Nattokinase has become one of those supplements that generates a lot of excitement in cardiovascular health circles. The claims are bold: it dissolves blood clots, lowers blood pressure, prevents atherosclerosis. But as someone who has spent time wading through the actual research, I can tell you the picture is more nuanced than the marketing suggests.

The enzyme comes from natto, a traditional Japanese food made by fermenting soybeans with Bacillus subtilis. If you’ve never encountered natto, it has a distinctive stringy texture and pungent smell that takes some getting used to. The Japanese have eaten it for centuries, and the idea that it might have cardiovascular benefits isn’t unreasonable given that Japan has relatively low rates of heart disease.

But there’s a significant leap between “this traditional food might be healthy” and “this isolated enzyme will prevent heart attacks.” Let me walk through what the clinical research actually shows.

What is nattokinase?

Nattokinase is a serine protease enzyme that researchers first isolated from natto in the 1980s. What makes it interesting is its fibrinolytic activity, meaning it can break down fibrin, the protein that forms the structural framework of blood clots.

In laboratory studies, nattokinase doesn’t just dissolve fibrin directly. It also activates other fibrinolytic enzymes in the body, including tissue plasminogen activator (t-PA) and pro-urokinase [1]. This creates a kind of cascade effect that theoretically makes it more potent than its direct action alone would suggest.

Compared to pharmaceutical clot-busting drugs like urokinase and streptokinase, nattokinase has a longer half-life in the blood. Those drugs work for maybe 20 minutes before they’re broken down. Nattokinase appears to remain active for 8 hours or more after ingestion [2]. Whether this translates into meaningful clinical benefits is another question entirely.

How much nattokinase should you take?

Nattokinase activity is measured in Fibrinolysis Units (FU), which tells you how effectively a given amount can dissolve fibrin in laboratory conditions. Most clinical trials have used doses between 2,000 and 5,000 FU per day.

The honest answer is that we don’t have enough data to determine an optimal dose. Researchers have used the 2,000-5,000 FU range because it seems to produce measurable effects without obvious safety concerns, not because anyone has systematically tested different doses to find the sweet spot.

What are the potential benefits of nattokinase?

1. May reduce thrombosis risk

Blood clots form when platelets and clotting factors come together in response to injury. This is normally protective, but when clots form inappropriately in arteries or veins, you get deep vein thrombosis, pulmonary embolism, heart attacks, or strokes.

An open-label trial followed 45 adults across three groups: healthy participants, those with cardiovascular disease, and dialysis patients. All took nattokinase (2,000 FU per capsule, two capsules daily) for two months. The study found that fibrinogen and clotting factors VII and VIII all decreased across all groups [1].

A separate double-blind, placebo-controlled trial in 12 healthy men found that nattokinase increased D-dimer and fibrin degradation products in the blood, indicating enhanced fibrinolytic activity. The effect lasted roughly 8 hours after a single dose [2].

My honest assessment: these results are interesting but preliminary. We’re talking about small studies measuring surrogate markers, not actual clinical outcomes like heart attacks or strokes. The 45-person trial wasn’t even blinded, which means placebo effects could have influenced the results. I wouldn’t take nattokinase expecting it to prevent blood clots based on this evidence alone.

2. May slow atherosclerosis progression

Atherosclerosis is the gradual hardening of arteries through plaque buildup. It progresses silently for decades before potentially triggering a heart attack or stroke.

A randomised controlled trial compared nattokinase to simvastatin (a common statin drug) in 82 patients with high cholesterol over 26 weeks. Researchers measured carotid artery intima-media thickness (CCA-IMT), a standard marker for atherosclerosis progression [3].

Both groups showed reduced CCA-IMT and smaller carotid plaques, but the nattokinase group actually showed greater reductions in these measures. Meanwhile, simvastatin was better at lowering LDL cholesterol, triglycerides, and total cholesterol. Interestingly, nattokinase increased HDL (the “good” cholesterol) more than simvastatin did.

This is one of the more promising studies on nattokinase, though it comes with caveats. The participants were Chinese, and we don’t know if the results would replicate in other populations. And comparing to simvastatin isn’t quite fair since statins have decades of outcome data showing they actually prevent heart attacks and deaths, not just surrogate markers.

3. May lower blood pressure

Hypertension affects roughly 1.3 billion people worldwide and contributes to an estimated 7.5 million deaths annually from heart disease, stroke, and kidney failure.

A randomised, double-blind, placebo-controlled trial enrolled 86 participants with prehypertension or stage 1 hypertension. After 8 weeks of taking 2,000 FU of nattokinase daily, the treatment group showed blood pressure reductions of 5.55 mmHg systolic and 2.84 mmHg diastolic compared to placebo [4].

Those reductions are modest but meaningful. For context, a 5 mmHg reduction in systolic blood pressure is associated with roughly a 10% reduction in stroke risk at the population level. However, we need larger trials and longer follow-up to know whether these effects persist and translate into actual cardiovascular event prevention.

If you have hypertension, nattokinase isn’t a substitute for proven treatments. But it might be worth discussing with your doctor as an adjunct approach, particularly if you’re already making lifestyle changes.

4. May improve cholesterol levels

Dyslipidaemia, particularly elevated LDL cholesterol, drives atherosclerosis development. Guidelines worldwide target LDL reduction as the primary treatment goal for cardiovascular risk reduction.

A randomised, double-blind, placebo-controlled study followed 47 patients with hyperlipidaemia for 6 months. Participants were divided into three groups: nattokinase alone, nattokinase combined with red yeast rice extract, and placebo [5].

The combination group showed improvements in all lipid measures starting from month one. By the end of the study, they had reduced triglycerides by 15%, total cholesterol by 25%, LDL cholesterol by 41%, and increased HDL cholesterol by 7.5%.

The nattokinase-only group didn’t show significant effects until month six, and the improvements were less dramatic than the combination group.

Here’s what I take from this: nattokinase alone isn’t particularly impressive for cholesterol. If you’re interested in natural approaches to lipid management, the combination with red yeast rice looks more promising. But red yeast rice contains monacolin K, which is chemically identical to lovastatin (a prescription statin), so you’re essentially taking a statin with extra steps. That comes with its own considerations, including the need for consistent dosing and monitoring for muscle problems.

5. May help shrink nasal polyps

This one surprised me. Nasal polyps are inflammatory growths in the sinuses that can cause chronic congestion, loss of smell, and recurrent infections. They’re typically treated with steroids or surgery.

An in vitro study found that nattokinase solution reduced the size of nasal polyp tissue through its fibrin-degrading properties. It also reduced the viscosity of mucus compared to saline [6].

I should be clear: this was a laboratory study, not a human trial. Applying an enzyme directly to excised tissue in a dish is very different from taking a capsule and hoping enough reaches your sinuses to have an effect. I wouldn’t take nattokinase for nasal polyps based on current evidence, but it’s an interesting area for future research.

Is nattokinase safe?

Nattokinase derived from natto has been part of the Japanese diet for centuries, so we have reasonable confidence in its safety when consumed as food. The fermented soybeans themselves are unlikely to cause problems for most people.

Supplement forms are a different matter. Most clinical trials have lasted only a few months, and we don’t have good long-term safety data. Within those shorter timeframes, nattokinase appears well-tolerated, with few reported side effects.

The main concern isn’t toxicity but rather the anticoagulant effects. Any substance that interferes with blood clotting carries bleeding risks, and those risks increase when combined with other blood-thinning agents.

Safety precautions (6 contraindications)

Pregnancy, breastfeeding, and children: We simply don’t have safety data for these populations. Without evidence that it’s safe, the prudent approach is to avoid it.
Bleeding disorders: If you have conditions that impair blood clotting, nattokinase could worsen bleeding risk. This includes haemophilia and von Willebrand disease.
Surgery: Stop taking nattokinase at least two weeks before any scheduled surgery. The anticoagulant effects could increase bleeding during and after the procedure.
Anticoagulant medications: The combination of nattokinase with blood thinners is potentially dangerous. This includes aspirin, clopidogrel, warfarin, heparin, enoxaparin, and NSAIDs like ibuprofen, naproxen, and diclofenac. Taking both could significantly increase bleeding risk.
Blood pressure medications or hypotension: Since nattokinase may lower blood pressure, combining it with antihypertensive drugs could cause blood pressure to drop too low. People who already have low blood pressure should be particularly cautious.
Liver or kidney impairment: We don’t know how impaired organ function affects nattokinase metabolism or clearance. Until we have safety data for these populations, it’s best to avoid it.

The bottom line

Nattokinase has some genuinely interesting properties. The fibrinolytic activity is real, and there’s biological plausibility for cardiovascular benefits. But biological plausibility isn’t proof of clinical benefit.

The human trials to date are small, short-term, and focused on surrogate markers rather than actual health outcomes. Nobody has shown that taking nattokinase prevents heart attacks, strokes, or cardiovascular death. Maybe it does, but we don’t have the evidence yet.

If you’re interested in trying nattokinase, it’s probably safe for most healthy adults at standard doses. But don’t treat it as a substitute for proven interventions like blood pressure medication, statins, or lifestyle changes. And absolutely discuss it with your doctor if you take any blood-thinning medications.

For another enzyme with blood-clot-dissolving properties, you might also look into lumbrokinase, which comes from earthworms and has a similar (though less studied) mechanism.

References

Hsia CH, Shen MC, Lin JS, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009;29(3):190-196. https://pubmed.ncbi.nlm.nih.gov/19358933/
Kurosawa Y, Nirengi S, Homma T, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479826/
Ren NN, Chen HJ, Li Y, et al. Efficacy and safety of nattokinase in patients with hyperlipidemia: a randomized controlled trial. Nat Med J China. 2017;97(26):2038-2042. https://pubmed.ncbi.nlm.nih.gov/28763875/
Kim JY, Gum SN, Paik JK, et al. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens Res. 2008;31(8):1583-1588. https://pubmed.ncbi.nlm.nih.gov/18971533/
Yang NC, Chou CW, Chen CY, et al. Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia. Asia Pac J Clin Nutr. 2009;18(3):310-317. https://pubmed.ncbi.nlm.nih.gov/19786378/
Takabayashi T, Imoto Y, Sakashita M, et al. Nattokinase, profibrinolytic enzyme, effectively shrinks the nasal polyp tissue and decreases viscosity of mucus. Allergol Int. 2017;66(4):594-602. https://pubmed.ncbi.nlm.nih.gov/28389065/
National Health Service. Complementary and alternative medicines. https://www.nhs.uk/conditions/complementary-and-alternative-medicine/
Mayo Clinic. Nattokinase. https://www.mayoclinic.org/drugs-supplements-nattokinase/art-20507494