Can Nattokinase Reverse Atherosclerosis?

Okay, I'm about to show you something, but you have to promise not to let it freak you out or intimidate you. Promise? You ready? This. This is a little summary of the research I've been doing over the past few days. I've been diving deep into the research on one of the most misunderstood and most talked about supplements in heart health: nattokinase. Nattokinase. Nattokinase. What is it? Where does it come from? And can it actually reverse atherosclerosis? The answer might surprise you, but the how— that's this— even more so. This enzyme, born of fermented Japanese soybeans and rooted in over 1,000 years of tradition, comes with claims as bold as its samurai-era origins. But does the science actually back it up? Some studies link nattokinase to lower cardiovascular mortality, others suggest it might improve lipid markers or even reverse arterial plaque. This is one of those rare supplements that might actually deliver. Maybe. The data have limits, and the nuances matter. We're gonna get into those. So in this video, I'm gonna break down everything about nattokinase: what it is, how it works, what the research really says. And if you stick around, I promise, by the end, what looks like a bunch of squiggles in doctor scratch might just clot together into something clear and useful. Let's see if I can deliver. This signal was specific for natto. They had a 25% lower risk of dying from cardiovascular disease, and they observed something striking: plaque surface area decreased by 36%. That's pretty impressive. The data are surprisingly promising, certainly worth your attention. So today's video is going to be broken down into 4 chapters. First, we're going to review what natto is, including its legendary origins, lore, and its link to decreased death from cardiovascular disease. Then in Chapter 2, we're going to review a human study suggesting that nattokinase may improve or even reverse atherosclerosis. In Chapter 3, which in my opinion is the best chapter and where we're diving deep into mechanisms, we'll break down the fascinating mechanisms by which nattokinase is thought to work and support your cardiovascular health. It's pretty cool, and there is going to be some biochem and, uh, med school knowledge, so brace yourself. And finally, we're going to cover dosing protocols, which as we'll see, play crucial roles in determining nattokinase's potential efficacy. I'll also note, when you're done here, definitely check out the Stay Curious Metabolism newsletter associated with this video. This is where you're not only going to find all the reference links and more details and data, but also additional information on how to build a killer—well, hopefully not actually a killer—5-ingredient heart health stack. But with that, let's get into Chapter 1: Origins, Lore, and Cardiovascular Longevity. Natto itself is a traditional Japanese fermented soybean. It's created by fermenting soybeans with the bacteria Bacillus subtilis. There are several stories about the origins of natto, but it's clear its consumption dates back to about 1,000 years ago in Japan. One account that I like traces it to the samurai Minamoto no Yoshi. I probably mispronounced that, but there's my attempt. Anyway, this is an 11th century Japanese warrior, and according to legend, his troops and him were boiling soybeans for their horses when they were attacked. In a hurry, they packed up the beans in straw bags and fled. But by the time they opened the bags a day later, the beans had naturally fermented, and rather than give them to their horses, they evidently tried them, and natto was born. And in the centuries since, natto intake has been associated with longer life and lower rates of cardiovascular disease and cardiovascular disease-related death. So for example, one study followed 29,000 participants for 16 years and tracked cardiovascular mortality—death from heart disease. And in people with the highest quartile—highest quarter—of natto consumption compared to those with the lowest, they had 25% lower risk of dying from cardiovascular disease. But of course this is an observational study, right? So you could reasonably worry about healthy user bias. That's fair, I would. But what's especially interesting is in this study the researchers found no significant associations between cardiovascular mortality and total soy protein intake or other soy including foods. The signal was specific for natto. Let that fact ferment for a minute. This pattern supports the idea that there may be something unique about natto itself. Enter the enzyme nattokinase, an enzyme made during the fermentation process by the Bacillus subtilis bacteria, and it's thought to have cardioprotective properties, which we're going to review in the rest of this video. So that brings us to Chapter 2: Does nattokinase itself improve atherosclerosis? Well, in one study involving 1,062 participants, researchers administered 10,800 units of nattokinase per day over the course of the year. And they observed something striking: a measurable regression of atherosclerosis. Specifically, they used ultrasounds measuring plaque in the carotid arteries, which carry blood from the heart to the brain. They assessed both carotid intima-media thickness and the carotid plaque surface area—metrics for evaluating atherosclerosis, the amount of plaque there is in arteries. And after 1 year, 12 months of nattokinase supplementation, carotid intima-media thickness decreased by 21.7% and plaque surface area decreased by 36%. The researchers also measured changes in participants' lipids and found a 15.7% reduction in triglycerides, 18.1% drop in LDL, and 15.8% increase in HDL cholesterol. That's pretty impressive. That said, it is important to note that this was not a randomized controlled trial. We'll get into some of those a little bit later. But this study lacked a control group. Participants were compared to their own baseline measurements, so while the results are promising, I think they are, confounding variables cannot be ruled out. But again, I find this promising, especially given that nattokinase is a widely available and common supplement, and again we're going to get into some RCTs in a bit. One addition though I do want to highlight that I appreciated in this study's discussion was the authors' commentary on nattokinase dosing. We're going to discuss this in greater depth in a little bit, but they clearly explain the inconsistent literature by noting that prior studies, including some RCTs, failed to show benefits of nattokinase because they used much lower doses, for example just 2,000 units versus the 10,800 units used in this trial. So, in a word, these findings are promising if not definitive, but certainly worth your attention, or at least worth my attention, evidently. But now, let's get to the most fun part. Chapter 3: The cardioprotective mechanisms of nattokinase. We're going to focus on 3: the antithrombotic effect—that's anti-blood clotting—antihypertensive effect—blood pressure—and antioxidant effects. There are more subcategories we could explore, but for the interest of balancing nuance and clarity, we're going to focus on these three. So let's start with antithrombotic. A thrombus is the medical term for a blood clot. When clots form inside blood vessels, whether in large arteries or in tiny vessels of the microvasculature, they can block delivery of nutrients and oxygen to tissue. This can lead to what's called an infarction, which is exactly what happens in a heart attack or most strokes. Clot formation is driven by something called the coagulation cascade. This is a complex chain of reactions that medical students love to hate, and which I've represented in this little doodle, which we're going to return to later, as this little waterfall of arrows, not to overwhelm you because this is a simplified version. Anyway, think of it like a domino chain. One factor activates the next, which activates the next, which activates the next, and so on. This is why it's called the coagulation cascade, and eventually this leads to the activation of fibrin, a sticky compound that weaves itself into a mesh and traps platelets, forming a stable clot. I think of it as like Spider-Man's web. And this fibrin meshwork is the structural backbone of blood clots, but breaking it down, a process known as fibrinolysis, for fibrin and lysis, break down, reduces the overall clottiness of the blood and supports cardiovascular health. And this is where nattokinase comes in. Nattokinase has natural fibrinolytic activity, which means it directly breaks down fibrin again, fibrinolytic—lysis, break down—and dissolves blood clots. But it doesn't stop there. It also alters the activity of tissue plasminogen activator and levels of plasminogen activator inhibitor 1, two key regulators of your body's natural clot-busting system. And nattokinase reduces platelet aggregation. So I know that's a lot of jargon—you'll understand it when you review this—but in summary, nattokinase directly degrades the fibrin meshwork, breaking down clots. It modulates regulatory enzymes in the coagulation cascade, or just beyond, including tPA and PIA-1, and it reduces platelet aggregation, lowering clot formation risk. This is the antithrombotic activity of nattokinase and one of the primary ways nattokinase might protect the cardiovascular system. Now, that's part 1 of mechanisms. Let's get into part 2: antihypertensive effects, its impact on blood pressure. Now, to understand how this works, we need to dip into some more biochemistry. How you doing there, doctor? I know you can hang on. Anyway, one of the body's primary systems for regulating blood pressure, it's called the renin-angiotensin system. First year medical school. Here's the short version. The kidneys can release an enzyme called renin. When renin acts on a liver-produced protein called angiotensinogen, this converts it into angiotensin I. This is an inactive precursor. But then another enzyme, a key enzyme called angiotensin-converting enzyme, or ACE, which is primarily made by the lungs, converts this angiotensin I into angiotensin II. This angiotensin II is a potent molecule that does a few things. One, it constricts blood vessels, raising blood pressure, and it promotes the retention of sodium, salt, and water by the kidneys, which further increases blood volume and increases blood pressure. So basically now we're done with medical school stuff. But this enzyme, ACE, it's the key enzyme in the cascade, and it's the target of many widely prescribed blood pressure medications known as ACE inhibitors. These end in the suffix -pril. You might even have some in your medicine cabinet right now. Drugs like lisinopril or olanopril. They're very common medications. And interestingly, nattokinase, this enzyme from fermented soybeans, inhibits ACE2. It's an ACE inhibitor, leading to reduced vascular resistance, decreased blood pressure, and pressure on the artery walls, helping to improve overall cardiovascular risk by basically decreasing turbulent flow and vessel stress. Pretty cool, right? But if those mechanistic data aren't quite selling you, here's some human randomized controlled trial data. In one study, participants received either 2,000 units of nattokinase daily or a placebo control, and compared to the placebo group, those taking the nattokinase supplement experienced reductions in blood pressure of 5.6 millimeters of mercury in systolic blood pressure and 2.8 in diastolic. To put that in perspective, because I know the numbers might not mean anything to you, "This reduction is comparable to what's typically achieved with strict adherence to conventional dietary interventions, specifically the DASH diet." So bottom line, nattokinase does reduce blood pressure. We've gone over how, and we've shown randomized controlled trial data suggesting it actually works. And importantly— this is a key caveat— the effect was seen at only a 2,000 unit dose. We're going to note this later, but just put a sticky note on that dose. Okay, moving on to mechanism 3: antioxidant. This third proposed mechanism behind nattokinase's cardioprotective effects has to do with its ability to reduce oxidative stress, which is a core pathophysiological process that contributes to chronic disease, including heart disease. Oxidative stress occurs when the production of reactive oxygen species, harmful byproducts of metabolism, overwhelms the body's antioxidant defenses, and this imbalance can create damage to critical biomolecules like lipids, proteins, and carbohydrates, and perpetuates inflammation, dysfunction of blood vessels, and overall chronic disease progression. Nattokinase is thought to work by upregulating key antioxidants in the body's internal natural antioxidant defense network. So in effect, nattokinase may reduce overall oxidative stress, and thus provide additional cardiovascular protection by preventing the oxidation of LDL particles, protecting the vascular endothelium—cells lining blood and so on. Now, let's return to this little sketch. Look at it. Look at what you just walked through. If you understand even half of this, you should be really proud of yourself. Now that brings us to Chapter 4: Dosing Nattokinase. When it comes to dosing, prior studies have used a wide range of doses. However, based on the existing literature, I suggest aiming for at least 6,000 units, or specifically fibrinolytic units per day. For potential therapeutic effect. While lower doses, like the 2,000 that we reviewed in the other RCT, have shown some positive benefits, there are not consistent data, so I really think higher doses may have added benefits. And generally this is limited not by human toxicity, but by cost. Nattokinase appears to be pretty well tolerated in humans, with no toxicity observed up to 14,000 units per day in adult participants. There's been toxicity in rat studies, but that's at like like human equivalence of 13.4 million or something crazy. Now, if you want more specifics on brands and my thoughts on building a stupendous 5-ingredient heart health stack, check out the deeper dive at the Stay Curious Metabolism newsletter. But anyway, now I want to wrap up. At this point, nattokinase is not just a buzzword, it's a fascinating compound with real biological plausibility, encouraging human data, from associational data to human randomized controlled trials, and a broad suite of mechanisms of action that span clot breakdown, blood pressure regulation, and oxidative stress reduction. Is nattokinase a miracle? No. Is what I've shared definitive proof that nattokinase reverses heart disease? No, it's not definitive, but for a widely available enzyme derived from an ancient fermented bean, the data are surprisingly promising. Now, my final question for you is: did I deliver on my promise to make this make some sense? I hope you did. You get to grade me. Stay curious, and thanks for sticking through.