Nattokinase is an enzyme extracted from natto, the fermented soybean dish eaten across Japan for breakfast. That food origin is a genuine story — nattokinase is produced by the same Bacillus subtilis var. natto fermentation used to make natto itself, not synthesised in a lab. Brands abroad ask for it by name because of that story and because of a body of small human trials on blood-flow-related markers.
This guide is for brand owners planning a nattokinase product made in Japan. It covers what the human trials measured and found, the enzyme-activity unit the ingredient is specified in, a safety point worth knowing about anticoagulant medicines, the soy allergen question, and what to fix before asking for a quotation.
Health supplements are foods, not medicines, and are not a substitute for medical treatment. Nothing here is a claim that any product prevents, treats or cures a disease.
💬 Planning a nattokinase product made in Japan? We check the full formula against Japanese food law first. See Japan-made supplement OEM.
What the research shows
Small, short randomised trials and a 2023 meta-analysis report a modest reduction in blood pressure with nattokinase, but the largest and longest trial, 265 adults over a median of 3 years, found no difference from placebo; the evidence is mixed.
| Study | Design | Reported result |
|---|---|---|
| Randomised, double-blind, placebo-controlled trial, Hypertension Research 2008 (PMID 18971533) | 86 adults aged 20–80 with untreated systolic blood pressure 130–159 mmHg; nattokinase 2,000 FU/capsule daily for 8 weeks; 73 completed | Net change versus placebo: systolic blood pressure −5.55 mmHg (95% CI −10.5 to −0.57, p<0.05); diastolic blood pressure −2.84 mmHg (95% CI −5.33 to −0.33, p<0.05) |
| Randomised, double-blind, placebo-controlled, multicentre trial, North America, Integrated Blood Pressure Control 2016 (PMC5066864, PMID 27785095) | 79 enrolled, 74 completed adults with elevated blood pressure (systolic ≥130 or diastolic ≥90 mmHg), on no blood-pressure medication; nattokinase 100 mg/day (≥2,000 FU) for 8 weeks | Diastolic blood pressure fell from 87 to 84 mmHg with nattokinase versus no change on placebo (p<0.04); systolic blood pressure showed a within-group downward trend (144 to 140 mmHg, p<0.1) not significant between groups; von Willebrand factor fell 15% on nattokinase, a statistical trend (p<0.09) |
| Randomised, double-blind, placebo-controlled trial, Clinical Hemorheology and Microcirculation 2021 (PMID 33843667) | 265 adults, median age 65.3, without clinical evidence of cardiovascular disease; nattokinase 2,000 FU daily or placebo for a median of 3 years | Rate of change in carotid artery intima-media thickness and arterial stiffness did not differ from placebo; no significant effect on blood pressure or any laboratory measure |
| Systematic review and meta-analysis, Reviews in Cardiovascular Medicine 2023 (PMC11266782, PMID 39076715) | 6 randomised controlled trials, 546 participants | Systolic blood pressure mean difference −3.45 mmHg and diastolic −2.32 mmHg versus placebo; blood glucose slightly higher and, at lower total doses, total and LDL cholesterol higher in the nattokinase groups |
| Case reports cited in a 2018 narrative review, Biomarker Insights (PMC6043915, PMID 30013308) | Two published case reports: a patient on aspirin plus nattokinase (400 mg/day) with an acute cerebellar haemorrhage; a patient who substituted nattokinase for warfarin after a mechanical valve replacement and developed a thrombus | The reviewers concluded that potential drug interactions for nattokinase “are not currently known” and called for more data, particularly for patients also taking cardiovascular drugs |
Caveats worth keeping in view:
- Size and duration. The 8-week blood-pressure trials above enrolled well under 100 people each; the meta-analysis pooled only 546 people across 6 studies. The one longer, larger trial (265 people, median 3 years) found no effect on its carotid artery measures, blood pressure or laboratory measures.
- Funding. The 2016 North American trial was sponsored by the distributor of the nattokinase product tested. Authors reported no personal financial interest in the outcome. Read the funding line of any study you plan to cite.
- Mixed secondary findings. The 2023 meta-analysis also reported slightly higher total cholesterol and blood glucose in the pooled nattokinase groups — a reminder to read the whole paper, not only the headline blood-pressure result.
- Case reports, not trial data. The bleeding-related case reports above are single patients, not controlled trials, and both involved combination with another blood-thinning drug. They point to a caution, not a quantified risk.
Checked against the published abstracts on 12 October 2026.
What Japanese products say
Nattokinase appears in Japan’s Foods with Function Claims system with notifications tied to peripheral blood flow, alongside its long history as a component of an everyday fermented food.
Natto itself has been eaten in Japan for centuries with no special regulatory status beyond ordinary food. Nattokinase, extracted and concentrated from the same fermentation, is a different case: some Japanese products carry a Foods with Function Claims notification to the Consumer Affairs Agency, with function wording addressing peripheral blood flow. As with any Foods with Function Claims notification, the notifying business is responsible for the evidence behind its own wording, and the notification applies to that Japanese product in the Japanese market — it does not transfer to a different formulation, a different market, or a different claim.
Two points for a brand abroad:
- A Japanese notification is not a global endorsement. It is tied to a specific product, dose and evidence file submitted to Japan’s Consumer Affairs Agency. Your own market’s rules govern what you can say on your label.
- The food story and the function claim are two separate facts. Natto’s long food history in Japan is real and worth telling. A specific blood-flow function claim on a Japanese product is a separate, narrower regulatory fact that does not automatically apply to your product or market.
💬 Need an evidence summary for your regulatory adviser that separates the trial data from any Japanese notification wording? We prepare it with the manufacturing documents. Tell us your market.
Wording that stays on safe ground
Describe nattokinase by its food origin and what has been studied, never by a blood pressure, blood clot, circulation or cardiovascular outcome for the product.
| Safer wording | Wording to avoid |
|---|---|
| ”An enzyme from the traditional Japanese fermented food natto" | "Lowers blood pressure”, “dissolves clots”, “improves circulation” or any cardiovascular claim |
| ”Studied for fibrinolysis-related markers in small human trials” | Naming a disease it prevents, treats or cures |
| ”Contains nattokinase, specified in fibrinolytic units (FU), per serving" | "Clinically proven” without naming the study and its limits |
How nattokinase is formulated
Nattokinase is specified by enzyme activity in fibrinolytic units (FU), not by a plain weight amount, because its biological activity — not its raw weight — is what a study dose or a quality standard refers to.
1 FU is defined as the enzyme activity needed to break down a standard amount of fibrin (or, in some assay methods, to release a set amount of tyrosine) under fixed laboratory conditions. A Japanese industry association that certifies nattokinase raw materials sets a minimum raw-material potency of 20,000 FU per gram for certification and recommends a minimum daily intake of 2,000 FU — the same order of magnitude used as the daily dose in the trials above (2,000–8,000 FU/day). A material’s weight in milligrams says little on its own; ask the supplier for the FU/g assay result on the certificate of analysis, and specify the finished product’s daily FU content, not only its weight.
| Dosage form | Why brands choose it | What to weigh up |
|---|---|---|
| Enteric-coated soft or hard capsule | Common for enzyme ingredients, protects activity through the stomach | Shell material and dietary suitability |
| Hard capsule (non-enteric) | Simple, lower cost | Enzyme stability depends on the specific raw material’s processing |
| Tablet | Familiar format, low cost per serving | Heat and pressure during tableting can affect enzyme activity; confirm with the supplier |
Decisions that shape the specification:
- Potency (FU/g) and daily FU target. Fix the finished product’s daily FU content first, then work back to the raw-material amount needed, based on the supplier’s assay.
- Vitamin K2 content. Whole natto is very high in vitamin K2, and vitamin K2 is itself relevant to people taking the anticoagulant warfarin, since it works against warfarin’s mechanism. Nattokinase raw material is a separate, manufactured ingredient extracted from the fermentation broth, and its vitamin K2 content depends on the specific manufacturing process. Ask the supplier for the vitamin K2 assay result on the certificate of analysis for the exact material you plan to use — do not assume a figure without seeing the specification.
- Enteric coating or stability data. If the supplier claims the enzyme survives stomach acid, ask for the stability data behind that claim.
- Companion ingredients. Nattokinase is sometimes combined with other ingredients aimed at healthy ageing or vascular-support positioning. Every companion ingredient needs its own check against Japanese food law, and against the product-claim limits above — a companion ingredient cannot be used to smuggle in a blood pressure or circulation claim that nattokinase itself cannot carry.
A safety point worth flagging to customers
Because nattokinase has fibrinolytic (clot-related enzyme) activity, sources covering drug-supplement interactions note that people already taking an anticoagulant or antiplatelet medicine — for example warfarin or aspirin — should talk to their doctor before using a nattokinase product, due to a theoretical bleeding-risk interaction. This is sensible safety advice to carry on a label or in customer-facing material, worded as advice to consult a doctor — not as a claim that the product affects blood clotting, circulation or any disease.
The check that comes first
Every ingredient must be permitted in foods in Japan, or a Japanese factory cannot make the product.
Nattokinase itself, and natto more broadly, are established Japanese foods. The more common formulation question is the allergen declaration: nattokinase is derived from soybean, and soybean sits on Japan’s list of allergens businesses are recommended, but not legally required, to declare — a different rule from many destination markets, where soy is a mandatory allergen. Confirm your destination market’s own soy-labelling rule before finalising the label. See the Japan-made supplement OEM page, and compare with our astaxanthin and collagen peptide guides if you are building a combined healthy-ageing formula.
Before you ask for a quotation
A factory can quote accurately once the potency, the daily FU target, the form and the packaging are fixed.
- Nattokinase raw material and its assayed potency (FU/g)
- Target FU per daily serving, and servings per pack
- Dosage form, including whether enteric coating is required
- Companion ingredients and their amounts
- Your destination market’s soy-allergen labelling rule
- Countries you will sell in, and first order and annual volume
💬 Ready to design a Japan-made nattokinase product? Send us the concept — potency, daily FU target, form and the countries you will sell in.
Frequently asked questions
1. What is nattokinase, and how is it different from natto?
Nattokinase is an enzyme produced during the fermentation that makes natto, the traditional Japanese fermented soybean food. Natto is the whole food; nattokinase is one enzyme extracted and concentrated from that fermentation for use as a supplement ingredient.
2. Does nattokinase lower blood pressure?
Small, short randomised trials and a 2023 meta-analysis report a modest reduction in blood pressure with nattokinase versus placebo, but a 3-year trial in 265 adults found no effect on blood pressure, so the evidence is mixed. Describe nattokinase as studied for blood-flow-related markers, not as a blood-pressure product.
3. Why is nattokinase specified in FU rather than milligrams?
FU (fibrinolytic units) measures the enzyme’s actual activity, which is what the human trials dosed and what industry quality standards reference. A milligram weight alone does not tell you the activity level, so ask your supplier for the FU/g assay result.
4. Should people on blood-thinning medicine avoid nattokinase?
Sources covering drug-supplement interactions advise that people taking an anticoagulant or antiplatelet medicine, such as warfarin or aspirin, should talk to their doctor before using a nattokinase product, because of a theoretical bleeding-risk interaction. This is general safety advice, not a claim about what the product does to blood clotting.
5. Does nattokinase need a soy allergen declaration?
It depends on the market. In Japan, soybean sits on the recommended, not mandatory, allergen list. Many destination markets treat soy as a mandatory allergen, so confirm your own market’s rule before finalising the label.
Sources: “Effects of nattokinase on blood pressure: a randomized, controlled trial”, Hypertension Research 2008 (PMID 18971533); “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”, Integrated Blood Pressure Control 2016 (PMC5066864, PMID 27785095); “Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials”, Reviews in Cardiovascular Medicine 2023 (PMC11266782, PMID 39076715); “Nattokinase atherothrombotic prevention study: A randomized controlled trial”, Clinical Hemorheology and Microcirculation 2021 (PMID 33843667); “Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases”, Biomarker Insights 2018 (PMC6043915, PMID 30013308); Japanese industry association certification standard for nattokinase; Consumer Affairs Agency Foods with Function Claims notifications; Consumer Affairs Agency food allergen labelling guidance. Checked on 12 October 2026.