Component
NSK-SD fermented soybean extract
30% fermented soybean extract powder and 70% resistant dextrin from corn starch, standardised to 20,000-28,000 FU/g, with vitamin K2 removed during manufacture to a specification of 0.1 ppm or less. This is the preparation used in most of the human trials recorded here.
19 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
What it acts on
Average diastolic blood pressure fell from 87 to 84 mmHg with nattokinase against no change on placebo over eight weeks, reaching 86 to 81 mmHg in males.
Experimental context and source evidence
- duration
- 8 weeks
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (79 enrolled, 74 completed, systolic 130 or above or diastolic 90 or above)
- exposure
- NSK-SD, 100 mg per day
- limitations
- Randomized, double-blind, placebo-controlled and multicentre, with industry sponsorship and several exploratory subgroup analyses. The dose is stated in milligrams, not FU, so it is not directly comparable with the 2,000 FU trials without the product specification.
- organism
- Human (79 enrolled, 74 completed, systolic 130 or above or diastolic 90 or above)
- plain_language
- Average diastolic blood pressure fell from 87 to 84 mmHg with nattokinase against no change on placebo over eight weeks, reaching 86 to 81 mmHg in males.
- primary_references
- 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. (2016) https://pubmed.ncbi.nlm.nih.gov/27785095/ DOI: 10.2147/IBPC.S99553
- route
- In vivo, oral
- tissue
- Arterial blood pressure
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1016–1016
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (79 enrolled, 74 completed, systolic 130 or above or diastolic 90 or above) · source_derived_draft · unverified_draft
Average diastolic blood pressure fell from 87 to 84 mmHg with nattokinase against no change on placebo over eight weeks, reaching 86 to 81 mmHg in males.
Complete structured claim and evidenceProthrombin time and fibrinogen showed no detected difference in the same study.
Experimental context and source evidence
- duration
- Single dose, sampling to 8 h
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (12 healthy young males)
- exposure
- NSK-SD, 2,000 FU single dose
- limitations
- A measured null in a twelve-person crossover, so absence of a detected effect rather than evidence of none. It contrasts with the eight-week study, where prothrombin time did rise within group.
- organism
- Human (12 healthy young males)
- plain_language
- Prothrombin time and fibrinogen showed no detected difference in the same study.
- primary_references
- A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. (2015) https://pubmed.ncbi.nlm.nih.gov/26109079/ DOI: 10.1038/srep11601
- route
- In vivo, oral
- tissue
- Plasma
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 906–906
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (12 healthy young males) · source_derived_draft · unverified_draft
Prothrombin time and fibrinogen showed no detected difference in the same study.
Complete structured claim and evidenceFactor VIII activity declined significantly at 4 and 6 h after the same single dose.
Experimental context and source evidence
- duration
- Single dose, sampling to 8 h
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (12 healthy young males)
- exposure
- NSK-SD, 2,000 FU single dose
- limitations
- Within the normal range. No direct proteolytic cleavage of factor VIII by purified nattokinase has been shown anywhere in the retrieved evidence, so the step producing this is unidentified.
- organism
- Human (12 healthy young males)
- plain_language
- Factor VIII activity declined significantly at 4 and 6 h after the same single dose.
- primary_references
- A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. (2015) https://pubmed.ncbi.nlm.nih.gov/26109079/ DOI: 10.1038/srep11601
- route
- In vivo, oral
- tissue
- Plasma
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 873–873
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (12 healthy young males) · source_derived_draft · unverified_draft
Factor VIII activity declined significantly at 4 and 6 h after the same single dose.
Complete structured claim and evidenceA single 2,000 FU oral NSK-SD dose produced anti-nattokinase immunoreactivity in serum that rose significantly from baseline between 2 and 24 h and peaked at about 13.3 +/- 2.5 h.
Experimental context and source evidence
- duration
- Single dose, sampling to 48 h
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (11 healthy adults, 5 male and 6 female, ages 21-65)
- exposure
- NSK-SD softgel, 2,000 FU, about 100 mg
- limitations
- No control group and a non-validated polyclonal rabbit anti-nattokinase capture ELISA. EFSA reviewed this study and noted the same limitations, adding that it did not assess the biological activity of nattokinase in blood. The authors themselves recommend that future work look separately for intact enzyme and for bioactive peptides.
- organism
- Human (11 healthy adults, 5 male and 6 female, ages 21-65)
- plain_language
- A single 2,000 FU oral NSK-SD dose produced anti-nattokinase immunoreactivity in serum that rose significantly from baseline between 2 and 24 h and peaked at about 13.3 +/- 2.5 h.
- primary_references
- A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose. (2013) https://pubmed.ncbi.nlm.nih.gov/23709455/
- route
- In vivo, oral
- tissue
- Serum
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 818–818
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (11 healthy adults, 5 male and 6 female, ages 21-65) · source_derived_draft · unverified_draft
A single 2,000 FU oral NSK-SD dose produced anti-nattokinase immunoreactivity in serum that rose significantly from baseline between 2 and 24 h and peaked at about 13.3 +/- 2.5 h.
Complete structured claim and evidenceActivated partial thromboplastin time was prolonged significantly at 2 and 4 h after the same single dose.
Experimental context and source evidence
- duration
- Single dose, sampling to 8 h
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (12 healthy young males)
- exposure
- NSK-SD, 2,000 FU single dose
- limitations
- Within the normal range. This is one of the two findings that make an additive effect with an antithrombotic drug biologically plausible.
- organism
- Human (12 healthy young males)
- plain_language
- Activated partial thromboplastin time was prolonged significantly at 2 and 4 h after the same single dose.
- primary_references
- A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. (2015) https://pubmed.ncbi.nlm.nih.gov/26109079/ DOI: 10.1038/srep11601
- route
- In vivo, oral
- tissue
- Plasma
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 895–895
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (12 healthy young males) · source_derived_draft · unverified_draft
Activated partial thromboplastin time was prolonged significantly at 2 and 4 h after the same single dose.
Complete structured claim and evidenceBlood antithrombin concentration was higher at 2 and 4 h after the same single dose.
Experimental context and source evidence
- duration
- Single dose, sampling to 8 h
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (12 healthy young males)
- exposure
- NSK-SD, 2,000 FU single dose
- limitations
- Within the normal range. A rise in an inhibitor is harder to explain by proteolysis than a fall would be.
- organism
- Human (12 healthy young males)
- plain_language
- Blood antithrombin concentration was higher at 2 and 4 h after the same single dose.
- primary_references
- A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. (2015) https://pubmed.ncbi.nlm.nih.gov/26109079/ DOI: 10.1038/srep11601
- route
- In vivo, oral
- tissue
- Plasma
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 884–884
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (12 healthy young males) · source_derived_draft · unverified_draft
Blood antithrombin concentration was higher at 2 and 4 h after the same single dose.
Complete structured claim and evidenceD-dimer concentrations rose significantly 6 and 8 h after a single 2,000 FU oral dose.
Experimental context and source evidence
- duration
- Single dose, sampling to 8 h
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (12 healthy young males)
- exposure
- NSK-SD, 2,000 FU single dose
- limitations
- Double-blind placebo-controlled crossover, but very small, with multiple time-point comparisons and no measurement of what was absorbed. All changes stayed within the normal reference range.
- organism
- Human (12 healthy young males)
- plain_language
- D-dimer concentrations rose significantly 6 and 8 h after a single 2,000 FU oral dose.
- primary_references
- A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. (2015) https://pubmed.ncbi.nlm.nih.gov/26109079/ DOI: 10.1038/srep11601
- route
- In vivo, oral
- tissue
- Plasma
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 851–851
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (12 healthy young males) · source_derived_draft · unverified_draft
D-dimer concentrations rose significantly 6 and 8 h after a single 2,000 FU oral dose.
Complete structured claim and evidenceFibrin and fibrinogen degradation products rose significantly 4 h after the same single dose.
Experimental context and source evidence
- duration
- Single dose, sampling to 8 h
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (12 healthy young males)
- exposure
- NSK-SD, 2,000 FU single dose
- limitations
- As above. Within the normal range.
- organism
- Human (12 healthy young males)
- plain_language
- Fibrin and fibrinogen degradation products rose significantly 4 h after the same single dose.
- primary_references
- A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. (2015) https://pubmed.ncbi.nlm.nih.gov/26109079/ DOI: 10.1038/srep11601
- route
- In vivo, oral
- tissue
- Plasma
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 862–862
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (12 healthy young males) · source_derived_draft · unverified_draft
Fibrin and fibrinogen degradation products rose significantly 4 h after the same single dose.
Complete structured claim and evidenceEFSA concluded that the information provided on absorption, distribution, metabolism and excretion did not allow conclusions to be drawn on the absorption of active nattokinase or any functional metabolites derived from it.
Experimental context and source evidence
- duration
- Dossier review
- evidence_access
- EFSA Journal opinion retrieved and read in full during this curation. Quoted figures are from the opinion text and its specification tables.
- experimental_model
- Regulatory assessment
- exposure
- NSK-SD, up to 100 mg/day
- limitations
- The Panel noted in the same passage that nattokinase has in vitro fibrinolytic activity and in vivo thrombolytic activity in animals when administered parenterally, which is the distinction this chapter turns on. An applicant assay of the softgel product at pH 2.0 mimicking gastric fluid was submitted; the opinion records that the results were provided but does not state what they showed.
- organism
- Regulatory assessment
- plain_language
- EFSA concluded that the information provided on absorption, distribution, metabolism and excretion did not allow conclusions to be drawn on the absorption of active nattokinase or any functional metabolites derived from it.
- primary_references
- Safety of fermented soybean extract NSK-SD as a novel food. (2016) DOI: 10.2903/j.efsa.2016.4541 Not indexed in PubMed.
- route
- In vivo, oral
- tissue
- Whole-body disposition
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 840–840
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Regulatory assessment · source_derived_draft · unverified_draft
EFSA concluded that the information provided on absorption, distribution, metabolism and excretion did not allow conclusions to be drawn on the absorption of active nattokinase or any functional metabolites derived from it.
Complete structured claim and evidenceNet changes of -5.55 mmHg systolic and -2.84 mmHg diastolic against placebo were reported after eight weeks at 2,000 FU per day.
Experimental context and source evidence
- duration
- 8 weeks
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (86 randomized, 73 completed, untreated systolic 130-159 mmHg, ages 20-80)
- exposure
- Nattokinase, 2,000 FU per capsule
- limitations
- Randomized, double-blind and placebo-controlled, but small and short, with industry affiliations. The confidence intervals reach close to zero (-10.5 to -0.57 and -5.33 to -0.33). No mechanistic mediator beyond plasma renin activity was measured.
- organism
- Human (86 randomized, 73 completed, untreated systolic 130-159 mmHg, ages 20-80)
- plain_language
- Net changes of -5.55 mmHg systolic and -2.84 mmHg diastolic against placebo were reported after eight weeks at 2,000 FU per day.
- primary_references
- Effects of nattokinase on blood pressure: a randomized, controlled trial. (2008) https://pubmed.ncbi.nlm.nih.gov/18971533/ DOI: 10.1291/hypres.31.1583
- route
- In vivo, oral
- tissue
- Arterial blood pressure
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 994–994
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (86 randomized, 73 completed, untreated systolic 130-159 mmHg, ages 20-80) · source_derived_draft · unverified_draft
Net changes of -5.55 mmHg systolic and -2.84 mmHg diastolic against placebo were reported after eight weeks at 2,000 FU per day.
Complete structured claim and evidenceThe net change in plasma renin activity was -1.17 ng/mL/h against placebo in the same trial.
Experimental context and source evidence
- duration
- 8 weeks
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (73 completers with elevated blood pressure)
- exposure
- Nattokinase, 2,000 FU per day
- limitations
- The only mediator measured in that trial. Its direction is not reproduced by the North American trial, where an exploratory low-renin subgroup moved the other way.
- organism
- Human (73 completers with elevated blood pressure)
- plain_language
- The net change in plasma renin activity was -1.17 ng/mL/h against placebo in the same trial.
- primary_references
- Effects of nattokinase on blood pressure: a randomized, controlled trial. (2008) https://pubmed.ncbi.nlm.nih.gov/18971533/ DOI: 10.1291/hypres.31.1583
- route
- In vivo, oral
- tissue
- Plasma
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1005–1005
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (73 completers with elevated blood pressure) · source_derived_draft · unverified_draft
The net change in plasma renin activity was -1.17 ng/mL/h against placebo in the same trial.
Complete structured claim and evidenceA decrease in von Willebrand factor was seen in the female participants taking nattokinase, at p < 0.1.
Experimental context and source evidence
- duration
- 8 weeks
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (74 completers with elevated blood pressure)
- exposure
- NSK-SD, 100 mg per day
- limitations
- Exploratory, sex-restricted and above the conventional significance threshold. It is the only human measurement in this chapter that touches the von Willebrand factor mechanism, which makes it worth recording and makes over-reading it easy.
- organism
- Human (74 completers with elevated blood pressure)
- plain_language
- A decrease in von Willebrand factor was seen in the female participants taking nattokinase, at p < 0.1.
- primary_references
- 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. (2016) https://pubmed.ncbi.nlm.nih.gov/27785095/ DOI: 10.2147/IBPC.S99553
- route
- In vivo, oral
- tissue
- Plasma
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1027–1027
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (74 completers with elevated blood pressure) · source_derived_draft · unverified_draft
A decrease in von Willebrand factor was seen in the female participants taking nattokinase, at p < 0.1.
Complete structured claim and evidenceAmong participants with baseline plasma renin activity below 0.29 ng/mL/h, 66% showed an increase after eight weeks against 8% on placebo, at p < 0.1.
Experimental context and source evidence
- duration
- 8 weeks
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human, exploratory low-renin subgroup
- exposure
- NSK-SD, 100 mg per day
- limitations
- A post-hoc subgroup at p < 0.1, in the opposite direction to the whole-group fall reported by the Korean trial. Recorded as a conflict rather than resolved.
- organism
- Human, exploratory low-renin subgroup
- plain_language
- Among participants with baseline plasma renin activity below 0.29 ng/mL/h, 66% showed an increase after eight weeks against 8% on placebo, at p < 0.1.
- primary_references
- 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. (2016) https://pubmed.ncbi.nlm.nih.gov/27785095/ DOI: 10.2147/IBPC.S99553
- route
- In vivo, oral
- tissue
- Plasma
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1038–1038
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human, exploratory low-renin subgroup · source_derived_draft · unverified_draft
Among participants with baseline plasma renin activity below 0.29 ng/mL/h, 66% showed an increase after eight weeks against 8% on placebo, at p < 0.1.
Complete structured claim and evidenceIn a 90-day oral study in Sprague-Dawley rats at 0, 100, 300 and 1,000 mg/kg body weight per day, the no-observed-adverse-effect level was 1,000 mg/kg per day, the highest dose tested.
Experimental context and source evidence
- duration
- 90 days
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Rat (Sprague-Dawley, 12 per sex per group)
- exposure
- NSK-SD at 21,900 FU/g, up to 1,000 mg/kg body weight per day
- limitations
- A NOAEL at the highest dose tested is a floor, not a ceiling. The material was non-mutagenic and non-clastogenic in vitro, and a 4-week human tolerance study at 10 mg/kg per day reported no problems. None of this tests interaction with antithrombotic drugs or long-term disease outcomes. This study and the regulatory opinion share the same applicant dossier and are not independent of one another.
- organism
- Rat (Sprague-Dawley, 12 per sex per group)
- plain_language
- In a 90-day oral study in Sprague-Dawley rats at 0, 100, 300 and 1,000 mg/kg body weight per day, the no-observed-adverse-effect level was 1,000 mg/kg per day, the highest dose tested.
- primary_references
- Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. (2016) https://pubmed.ncbi.nlm.nih.gov/26740078/ DOI: 10.1016/j.fct.2015.12.025
- route
- In vivo, oral gavage
- tissue
- Subchronic oral toxicology battery
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1379–1379
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Rat (Sprague-Dawley, 12 per sex per group) · source_derived_draft · unverified_draft
In a 90-day oral study in Sprague-Dawley rats at 0, 100, 300 and 1,000 mg/kg body weight per day, the no-observed-adverse-effect level was 1,000 mg/kg per day, the highest dose tested.
Complete structured claim and evidenceThere was no significant effect on blood pressure over the same three years.
Experimental context and source evidence
- duration
- Median 3 years
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (265 randomized, low cardiovascular risk)
- exposure
- Nattokinase, 2,000 FU per day
- limitations
- This is the direct contradiction of the eight-week blood-pressure trials and of the pooled estimate. The populations differ: these participants were low-risk and not selected for elevated blood pressure.
- organism
- Human (265 randomized, low cardiovascular risk)
- plain_language
- There was no significant effect on blood pressure over the same three years.
- primary_references
- Nattokinase atherothrombotic prevention study: A randomized controlled trial. (2021) https://pubmed.ncbi.nlm.nih.gov/33843667/ DOI: 10.3233/CH-211147
- route
- In vivo, oral
- tissue
- Arterial blood pressure
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1126–1126
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (265 randomized, low cardiovascular risk) · source_derived_draft · unverified_draft
There was no significant effect on blood pressure over the same three years.
Complete structured claim and evidenceCarotid arterial stiffness likewise did not differ from placebo over the same period.
Experimental context and source evidence
- duration
- Median 3 years
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (265 randomized, low cardiovascular risk)
- exposure
- Nattokinase, 2,000 FU per day
- limitations
- The co-primary endpoint of the same trial.
- organism
- Human (265 randomized, low cardiovascular risk)
- plain_language
- Carotid arterial stiffness likewise did not differ from placebo over the same period.
- primary_references
- Nattokinase atherothrombotic prevention study: A randomized controlled trial. (2021) https://pubmed.ncbi.nlm.nih.gov/33843667/ DOI: 10.3233/CH-211147
- route
- In vivo, oral
- tissue
- Carotid artery ultrasound
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1115–1115
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (265 randomized, low cardiovascular risk) · source_derived_draft · unverified_draft
Carotid arterial stiffness likewise did not differ from placebo over the same period.
Complete structured claim and evidenceThere was no significant effect on any laboratory determination, covering metabolic factors, blood rheology, coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage activation markers.
Experimental context and source evidence
- duration
- Median 3 years
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (265 randomized, low cardiovascular risk)
- exposure
- Nattokinase, 2,000 FU per day
- limitations
- The broadest measured null in the chapter, and it covers the same classes of marker that the short trials moved. Assay panels differ between studies, and a null over three years does not exclude a transient change hours after a dose.
- organism
- Human (265 randomized, low cardiovascular risk)
- plain_language
- There was no significant effect on any laboratory determination, covering metabolic factors, blood rheology, coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage activation markers.
- primary_references
- Nattokinase atherothrombotic prevention study: A randomized controlled trial. (2021) https://pubmed.ncbi.nlm.nih.gov/33843667/ DOI: 10.3233/CH-211147
- route
- In vivo, oral
- tissue
- Blood laboratory panel
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1137–1137
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (265 randomized, low cardiovascular risk) · source_derived_draft · unverified_draft
There was no significant effect on any laboratory determination, covering metabolic factors, blood rheology, coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage activation markers.
Complete structured claim and evidenceOver a median three years at 2,000 FU per day, the annualized rate of change in carotid intima-media thickness did not differ from placebo.
Experimental context and source evidence
- duration
- Median 3 years
- evidence_access
- Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
- experimental_model
- Human (265 randomized, median age 65.3, no clinical cardiovascular disease)
- exposure
- Nattokinase, 2,000 fibrinolytic units per day
- limitations
- Double-blinded and randomized, and by far the longest trial here. The null applies to this dose, this formulation, this low-risk population and these endpoints; it is not evidence that every product or dose is inert. It is also not an active-enzyme pharmacokinetic study.
- organism
- Human (265 randomized, median age 65.3, no clinical cardiovascular disease)
- plain_language
- Over a median three years at 2,000 FU per day, the annualized rate of change in carotid intima-media thickness did not differ from placebo.
- primary_references
- Nattokinase atherothrombotic prevention study: A randomized controlled trial. (2021) https://pubmed.ncbi.nlm.nih.gov/33843667/ DOI: 10.3233/CH-211147
- route
- In vivo, oral
- tissue
- Carotid artery ultrasound
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1104–1104
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (265 randomized, median age 65.3, no clinical cardiovascular disease) · source_derived_draft · unverified_draft
Over a median three years at 2,000 FU per day, the annualized rate of change in carotid intima-media thickness did not differ from placebo.
Complete structured claim and evidenceVitamin K2 is removed during NSK-SD manufacture, to a specification of 0.1 ppm or less, and was not detected in any of five analysed batches.
Experimental context and source evidence
- duration
- Not applicable
- evidence_access
- EFSA Journal opinion retrieved and read in full during this curation. Quoted figures are from the opinion text and its specification tables.
- experimental_model
- Product specification and batch analysis
- exposure
- NSK-SD, 30% fermented soybean extract and 70% resistant dextrin, 20,000-28,000 FU/g
- limitations
- This is the specification of one product. It does not describe crude fermentation powders or supplements from other manufacturers, and it is the reason natto and NSK-SD must be modelled separately in any question about vitamin K antagonists.
- organism
- Product specification and batch analysis
- plain_language
- Vitamin K2 is removed during NSK-SD manufacture, to a specification of 0.1 ppm or less, and was not detected in any of five analysed batches.
- primary_references
- Safety of fermented soybean extract NSK-SD as a novel food. (2016) DOI: 10.2903/j.efsa.2016.4541 Not indexed in PubMed.
- route
- In vivo, oral
- tissue
- Standardised fermented soybean extract
Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1357–1357
Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Product specification and batch analysis · source_derived_draft · unverified_draft
Vitamin K2 is removed during NSK-SD manufacture, to a specification of 0.1 ppm or less, and was not detected in any of five analysed batches.
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.