Nattokinase: effects and side effects, from 341 studies
Every human trial of nattokinase, read and reported: what it does for plaque, blood pressure and clotting, and where the best trial found nothing.
How it is supposed to work
Nattokinase is a fibrinolytic serine protease: an enzyme that cuts fibrin, the protein mesh a blood clot is built from. In a test tube it does this readily, which is where its reputation came from.
The step that has to hold for any of that to matter to you is the one in between. An enzyme taken by mouth meets stomach acid and digestive proteases, and most protein arriving there is taken apart into amino acids rather than absorbed intact. Whether enough nattokinase survives that journey, crosses the gut wall and reaches the bloodstream still folded and working, is the question the human trials are really testing.
What does the research on nattokinase say?
PubMed indexes 341 studies on nattokinase. Most of them cannot tell you whether it works in a person: 187 carry no human or animal label at all, which is laboratory work, methods papers and reviews, and 47 are animal only. That leaves 107 with a person in them. Something that dissolves fibrin in a dish, or in a rat, may do nothing in a human being.
So this analysis rests only on human evidence: 11 clinical trials and 2 systematic reviews. Every one of them is listed at the foot of this page with its PMID. Where a trial found nothing, that is reported here in the same detail as the trials that found something.
Nattokinase has a consistent, measurable effect on clotting factors and a modest effect on blood pressure. Its large effect on arterial plaque comes from studies of people who already had plaque. In healthy people with little plaque to remove, the best-controlled trial found no effect at all.
What is nattokinase and how does it work?
Nattokinase is a fibrinolytic serine protease extracted from natto, a Japanese food made by fermenting soybeans with Bacillus subtilis.
A review of its mechanism reports that it hydrolyses fibrin directly, converts endogenous prourokinase to urokinase, degrades plasminogen activator inhibitor (PAI-1) and raises tissue plasminogen activator (t-PA) [13]. That review does not compare its activity against pharmaceutical thrombolytics.
Is nattokinase a blood thinner?
This is where the human evidence agrees with itself most closely.
Does nattokinase lower blood pressure?
A few mmHg sounds small. In population terms it is not nothing, but it is also not a substitute for treating diagnosed hypertension.
Does nattokinase help with arterial plaque?
Now the trial that has to be read alongside those two.
Two things separate Hodis from Chen and Ren, and both are plausible: the participants were healthy and low-risk, so there was little established plaque to break down; and the dose was 2,000 FU, well under the 6,000-10,800 FU used in the trials that saw plaque change. These are reasonable explanations, not proven ones. What can be said with confidence is narrower than the headline number: the plaque evidence comes from people who already had disease, at high doses, in trials that were not double-blinded.
Note that 2,000 FU is not an inert dose in general. Kim 2008 found blood pressure effects at exactly that dose [5]. The threshold argument applies specifically to plaque.
Does nattokinase do anything for memory?
Does nattokinase lower cholesterol?
This is where the supplement literature is easiest to misread, so it is worth being exact.
Do not take nattokinase expecting lower cholesterol. Every human trial that found a lipid benefit used it alongside red yeast rice, and the one trial that separated them found nattokinase alone did nothing. Hsia 2009 also found lipids unaffected.
Does nattokinase prevent thrombosis?
What are the side effects of nattokinase?
Across every human trial identified, no serious adverse events were reported at doses up to 10,800 FU/day.
Chen 2022 recorded no noticeable adverse effects at 10,800 FU/day across 1,062 participants [1], and the Li 2023 meta-analysis reported no notable adverse events across its 6 trials [3]. Hsia 2009 reported none across 45 subjects [7]. Several other abstracts report no safety data at all, and are not counted here either way.
Cautions. Nattokinase measurably shifts fibrinolytic and coagulation markers [8][7]. Anyone taking anticoagulants should discuss it with a doctor and monitor accordingly. Anyone allergic to fermented soy should avoid it. There is insufficient data in pregnancy and breastfeeding.
What does the evidence support, and what not?
| Outcome | Strength of human evidence |
|---|---|
| Lowers fibrinogen, factor VII and factor VIII | Consistent across trials, though the largest is open-label |
| Shifts fibrinolytic markers after a single dose | Double-blind crossover, changes within normal range |
| Lowers blood pressure by a few mmHg | Meta-analysis of 6 RCTs plus an individual RCT |
| Reduces existing arterial plaque at 6,000-10,800 FU | Large effects, but from non-blinded studies of people with disease |
| Prevents atherosclerosis in healthy people at 2,000 FU | No effect, in the longest and best-controlled trial |
| Improves global cognition | No effect in the only RCT to test it |
| Lowers cholesterol on its own | Not supported; effects come from red yeast rice combinations |
How much nattokinase a day, and when to take it?
- Blood pressure: 2,000 FU/day was effective over 8 weeks [5]. That trial did not run longer, so it says nothing about maintenance.
- Existing plaque: 6,000 FU/day over 26 weeks [4] and 10,800 FU/day over 12 months [1] are the doses where plaque change was measured. 3,600 FU/day produced nothing in the same cohort.
- Above 10,800 FU/day: not tested. No claim is made.
Nattokinase is not a treatment for diagnosed cardiovascular disease, and nothing here should replace medical advice.
Sources
- 1.Chen H, et al. Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: a clinical study with 1,062 participants. Frontiers in Cardiovascular Medicine, 2022. PMID: 36072877↩
- 2.Hodis HN, et al. Nattokinase atherothrombotic prevention study: a randomized controlled trial (n=265, median 3 years). Clinical Hemorheology and Microcirculation, 2021. PMID: 33843667↩
- 3.Li X, et al. Nattokinase supplementation and cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials (6 RCTs, n=546). Reviews in Cardiovascular Medicine, 2023. PMID: 39076715↩
- 4.Ren NN, et al. A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia (n=82, 76 completed). Zhonghua Yi Xue Za Zhi, 2017. PMID: 28763875↩
- 5.Kim JY, et al. Effects of nattokinase on blood pressure: a randomized, controlled trial (n=86, 73 completed). Hypertension Research, 2008. PMID: 18971533↩
- 6.Zhang K, et al. Nattokinase supplementation for cognitive enhancement in asymptomatic intracranial/carotid stenosis: a randomized controlled trial (ICC-PACS, n=120). Journal of Stroke and Cerebrovascular Diseases, 2026. PMID: 41325794↩
- 7.Hsia CH, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects (n=45, open-label). Nutrition Research, 2009. PMID: 19358933↩
- 8.Kurosawa Y, et al. A single dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles (n=12, double-blind crossover). Scientific Reports, 2015. PMID: 26109079↩
- 9.Yang NC, et al. Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia (n=47). Asia Pacific Journal of Clinical Nutrition, 2009. PMID: 19786378↩
- 10.Liu X, et al. The effect of nattokinase-Monascus supplements on dyslipidemia: a four-month randomized, double-blind, placebo-controlled clinical trial (n=113). Nutrients, 2023. PMID: 37836525↩
- 11.Cesarone MR, et al. Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial (n=204). Angiology, 2003. PMID: 14565628↩
- 12.Gallelli G, et al. Data recorded in real life support the safety of nattokinase in patients with vascular diseases (n=153). Nutrients, 2021. PMID: 34199189↩
- 13.Weng Y, et al. Nattokinase: an oral antithrombotic agent for the prevention of cardiovascular disease. International Journal of Molecular Sciences, 2017. PMID: 28264497↩