Supplements

Nattokinase

Updated · 19 sources

Nattokinase is an enzyme extracted from natto, a Japanese food made by fermenting soybeans with the bacterium Bacillus subtilis var. natto. It breaks down fibrin, the protein mesh that holds blood clots together, and is sold as a dietary supplement for “circulation” and heart health. The largest and longest placebo-controlled trial, the 3-year Nattokinase Atherothrombotic Prevention Study (NAPS), found no effect on artery-wall thickening, arterial stiffness, blood pressure or any laboratory measure.

Nattokinase is often promoted to people using anabolic steroids as a way to “thin” blood that has become thick from a high hematocrit (the share of blood made up of red cells). That claim does not hold up: dissolving fibrin does not reduce the number of red blood cells, and no human study has shown that nattokinase lowers hematocrit. Case reports link it to serious bleeding, especially when combined with aspirin or anticoagulants.

This page summarizes what the trials, case reports and regulators report. It is for education only and is not medical advice.

Property Detail
Type Subtilisin-like serine protease (a protein-cutting enzyme), 275 amino acids, about 27.7 kDa
Source Natto (fermented soybeans); produced by Bacillus subtilis var. natto
Discovered Described and named in 1987 by Sumi and colleagues in Japan
Potency unit Fibrinolytic units (FU); about 100 mg of the common NSK-SD ingredient equals 2,000 FU
Doses studied in trials 2,000 FU/day (NAPS, blood pressure trials); 8,000 FU/day (2026 cognition trial); 10,800 FU/day (retrospective Chinese study)
Pharmacokinetics One pilot study (11 people): enzyme detected in blood, with peak levels about 13 h after a 2,000 FU dose
Best-tested outcome No effect on atherosclerosis progression over 3 years (NAPS, 265 adults)
Hematocrit No study shows it lowers hematocrit or red cell mass
Main risk Bleeding, especially with aspirin, antiplatelet drugs or anticoagulants
US status Dietary supplement; not an FDA-approved drug
WADA status Not named on the 2026 Prohibited List

What it is

In 1987, Japanese researchers reported strong fibrin-dissolving activity in natto, about 40 plasmin units per gram, and named the responsible enzyme nattokinase. It also digested a laboratory substrate used to measure plasmin, the body’s own clot-dissolving enzyme (Sumi et al., Experientia 1987). Later work characterized it as a subtilisin-like serine protease of 275 amino acids and 27.7 kDa (Pais et al., Clin Hemorheol Microcirc 2006).

Supplements are purified extracts. A widely studied ingredient, NSK-SD, is a fermented soy extract from which vitamin K2 has been removed (Jensen et al., Integr Blood Press Control 2016). This matters because natto is a source of vitamin K2 (as menaquinone-7, MK-7), and natto-derived MK-7 supplements of 50 µg/day or more may interfere with oral anticoagulants such as warfarin (Schurgers et al., Blood 2007); see vitamin K2.

Clotting and fibrinolysis in brief

Clotting ends with the formation of fibrin strands that bind platelets and red cells into a clot. Fibrinolysis is the process that later dissolves fibrin; its breakdown products, such as D-dimer, are measured in blood. Nattokinase is proposed to act on this second step. It does not destroy red blood cells or reduce how many the bone marrow makes.

How it acts in the body

The best human data on what a dose does come from a small crossover trial. Twelve healthy young men took a single 2,000 FU dose of nattokinase (NSK-SD) or placebo (Kurosawa et al., Sci Rep 2015):

Marker Change after nattokinase
D-dimer Higher at 6 and 8 h
Fibrin/fibrinogen degradation products Higher at 4 h
Factor VIII activity Lower at 4 and 6 h
Antithrombin Higher at 2 and 4 h
Activated partial thromboplastin time (aPTT) Longer at 2 and 4 h

All values stayed within the normal range. The study shows measurable effects on clotting and clot breakdown, but it was a single dose in 12 people and did not test clinical outcomes.

Absorption

Enzymes are proteins and are usually digested in the gut, so whether nattokinase reaches the blood intact has been debated. In a pilot study, 11 healthy adults took one 2,000 FU capsule. An antibody test detected nattokinase in serum, with peak levels at about 13.3 hours after the dose and significant increases from 2 to 24 hours. The authors called for larger studies and noted that intact enzyme and active fragments still need to be distinguished (Ero et al., Altern Ther Health Med 2013). No standard half-life has been established.

Regulatory status

In the US, nattokinase is sold as a dietary supplement and is not approved by the FDA to prevent or treat any disease. A safety assessment of the NSK-SD ingredient found no mutagenic or chromosome-damaging effects in lab tests, no adverse effects in rats at up to 1,000 mg/kg/day for 90 days, and good tolerance of 10 mg/kg/day for 4 weeks in healthy volunteers (Lampe and English, Food Chem Toxicol 2016). These are toxicity studies, not tests of bleeding risk in people taking other blood thinners.

What the research shows

Atherosclerosis: the NAPS trial

NAPS is the largest and longest placebo-controlled nattokinase trial. Researchers at the University of Southern California randomized 265 adults with a median age of 65.3 years and no cardiovascular disease to 2,000 FU of nattokinase daily or a matching placebo (Hodis et al., Clin Hemorheol Microcirc 2021; ClinicalTrials.gov NCT02080520).

Outcome Result after median 3 years
Carotid intima-media thickness progression (artery-wall thickening, primary outcome) No significant difference vs placebo
Carotid arterial stiffness No significant difference
Blood pressure No significant effect
Blood rheology, coagulation, fibrinolysis, inflammation and metabolic labs No significant effect on any laboratory measure
Global cognition (registry results) Same change in both groups
Serious adverse events (registry results) 13 of 132 on nattokinase vs 15 of 133 on placebo

The authors concluded that nattokinase “has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk” for cardiovascular disease. The trial did not include people with high cardiovascular risk or those using anabolic steroids.

A Chinese study of 1,062 participants reported reductions in carotid wall thickness, plaque size and lipids at 10,800 FU/day for 12 months, and no benefit at 3,600 FU/day (Chen et al., Front Cardiovasc Med 2022). The authors described it in the full text as a retrospective study, not a randomized controlled trial, and several authors were affiliated with a biotechnology company, Sungen Bioscience. It cannot establish cause and effect.

Blood pressure

Study Design Dose Result
Kim et al., Hypertens Res 2008 Double-blind RCT, 86 Korean adults with prehypertension or stage 1 hypertension; 8 weeks (73 completed) 2,000 FU/day Systolic −5.6 mmHg and diastolic −2.8 mmHg vs placebo; lower renin activity
Jensen et al., Integr Blood Press Control 2016 Double-blind RCT, 79 North American adults with high blood pressure; 8 weeks (74 completed) 100 mg/day NSK-SD Diastolic 87 → 84 mmHg vs unchanged on placebo; larger drop in men
Hodis et al., 2021 (NAPS) 265 older adults, mostly normal blood pressure; 3 years 2,000 FU/day No effect
Li et al., Rev Cardiovasc Med 2023 (meta-analysis) 6 RCTs, 546 participants Various Systolic −3.5 mmHg, diastolic −2.3 mmHg

The short trials suggest a small blood pressure effect in people with raised blood pressure; the longest trial found none in a lower-risk group. These effects are smaller than those of standard drugs such as telmisartan or amlodipine.

Cholesterol

The same meta-analysis found that nattokinase did not lower cholesterol. At relatively low total doses, total cholesterol (mean difference +5.3 mg/dL) and LDL (+6.5 mg/dL) were slightly higher and HDL slightly lower (−2.8 mg/dL) than with placebo, and blood glucose rose slightly. Higher total doses showed no significant HDL or LDL change (Li et al., 2023). Several commercial products combine nattokinase with red yeast rice, so lipid effects in those trials may come from the statin-like monacolins rather than the enzyme.

Cognition

In a 2026 Chinese trial, 120 adults with symptom-free narrowing of brain or neck arteries took 8,000 FU/day or placebo for 6 months. Global cognition did not differ; an exploratory analysis found better visuospatial scores (Zhang et al., J Stroke Cerebrovasc Dis 2026).

Does nattokinase lower hematocrit?

This is the main reason many anabolic steroid users take nattokinase, so it is worth separating the claim from the evidence.

What hematocrit is. Hematocrit is the percentage of blood volume made up of red blood cells. Androgens stimulate red cell production. In a prospective study of 100 men performing an AAS cycle, mean hematocrit rose by 0.03 L/L (3 percentage points) and returned to baseline within 3 months after stopping (Smit et al., Andrologia 2022). A high hematocrit makes blood more viscous mainly because there are more red cells.

What nattokinase does. It acts on fibrin and clotting factors. Nothing in its known mechanism reduces red cell production or removes red cells from circulation.

What the studies show:

  • In a test tube, adding nattokinase to blood samples reduced red cell clumping (aggregation) and blood viscosity at low flow rates in a dose-dependent way (Pais et al., 2006). This was an in vitro study; it did not measure hematocrit and did not test people.
  • In NAPS, nattokinase for 3 years had no significant effect on blood rheology measures or any other laboratory value (Hodis et al., 2021).
  • We found no human trial that measured hematocrit or hemoglobin as an outcome of nattokinase, and none in people with erythrocytosis (high red cell counts) from testosterone or AAS.

So there is no evidence that nattokinase lowers hematocrit, and no evidence that it reduces the clotting risk linked to a high hematocrit. Adding an enzyme that promotes bleeding does not address the cause. Pages on related topics include EPO, iron, low-dose aspirin and rusfertide, a drug studied for high red cell counts in polycythemia vera.

Side effects and risks

Bleeding and clotting case reports

Placebo-controlled trials have not shown excess bleeding, but they were small and excluded people on blood thinners. Case reports describe serious events:

Report What happened
Chang et al., Intern Med 2008 A patient taking aspirin after a stroke developed bleeding in the cerebellum after 7 days of nattokinase 400 mg/day; MRI showed multiple cerebral microbleeds (tiny old bleeds)
Ramachandran et al., Cureus 2021 An older woman taking nattokinase developed bleeding into the abdominal cavity (hemoperitoneum) and died; the authors warned against its use
Elahi et al., Proc (Bayl Univ Med Cent) 2015 A patient with a mechanical aortic valve replaced warfarin with nattokinase; after nearly a year, a clot formed on the valve and required repeat valve surgery

The last case shows the opposite risk: nattokinase is not a substitute for proven anticoagulants. A 2025 review of anti-atherosclerotic supplements, including nattokinase, warned that their benefits “may be limited by bleeding risk or drug interactions” and that product quality varies (Dobre et al., Int J Mol Sci 2025).

Tolerability in trials

In NAPS, serious adverse events were similar in the two groups (13 of 132 vs 15 of 133) (ClinicalTrials.gov NCT02080520). The meta-analysis reported no notable adverse events in the six included trials (Li et al., 2023).

Interactions and cautions

  • Aspirin, clopidogrel and other antiplatelet drugs: possible added bleeding risk (see the cerebellar hemorrhage case).
  • Warfarin, apixaban, rivaroxaban and other anticoagulants: not studied together; the single-dose study showed a prolonged aPTT.
  • Fish oil and icosapent ethyl: both carry their own bleeding warnings; see fish oil and icosapent ethyl.
  • Surgery and injections: changes in clotting markers were still present 8 hours after one dose, the last time point in the Kurosawa study; how long effects last with daily use has not been defined.
  • Soy allergy: the enzyme is produced by fermenting soybeans.
  • Vitamin K2 content: whole natto is rich in vitamin K2, which interacts with warfarin; check whether a product is K2-free.

Nattokinase is a legal dietary supplement in the US. It is not named on the WADA 2026 Prohibited List. Methods that manipulate blood, such as transfusion, are prohibited separately, but an oral enzyme is not.

Key takeaways

  • A clot-dissolving enzyme from natto. Nattokinase breaks down fibrin; one 2,000 FU dose raised D-dimer and prolonged aPTT within normal ranges in healthy men.
  • The best trial was negative. NAPS (265 adults, 3 years) found no effect on artery-wall thickening, stiffness, blood pressure or laboratory markers.
  • Small blood pressure effects in short trials. Meta-analysis: about −3.5/−2.3 mmHg; no cholesterol benefit.
  • It does not lower hematocrit. No human study shows a reduction in hematocrit or red cell mass; the main supporting data are a test-tube viscosity study.
  • Bleeding is the key risk. Case reports include a brain bleed with aspirin and a fatal abdominal bleed; one patient who swapped warfarin for nattokinase developed a valve clot.
  • Untested in steroid users. No trial has examined nattokinase for any AAS-related problem.

Sources

  1. Sumi H, Hamada H, Tsushima H, et al. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet. Experientia. 1987;43(10):1110–1111. PubMed.
  2. Pais E, Alexy T, Holsworth RE Jr, et al. Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity. Clin Hemorheol Microcirc. 2006;35(1-2):139–142. PubMed.
  3. 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. PubMed.
  4. Ero MP, Ng CM, Mihailovski T, et al. A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose. Altern Ther Health Med. 2013;19(3):16–19. PubMed.
  5. Lampe BJ, English JC. Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. Food Chem Toxicol. 2016;88:87–99. PubMed.
  6. Hodis HN, Mack WJ, Meiselman HJ, et al. Nattokinase atherothrombotic prevention study: a randomized controlled trial. Clin Hemorheol Microcirc. 2021;78(4):339–353. PubMed.
  7. University of Southern California. Nattokinase Atherothrombotic Prevention Study (NAPS), NCT02080520: study record and results. ClinicalTrials.gov.
  8. Chen H, Chen J, Zhang F, et al. Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: a clinical study with 1,062 participants. Front Cardiovasc Med. 2022;9:964977. PubMed.
  9. 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. PubMed.
  10. Jensen GS, Lenninger M, Ero MP, et al. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial. Integr Blood Press Control. 2016;9:95–104. PubMed.
  11. Li X, Long J, Gao Q, et al. Nattokinase supplementation and cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials. Rev Cardiovasc Med. 2023;24(8):234. PubMed.
  12. Zhang K, Zhang X, Wang A, et al. Nattokinase supplementation for cognitive enhancement in asymptomatic intracranial/carotid stenosis: a randomized controlled trial. J Stroke Cerebrovasc Dis. 2026;35(1):108511. PubMed.
  13. Smit DL, Grefhorst A, Buijs MM, et al. Prospective study on blood pressure, lipid metabolism and erythrocytosis during and after androgen abuse. Andrologia. 2022;54(4):e14372. PubMed.
  14. Chang YY, Liu JS, Lai SL, et al. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467–469. PubMed.
  15. Ramachandran L, Aqeel A, Jafri A, et al. Nattokinase-associated hemoperitoneum in an elderly woman. Cureus. 2021;13(12):e20074. PubMed.
  16. Elahi MM, Choi CH, Konda S, et al. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis. Proc (Bayl Univ Med Cent). 2015;28(1):81–82. PubMed.
  17. Schurgers LJ, Teunissen KJ, Hamulyák K, et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007;109(8):3279–3283. PubMed.
  18. Dobre MZ, Virgolici B, Doicin IC, et al. Navigating the effects of anti-atherosclerotic supplements and acknowledging associated bleeding risks. Int J Mol Sci. 2025;26(20). PubMed.
  19. World Anti-Doping Agency. The 2026 Prohibited List (in effect January 1, 2026). 2025. WADA.