By Dr. Matt Gianforte, D.C. | Functional Medicine Clinician
A blood pressure reading that keeps creeping up, cold hands, or a family history of heart trouble leads many adults to look up nattokinase benefits. The enzyme is sold as a natural way to support circulation, and the claims online range from careful to overstated. The research sits somewhere in the middle, and the safety side matters just as much as the benefits.
Nattokinase is an enzyme made when soybeans are fermented into natto, a Japanese food, and it can break down fibrin, the protein mesh that holds a blood clot together. Small trials suggest it may modestly lower blood pressure and shift clotting markers, but the longest trial found no effect on artery health in low-risk adults. Because it acts on clotting, it carries real bleeding risk for anyone on blood thinners or heading into surgery.
- Nattokinase digests fibrin and also supports the body's own clot-clearing system, called fibrinolysis.
- Two 8-week trials, and six trials pooled together, found modest drops in blood pressure compared with placebo.
- A 3-year trial that followed 265 healthy older adults found no effect on artery health or blood pressure.
- Most human studies used 2,000 fibrinolytic units (FU) a day, and most of them were small or short.
- Nattokinase does not replace a prescribed blood thinner, and combining the two may raise the risk of serious bleeding.
What Nattokinase Is and Where It Comes From
Those mixed findings make more sense once the source of the enzyme is clear. Natto is made by fermenting soybeans with the bacterium Bacillus subtilis, which makes the enzyme (Weng et al., 2017). Researchers in Japan first described the enzyme in 1987, after they found that natto broke down fibrin in lab testing (Sumi et al., 1987). Supplements list their strength in fibrinolytic units (FU), a measure of how active the enzyme is against fibrin rather than how much it weighs.
Natto is very rich in vitamin K2, with about 850 micrograms in a 3-ounce serving, according to the NIH Office of Dietary Supplements. Some nattokinase extracts have the vitamin K2 removed, including the one used in a North American blood pressure trial (Jensen et al., 2016). That background makes the research easier to weigh.
What the Research Says About Nattokinase Benefits
The research falls into three groups: short clotting studies, 8-week blood pressure trials, and one long trial of artery health. When 12 healthy young men took a single 2,000 FU dose, markers of clot breakdown rose within 4 to 8 hours. These changes all stayed within the normal range (Kurosawa et al., 2015).
Over 2 months at 4,000 FU a day, 45 people saw fibrinogen, factor VII and factor VIII, three proteins that drive clotting, fall steadily (Hsia et al., 2009). That study had no placebo group, so it shows a direction rather than proof. The blood pressure trials are stronger because they used a placebo.
In Korea, 86 adults with untreated, elevated blood pressure took 2,000 FU or a placebo for 8 weeks. Systolic pressure fell 5.55 mmHg more than with placebo (Kim et al., 2008). In a North American trial of 79 adults, average diastolic pressure fell from 87 to 84 mmHg in the group taking 100 mg a day, while the placebo group stayed at 87 (Jensen et al., 2016).
When researchers pooled six randomized trials with 546 people, they found average drops of 3.45 mmHg systolic and 2.32 mmHg diastolic compared with placebo (Li et al., 2023). The same review also found less welcome results. Lower total doses were linked to higher total and LDL cholesterol and lower HDL cholesterol, and blood sugar rose slightly compared with placebo.
The longest study gives the most sobering answer. In a double-blind trial, 265 adults with a median age of 65 and no heart disease took 2,000 FU or a placebo for a median of 3 years. Nattokinase did not slow artery wall thickening or stiffening, and it had no significant effect on blood pressure or any lab marker measured (Hodis et al., 2021).
Taken together, the research suggests nattokinase may modestly lower blood pressure in people whose readings are already elevated, while long-term benefits for artery health in healthy, low-risk adults have not been shown.
Most of these studies were small or short, and at least one was funded by a maker of the enzyme, so the results call for caution. Knowing what nattokinase acts on helps explain both its promise and its limits.
Root Cause: How Clotting Balance Shapes Circulation
Healthy circulation depends on a steady balance between forming clots and clearing them. When a vessel is injured, the body turns fibrinogen into fibrin, which forms a sticky mesh that seals the leak. Once the repair is done, the fibrinolytic system breaks that mesh down so blood can flow freely again.
A road crew offers a simple picture of this balance. The crew puts up barriers to protect a repair, then takes them down when the work is finished. If barriers go up too easily or come down too slowly, traffic backs up. In the same way, higher levels of the clotting proteins factor VII and factor VIII are linked to greater heart risk (Weng et al., 2017).
Nattokinase works on the cleanup side of the crew. It digests fibrin directly, it turns a precursor called prourokinase into urokinase, an enzyme that starts clot breakdown, and it breaks down PAI-1, a protein that normally slows fibrinolysis (Weng et al., 2017). Studies also indicate that the enzyme can be absorbed from the intestine after it is taken by mouth.
Blood thickness plays a part as well. In blood samples tested in a dish, nattokinase reduced red blood cell clumping and lowered blood thickness at slow flow (Pais et al., 2006). In 9 healthy men, hands warmed up faster after a cold water soak with nattokinase than with placebo (Nara et al., 2023).
Clotting balance is only one piece of circulation, though. Inflammation and insulin resistance also strain blood vessels, as this guide to insulin resistance and inflammation explains. That wider view shapes how nattokinase fits into a functional medicine plan.
A Functional Medicine Protocol for Using Nattokinase
Because nattokinase changes how blood clots, a functional medicine approach starts with safety and measurement. Practitioners typically work through these steps, so the enzyme is tested against real numbers.
- Review every medication and supplement with a clinician first, with special attention to blood thinners, aspirin and other products that affect bleeding.
- Record a starting point, such as a week of home blood pressure readings and any labs a clinician orders, which may include a lipid panel and hs-CRP.
- Choose one nattokinase product that lists its strength in FU, since most human studies used 2,000 FU a day.
- Take it as the label or clinician directs for about 8 weeks, which matches the length of the blood pressure trials.
- Recheck the same numbers, and stop and call a clinician if there is unusual bruising, bleeding gums, nosebleeds or dark stools.
- Tell any surgeon or dentist about nattokinase well before a procedure, so they can advise on timing.
Inflammation testing fits the second step, because hs-CRP adds context that blood pressure misses. This overview of C-reactive protein levels explains that marker. The table below shows how the main studies lined up on nattokinase dosage and results.
| Study | Who took part | Daily amount | Length | What happened |
|---|---|---|---|---|
| Kurosawa et al., 2015 | 12 healthy young men | 2,000 FU, single dose | 8 hours | Clot breakdown markers rose, within normal range |
| Hsia et al., 2009 | 45 adults, no placebo group | 4,000 FU | 2 months | Fibrinogen, factor VII and factor VIII fell |
| Kim et al., 2008 | 86 adults with elevated blood pressure | 2,000 FU | 8 weeks | Blood pressure fell more than with placebo |
| Jensen et al., 2016 | 79 adults with elevated blood pressure | 100 mg | 8 weeks | Diastolic pressure fell more than with placebo |
| Hodis et al., 2021 | 265 healthy older adults | 2,000 FU | About 3 years | No change in artery health or blood pressure |
Supplement Support for Circulation
Once a clinician has cleared it and the baseline numbers are recorded, the product is the next choice. Two nattokinase options and one omega-3 fit this protocol, and most people would pick only one of the nattokinase products.
Nattokinase 60 Capsules by XYMOGEN provides nattokinase as a fibrinolytic enzyme from fermented natto, dosed in FU, to support fibrin breakdown and healthy blood viscosity. The bottle is a 30-day supply at 2 capsules a day, and its label advises caution with anticoagulant medications. Shop Nattokinase 60 Capsules →
Nattokinase Pro by Enzyme Science is a high-potency nattokinase with enteric protection, so the enzyme is released in the intestine. Its label directs 1 to 2 capsules on an empty stomach between meals, and it is not recommended for people on blood thinners without provider guidance. Shop Nattokinase Pro →
Omega-3 fats take a different route, since EPA and DHA from supplements lower triglyceride levels, according to the NIH Office of Dietary Supplements. Omega MonoPure 1300 EC by XYMOGEN provides 1,300 mg of EPA and DHA per softgel in a monoglyceride form, with a label dose of 1 to 2 softgels daily. High doses of omega-3s may cause bleeding problems with anticoagulants, so pairing them with nattokinase is a question for a clinician. This guide to CoQ10 vs fish oil covers where omega-3s fit. Shop Omega MonoPure 1300 EC →
Supplements work best on top of healthy daily habits. Explore practitioner-grade supplement protocols at drmattgianforte.com.
Lifestyle Integration for Healthy Circulation
No enzyme can outwork daily habits, so the lifestyle side of the plan matters as much as the capsule. Regular movement keeps blood flowing, and short walks that break up long hours of sitting are an easy start. A plant-forward plate with vegetables, beans, nuts, seeds and whole grains supports the same goal.
People who enjoy natto as a food should keep its vitamin K2 content in mind. Anyone taking warfarin needs a steady vitamin K intake, because sudden changes can raise or lower the drug's effect (NIH Office of Dietary Supplements). Sleep and stress belong in the plan too, since both show up in blood pressure readings.
More products are gathered in the heart and blood sugar collection. Even with good habits in place, some situations call for a clinician before nattokinase is started.
When to See a Clinician: Bleeding Risk and Medications
The action that makes nattokinase interesting also makes it risky for some people. In one case report, a patient on aspirin after a stroke had bleeding in the brain after 7 days of nattokinase at 400 mg a day (Chang et al., 2008). Brain scans also showed several tiny earlier bleeds called microbleeds, which the authors believe made bleeding more likely.
The opposite mistake is just as serious. A patient with a mechanical heart valve swapped warfarin for nattokinase. After nearly a year, a clot formed on the valve, which then had to be replaced (Elahi et al., 2015). Reviewers also note that nattokinase, omega-3s, garlic and other heart supplements may be limited by bleeding risk or drug interactions (Dobre et al., 2025).
Nattokinase is not a substitute for a prescribed blood thinner. Don't stop or change prescribed medication without talking to your clinician.
A clinician should review nattokinase first in any of these situations:
- Taking an anticoagulant such as warfarin, or any other prescribed blood thinner.
- Taking aspirin or another antiplatelet medication, even at a low daily dose.
- Having a planned surgery, dental procedure or other procedure that could cause bleeding.
- Having a bleeding disorder, a past stroke or a past bleed in the brain.
- Already taking other supplements that may affect bleeding, such as high-dose omega-3s or garlic.
- Being pregnant or nursing, or taking several daily medications.
Sudden severe headache, weakness on one side of the body, chest pain or bleeding that will not stop need emergency care right away. Checking these points first keeps the protocol safe.
Conclusion: A Balanced View of Nattokinase Benefits
Nattokinase benefits are real but modest so far, with small blood pressure drops in 8-week trials and shifts in clotting markers. The longest trial found no benefit for artery health in healthy, low-risk adults, and bleeding risk rises with blood thinners, antiplatelets and surgery. The best use of the enzyme is a measured trial with a clinician, built on daily habits that support circulation.
Practitioner-grade protocols for cardiovascular support are available at drmattgianforte.com, formulated with the same clinical-quality supplements used in functional medicine practice. Explore the Protocol →
FAQ
What are the main nattokinase benefits?
The best-supported nattokinase benefits are modest drops in blood pressure in adults with high readings and shifts in clotting markers that favor clot breakdown. Long-term heart benefits have not been shown.
How much nattokinase should I take per day?
Most human studies used 2,000 FU a day, and one open study used 4,000 FU a day for 2 months. The right nattokinase dosage depends on the product label, other medications and bleeding risk, so it should be set with a clinician.
Does nattokinase lower blood pressure?
Two 8-week randomized trials found small drops in blood pressure with nattokinase compared with placebo, and pooled data from six trials agreed. The 3-year trial in healthy, low-risk adults found no blood pressure effect, so results may depend on the starting point.
Is nattokinase safe with blood thinners or aspirin?
Nattokinase should not be combined with blood thinners or aspirin unless a clinician approves it, because a case report linked that mix with bleeding in the brain. It should never replace a prescribed blood thinner either.
Should nattokinase be stopped before surgery?
Anyone taking nattokinase should tell the surgeon or dentist well before a procedure, because it affects clotting. The surgical team can then decide when to pause and restart it.
Is eating natto the same as taking nattokinase?
Not quite, because natto is also rich in vitamin K2, while some extracts have it removed. People taking warfarin should keep vitamin K intake steady and check with a clinician before adding natto.
References
- Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet. Experientia. 1987. PubMed 3478223
- Weng Y, Yao J, Sparks S, Wang KY. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. Int J Mol Sci. 2017. PubMed 28264497
- Kurosawa Y, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015. PubMed 26109079
- Hsia CH, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009. PubMed 19358933
- Kim JY, et al. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens Res. 2008. PubMed 18971533
- Jensen GS, Lenninger M, Ero MP, Benson KF. 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. PubMed 27785095
- Li X, et al. Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Rev Cardiovasc Med. 2023. PubMed 39076715
- Hodis HN, et al. Nattokinase atherothrombotic prevention study: A randomized controlled trial. Clin Hemorheol Microcirc. 2021. PubMed 33843667
- Pais E, Alexy T, Holsworth RE Jr, Meiselman HJ. Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity. Clin Hemorheol Microcirc. 2006. PubMed 16899918
- Nara N, et al. A single dose of oral nattokinase accelerates skin temperature recovery after cold water immersion: A double-blind, placebo-controlled crossover study. Heliyon. 2023. PubMed 37483751
- Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008. PubMed 18310985
- Elahi MM, Choi CH, Konda S, Shake JG. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis. Proc (Bayl Univ Med Cent). 2015. PubMed 25552810
- Dobre MZ, et al. Navigating the Effects of Anti-Atherosclerotic Supplements and Acknowledging Associated Bleeding Risks. Int J Mol Sci. 2025. PubMed 41155474
- NIH Office of Dietary Supplements. Vitamin K: Fact Sheet for Health Professionals. ods.od.nih.gov
- NIH Office of Dietary Supplements. Omega-3 Fatty Acids: Fact Sheet for Consumers. ods.od.nih.gov
This article is for education and isn't medical advice. Readers should talk with their own healthcare provider about their situation.
These statements have not been evaluated by the Food and Drug Administration. Products and information on this site are not intended to diagnose, treat, cure, or prevent any disease. Consult your healthcare provider before starting any supplement.
