Transcription
Can an enzyme from sticky soybeans actually help your heart? It's called nattokinise and it comes from natto, a fermented food eaten in Japan for centuries. This enzyme is gaining popularity because it helps break down blood clots and reduce plaque in arteries. Some studies show it even lowers triglycerides and improves cholesterol oxidation without the side effects of statins. It may also reduce inflammation and thin the blood, which is thought to support overall cardiovascular health. And while the science on metabolism is still early, there is some evidence it could even help with insulin sensitivity as well.
This is lecture 105 of the metabolic classroom. Looking to improve your own metabolic health? Visit insuliniq.com for courses, coaching, consultations, and a 10-day free community membership trial. To dive deep into the science behind metabolic health, become an insider at benbickman.com, where you'll enjoy my exclusive content, add free podcasts, live stream Q&A access, and more.
Welcome to the Metabolic Classroom. I'm Benjamin Bickman, a biomedical scientist and professor of cell biology. In this mini lecture, as I like to call them, we're exploring nattokinise. Nattokinise, an enzyme from natto, which is a fermented soybean dish from Japan. This has very recently gained a lot of fame for dissolving blood clots and boosting cardiovascular health. Over the course of the mini lecture, we're going to fake focus on its main claims, which is breaking down clots, supporting cardiovascular health, and even improving lipids and reducing inflammation. And throughout all of this, of course, we will rely heavily on the evidence that may support any of these claims. Um, and as always, of course, the evidence underpins everything I like to do within these many lectures. And thanks again for tuning in and being my honorary students. But let's just see whether any of these claims live up to the expectations with this increasingly famous enzyme.
All right. Now, let's talk about the enzyme itself. So nattokinace is an enzyme produced by the bacterium basilus subtillus and it is active during the fermentation of soybeans into what is called natto which is a very sticky very pungent but very staple food in Japan. For centuries natto has been a dietary mainstay in Japan linked to lower heart disease rates. And indeed, perhaps this is part of why in Japan, heart disease is just so consistently low. Maybe it's because of the broad widespread consumption of this heartalthy food.
Now, nattokinise, the enzyme, which is extracted from natto, is sold now as its own individual supplement. Typically, if you're buying the supplement, you're getting it or you're encouraged to get it at around the dose of 100 to 200 milligrams a day. Now, sometimes it'll be expressed as milligrams. Other times it'll be expressed as something called FUS, which makes it sound like I am insulting you a little bit or telling you where to go, but it's actually it stands for fibbronolytic units, fibbronolytic units or FU. And that is 2,000 to 4,000 fibbronolytic units daily. Anyway, pardon me. I I do have a lot of older brothers and I was raised in a home where everyone had a very rich sense of humor. Anyway, uh these this is the dose that is touted for its cardiovascular benefits.
Its primary claim to fame is, as I'm kind of alluded to, the ability to break down fibbrin. Now, I'm going to talk more about this in just a moment. Um, as I give you a little bit of a primer on blood physiology, but fibbrin is a mesh, this protein mesh or these little strings that form the binding part of the blood clot. Um, but because the nattokinise can break down the fibbrin, it makes it a very natural what's called thrombolytic agent. So, breaking down the blood clots, that's just a complicated term for that. Now, unlike the other compounds that are abundant in soy, some of which are good, some of which are maybe a little problematic, but all plants seem to have a little bit of both, nattokinise is very specific for targeting blood clots and vascular health, which are thought to be critical for preventing heart attacks and strokes, or helpful for preventing heart attacks and strokes, I should say. But let's explore the uh main actions of nattokinise namely the blood the clot dissolution or the dissolving of the clot as well as some of the effects on blood lipids and even inflammation.
All right. So the the main feature of nattokinise is the fibbrinolytic activity the ability to dissolve blood clots. To understand this let's talk a little bit about fibbrin. Now as I mentioned fibbrin is this stringy protein that forms if you will the scaffolding of the blood clots what is weaving around it when the blood when a blood vessel is injured the what's called the coagulation cascade which is just a series of one protein activating another protein activating another protein and so on. Eventually at the very end of this pathway or this cascade of events we have the conversion of a protein called fibbrinogen into fibbrin. Now just as a point of physiology whenever you hear of a protein with the suffix inogen it means it's the precursor form of what's going to become a more active version of that very protein. So at the end we have fibbrinogen which gets split apart into fibbrin the active version of the protein and then it's fibbrin which polymerizes or starts to kind of bind all together into a mesh that weaves around another type of cell in the blood called platelets. And then this weaving and meshing of platelets and fibbrin is what will ultimately trap the red blood cells and in blood uh in and prevent it from leaking out. This is what forms the stable clot to stop bleeding.
Now the mesh is vital for healing but can become harmful if clots persist in these thrombotic states or blood clot states. And you've of course you're familiar with blood clots and the risk of a blood clot becoming uh causing a heart attack or causing a stroke. Now nattokinace steps in by breaking down the fibbrin preventing or dissolving these clots from uh so preventing them from forming in the first place or more readily breaking them down. Now naturally there's a balance there. you need the ability to form some clots like you need to be able to stop bleeding but in instances where someone may be forming a clot too readily like causing a stroke then you definitely want to be able to break it down or stop it from ever happening. So to say all of this another way, nattokinise is helping the fibbrin either not form its stringy scaffolding or snip it apart more readily. And indeed nattokinace will work by directly degrading the fibbrin and boosting the body's clot degrading pathways.
Now one of the ways it does this indeed the primary way is by activating now you're going to hear a little bit of the lesson I just taught you. Um, it activates tissue plasmminogen activator which converts plasmminogen. Now you hear the inogen meaning that it's the inactive version of what it's going to turn into. So plasmminogen turns into plasmine which is kind of like scissors if you will that will snip apart the strings of fibbrin thereby letting the clot dissolve. So the platelets which had been forming kind of the bulk of the clot fiber and holding it all together and squeezing it all together as you cut apart the scaffolding or the strings now the platelets can just go on their way which helps the blood stop aggregating or locking up thinning the blood but also doing so without the risk of really heavy bleeding with other blood thinning medications like warerin or couadin. Warfin is one of the more common blood thinners, but one of the problems with these drug-based versions is that it might be a little too much of a good thing. And so it can be a little tricky to optimize the dose to help the blood not be too thin.
But the evidence supporting these effects is pretty solid. A 2015 study in scientific reports tested a single dose of 2,000 fibbrronolytic units. That was a a pretty modest dose in healthy individuals and found increased dimer levels. Now that's the first time you've heard that term dimer. When I teach these concepts to students, I share with them as I will with you that d-dimer is the is a sign in the blood of a clot breaking down. So when you think about the strings of fibbrin, when you come in with the scissors and start cutting them apart, those little fragments are what's called d-dimer. So it's a sign of clot breakdown. So within just hours of that dose, so this was a very quick effect. They gave guys they gave subjects this 20,000 unit dose and then within hours they were able to detect increased levels of this marker of clot breakdown. Another 2008 study showed that a higher dose 4,000 units daily for 8 weeks, so now it's a long-term study, reduced fibbrronogen levels by 9% in healthy adults, which is of course going to lower the clotting risk over time. So very real benefits um at pretty normal doses.
Now let's move on from the general clotting aspect which is the main one to the other claim that people will make with nattokinise which is that it just helps overall cardiovascular health because nattokinas's cardiovascular benefits do appear to go beyond just dissolving clots including targeting atherosclerosis the buildup of plaques in arteries particularly in the heart that can then lead to heart attacks and strokes if it's happening anywhere else. Two human studies highlight the potential to reduce plaques and have a generally favorable effect on vascular health. There's one study that comes to mind, a 2022 study that was published in Frontiers in Cardiovascular Medicine, which followed 1,00 a little over a thousand patients with confirmed corateed artery plaques. Um, and they followed them for over 12 months. So, what they were doing is looking at the corateed artery in the the vessels that are going up the neck. Now they had a group in a high dose which was a group taking just over 10,000 units of nattokinise daily and they actually saw a significant reduction in the plaque size in and what's called the intima media thickness. That's something called IMT. It's very commonly measured now. Uh and it's a measure of arterial wall thickening. And then they compared the changes in the plaque size and the IMT in people taking that 10,000 unit dose versus placebo. So there's a placebo group meaning it's a a randomized trial. They also had lower cholesterol um LDL and triglycerides even more importantly but even a slight boost in HDL suggesting that nattokinise is probably improving atherosclerosis risk with multiple lipid changes.
Now, you know of my somewhat indifference to LDL changes, but a reduction in triglycerides and an increase in HDL, that's going to improve the triglyceride to HDL ratio, which is one of the most consistent best markers or predictors for heart disease. Now, I'd mentioned there were two studies. So, let's talk about the second one. This one was much much smaller. It was just about 80 patients and they looked at corateed atherosclerosis again and they received a more modest dose but it was also coupled with a different group taking a statin which is uh one of the more common statins simveastatin and it was about it was a half a year so about a six-month study the nattokinise group experienced a 37% reduction in corateed plaque size and a significant reduction in IM MT in fact it outperformed the statin which reduced plaque size by only about 25%. So nattokinise also lowered cholesterol or I should say triglycerides which is the one I care most about. And as I noted earlier they found again a slight increase in HDL. So this suggests that this simple enzyme extracted from this Japanese staple can rival or even outperform some of the pharmaceutical equivalents. Of course, I would add all ideally or I suspect without any of the significant side effects that come with those pharmaceutical alternatives, but the findings are pretty impressive as reducing plaque size and arterial thickening improves blood flow and lowers cardiovascular risk.
Now, unfortunately, neither of these studies measured calcified plaque in the coronary arteries. what you've heard me talk before about the value of coronary artery calcium tests or CAC scans. I I would have loved to see that. It hasn't been done. I haven't been able to find any evidence. But the evidence that I just shared is certainly promising, very relevant in their own right. Uh and it does suggest an overall mechanism of improving heart disease. And just to put all that in perspective, heart disease continues to be the number one killer in much of the world.
All right, now let's talk a little more about how this might be happening by looking at specific effects on triglycerides and lipid peroxidation. I've already mentioned a couple human studies showing that nattokynise supplementation lowers triglycerides. Triglycerides is or are a critical marker of cardiovascular health. far better at predicting heart disease risk than just LDL cholesterol. But even beyond that, there could be evidence that nattokinise can help reduce lipid peroxidation, which is a very important factor in heart disease. Human studies show the ability to reduce triglycerides. I've cited some studies. Um, but the same 2022 study I mentioned earlier did report that significant drop in triglycerides. Another 2017 study showed the same in fact compared to statins that was the other study I just shared as well. So we can note the consistent reduction in triglycerides. Um part of the mechanism for this could be that nattokinise has been shown to boost the activity of an enzyme I've spoken about previously in different uh episode of the metabolic classroom called lipoprotein lipase. Lipoprotein lipase is important in this context because it clears triglycerides from the blood. Now there are no human studies to confirm the activation of LPL lipoprotein lipase. It is probably part of the mechanism though based on the other studies animal and cell studies. But nattokinise has also been shown to activate hormone sensitive lipase to help with the breakdown of stored triglycerides and even potentially have some inhibition of HMG COA reductase which is the main enzyme involved in the synthesis of cholesterol that is in fact the main target of statins but again nattokinace outperforms statins apparently when you actually are measuring the blood vessels themselves.
Now I'd mentioned lipid peroxidation. This is where fats in for example LDL molecules can get oxidized or to be more precise per oxidized and then become highly problematic. Just to put this in a little bit of perspective, I've mentioned a couple times my somewhat indifference to LDL as a marker of heart disease. There are many many studies to show that LDL is a terrible predictor. And yes, there are studies to show that it is a predictor. How can we reconcile some of this disperate data? Part of it could be the degree to which the LDL molecule has undergone some degree of peroxidation because peroxidation or oxidized LDL is much better statistically at following or tracking people who have an increased risk of heart disease. Well, natto extracts have been shown to reduce lipid peroxidation in rodents. So that's going to lower oxidized LDL which is thought to be so problematic because the oxidized LDL molecule will be rapidly engulfed or readily engulfed by macrofasages. And the more the macrofasages are eating these fat heavy lipoproteins the more they become really big very pro-inflammatory angry if you will foam cells that's just this particular version this fat loaded version of the macrofase and but the macrofase won't do that if it's just LDL that's not undergone some glycation or peroxidation but peroxidation in this case so again rodent studies to show that natto extracts reduce lipid peroxidation. Now the human studies are lacking in this. There's nothing in humans to confirm this effect that I was able to find. But it nevertheless suggests nattokinise may protect protect against oxidized LDL's harmful effects well by just reducing the peroxidation of LDL in the first place. But that becomes a very relevant mechanism if it is something happening in humans. So the combination of these things namely lowering triglycerides perhaps by activating lipoprotein lipase and the peroxidation reducing effects are very promising and it definitely would suggest a mechanism whereby nattokinise is able to ease the cardioabolic complications and thereby improve heart health. But again, we do need human data to confirm the rodent data that I'm relying on to come to some of those conclusions.
Now, what about some limitations as we near the end? Of course, nothing is a magic bullet and nattokinise isn't either. The strongest evidence for clot dissolution and cardiovascular benefits is the main thing. But some of the studies I mentioned here use natto, not the isolated nattokinise, which is what people are getting uh when they're getting supplements. So that can muddy some of the conclusions. The human trials are a little small, some are kind of short. the dose ranges by quite a bit, 2,000 units up to 10,000 units, which can make it a little difficult to pin down. Also, there are some concerns about bioavailability where a paper published just this year in 2025 showed that only about a quarter of the enzymes activity actually survives digestion. Now, there may be some future technology that is going to create some small peptides as that's becoming such a hot topic that can leverage that a little better. But in the meantime, you just have to be mindful of the fact that the quality of the supplement with nattokinise is probably going to be quite important and you're not going to be generally getting as much possibly as you think.
Now despite all of this uh the safety for the supplement is generally considered to be quite good with no toxicity seen at high doses in rodents where you can you know do a little more than you could in humans but there is still the risk of bleeding um having a hard time stopping bleeding and of course I'm not your physician but all the more reason to be very careful if you are on anti-coagulants or any kind of blood pressure medications. S.
Now before I finish, as you know, I'm always curious about metabolism and especially fat cells and insulin resistance. Some studies hint that nattokinise might influence atapost tissue and insulin sensitivity. In particular, a 2020 study found that nattokinise reduced fasting insulin and glucose in women with obesity and diabetes. So that suggests a potential insulin sensitizing effect. That was the only human study I could find. Animal work has shown that natto uh natto not nattokinise but the natto extract reduced fat cell size and lipid accumulation in obese rodents. So there could be something else happening at the fat cell that could be reflective of the increased activation of hormone sensitive lipase that I mentioned earlier. This is again a topic I've discussed previously, but hormone sensitive lipase is one of the key enzymes that tells the fat cell to break down its stored fats, releasing the triglycerides as fatty acids into the blood to ideally be burned, either burned for energy or even turned into ketones. But once again, some of this work I'm citing didn't use the pure nattokinise enzyme. And once again, the human data is a bit lacking. So some of what I've been talking about is a combination of clinical outcomes in humans with mechanistic insight from rodents. Um, but and the idea that nattokinise is directly improving fat cell health is of course a bit speculative still. For now, nattokinas's main stage is definitely the cardiovascular health as the human evidence is so supportive of it. not fat cells for now, but even some limited human evidence suggesting some improvements in insulin sensitivity, which of course is always going to be valuable.
Now, what does this mean for you? First, my recommendation, I always like to kind of default to whole food. So, if you are interested in trying this, I'd suggest maybe trying the natto, the the the actual food version of this, if you can acclimate to the pretty strong taste, very pungent, very strong. A small serving delivers nattokynise naturally. By that I mean you're going to be getting some dose, some level of the enzyme itself produced by the fermenting bacteria, but also you're going to get some of the complimentary amino acids and vitamins and minerals which may help the enzyme work a little better. If the supplements are your choice, then I mentioned the general doses earlier, 100 to 200 milligrams daily or in that lower range of the 2 to 4,000 units. That's what's been mostly studied. But again, one of the studies I shared with you had people going up to 10,000 units. But of course, check with your clinician, especially if you're on any other kinds of medications.
In conclusion, nattokinise is a fascinating enzyme with a strong track record for breaking down clots and supporting overall heart health. The ability that it's been shown to improve lipid status, particularly the potential to improve lipid peroxidation really does add to its complement of cardiovascular mechanisms, making it a potential natural ally for your vascular wellness and health. Thanks for listening and I hope learning. Remember, more knowledge, better health.
Looking to improve your own metabolic health? Visit insuliniq.com for courses, coaching, consultations, and a 10-day free community membership trial. To dive deep into the science behind metabolic health, become an insider at benbickman.com, where you'll enjoy my exclusive content, add free podcasts, live stream Q&A access, and more.