Reverse Heart Disease in 1 Year (Proven in RCT)

When I was 23 years old, I developed extraordinarily high cholesterol. I was told repeatedly that my cholesterol was so high, I will be developing plaque in my arteries within years, and I'd probably have my first heart attack by age 30. But I never did. In fact, my arteries are perfectly clean even on the most sensitive cardiovascular imaging, and the reason why has been a source of debate. Special genetics? I don't think so. A fluke of fate? That's not very scientific. Just not enough time? Well, maybe, but that skirts around the question and doesn't explain why the predictions made about my heart were wrong in the first place. I think it comes down to 2 things that I do every single day, both of which reduce inflammation in my arteries, and one of which has been shown to cause plaque regression in a human randomized controlled trial published this year. And the best part is, Both of them are free. They seem obvious, but they act on your arteries in ways that blew my mind and I know will blow yours. They are sleep and exercise. And when I read the first paper we're going to discuss, it introduced me to a completely new concept around heart health. So come with me on this journey because I am about to open your eyes before you close them later tonight. Mutations you didn't ask for expanding right now, quietly driving a leading cause of death worldwide. That's kind of crazy. And really scary, if you've been told to fixate on cholesterol, odds are no one has ever mentioned exercise beats the GLP-1 drug for cardiovascular benefits. And giving my body just a chance to heal itself and protect itself better. Quick roadmap for this video. In part 1, we're going to talk about something called the clones in your bones, a risk factor for heart disease you've probably never heard about. In part 2, we're going to talk about data from a 90,000-person study on sleep and exercise before part 3, Which we're going to call reversing atherosclerosis for free. And then we're going to bring it all home in part 4, where I talk about bonus tools to protect your arteries. And as always, all the associated references and more information can be found at the associated newsletter at our bestselling science newsletter at staycuriousmetabolism.com. But with that, let's roll and talk about the clones in your bones. Let's begin somewhere unexpected. A new study just published in the journal Nature reveals that sleep and exercise can tame Mutant blood cells that drive heart disease. Yeah, really. And if you haven't heard about this study, one reason it probably didn't make headlines is it's too bogged down in abbreviations and jargon for most science journalists to make sense of it. Things like TRP53 loss of function or DMNT3AR8882H, JAK2V617F— I could go on, but I won't. I'm going to spare you the alphabet soup and introduce you to just one phrase you need to know. Clonal hematopoiesis. It's pretty simple, actually. Clonal is obvious— it refers to clones. And hematopoiesis refers to the generation of new blood cells at its birth site, the bone marrow. The prefix hemato refers to blood, and poiesis just means production. So clonal hematopoiesis just refers to the production of new blood cells, including immune cells, that are clones of each other. Okay, so why should you care? Well, think of your bone marrow like an ecosystem. A healthy one is diverse. There are thousands, tens of thousands, hundreds of thousands of cell lineages coexisting. And clonal hematopoiesis is like when one lineage stops playing nice with the others. It's like an invasive species and it starts crowding out everyone else, all the other cell lineages. And the lineage that wins tends to be aggressive and inflammatory. It picks up a mutation That hands it a survival advantage, it expands, and it tilts your whole immune system ecosystem towards a chronic inflammatory state. Now, you might be picking up on a parallel to cancer here, and if you are, that's actually a good analogy. This isn't full-blown cancer, but it's the same plot— a population of cells gains an edge and outcompetes its neighbors. Except here, the particular winners are inflammatory, and then— They sneak from your bone marrow into your artery wall and fire up atherosclerosis. So the consequence of all of this is summed up in the opening line of the paper which reads, clonal hematopoiesis activates inflammation and increases the risk of atherosclerosis. So in other words, mutations you didn't ask for expanding right now in your bone marrow may be quietly driving a leading cause of death worldwide. Heart disease. And I really want to highlight this so it's not missed: immune cells are born in the bone marrow, they go into the blood, and then to the heart. Bone to blood to heart. So the generation of mutants in their birthplace, the bone, can directly damage the heart, as these nomadic inflammatory cells traverse your arteries. That's kind of crazy and really scary, though don't worry, I'm going to show you how to address it. But first, let's be clear: clonal hematopoiesis is not some rare exotic condition, even if the name sounds esoteric. It becomes more common with every decade of life, and most older adults who have it have no clue that it's there. If you've been told to fixate on cholesterol or ApoB, odds are no one has ever mentioned the mutant inflammatory cells that might be doing real damage. Why don't we know about this? Why don't we talk about this? Well, in a nutshell, my answer is we don't have a drug for it. Typically, doctors and medicine measure what we can act on, And this isn't something for which there is a simple pharmaceutical or pill. But the good news is you can act to fight these inflammatory clones, and I'm about to show you how in part 2, Don't Sleep on Exercise. Let's start with the human data. What the researchers did was amass 2 large datasets, the UK Biobank and the All of Us Research Program, with over 90,000 individuals in total. And physical activity was measured using using activity monitors, allowing researchers to examine the associations between activity, in particular moderate to vigorous physical activity, and the degree of this clonal hematopoiesis— think the inflammatory clones born in your bone marrow that contribute to heart disease. And what the researchers found was that more physical activity tracked with less clonal hematopoiesis, but selectively in certain clones and not others. Hold on to that thought because it's important and we will return to it, but the pattern held across both datasets, both cohorts, and in men and in women. Now, the easy dismissal that might be coming to your mind, and if it is, that's not a bad thing, is that exercisers are simply leaner and healthier to begin with, so of course their blood will look cleaner, right? But the association also survived even after adjusting for body weight and BMI, This wasn't exercise working just through the scale; it was reaching the clones directly. Exercise somehow reaching into your bone marrow and changing the milieu there to change what clones are born, bred, and disseminated into your body. But remember the other side of the lifestyle coin as well—the yang to exercise's yin. Sleep. They are sleep and exercise. Sleep acts similarly on clonal hematopoiesis, but through a non-redundant complementary mechanism. That's a lot of big words for. a simple idea: exercise and sleep stack on top of one another to protect your arteries from mutant clone cells and inflammation. That's really cool, right? But I'm sure you're wondering, how? How can something as simple as going for a run or getting a good night's sleep selectively target harmful mutant cells while leaving healthy blood cells intact? So let's dig into that. Here's what the researchers did. They built an elegant system. They developed mice with different mutations, each of which had blood that was 10% mutant and 90% normal. They then randomized the mice to 3 groups: sedentary, lazy mice, exercising mice, and mice who had their sleep disrupted. They then tracked the expansion of the mutant clone blood cells over 12 weeks. And here's what happened. In the sedentary animals, the mutant clones steadily expanded. In the animals that exercised, expansion was completely stopped for some mutants. And in the group that had sleep disruption? The clones expanded even faster, resulting in significantly more mutant cells in the blood than in either 2 groups. But there's also an important nuance here we can't miss. Exercise suppressed certain clones, but not the generation of blood cells in general. Obviously you wouldn't want that— that would make you tired, anemic, and destroy your immune function— so there's specificity here. Exercise and sleep aren't like a grenade, they're like cellular snipers, and they have their crosshairs locked on these inflammatory mutant cells. Okay, but how does it really work? Well, at a high level, different mutations are going to cause different cells to make different proteins and different receptors on their surfaces. For that reason, those cells end up being more vulnerable to certain environments— environments caused by sleep and exercise. In the sniper analogy, It's like normal cells are well camouflaged, and the mutant cells you want to take out are running around with a reflective vest. But there's more too, because sleep and exercise weren't just affecting clonal hematopoiesis in the bone marrow. They also changed how these cells behaved once they entered the rest of the body. For example, sleep disruption increased levels of a receptor on mutant clones that triggers an inflammatory cascade within the artery wall. In other words, sleep disruption made the clones inside the artery even more inflammatory. But conversely, a good night's sleep would do the opposite— calm the inflammation of the clones in the artery wall. And exercise also acted on the clones once they entered the blood. Exercise activated neurons in the brainstem that altered hormones like adrenaline throughout the body. These hormones then bind on to receptors on immune cells and turn down inflammatory signaling. Which means— and I really cannot overstate this, please hear me— That exercise and sleep protect the heart against this mutant inflammatory pathway in 2 ways each: by slowing the expansion of mutant clones in the bone marrow, their birthplace, and then by reprogramming those mutants once they're in the artery wall, reducing the inflammatory damage they ultimately cause. Pause and sit with that, because when you really start to internalize it, it's pretty mind-blowing. But now you're probably asking, does this actually impact heart disease? Like plaque in arteries. Well, yeah, you can actually see that here. What you're looking at is plaque area in the arteries of animals carrying these mutant cells. That's the orange line. It's kind of the control baseline. And when you fragment their sleep, disrupt their sleep, that's the red line in the square. What you see, sleep disruption makes plaques in arteries bigger, much worse. Exercise, the blue line in the square, causes plaques to get smaller, maybe even regress— we'll get into that in a minute. But this is a clear signal that exercise and sleep change not just clonal hematopoiesis as some interesting biology. Exercise and sleep translate into meaningful differences in actual plaque in arteries. Now that's animals. What about in humans? That brings us to part 3: reversing atherosclerosis For free. Here's the deal. You can't exactly mutate human stem cells in living people to perform the same experiments we just reviewed in mice. There are ethics boards. So what do we have? Well, first, we have associational data in humans that line up with the mechanisms we just discussed. For example, night shift workers who have disrupted sleeps and circadian rhythms have about a 20% increased risk of cardiovascular disease events, like heart attacks and strokes, which is kind of crappy, but Can we go further? Can we tap into human randomized controlled trial data and show that we can regress plaque? We can, but before we get to that study, I want to tie this all up with one word that really is the overarching theme here: inflammation. If you strip away the jargon, the whole story reduces down to this: that with age, you accumulate clones that skew inflammatory. Inflammation in the artery is what drives plaque in your arteries, and exercise and sleep help by suppressing the clones that drive inflammation and by suppressing inflammation directly. So does this work in humans? Well, I already told you yes, and I want to focus in particular on a brand new study that was just published this year in Nature Metabolism. In this study, which was a randomized controlled trial, 130 adults were randomized to one of 4 groups. A placebo group, an exercise group, a group that was given a GLP-1 weight loss drug, and then a group that was given both the exercise and the GLP-1, and I'll give you the punchline. Exercise suppressed inflammation and led to a regression, a regression of atherosclerosis on imaging of arteries with ultrasound, a 7% regression in atherosclerosis over 1 year. Wow. And as a bonus, there was no significant benefit in the GLP-1 alone group. But don't just take my word for it— the authors themselves concluded that their findings suggest that the vascular adaptations are more sensitive to exercise-induced hemodynamic and anti-inflammatory effects than to the effects of the GLP-1. In a lot of words, in a nutshell, exercise beats the GLP-1 drug for cardiovascular benefits. Now, to be clear, I'm not saying the GLP-1s have no use here or that they aren't anti-inflammatory, but the emphasis of our story today is on the profound anti-inflammatory and cardiovascular benefits of exercise, which in this study were shown to reduce plaque to statistical significance, where the GLP-1 was not. And let me just double down on this because it's important. GLP-1s are useful tools. If you want, I have a whole masterclass on them. But they're not a replacement for lifestyle, including exercise. In fact, to get on my soapbox for a minute, I think in their best use case, They unlock the capacity for healthier lifestyles, better food choices, and more movement, and that can create a virtuous cycle. But let me get off my soapbox. Let's pull all of this together because I know it's a lot and it matters. Exercise and sleep aren't just good for you. What these new data are showing is that exercise and sleep can selectively reprogram how your immune cells develop. They can curtail the generation of inflammatory cells, and if those inflammatory cells do emerge, Exercise and sleep can suppress their activity to help protect your heart. And that brings us to the practical question: what can you actually do? So, tools to protect your arteries. Well, the obvious are prioritize sleep and exercise. No surprise there, right? That said, I will take a moment to point you to some deeper learnings on these topics for those who want to go the extra mile and not just on the treadmill. When it comes to sleep, I think too little attention is focused to quality compared to quantity. Yes, you do need enough sleep, but enough varies from person to person. We have a whole sleep masterclass video which I encourage you to check out, but if you don't, get your sleep basics dialed in. A cool, dark room at night. Reduce intense light exposure about 90 minutes before bed, including blue light. And if you really struggle with sleep, there are some supplements That might be able to help. I've really benefited from using a peptide called pinealon, which helps improve REM sleep. In fact, members of my community also attest it's incredibly effective at improving their REM sleep as much as doubling it. And there are also some prescription peptides that I've played around with to promote deep sleep, which I've linked more on below. Now, when it comes to exercise, aim for at least 150 minutes of moderate to vigorous physical activity per week, including a mix of aerobic and resistance training. Again, I provided specifics on possible workout routines elsewhere, including here and here. So I won't reinvent the wheel. Then, of course, the inevitable question turns to, well, are there supplements that may help as well? Well, once you're doing sleep and exercise right, there are a few. The primary supplement that's been shown to reverse atherosclerosis in humans, albeit in uncontrolled trials, is nattokinase. Again, we have more on that in dedicated content, but practically speaking, higher doses, around 10,000 fibrinolytic units, are more likely to be effective in promoting atherosclerotic plaque regression and suppressing inflammation in the artery wall. Another supplement worth considering for suppressing inflammation in the artery wall is called TUDCA. It's a bile acid that appears to act at least in part by going directly into the vascular wall and calming inflammation. Finally, I need to mention one more underappreciated contributor to arterial inflammation: microplastics. Microplastics are becoming an increasingly unavoidable part of our environment, and research published in highly regarded medical journals like the New England Journal of Medicine have found that microplastics accumulate in human arterial plaques where they are engulfed by immune cells and promote inflammation, and this is associated with a 350% higher risk of cardiovascular events. The biological mechanisms are clear, the human data are concerning, and reducing this source of inflammation to me just seems reasonable and prudent. So what do I do? Well, there's the obvious— avoiding plastic water bottles when possible and never ever heating food in plastic containers. And one more part of my health routine, something I genuinely use daily, is a microplastic-binding probiotic by Winnow Labs. This is what I use. If you want to use it too, there's a link below with a discount code. Stay curious. Anyway, the reason I use it is it was specifically engineered to create a kind of internal shield by combining several bacterial strains that bind microplastic up like Velcro, which you can see here. And this means more microplastics are being pooped out of your body rather than absorbed into it. And personally, I'd rather whatever microplastics get into my mouth end up in my toilet rather than inflaming my arteries. Sound reasonable? But let's now bring this all home and reflect back on where we started. Over 7 years ago, I was told that my high cholesterol would clog my arteries. That was wrong, at least to date, and while I don't have a clone of myself to perform a randomized controlled trial on, I think one of the big reasons my arteries remained healthy to this day is remarkably obvious on the surface and remarkably complex and beautiful Underneath, as we've just discussed. By simply being consistent with exercise and sleep to the best of my ability— I'm certainly not always perfect— I've likely been changing my biology from the inside out— my bones, my blood, my arteries— slowing the emergence of inflammatory immune cell clones, calming inflammation they create, and giving my body just a chance to heal itself and protect itself better. That's power you have too. And that Is worth taking a beat to think about.