is this? It's because their lipoprotein particles tend to be smaller and denser, so you need more particles to carry the same amount of cholesterol. Total sense. Now, the mainstream cardiology position is that particle number matters more than cholesterol content, and therefore APO-B is a better predictor of cardiovascular risk than LDLC. Well, is that reasonable? In the context of metabolic dysfunction, maybe yes, but ApoB does capture something that LDLC can miss in insulin sensitive individuals or insulin resistance people. Here's the big question. If ApoB is genuinely more useful than LDLC, why did everyone ignore it then for 30 years? And this is when we enter the golden age of statins or why LDLC became the king. if we rewind to the late 1980s and 1990s, a new class of drug hit the market that would go on to become some of most profitable pharmaceutical products in human history. Enter statins. And you've probably heard of statins. I mean, these drugs, they're bloody brilliant at one thing in particular, lowering LDLC and dramatically, reliably by 30 to 50 % in most people. They also obviously lowered ApoB, but not nearly as much, typically 20%. Now, put yourself in the shoes of a pharmaceutical executive. You've got a drug that lowers marker A by 50 % or lowers marker B by 20%, let's just say. Which marker do you want the entire medical profession to focus on? Right, well obviously, marker A, you know, because it's 50%. And so LDLC became the single most important number in cardiovascular medicine. Guidelines were written completely and utterly around it. Risk calculators, they incorporated it. Every GP surgery started testing it with a religious fervor. Target levels were established. Get it below 100 milligrams per deciliter. No, actually below 70 milligrams per deciliter. Well, go as low as you can. Meanwhile, ApoB, that perfectly good test, that had been available since 1990 just gathered dust in the corner. At their commercial peak, statins were generating over $30 billion in annual revenue. Lipitor alone was pulling in $13 billion a year. These weren't just successful drugs, they were a license to print money. And this is where we get to the patent cliff. It's basically when the money tap turns off, patents, unfortunately for the pharmaceutical companies, expire. Zocor went generic in 2006, Lipitor in 2011, Cresta in 2016. So when a blockbuster drug goes generic, something economically brutal happens. The price collapses. So what once cost $150 per month is now available for $25 per month, sometimes less than $10. So a year's supply of generic statins in the US now costs under $300 US dollars. For the pharmaceutical companies that had built this entire revenue empire around these molecules, this was a financial apocalypse basically. Billions upon billions in annual income vanished. So the question was obvious. What do we do next? Well the answer was... The pesky inhibitors. P-C-S-K inhibitors. They're brilliant. They were new. Right around 2015-2018 a new class of cardiovascular drugs arrived. PCSK9 inhibitors. These are not pills. They're injectable biologics, fancy bio-engineered proteins you inject subcontinuously every 2-4 weeks. And here's the critical detail. They lower ApoB substantially more than statins ever did. We're talking 50-60 % reductions in ApoB. They're pretty impressive numbers. They also lower LDLC of course as a sort of side hustle, but their particular competitive advantage is what they do to APO-B. It's here where things get expensive. A year supply of PESCE, which is what I call them, or PCSK9 inhibitors, costs approximately $5,000 to $6,000 per patient in the US. They have come down a bit recently. Now compare that to under $300 per year for the generic statins. So the global market for PESCE inhibitors generated $3.7 billion in 2024. is projected to reach 18 billion by 2035 and in a development that is absolutely certain, not completely coincidental, not suspicious, it was precisely around this time that the medical establishment began urgently rediscovering ApoB. Suddenly around 2015-2020 cardiology conferences started buzzing about ApoB. Guidelines began incorporating it. Doctors started ordering it. Medical journals published papers about it. ApoB is the marker we should really be measuring. Sound familiar? Anyway, it's better reflection of cardiovascular risk than LDLC is what they say. We should have been paying attention to this all along. This is the future of lipid management. Well, all of that is actually technically true, but it had been measurable for 30 years. Nobody urgently cared about ApoB when the only drugs available, statins, were better at lowering LDLC and were about to go generic anyway. the moment a $5,000 per year drug arrived that was particularly good at lowering ApoB, suddenly ApoB became the most important number in cardiology. Funny. Funny how that works, isn't it? Hmm. Bit odd. Anyway, this is where we get on to a billion dollar question. Does ApoB actually matter? I'll add some nuance that nobody seems to be talking about. So I want to be clear. I'm not saying ApoB is meaningless. It measures something real. In the context of metabolic dysfunction, some people call it insulin resistance or metabolic syndrome or type 2 diabetes, ApoB can indeed capture elevated particle numbers that LDLC might miss. That's true. Now the mainstream cardiology position is that elevated ApoB is the causal driver of cardiovascular disease and lowering it reduces risk. That's the official story. That's what the guidelines say. But here's where things get considerably more interesting. And it might make me seem a bit controversial, but the data supporting a straightforward causal relationship between ApoB and cardiovascular disease is actually quite messy. A study in the Journal of the American College of Cardiology examined over three and a half thousand patients with established coronary artery disease who were aggressively treated with statins to get their LDLC below 70 milligrams per deciliter. Despite this, more than 20 percent continued to show plaque progression. And here's the kicker. Changes in LDLC levels were not independently associated with whether plaque progressed. What mattered was glucose levels. triglyceride levels, blood pressure and HDL. In other words, the metabolic markers predicted plaque progression were not ApoB, they were not LDLC. And then there's the explosive controversy around the Keto-CTA study, which has now been retracted at the office request due to the method concerns around that. And he examined leaned lean metabolically healthy individuals on ketogenic diets who had very high LDLC and elevated ApoB, the so-called lean mass hyper-responders. And the initial findings suggested that neither total ApoB exposure nor changes in ApoB were associated with plaque progression. That was in these metabolically healthy individuals, by the way. Now, the retraction means we can't cite it as a definitive piece of evidence. But the finding isn't fringe. It's genuinely an unresolved question. does high ApoB carry the same risk in metabolically healthy versus metabolically dysfunctional individuals? Now mainstream cardiology hasn't satisfactorily answered that question. So now we want to go onto that metabolic context and it's one that everyone ignores. Here's what the data increasingly suggests. The relationship between ApoB and cardiovascular disease is heavily context dependent. Seems obvious to me, to be honest. Elevated ApoB in the setting of someone that has high triglycerides, low HDL, poor glucose control, chronic inflammation. Well, it's likely going to be quite different from elevated ApoB in someone who is metabolically healthy or lean or very good with their glucose management and control and their triglycerides are very low. Now, in the first scenario, elevated ApoB is a consequence of metabolic dysfunction. The liver is churning out excess VLDL particles because it's overwhelmed by visceral fat, insulin signaling that's gone bit haywire and chronic carbohydrate overload. Now in the second scenario, it's considerably less clear what it means. But here's the thing. Addressing upstream metabolic dysfunction through dietary changes, weight loss, carbohydrate restriction, etc. consistently lowers upper B levels naturally. not with a pharmaceutical suppressing the number. You don't need that expensive drug. But by resolving the reason the number was elevated in the first place. So let's now cover those two approaches which have two obviously very different price tags. So let's say your doctor orders an ApoB test and it comes back elevated. What do do now? Well, you've got the pharmaceutical approach. Your ApoB is high. Here's a prescription for a pesky 9 inhibitor. Inject this every two weeks. That'll be $5,000 per year. Please come back in six months for another blood test. Kaching. That's it. That's basically it. Or you've got the metabolic approach. Your ApoB is high, likely because you've got a problem with your insulin and your liver is overproducing lipoprotein particles. Too much carbohydrates coming in. So let's cut the refined carbohydrates and the seed oils, increase your protein. and healthy fats. Lose the visceral fat, improve your insulin management. Let's retest in three months. Now one of these approaches is projected to generate 18 billion US dollars in annual revenue by 2035. The other involves some steak, some eggs, bit of butter and considerably fewer injections. Can you guess which one gets promoted in medical conferences and in the guidelines? Well, here's the fundamental question you see that nobody mainstream cardiology wants to actually grapple with. And it's a question that we need to answer. And it's this is lowering a number with an expensive drug, the same as addressing the underlying condition that elevated the number in the first place. If elevated ApoB is a consequence of metabolic dysfunction, and in most cases it is, then suppressing the number with a pharmaceutical solution doesn't fix the actual problem. It's like unplugging your car's check engine light and calling it fixed. The metabolic dysfunction is still there. The problem with carbohydrate intolerance, the chronic inflammation, still there. The visceral adiposity is still there. You've just made one number look better on a blood test. So a well-formulated, low-carb, ketogenic or carnivore diet does address these upstream causes. It seems to lower triglycerides often quite dramatically. It raises HDL and improves your insulin numbers. It reduces visceral fat. It shifts LDL particles towards the larger, less dense types. It lowers ApoB naturally. And a 2022 randomized controlled feeding trial confirmed this directly. A low carbohydrate diet improved insulin sensitivity, dyslipidemia and lowered ApoB without adverse effects. not by suppressing a number, but by fixing the thing that was causing the number to be elevated. So, here's the story in plain English. A blood marker called ApoB has been available since 1990. For three decades it's at largely ignored whilst the medical world obsessed over LDLC, the number that statins were particularly good at lowering. That's it. Then statins went generic, pharmaceutical profits evaporated, and a new class of $5,000 per year drugs arrived that were especially good at lowering ApoB. And suddenly, yep, suddenly ApoB became the most important cardiovascular marker we should all be measuring. Is ApoB useful? In context, yes. Particularly in metabolically dysfunctional individuals, where it captures information LDLC might miss. I can't emphasize that enough. I'm not anti this number. Is it a definitive causal driver of cardiovascular disease? The data is very messy. And it doesn't give you simple yes. Metabolic context matters enormously. And the question of whether lowering it with drugs produces the same outcomes as addressing the underlying metabolic dysfunction remains genuinely unresolved. But is the timing of its rediscovery suspiciously aligned with pharmaceutical profit motives? I'm going to let you draw your own conclusions on that one. Hmm. So, remember, treating a number is not the same as treating a disease. And that number has been available since before most of your doctors finished their medical school diplomas. And the punchline? The revolutionary new marker everyone's suddenly excited about has been collecting dust on lab shelves since 1990. It took a five billion dollar industry to remember it was there. So... Who says medicine doesn't make you have a good sense of humour? I'm still smiling because I find the irony of it all quite mind-numbing to be absolutely frank with you. Anyway, thank you for listening. I hope you enjoyed that story. And if you've got to the end and you did enjoy this video, please consider liking, commenting and sharing. Subscribing to the channel really does help. I know we all say it sounds very boring, but it does genuinely help. Now, if you've got to the end and you didn't like this video, then please comment on why you didn't like it and what you think is wrong with it because I always like to hear the outside of the the opinion really. But those facts seem very hard to dismiss. The coincidence is very strong with this one. Anyway, thank you for listening and I'll see you on the next video.