Supplement
Nattokinase
Blood pressure reduction in adults with pre-hypertension or stage 1 hypertension.
Nattokinase is made from fermented soybeans. In adults with mildly high blood pressure, studies found that it lowered blood pressure. That is the only use with good support. It did not lower cholesterol or shrink plaque in the neck arteries, and one pooled review found blood fats moved the wrong way. It breaks down blood clots in people, so it can raise bleeding risk in people with bleeding problems or recent surgery.
A letter describes the human evidence, not the product, the manufacturer, or the ingredient's worth.
See the full evidence record →Who responds: this record's trial reading reports no subgroup that identifies who responds.
Blood pressure in pre-hypertension and stage 1 hypertension at 2,000 FU/day. Tested and null for cholesterol and carotid plaque.
A grade describes the intervention that was tested. Where the product on the shelf differs from it, this says so.
How this letter has changed · latest: October 2026 · Corrected
Jensen et al. (PMID 27785095) reported a significant between-group difference for diastolic pressure only; the record said both. Hodis et al. (PMID 33843667) enrolled healthy people not selected for raised pressure, which the record now says. Li et al. (PMID 39076715) also found lipids moved in the unfavorable direction, now stated. A duplicated description of Yang et al. (PMID 19786378) was removed, along with a sentence about red yeast rice that no cited paper supported. A PubMed search found no new trial; the letter is unchanged.PMID 27785095 PMID 33843667 PMID 39076715 PMID 19786378
Every change to a letter on this site is dated and published. The full evidence log →
2,000 FU/day, which is the dose used in the trials that showed blood pressure reduction. Doses above roughly 4,000 FU/day have not been tested in any randomized controlled trial People are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect..
The trial dose of nattokinase is an activity, not a number of milligrams. The 2008 trial used 2,000 FU/day; the 2016 North American trial used 100 mg/day NSK-SD, a vitamin-K2-removed fermented soy preparation. Non-soy sources have no comparative data showing they are equivalent.
In the cited 8-week trial, one capsule was taken each morning (PMID 27785095). The summaries of the other cited trials do not state a time (PMID 18971533, PMID 33843667).
Checked against the full report for 1 of the 3 cited studies, and the published summary for the rest. What the cited trials did, not a schedule. Every supplement, by trial timing →
How to buy this: quality criteria, not a brand
2,000 FU/day for 8 weeks (Kim 2008). Jensen 2016 (PMID 27785095) used 100 mg/day of NSK-SD.
Adults with pre-hypertension or stage 1 hypertension. In normotensive low-risk adults, a 3-year randomized trial found no blood pressure effect.
Fibrinolytic units (FU) per serving. Milligram labeling alone does not tell you the studied dose.
Doses above roughly 4,000 FU, which no randomized trial has tested. Plaque-regression or cholesterol claims, which randomized trials did not support. Combination products with red yeast rice, where any lipid effect comes from monacolin K, a statin, not from nattokinase.
The grade and these criteria are set only from published human randomized controlled trials. EBL has no commercial relationship with any nattokinase seller and links to none from this page.
Active bleeding, recent surgery, and any bleeding disorder. Nattokinase has fibrinolytic activity in humans, so this is a genuine caution rather than a theoretical one. Soy allergy, since it is fermented from soybeans.
Anticoagulants and antiplatelets, including warfarin, heparin, the direct oral anticoagulants and aspirin. A single oral dose has been shown to shift human thrombolysis and anticoagulation markers, so the effect is additive and measurable rather than inferred, and this combination belongs with the prescriber. Antihypertensives: additive blood-pressure lowering. BTK inhibitors such as ibrutinib impair platelet function by a different route, so the two bleeding effects would sit on top of each other; no study of the combination exists.
Nattokinase shifts human clotting markers. A single oral dose of nattokinase measurably altered thrombolysis and anticoagulation markers in humans, so the anticoagulant caution rests on a measured effect rather than an inferred one. Kurosawa et al. (Scientific Reports, 2015; PMID 26109079): a single dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Hodis et al. (Clinical Hemorheology and Microcirculation, 2021; PMID 33843667): nattokinase atherothrombotic prevention study, a randomized controlled trial.
Nattokinase and ibrutinib: two bleeding routes, no combined study. Ibrutinib impairs platelet function, and in patients it produced unstable thrombus formation on collagen that acalabrutinib did not. A single oral dose of nattokinase measurably altered human thrombolysis and anticoagulation markers. The two act on bleeding by different routes. A PubMed search in September 2026 located no study giving nattokinase with a BTK inhibitor, so the combined effect is unmeasured. Bye et al. (Blood Advances, 2017; PMID 29296914): severe platelet dysfunction in lymphoma patients receiving ibrutinib, absent with acalabrutinib. Kurosawa et al. (Scientific Reports, 2015; PMID 26109079): a single dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.
Blood pressure, measured at baseline and retested at 8 weeks, which is the trial duration. Lipid panel is not a useful tracking target for nattokinase, since randomized trials show no lipid benefit.
Primary evidenceFive papers, each linked to its PubMed record.
Kim et al. (Hypertension Research, 2008, PMID: 18971533), randomized double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends. placebo-controlled trial, n=86 (73 completed), nattokinase 2,000 FU/day for 8 weeks in adults with untreated systolic pressure of 130 to 159 mmHg. Net change vs control: systolic -5.55 mmHg (95% CI -10.5 to -0.57) and diastolic -2.84 mmHg (95% CI -5.33 to -0.33). Jensen et al. (Integrated Blood Pressure Control, 2016, PMID: 27785095), randomized double-blind placebo-controlled multicenter North American trial, n=79 (74 completed), 100 mg/day nattokinase (NSK-SD) for 8 weeks: diastolic pressure fell from 87 to 84 mmHg with no change on placebo (P<0.05); a systolic reduction, larger in men, is reported without a between-group test. Li et al. (Reviews in Cardiovascular Medicine, 2023, PMID: 39076715), meta-analysis of 6 randomized controlled trials, n=546: systolic -3.45 mmHg and diastolic -2.32 mmHg vs placebo; the same analysis found total and LDL Low-density lipoprotein cholesterol, the cholesterol fraction most closely tied to plaque in the arteries. cholesterol higher and HDL cholesterol lower with nattokinase. NULL FINDINGS: Hodis et al. (Clinical Hemorheology and Microcirculation, 2021, PMID: 33843667), the Nattokinase Atherothrombotic Prevention Study, randomized double-blind trial, n=265, median age 65.3, nattokinase 2,000 FU vs placebo for a median of 3 years in healthy people without cardiovascular disease and at low cardiovascular risk, not selected for raised blood pressure. No significant difference in carotid intima-media thickness or carotid arterial stiffness, and no significant effect on blood pressure or any laboratory measure. Yang et al. (Asia Pacific Journal of Clinical Nutrition, 2009, PMID: 19786378), randomized double-blind placebo-controlled trial, n=47 hyperlipidemic patients, 6 months: after controlling for baseline levels, only the nattokinase plus red yeast rice group, not the nattokinase-alone group, differed from placebo in total cholesterol, LDL cholesterol and the total to HDL ratio. Nattokinase carries no lipid claim here.
Graded B rather than A because blood pressure is a surrogate biomarker A measurable sign in the body, such as a blood test value, used to track a condition or the effect of a treatment., which caps at Grade B under the EBL rubric regardless of trial quality. The evidence is not uniform. The meta-analysis of 6 trials supports a blood pressure reduction, but the longest and most rigorous individual trial (Hodis 2021, 3 years, n=265) found no blood pressure effect. The populations differ in a way that plausibly explains this: Kim 2008 enrolled subjects with pre-hypertension or stage 1 hypertension, while Hodis 2021 enrolled individuals at low cardiovascular risk without hypertension. The reasonable reading is that nattokinase lowers blood pressure in people whose blood pressure is elevated and does not in people whose blood pressure is normal. Two widely marketed claims are not supported. Carotid plaque regression: the only randomized trial to test this endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. (Hodis 2021) was null over 3 years. The frequently cited 10,800 FU plaque-reduction result is Chen et al. 2022 (Frontiers in Cardiovascular Medicine, PMID: 36072877), which PubMed indexes as a Journal Article and not as a Randomized Controlled Trial, which describes no randomization or placebo arm, which lists authors employed by a nattokinase manufacturer (Sungen Bioscience Co. Ltd.), and which carries a published erratum. It does not meet the EBL inclusion standard of published human randomized controlled trials and is therefore not used to support any grade. Cholesterol lowering: Yang 2009 found no lipid effect from nattokinase alone, and the Li 2023 meta-analysis found total cholesterol and LDL higher and HDL lower versus placebo. Grade upgrade to A would require a randomized controlled trial with hard clinical cardiovascular endpoints such as mortality or MACE Major adverse cardiovascular events: heart attack, stroke and cardiovascular death counted together as one trial outcome..
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These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. The grade on this page describes the strength of published human trial evidence in the populations studied. It is not a recommendation for any individual and is not medical advice. Starting, stopping or changing any supplement or medication is a decision for your physician.
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How EBL searched for the trials (1 search)
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nattokinase[tiab] AND (randomized[tiab] OR randomized[tiab] OR meta-analysis[tiab]) AND ("blood pressure"[tiab] OR hypertension[tiab])Grades move when new trials publish. A free monthly email lists every grade EBL moved, with the reason and the trial behind it: the sign-up is on the Evidence Log →