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A Supplement that Might Replace Many Drugs​

Nattokinase, a readily available, safe, inexpensive supplement, appears to have cardiovascular benefits that at first are hard to believe.​

I can’t do it. I just can’t stomach starting another heart disease article – as appears to be the custom – by wasting your time explaining the grim statistics regarding cardiovascular disease. They’re ugly. You know that.

What you need instead are solutions, solutions to thwart the many maddening things that can affect the operation of the heart. We should be able to maintain the working integrity of this biological pump, keep it beating strong, keep its pipes clear of gunk, and keep the blood that flows through it clean and fluid until we’re ready to leave this mortal coil either on our own terms or getting hit on the head by some other falling anvil of catastrophe, and not by something so mundane as faulty plumbing.

Sure, medical science has lots of answers. We’ve got lifestyle modifications (i.e., exercise and diet), psychological interventions (stress relief), surgical interventions, and drugs, all of which have shown varying degrees of success. We’ve also got supplements but mention any of them – other than maybe prescription fish oil or coenzyme Q10 – to most cardiologists and they’ll make a face, the same face they’d make if you held a small turd underneath their noses.

But there’s a relatively unknown supplement – at least in the Western world – that they should take a whiff of. It appears to be the medicinal utility player of all medicinal utility players as it’s antithrombotic (clot-busting), antihypertensive (blood pressure lowering), anticoagulant (blood thinning) and anti-atherosclerotic (plaque dissolving).

Its name is “nattokinase,” and some researchers think it has the potential to replace several prescribed heart medications while also ensuring that the hearts of healthy people stay healthy.

Nattokinase is an enzyme derived from Natto, a traditional Japanese food made from fermented soybeans that’s often eaten for breakfast. It’s pretty gross looking, at least to those that aren’t accustomed to it. It looks like zombified soybeans that leave long, cheesy strings of organic matter when you pull them apart with chopsticks.

Natto has been around for at least 2,000 years, and people who ate it regularly seemed to be less prone to developing heart disease. It wasn’t until 1987 that a team of Japanese researchers figured out that natto contained a potent fibrinolytic (clot-preventing) enzyme that they named nattokinase.

Since then, a relatively small number of compelling studies on both animals and humans have confirmed that finding, along with discovering that it also has the aforementioned antithrombic, antihypertensive, and anti-atherosclerotic properties.

I’ll readily admit that there hasn’t been enough research on nattokinase to cast all doubt as to its efficacy away, but there’s a reason for that – nattokinase can’t be patented. No one’s going to get rich off it, let alone be compensated for what they spent to conduct a study on it.

Nevertheless, the studies that have been done are pretty convincing, at least to me. Consider that there’s no other drug or supplement that possesses multiple CVD preventative and alleviating pharmacologic effects. What’s more, it can be taken orally in capsule form, it’s ridiculously inexpensive, and its safety record is, so far, impeccable.

Let’s take a relatively painless look at the supportive research.


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Clot formation is a common and serious pathology that’s the underpinning of heart disease, stroke, and embolisms. It’s why heart patients and people who want to avoid becoming heart patients use aspirin or various prescription blood thinners.

In 2016 (Fujita, et al.) studied the effects of nattokinase on chemically induced blood clots in the tails of rats. A relatively modest concentration of the enzyme wiped out 88% of the thrombi within 6 hours, while another rat study found that nattokinase extended the lives of mice with pulmonary thrombosis (Yang, 2013).

An early human trial found that oral administration was found to enhance clot-busting activity in the plasma (Sumi, 2004), while a more recent human trial found that two months of nattokinase administration reduced the levels of several clot-forming blood factors. Even a single dose of nattokinase significantly reduced levels of those clot-forming factors in just 4 hours (Kurosawa, 2015).

Nattokinase appears to destroy clots through several mechanisms. Most prominently, it leads to an increase in Tissue Plasminogen Activator (TPA), a potent clot buster that’s often administered to heart or stroke patients in hospital ERs. Nattokinase also kneecaps a serine-protease inhibitor known as PAI-1 (Plasminogen Activator Inhibitor-1) that plays a role in clotting. Lastly, nattokinase enhances the production of urokinase, another clot-dissolving agent.

Atherosclerosis is the primary cause of heart disease and stroke. The blood vessels clog up with organic and inorganic deposits, much the same as the pipes in an old house that doesn’t have a water softener. Nattokinase, however, appears to act as a medicinal Liquid Plumber.

Several animal studies show that supplementing with a dietary natto extract suppresses the thickening of the carotid artery when compared to control animals (Suzuki, 2003), while a recent human study found that daily nattokinase supplementation was an effective way to suppress the progression of plaques in people with atherosclerosis. Remarkably, this reduction was more significant than that seen with a daily dose (20 mg) of a common statin drug (simvastatin) (Ren, 2017).

Along the same lines, 26 weeks of nattokinase administration to human subjects significantly reduced serum triglycerides, total cholesterol, and LDL cholesterol – the holy trinity of causal factors in heart disease (Ren, 2017).

While the mechanisms behind nattokinase’s anti-atherosclerotic effects aren’t known, they’re thought to be through the combination of its antithrombotic, anticoagulant, antioxidant, and lipid-lowering properties.

When blood pressure is consistently high, it causes the heart to work all the harder while also weakening the integrity of the blood vessels. Eventually, your heart goes John Henry, Steel-Driving-Man and gives out, but not necessarily from doing hard work.

Nattokinase, however, appears to lower blood pressure. A randomized, double-blind study found that 8 weeks of nattokinase supplementation reduced both systolic and diastolic blood pressure by 5.55 and 2.84 millimeters of mercury, respectively (Kim, 2008).

A more recent study found similar results, with 8 weeks of nattokinase supplementation leading to beneficial changes in blood pressure in patients with hypertension (Jensen, 2016).

Again, the mechanism isn’t clear, but nattokinase is thought to inhibit angiotensin 1-converting enzyme, a substance that narrows blood vessels.

Lots of people take aspirin to prevent heart attacks, stroke, and atherosclerotic diseases, but studies comparing nattokinase with that old standby show it to be equal or superior to the task.

One study compared the two head-to-head, and nattokinase was found to have “excellent antiplatelet aggregation and antithrombotic activities in vitro and in vivo” (Jang, 2013). Another group found that nattokinase decreased fibrinogen (a blood clotting protein) levels in a cerebral ischemic model and concluded that nattokinase works in a similar way as aspirin (Park, 2012).

Still another found the enzyme to decrease blood cell aggregation and low-shear viscosity, which is exactly what aspirin does (Pais, 2006).


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One rather well-done double-blind study involving 265 individuals with a median age of 65.3 had disappointing results (Hodis, 2021) regarding nattokinase. Here, I’ll let them say it:

“After a median treatment of 3 years, nattokinase supplementation had no detectable effect on coagulation factors, fibrinolytic factors and platelet aggregation relative to placebo in NAPS (Nattokinase Atherothrombic Prevention Study).”

I’ll admit, at first, I was crestfallen. I nearly trash-canned the idea of writing this article. But then I started to think about it and re-read most of the studies. The one quoted above – the one that was dismissive of nattokinase – used only one dosage: 2,000 FU (FU is an unfortunate abbreviation for “fibrinolytic units,” which are a measure of a substance’s ability to break up clots).

Granted, 2000 FU is the recommended dosage in places like Europe, which is way ahead of the U.S. in its acceptance of nattokinase as a tool in the fight against heart disease, but it may not be the most efficacious dosage (even though some studies have shown promising results from that same allegedly small dosage).

Secondly, the study that dissed nattokinase consisted of healthy individuals, i.e., none of them had cardiovascular disease. As such, they may not have been representative of the population at large.

But never mind the latter shortcoming; it’s the former that deserves some additional scrutiny.

A newer study (Chen, 2022) of the effects of nattokinase, this one involving 1,062 individuals, directly challenged the findings of the 2,000 FU study. True, it wasn’t a randomized study, only a retrospective study, but the results were so compelling that the researchers felt they outweighed the study’s limitations.

In short, they compared lower dosages of nattokinase (3600 FU) with a dosage of 10,600 FU and found that the weaker dosage was ineffective, or at least not as effective as the higher dose. They point to many of the other studies of nattokinase and note that dosages have ranged by as much as tenfold, with some studies using as little as 1,200 FU.

However, when subjects were administered the 10,600 FU every day for 12 months, the dosage “effectively managed the progress of atherosclerosis and hyperlipidemia with a significant improvement in the lipid profile.” As evidence, they noted a significant reduction in the thickness of the carotid artery intima-media (the innermost two layers of the wall of an artery) and size of carotid plaques among the test subjects.

This improvement ranged from 66.5 to 95.4%, depending on the group (the patients with a higher success rate had combined the use of nattokinase with vitamin K2 and aspirin).

The dosage of 10,600 FU was not necessarily the minimum dosage needed to exert therapeutic effects, though. Another study done by some of the same authors (Ren, 2017) concluded the following:

“Our studies found that in patients with hyperlipidemia, nattokinase treatment of 26 weeks at 6,000 FU reduced total cholesterol, LDL-C, and triglycerides, and increased the level of HDL-C.”

Nattokinase appears to be remarkably safe. Rats have been given 1000/mg/k/day (100 times higher than an average human dose) for 28 days and then 90 days with no adverse effects. Human volunteers were given 10 mg/k/day for four weeks with no adverse effects. Another human trial had volunteers taking 4gkg/day for 30 days. Still nothing.

A lot of people who take a baby aspirin every day to ward off heart disease might be tempted to add nattokinase to the mix, and, if you recall, combining the two (along with vitamin K2) led to a superior reduction in atherosclerosis in a test group. However, aspirin is also a thrombolytic, and combining the two could theoretically lead to hemorrhagic stroke (bleeding in the brain).

While this doesn’t seem to be common, there’s at least one documented case of this in the medical literature (Chang, 2008), so I urge caution.

There’s one known contraindication, though: People who take Warfarin, Coumadin, Plavix, or any other prescription blood thinner shouldn’t take the nattokinase plunge without the advice and consent of their doctor.

I think you’ll agree that nattokinase appears to be a promising alternative in the prevention and treatment of cardiovascular diseases. Personally, I’ve given up taking a daily baby aspirin and instead take 6,000 FU of nattokinase a day in divided dosages. (Unfortunately, I can’t find any reliable research about whether capsules should be taken all at once or in divided doses, but instinct tells me to go the divided dosage route.)

One thing you should know is that a lot of nattokinase supplements are listed in milligrams per capsule instead of fibrinolytic units. No sweat. The conversion is easy. One hundred milligrams equals 2,000 FU, so, for example, I take two 100-mg capsules a day of Nattokinase.

However, before you decide to take the nattokinase plunge, there are a couple of things you should consider. First up, we still don’t know enough about nattokinase’s bioavailability or its metabolism. Researchers think it’s absorbed well enough, with peak levels occurring in about 13 hours. Despite the rather long time it takes for peak absorption, another study found that it reached peak thrombolytic activity in between 2 and 4 hours.

None of that should be a deal breaker, of course. It’s just that it would be nice to know these things if we’re about to lash our heart-health hopes onto a new supplement.

Also, as is often the case, we need more studies – a lot more studies. However, what’s out there so far looks really promising. I’ll let the authors of one nattokinase study conclude this article for me:

“In the near future, it is possible that patients with CVD may need only a single nattokinase pill to replace multiple drugs administered for the prevention and management of CVD, including tPA, antihypertensives, statins, aspirin, and warfarin. (Chen, 2018).”

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