I Stopped Using Nattokinase. Here’s Why.

Nattokinase is one of the most hyped supplements in cardiovascular health — claimed to lower blood pressure, shrink arterial plaque by 36%, and drop LDL cholesterol without a statin. I put a patient on it. Then I looked closer at the data. Now I've stopped.

In this video, I break down what the evidence actually shows:

✅ Blood pressure: Real, but modest. A 2023 meta-analysis of 6 RCTs found just 3.45 mmHg systolic reduction — roughly half the effect of a low-dose ACE inhibitor.

❌ Plaque reduction: The headline 36% plaque reduction comes from a single retrospective chart review (Chen 2022) with no control group, no randomization, co-administered confounders, and 5 of 10 authors employed by the supplement manufacturer. Meanwhile, the rigorous double-blind NAPS trial (Hodis 2021, n=265) found zero effect on carotid plaque.

❌ Lipid lowering: In randomized trials (Yang 2009, Hsia 2009), nattokinase alone doesn't move lipids. The signal only appears in non-randomized studies — often confounded by red yeast rice, which contains monacolin K (chemically identical to lovastatin).

📉 The case study: I put "Susan" on high-dose nattokinase for a year. Her arterial age went from 64 to 73. We stopped.

The lesson: Test. Don't guess. Never start a supplement without a plan to stop it if the numbers don't move.

⏱️ Chapters
0:00 Why I stopped using nattokinase
0:21 Meet Susan
1:46 What nattokinase actually is
2:14 How nattokinase works
5:00 Does it survive digestion?
6:14 The real signal: blood pressure
8:34 The plaque-regression claim
9:59 Problems with the 2022 study
13:09 The 2017 plaque study
14:50 The 36% plaque reduction problem
16:30 Does it lower ApoB or LDL?
19:31 Why plaque ultrasound is tricky
22:56 Safety and bleeding concerns
25:57 What’s actually in the bottle?
27:24 The NAPS trial
28:48 Was the dose too low?
30:29 Susan’s one-year follow-up
32:51 What if you take it anyway?
33:42 Final take: test, don’t guess

⚠️ This video is for education only and is not personal medical advice. Please talk with your own physician before starting or stopping any supplement or medication — especially if you take aspirin, clopidogrel, warfarin, Eliquis, Xarelto, Pradaxa, or any other blood thinner.

— PRODUCT POTENCY TESTING —
Natural Informant (Danny Curtin). "Nattokinase: We Tested Them All… Which Products Can You Trust?" https://youtu.be/K1l_g6-vdC4?si=h4oOnGEw_Vvh51cx

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🧬 About Dr. Lily Johnston
  
Dr. Johnston is a double board-certified vascular and general surgeon in San Diego, specializing in metabolic and cardiovascular prevention. She’s the founder of CorSight Health and a passionate advocate for reimagining how medicine approaches chronic disease.
  
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Transcript

SPEAKER_00 0:00

You guys have asked me about nato kinase since we started this channel, and you need to know why I don't use it anymore. If you guys are new here, I am Dr. Lily Johnston. I am board certified in vascular surgery, but I now specialize in cardiometabolic prevention. So hopefully you will never need me as a surgeon. Every week a patient asks me about natokinase, and honestly, most of what you guys have heard is overblown, and there is a part that's right, but it's smaller than most people think. And I want to tell you a story today because there was a patient who came to me and we started her on natokinase, and you also really need to know why we stopped. So this is Susan. She came to me with some established plaque in her carotid arteries. She's in her mid-60s, she's postmenopausal, and she's got a pretty strong family history of high cholesterol and blood lipids. And she had, understandably, some concerns about treating that in the classic way. Now, because she's my patient, she is obviously really maximized on the rest of her metabolic protocol. So her fasting insulin is low, her blood pressure is normal, she is doing high-intensity resistance training and cardio and some flexibility and mobility work. She's working on her sleep, like everything else, we are getting dialed in. It was just this last piece about her lipids and her plaque that we wanted to see what we could do about. And she had a lot of motivation to try some new things and was asking all the right questions. And she said, like most of my patients, I don't really want to start a statin, which I totally understand. Is there something else that I should be considering? And enter natto kinase. What is it? So this is an enzyme that is derived from fermented soybeans and the traditional Japanese food natto. And it was identified in 1987 and it is now widely sold as a cardiovascular supplement, in fact, mostly a cardiovascular fix-all. And it's a really, really interesting molecule because it works in so many different capacities in the cardiovascular system. So let me touch on a number of them here. This may not even be all that it does. This is what we know so far about natokinase. Firstly, it breaks up existing clots. So there is this molecule called fibrin, and you can think of it like little fibers, and the fibers crosslink together and they form this clot. It's a scaffold. The natokinase can actually break those fibers apart and cleave that bond. Secondly, there is a clot busting system in our body. So we make clots, but we also want the ability to break those clots down. And this is in a delicate balance, right? The pro-clotting, the pro-breakdown of clotting. What natokinase does is it releases the break on the clot breakdown system. So it allows us to more efficiently break down small little microclots that might be in our system, where there might be a tiny plaque rupture somewhere in an artery, right? The natokinase allows the clot breakdown system to go ahead and be uninhibited. Next, it actually increases a natural clot buster called TPA. This is the stuff that if you show up to an emergency department with a stroke like an hour ago, they might inject into your veins to like break up that clot and actively dissolve it, really. And the fourth thing it does is it actually lowers blood pressure. This is a totally separate mechanism, having nothing to do with clotting. It actually works on the angiotensin converting enzyme, which is the same pathway as the most popular blood pressure medications, like lysinopril, for example, right? That's a very common one that is an ACE inhibitor drug. Natokinase works on the same pathway and actually lowers blood pressure. The last thing that it does is that it stops platelets from sticking together. So this is actually a little separate from the fibrin and the clot busting pathways that we talked about. Separate mechanism. Platelets are the little anuclear cells that are helping your clots form, all right, separate from fibrin. Platelets aggregate together and they form this sticky little mush, and they have a lot of signaling molecules that now attracts fibrin and attracts other parts of this clotting process. And we think that there's actually some antiplatelet activity to nato kinase as well. So for all of these mechanisms, obviously it's super interesting to those of us who participate in working cardiovascular disease, right? All of these things could be contributing to the formation or acceleration of plaque. And we would want to know how effective is this at helping us stop these issues. The first question you should ask though is natokinase is an enzyme, right? That AIS on the end tells you that it's like an active molecule that's doing something. So it's not an inert um supplement, it's actually an enzyme that has function to it. And most proteins and enzymes will be degraded by the very acidic environment of our stomach. And a good question would be well, if you take this orally, which it that's how it's administered, um, how much of it makes it through the stomach? We don't have a great sense for this. There have been some sort of biochemical trials that have looked at the acid inactivation of nato kinase. And in fact, a good deal of it is inactivated by highly acidic environments. There is another study, though, that does show if you give people a measured dose of it and you measure blood levels later, you do find that there is some increase in the presence of these enzymes in the blood. So at least some of it makes it through your GI system, but how much, we don't know. Is it variable from person to person? It sure could be. So as you're thinking about, well, how much should I take and how much is getting into the system, just be aware that we don't really know. So let's talk about what nato kinase actually does well and what has been replicated and what I feel very confident in its capacity to achieve. Okay, the one finding that's been really well replicated in the scientific literature. It is blood pressure control. So a 2023 meta-analysis pooled six different randomized controlled clinical trials, and we see on aggregate with all those trials pooled together, a systolic blood pressure decrease of about three millimeters of mercury and a diastolic decrease of two millimeters of mercury. Now, that does not sound clinically super impressive to you, and it shouldn't. It's a modest effect, but it's honestly on the order of many things that we achieve in supplements and lifestyle impact on blood pressure control. So for a large study, this is actually not bad. It's not quite as significant as higher doses of prescription medications, but this is a real finding, and you know, at the individual level, it may be higher. Just remember this is a population average. So some people may respond quite a bit, others not as much. When you average it all out, we do see that this is a significant finding. So I'll show you the biggest RCT here was from Kim and uh 86 patients. They did 2,000 fibrinolytic units, FU. That's by the way, how natokinase is dosed. That's what you'll see on the bottle. It's the number of fibrinolytic units. And over eight weeks, they saw a five and a half point drop systolic and almost three-point drop in the diastolic pressure. And then again, below you have the numbers for the meta-analysis. So here's how I think about the blood pressure side of the natokinase thing. It does work, it's a modest effect, but it's not nothing, and we should consider that. It is not what I reach for when people ask me how to manage blood pressure. But if pharmacologic agents are not on the table for any reason, then I think it's a very reasonable thing to try and see. Again, we're gonna follow people over time and make sure that if they have high blood pressure, we bring it down into the appropriate range. So if you want it for your blood pressure, we'll not, I'm not gonna fight you about it. Uh, let's make sure the dose is correct for that particular indication. And I think that the evidence base here is pretty strong. Here's where we actually get into a little trouble, though, because the atherosclerosis or the plaque story, and this is really where social media and YouTube has like gotten this idea in the head that natokinase is gonna fix everybody's plaque forever. And in 2022, a study came out that I think like honestly made the internet lose its mind. Um, and I got sucked into the hype too, okay, because it was really, really interesting data. This was a study of over a thousand patients, and they took high dose natokinase. We'll talk about what that means in a bit, and it reduced carotid plaque, it reduced intimal medial thickness or the IMT. We talk about that when we talk about CIMT or the ultrasound tests I like that measure this thickness of the artery wall. And it even dropped LDL cholesterol about 18% without a statin. So on paper, this is the largest trial of natokinase that was ever conducted, and it was a big deal. This is how I got to know about natokinase, and this is the trial that made me try it for my patient, Susan, because it was new evidence, it was a big trial, it was published in an open access journal, and it made good sense to me, right? It seemed like it would do all the right things. And in particular, for a patient who had elevated APOB, I thought this might be a really exciting new avenue to pursue. Let's now talk a little bit about the paper itself, because in fact, the more I read it, there are some structural problems with how this study is designed, and it's important to understand these. First of all, this is a retrospective series of patients. It's not actually a trial. Uh, the you have no idea who got nato kinase or why. It just reports a thousand plus patients who did get it. And the how the dose was chosen is actually unclear. There was a subset of patients in this trial who got 3,600 FU per day. Most people got 10,800, but you don't know who got which dose or why they chose that, or how many patients were supposed to be in a trial. You don't have any power analysis, so you don't know if there was any way to detect change, which is in fact not necessary because there's no control group. So you can't detect a change. Um, that's not true. You can do pre and post. But the point here is there's no placebo group. There's not even a standard therapy group. There's just 10,000 uh a thousand patients that took this medicine. Okay. And so every change that you see in this trial, it's open label, right? Everybody knows they're getting the medicine is possibly regression of the mean. It's other lifestyle changes, it's patients doing other things because now somebody's paying attention to their plaque. And we just don't know what is related to the supplement itself versus what happened because people were being studied, right? Um, when you measure something, it will change, right? The minute you start measuring things, you begin to notice a difference whether it is your intervention or just the fact that you're measuring it. The last piece of this trial that's a big confounder is that some patients had vitamin K2 and aspirin also co-administered. We don't know who got that and why, but some people did and some people didn't. And they do break that out in the analysis a little later in the paper. But again, this is a big confounder. And uh, if you've seen the vitamin K piece we just uh released, you'll understand that there's some activity of vitamin K in the vascular system. So this is a big problem for the paper. The next piece that's interesting is that there's something of a conflict of interest here. If you look at the byline, meaning the authors of this study, about half of them work for Sungen Bioscience, who manufactures the nato kinase supplement that was used in the paper. And the issue about dosing may also be part of this. I am not certain about that. Um, certainly the established dose of 2,000 fibrinolytic units is what had been standardized by the European Food Safety Authority. And this paper took a totally different turn and picked a wildly higher dose of 10,800 units FUs. And we don't know where that came from. Uh as far as I know, they kind of pulled that out of thin air. And maybe that's to sell more natokinase, maybe it's because they had a pilot study somewhere. I don't know, but it's a little bit of a concern. If you go back to 2017, there is actually another paper that also supports reduction in plaque with natokinase. But a couple of things. One, only the abstract is available in English. The whole rest of the paper is published in Chinese. So I don't exactly know what it says. All I have is the abstract. And it's also the same research group. It's the same university. So it's not clear to me at all that this is uh a replicated finding. Rather, I think it's part and parcel, potentially, of the same study. This is, they say, randomized. You don't actually know what that means. They say randomized picking method, but I don't know. Does that mean they put names in a hat and pick them out? It's not a random number generator. I don't really what that means. And they um were not actually randomized to placebo, they were randomized instead to symphostatin as the control arm. And what they don't tell you is when they did the image analysis. So this was, you know, we had some people on natokinase, we had some people on symphostatin. We treated them for a period of time and then we looked with carotid ultrasound and we measured the plaque volume and the you know medial thickness. What they don't say is whether the ultrasound technicians were blinded to the treatment arm, right? You can have a significant amount of bias in your outcomes if your imaging texts aren't blinded. And it would be great if those studies were adjudicated in a central imaging lab where everybody was blinded, but I have no knowledge of whether they did that or not. So I have big concerns with how the imaging was done and the blinding or not uh in this particular study. Finally, let's just talk about this 36% reduction because that's an enormous number. And again, these are um relative risk reduction, right? They measured this in hundreds, tenths and hundreds of a millimeter in terms of plaque volume. So 36% sounds enormous. Uh, when you reduce something by half a millimeter, it's actually not as significant, really. And I will say that the symvostatin group was reduced by 11%. So everybody's plaque regressed a lot. And what I mean by a lot is if you take into consideration what we see when we have regression, plaque regression in sort of the most aggressive medical management trials that we have. And most of those involve intensive lipid lowering in addition to other gold-directed medical therapy. But the amount of plaque regression we see in our most intensive trials is typically less than 5%, right? It's not that big. And you should think for a minute, if we had something that actually reduced plaque by 36%, don't you think that everybody would be on top of that and prescribing it and like all over it? Um, I and yeah, I get it. Some of you are gonna say, well, it's you know, there's no financial interest in it. Of course, it's gonna be suppressed by big pharma and big medicine. And okay, I fine. But I just would like to point out that if the effect were really this big, I think this would be getting commercialized in a big way if everybody really believed that this were true. So the fact that I have not seen anybody pursue this as a bigger pharma molecule tells me uh people aren't necessarily buying this. The next piece about nato kinase is that many people will say that there is a signal for APOB reduction or LDLC reduction, right? Our atherogenic, nasty lipid particles that may or may not be causing trouble in the artery wall, but probably do cause some trouble if you already have plaque. The studies on this are actually very mixed. Okay. In randomized trials, we don't see a huge signal for a drop in the atherogenic or problem-causing lipid particles, the APOB molecules. Um, Yangin 2009 was there was a six-month RCT, did not find a significant change with natokinase by itself. And another study in 2009 said blood lipids were unaffected. There have been a couple of observational studies that showed that at lower doses you might actually get worsening of lip of the atherogenic lipids like APOB particles. And at higher doses, maybe you had a neutral or even a negative effect. Um, so the signal isn't nothing, but it's certainly not a consistent lowering of APOB. I do not have any confidence that at any dose we are going to see significant reductions in APOB. And I don't talk about this formally with the with the deck later, but Susan did not see any significant reduction in her APOB either after her year of high dose nato kinase therapy. And the other thing I'll point out is that many of these trials have been studied alongside red yeast rice, which is a natural supplement and it's one that actually the statins were based off of, right? They have this monocolin K molecule, which is identical to Lovastatin. So if you're taking red yeast rice or you're one of a thousand patients in China in this observational study that are doing a bunch of different things to optimize your uh cardiovascular health, and you're just thinking, what else could I do for myself? Maybe you're taking some red yeast rice on the side. So if your cholesterol is moving on natokinase, maybe that's related to the natokinase, but maybe it's related to other things that people are doing on their own with other supplements. Um could be citrus bergamot, could be berberine, could be any number of other things that people are doing on their own outside of a controlled environment that could be reducing their cholesterol. Okay. So I it's not that I don't believe that there was an 18% drop. It's just that I don't know whether this was truly related to the nato kinase. And there's not a good mechanism for it, right? We talked about all the things that I think natokinase does, but none of those are actually specific to lipid uh metabolism, right? They're related to clotting and clot busting pathways. They're even related to the blood pressure pathways and the um anti-itensin converting enzyme, but there's not actually a huge signal for lipid metabolism in what we know that nato kinase does. So it doesn't surprise me that overall, in the good controlled trials, our signal for a change in lipids is null. So again, I mentioned this when we talk about these two papers that come out of the uh Sun Yat-sen University in China. They're all based on ultrasound. And you know how much I love a good CIMT test, especially the tech detection of plaque, right? This is a big deal, and I am really excited about how sensitive CIMT is to small changes in the artery wall and inflammation there. But if you're gonna use plaque as the measurement to go for, just be aware that the plaque, because it is a three-dimensional structure, is the one that is most susceptible to a measurement error on the part of the sonographer or bias in the part of the sonographer. It is very easy to not quite get the peak of that plaque and measure it in a different way. So when I interpret a CIMT report and there is a change in plaque volume, that is the least reliable measurement on that report for me. Really, plaque is like a yes-no thing, and I'm interested in the quality of the plaque, right? Is it soft, echogenic, is it in the middle, heterogeneous? Those are the most important things to me, but I don't pay a huge amount of attention to whether it's 4.9 millimeters or 4.8 millimeters. Like the difference in that, um, based on how we do that test, is not that sensitive. The IMT, for reasons we can talk about in another video, is exquisitely sensitive, okay, because we make hundreds of measurements to get the one IMT number. It looks like one number, but it's actually the average of hundreds of measurements that we have gotten out of our way to make sure are as precise as we can make them. So looking at IMT, very helpful. Looking at total plaque volume based on ultrasound, not that helpful. If you're gonna look at total plaque volume, I would really much rather we did that with a CT-based modality. Okay, so when we're looking at these studies and they're saying plaque difference based on ultrasound, you know, again, when we're not blinded, I just don't have a lot of confidence that that's real. So to sum this up, we have two studies out of China that are showing us reduction in plaque with nato kinase. But one of them might have been randomized. I don't know. It's not clear exactly how their randomization was gonna work. The other is not actually even a trial, it's just a retrospective series. Neither of them had a placebo arm. The 2017 paper was. Compared against Symphostatin. The 2022 paper was just pre and post. As far as we know, the ultrasound texts were not blinded, they were not centralized. And so there's a lot of possibility for bias there. We don't have any idea whether there were pre-registered endpoints for this trial, meaning, did the study team say at the beginning, here is our hypothesis, this is what we expect to find. And here is how we're going to power our study, how many patients we're going to enroll to determine this. And finally, these are both the same study group, right? The same university. So this, in my opinion, has not been independently replicated outside of China or outside this one university. Okay, that doesn't make it wrong, but it means it's interesting and it's hypothesis generating. It does not mean that I'm going to take this as fact. And I want to talk a little bit about harm here because there is this idea that nato kinase must be totally safe. And what I will absolutely tell you up front is that in the randomized controlled trials that have been done looking at blood pressure and the NAPS study, which we'll talk about here in a minute, that actually did look at CIMT and atherosclerosis progression, all at the 2000 FU dose, none of those tests, or sorry, none of those studies showed any harm. There were no adverse events that were mentioned in those trials. And it seems to be safe, at least at these lower doses. The papers that have studied higher doses also didn't report any adverse outcomes. What we know is that this molecule is active in our clotting pathway. And at higher doses, it might create enough of an effect that you could actually truly thin the blood. And if you're already on blood thinners, you might get even more blood thinning than you bargained for. What we have are a number of case reports of adverse events. Now, is this related to the natokinase itself? Nobody knows. Okay. Again, randomized controlled trials at lower doses, we do not see any issues. We do see that coagulation factors move, right? If you give people a dose of natokinase, you'll test their blood levels of the anti-clotting factors and they change, but they stay in the normal range. At these low doses, you don't move your clotting cascade to a place where it tests as abnormal. It's different, but it's not abnormal. At higher doses, unclear because I haven't seen those data for anything in the 8,000, 10,000, 14,000 FU range where people are just taking this stuff. Okay. But here are the case studies that did show harm. There was one bleeding episode in a patient that was already taking aspirin. She was also taking natokinase and ended up with a cerebellar hemorrhage. A second study, excuse me, a second patient had bleeding on natokinase alone and developed bleeding in her abdomen. The third patient, perhaps thinking that because natokinase moves all of these clotting factors in our body and should be a blood-thinning agent, decided to substitute natokinase for their prescription blood thinner, warfarin or cumidin. And this patient had an artificial heart valve and developed clot on the heart valve, because in fact the nato kinase that that patient was taking was not strong enough to thin the blood to prevent clot from forming on the heart valve. So, all this to say, you don't really know what's going on. Or is your blood too thin? Is it not thin enough? We don't have any idea because we're guessing when we're taking this stuff, if we're not very proactive about measuring levels, testing our blood, testing our imaging to make sure that we are really doing what we're trying to do. Finally, if you have heard me talk about supplements before, you know supplements are regulated very differently than medications. All right. There is a dose that's on the bottle, but you don't know if that's what you're getting. And there's actually been Danny Curtin from Natural Informant. I will link his uh channel in the description for us, but he's done a couple of videos testing various natokinase brands and supplements. And here is uh just one of the figures from his video showing a almost fourfold difference in what you're getting versus what's advertised on the label. Um, all of the ones here were actually overdosed. I think I have seen another video of his where he tested some other brand and there was almost no activity in some of them. It's the Wild West. What I'll say about this is that for as far as I'm concerned, these data are only actually applicable to the specific batch that was tested here. The same brand, when they make a new batch, could have a wildly different outcome if we tested it again. It's not bad. I'm just telling you, supplements are imprecise at best. Okay, you may not be getting what they say you're getting. Are they adding reg yeast rice to it? You don't know. It's not been third-party tested much of the time. So if you have stuff, make sure it's third-party tested, make sure it's a high-quality brand that doesn't have anything else in there to derail your progress. Okay. Finally, there was an excellent randomized controlled clinical trial called NAPS. It was the uh natrokinase atherothrombotic prevention study. This was run by Howard Hotis. He, Dr. Hotis is a cardiologist out of USC, and he is an incredible researcher. And um, I think almost everything he publishes is gold. And they did a study using natokinase, again, based on all of this promise. And they have a very well-respected centralized imaging lab that has done CIMT quite a bit for years and years and years. So they studied over 250 patients for three years. They did carotid ultrasounds every six months, and this was blinded and placebo-controlled. Their primary outcome was change in CIMT or carotid intimomedial thickness and arterial stiffness. They found nothing. No change in CIMT, not even a change in blood pressure, no change in coagulation factors. So totally null study at the standard 2000 FU dose that has been shown for blood pressure in other studies in the past. So, in my mind, this is the best trial we have, at least at low doses, and it didn't show anything over a fairly long study period, right? Three years. Uh, that should be enough to really see some change at lower doses if we were going to see anything at all. Now, the usual rebuttal for this is that NAPS just use the wrong dose, right? 2000 FU just doesn't do anything. We have to go to a higher dose because, well, that's what the Chen study in 2022 used. They used the 10,800 fibroanalytic unit dosing. And so obviously that's just a dosing problem. We have to go higher. I get the point, but where is the dose response curve? Show me the study that looked at escalating doses and found that we had to go to a higher dose. What's the threshold? Is it 6,000? Is it 8,000? Is it 10,000? Nobody knows, okay? Is it possible that a higher dose could matter? Absolutely. Absolutely that's possible. And I completely acknowledge that, but we don't have the data, okay? 2,000 FU is what we know for blood pressure. We see no effect on CIMT at that dose based on Dr. Hodas' study. Um, some coagulation studies have gone up to 4,000, but the 10,000 study is really just the Chen paper. So whether it needs to be higher or whether that is just a spurious finding in a large retrospective series of a thousand patients, we don't know. So it's not that I'm ignoring the possibility that a higher dose is helpful. I just need to see better data for it and safety data for it. Because again, if our doses are going to go higher, I'm expecting more impact on our clotting factors. And that could change the safety signal that, you know, we say, well, it's very safe. Oh, it's been safe at the 2000s. I don't know about 10,000 because again, we only have one paper out of one center. So let's come back to Susan. I was excited. I will absolutely tell you, I was very excited about this paper in 2022 when it came out. I wanted to test it. Susan wanted to test it, so we did. We put her on 10,000, it might have even been 12,000 uh for a year. We did this for a whole year and then we measured. So I had a baseline CIMT and we repeated it one year later. We also repeated her labs. I told you we didn't see any change in her Apo B. But if the Chen study was right, I was hoping that her IMT would shrink or get smaller. And if Dr. Hodas was right, then maybe we'd see nothing. So here's what we found. Her CIMT progressed from 0.72 millimeters, the baseline test, to 0.81 millimeters. Um, that was a significant progression in the span of a year. What I'm showing you in the dotted line is what I would have expected for the average person with natural age-related progression and CIMT. She had a five-fold faster progression in her pla in her CIMT, excuse me. Her plaque burden stayed the same. So we measured 3.3 millimeters of plaque both at baseline and one year later. So it didn't get worse, but it didn't get any better. But this change in her IMT gave her an almost decade increase in her arterial age. It took her from being about at or lower than her chronologic age to significantly higher than her arterial age. And again, she is on a metabolic protocol, right? Her fasting insulin is less than five. Her blood pressure is like 110. And she's exercising, she's sleeping, she does not have sleep apnea, she's got a great social connection, right? The only thing that really stands out about Susan is her lipid panel and the presence of plaque. So we had to sort of scratch our heads and say, I don't know that this is working. In fact, I'm pretty sure it's not. So we stopped because to get 12,000 FU a day was six capsules. That's a fair amount of nanokinase. Uh, most of the supplements in the US are sold at 2,000 per capsule. So um that was quite a bit. And again, I just didn't see any evidence that it was helping her. Nothing moved in a good direction. So I couldn't argue with that, right? That is hard evidence. Now, some of you are gonna say, that's an n equals one. I don't care. I believe the trial of a thousand patients over your n equals one, to which I say, absolutely, no problem. I get it, I understand. So if you're gonna do it anyway, and many of you will, that's okay. Here's what I would ask you to think about. There is real fibrinolytic activity, meaning breakdown of clot. So be aware of that. If you are taking other blood-thinning agents or antiplatelet agents, um, please be cautious and maybe talk to your clinical team about the safety of that and think about the dose of the natokinase that you're taking. If you have had any bleeding in your brain, I would really encourage you not maybe to take natokinase. And if you're gonna have surgery, you might consider stopping it prior to elective surgery. The studies for natokinase were so exciting and they encouraged me to give this a try. But having retested Susan at a year, I gotta say, that data caused me to stop. And that is how I think we should think about all of the supplements and new techniques and interesting things that show up in the wellness space. Because the signal for blood pressure is real for patients. It's modest, but it's there. And for now, everything else is still waiting to be replicated. So, what I want for you is if you're gonna try it, by all means, I totally encourage you to experiment with this, but test, all right? Don't guess. Don't show me this paper and say it's working for me because you don't know unless you have imaging. If you've got imaging that showed CIMT regression or plaque regression, please let me know down in the comments, okay? I want to hear about it. And I will always be enthusiastic about new ways to manage and fight cardiovascular disease, but our enthusiasm by itself is not enough. Okay, that is not evidence. So we need to be honest about how strong the data for any particular intervention is going to be, and honest about the potential for harm. And we never start something without a plan to retest and change our course of action if it's not going the way we want. If you guys have not watched the video on how I think about supplements in general, that is a great place to go next. And you may be interested in the recent deep dive we did on vitamin K. That is another video I will link for you here. Please go give that a watch. Share this with somebody who needs to hear it. And until next time, guys, please take really good care.