Nattokinase in a Test Tube: What Blood Type Did and Did Not Change
Primary research located and verified via PubMed.
Nattokinase is the enzyme that appears when soybeans ferment, and for about a decade it has been sold in capsules for circulation and clot prevention. A study published in February 2026 asked whether it dissolves clots equally well in everyone's blood, sorted by ABO blood group and by age. The question is a good one. What the answer can tell you about your own supplement cabinet is narrower than the headline suggests.
What happened in the test tubes
Researchers at Marwadi University in Gujarat, India collected 1,796 blood samples covering all eight ABO and RhD blood groups from people aged 10 to 70 [1]. They formed clots in the laboratory, added nattokinase, and timed how long each clot took to dissolve. They then repeated the exercise in a separate set of 562 samples from nine locations across India.
Dissolution time varied by blood group. The slowest average came from AB-negative samples from women aged 66 to 70, at 2,660 seconds. The fastest came from O-positive samples from men aged 31 to 35, at 1,510 seconds. Ranked fastest to slowest, the groups came out O, then B, then A, then AB. The researchers found a significant interaction between age group, ABO group, and RhD factor (p = 0.005). Adding sex as a fourth variable produced no significant interaction at all (p = 1.000), and the difference between the male and female averages was roughly nine seconds, so sex does not explain this result. The team also ran a computer simulation of how nattokinase binds to fibrin in the presence of the RhD protein, and they say themselves that the simulation needs experimental confirmation.
All of this happened in a test tube, which limits how far any of it can be taken. Blood was drawn from people, but nobody swallowed a capsule and no cardiovascular outcome was measured. The authors are direct about this and call for large-scale validation in living people. A clot in glass has no blood flow, no vessel lining, and none of the body's own clot-regulating machinery, all of which the authors list among the things their work did not assess.
What nattokinase has done in actual people
The human trial record is mixed, and it is more useful than the test-tube work.
The most rigorous Western trial is NATPRO, conducted at the Keck School of Medicine at the University of Southern California [2]. The researchers randomized 265 people with a median age of 65 and no clinical cardiovascular disease to nattokinase 2,000 fibrinolytic units daily or matching placebo, then followed them for a median of three years with serial carotid ultrasound. The result was null. Carotid intima-media thickness and arterial stiffness changed at the same rate in both arms, and there was no effect on blood pressure or on any laboratory measure. Carotid intima-media thickness is the thickness of the inner layers of the neck artery wall, measured on ultrasound.
A 2023 systematic review pooling six randomized trials in 546 participants found lower blood pressure with nattokinase: systolic pressure lower by 3.45 mmHg (95% CI -4.37 to -2.18) and diastolic lower by 2.32 mmHg (95% CI -2.72 to -1.92) [3]. The lipid results in that same analysis were less favorable at lower total doses, where total cholesterol and LDL were higher and HDL was lower than in control groups, and blood glucose rose slightly as well (mean difference 0.40, 95% CI 0.20 to 0.60). Those authors concluded that nattokinase is a reasonable adjunct for blood pressure and that the lipid question is unsettled.
A much larger Chinese study of 1,062 participants reported benefit at 10,800 fibrinolytic units daily and nothing at 3,600 [4]. It describes no placebo group, PubMed indexes it with the keyword "retrospective study," and several of its authors are employed by a nattokinase manufacturer, so I put it in a different evidence tier from NATPRO. Those two studies also disagree about the effective dose by a factor of five, so nobody has settled the dose question yet.
Blood-type personalization is the wrong lesson to draw from this
I can already see how this study will get used. A result sorted by blood group is an easy thing to turn into personalized dosing advice, and blood-type-based supplement marketing has been circulating for decades without much behind it. This paper supplies no support for that. It reports how quickly an enzyme dissolved a clot in glass, in samples from one region of India, with the authors themselves asking for human trials before anybody adjusts a dose.
What I take from it clinically is narrower and more practical. Clot formation and clot breakdown are one balanced system, and that system responds to sleep, movement, hydration, inflammatory load, and hormonal status long before it responds to a capsule. When somebody comes to me worried about circulation, my first questions are about how much they move during an ordinary day, what their blood pressure has been, whether something inflammatory is part of it, and what else they are already taking. Nattokinase is sold to support fibrinolysis. In case the term is new, fibrinolysis is the body's process of breaking clots down. A supplement with a modest effect on fibrinolysis comes after all of that, never instead of it.
Bleeding is the part to raise with whoever manages your medications
The most useful human finding about nattokinase concerns bleeding rather than plaque. In a randomized trial of 100 people with borderline-to-moderate high cholesterol, eight weeks of nattokinase produced significantly greater increases in collagen-epinephrine closure time (p = 0.001) and activated partial thromboplastin time (p = 0.016) than placebo [5]. Activated partial thromboplastin time and prothrombin time both measure how long blood plasma takes to form a clot. Collagen-epinephrine closure time is the bench test used to check whether aspirin is producing its antiplatelet effect. Prothrombin time also increased within the nattokinase group over those eight weeks, though the published abstract does not report that increase as significantly greater than placebo.
In plain terms, this enzyme measurably affects clotting in living people. That is the whole point of taking it, and it is also why it should be on your medication list rather than in the vitamin drawer.
So the practical steps here are about disclosure rather than dosing. If you take nattokinase or are considering it, put it on the written medication list you hand to every clinician, particularly if you also take aspirin, a prescription blood thinner, or anything else that affects platelets. Tell your surgeon or your dentist well ahead of a procedure, because they will want to know. If you have a bleeding disorder, are pregnant, or have had a bleeding event, have that conversation before starting rather than after. Because the supportive studies disagree about dose by a factor of five, I am not going to hand you a number.
References
Bhatt TC, Bishoyi AK. Discovery of age and blood group associated variability in nattokinase mediated thrombolysis and its relevance to cardiovascular management. Sci Rep. 2026;16(1). PMID 41654604. https://doi.org/10.1038/s41598-026-38130-5 (original AANP digest link: https://pmc.ncbi.nlm.nih.gov/articles/PMC12946258/)
Hodis HN, Mack WJ, Meiselman HJ, et al. Nattokinase atherothrombotic prevention study: A randomized controlled trial. Clin Hemorheol Microcirc. 2021;78(4):339-353. PMID 33843667. https://doi.org/10.3233/CH-211147
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. PMID 39076715. https://doi.org/10.31083/j.rcm2408234
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. PMID 36072877. https://doi.org/10.3389/fcvm.2022.964977
Yoo HJ, Kim M, Kim M, et al. The effects of nattokinase supplementation on collagen-epinephrine closure time, prothrombin time and activated partial thromboplastin time in nondiabetic and hypercholesterolemic subjects. Food Funct. 2019;10(5):2888-2893. PMID 31070609. https://doi.org/10.1039/c8fo02324g
A note before you go
This article is educational and is not medical advice. It does not diagnose anything, and no dose is recommended anywhere in it. Nattokinase affects clotting, which means it can interact with aspirin, prescription anticoagulants, antiplatelet drugs, and surgical procedures. Please do not start, stop, or change it on the strength of a blog post. Talk it through with the clinician who manages your cardiovascular care, and tell every clinician you see that you take it. Written by Dr. Joyce Knieff, ND, LAc, of Yggdrasil Naturopathic.
If this resonates with what you're experiencing and you'd like to explore a naturopathic approach, book a consultation with our clinic.
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