Safety Profile
Known Safety Concerns
- GENUINE fibrinolytic enzyme — CONTRAINDICATED with warfarin/anticoagulants/antiplatelets (serious bleeding risk); stop 2 weeks pre-surgery; contraindicated in active bleeding; soy allergen trace
Contraindications
- GENUINE fibrinolytic enzyme — CONTRAINDICATED with warfarin/anticoagulants/antiplatelets (serious bleeding risk); stop 2 weeks pre-surgery; contraindicated in active bleeding; soy allergen trace
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Nattokinase is a serine protease enzyme extracted from natto — fermented soybeans prepared using Bacillus subtilis var. natto. It directly degrades fibrin and activates endogenous plasminogen → plasmin (thrombolytic activity), reducing blood viscosity and supporting cardiovascular health. Activity measured in FU (Fibrinolytic Units); typical supplement doses provide 2,000 FU per 100 mg capsule. Clinical RCTs show modest reduction in systolic blood pressure (~5.5 mmHg), diastolic blood pressure (~2.8 mmHg), and fibrinogen levels. CRITICAL SAFETY — GENUINE FIBRINOLYTIC ENZYMATIC ACTIVITY: CONTRAINDICATED with anticoagulants (warfarin, heparin, rivaroxaban, apixaban, dabigatran — serious additive bleeding risk), antiplatelet drugs (aspirin, clopidogrel, NSAIDs), and thrombolytics (tPA, streptokinase). Stop 2 weeks before any surgery. Contraindicated in: active bleeding, haemophilia, recent haemorrhagic stroke, peptic ulcer, retinal haemorrhage. Physician consultation mandatory in any patient on blood-thinning therapy. SOY ALLERGEN: derived from fermented soy — contains trace soy proteins; caution in soy allergy (check labelling for soy-free processing). Nattokinase supplements are distinct from whole natto food (which also contains Vitamin K2).
Biological and Chemical Classification
- Scientific Name
- Bacillus subtilis var. natto (enzyme)
Mechanism of Action
Information not yet available for this ingredient profile.
Clinical Evidence of Effectiveness
Information not yet available for this ingredient profile.
Pharmacokinetics
Information not yet available for this ingredient profile.
Recommended Dosage
Information not yet available for this ingredient profile.
SETI — Scientific Evidence Transparency Index
Executive Summary — Ingredient Assessment
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or RCT)
- Main clinical benefit observed: Specialty
- Evidence consistency: High consistency across studies (100%)
- GENUINE fibrinolytic enzyme — CONTRAINDICATED with warfarin/anticoagulants/antiplatelets (serious bleeding risk); stop 2 weeks pre-surgery; contraindicated in active bleeding; soy allergen trace
The available scientific evidence for Nattokinase indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.
Total SETI Score
High risk| Evidence quality | 10/40 |
| Evidence consistency | 20/20 |
| Safety signals | 0/20 |
| Study recency | 10/10 |
| Evidence transparency | 10/10 |
Evidence Summary
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or systematic review)
- 0 studies identified benefits or no safety concern (GREEN)
- 10 studies reported limited or advisory safety evidence (YELLOW)
Evidence Policy
Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.
Last updated: 06 აპრ 2026, 12:09
Evidence Distribution
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Observational / other LOW evidence YELLOWCorrection: Nattokinase-driven remodeling of tumor microenvironment enhances the efficacy of MSLN-targeted CAR-T cell therapy in solid tumors. ↗Zhao L et al.. Correction: Nattokinase-driven remodeling of tumor microenvironment enhances the efficacy of MSLN-targeted CAR-T cell therapy in solid tumors.. Cancer Immunol Immunother. 2026. PMID:41848865.PMID 41848865 ↗Journal Cancer Immunol ImmunotherYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41848865/
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Observational / other LOW evidence YELLOWIdentification and mechanistic characterization of novel ACE-inhibitory peptides derived from Nattokinase. ↗Peng S et al.. Identification and mechanistic characterization of novel ACE-inhibitory peptides derived from Nattokinase.. Food Chem. 2026. PMID:41844106.PMID 41844106 ↗Journal Food ChemYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41844106/
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Observational / other LOW evidence YELLOWCandidate treatments for long COVID: a narrative review of expert and patient-driven priorities. ↗Baptista SN et al.. Candidate treatments for long COVID: a narrative review of expert and patient-driven priorities.. Front Med (Lausanne). 2026. PMID:41836927.PMID 41836927 ↗Journal Front Med (Lausanne)Year 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41836927/
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Observational / other LOW evidence YELLOWEnhanced production of Nattokinase by Bacillus aryabhattai RP6 isolated from fermented Brassica oleracea. ↗Prasanna R et al.. Enhanced production of Nattokinase by Bacillus aryabhattai RP6 isolated from fermented Brassica oleracea.. BMC Biotechnol. 2026. PMID:41814289.PMID 41814289 ↗Journal BMC BiotechnolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41814289/
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Observational / other LOW evidence YELLOWNattokinase-Related Aggravation of Histamine Intolerance in Diamine Oxidase Deficiency: A Rare Clinical Observation. ↗Keskinel I. Nattokinase-Related Aggravation of Histamine Intolerance in Diamine Oxidase Deficiency: A Rare Clinical Observation.. J Coll Physicians Surg Pak. 2026. PMID:41792082.PMID 41792082 ↗Journal J Coll Physicians Surg PakYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41792082/
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Observational / other LOW evidence YELLOWNattokinase Attenuates Acute Cerebral Infarction in a Rat Model of Middle Cerebral Artery Occlusion. ↗Tanikawa T et al.. Nattokinase Attenuates Acute Cerebral Infarction in a Rat Model of Middle Cerebral Artery Occlusion.. In Vivo. 2026. PMID:41760340.PMID 41760340 ↗Journal In VivoYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41760340/
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Observational / other LOW evidence YELLOWCorrection to: Nattokinase attenuates bisphenol A or gamma irradiation-mediated hepatic and neural toxicity by activation of Nrf2 and suppression of inflammatory mediators… ↗Elbakry MMM et al.. Correction to: Nattokinase attenuates bisphenol A or gamma irradiation-mediated hepatic and neural toxicity by activation of Nrf2 and suppression of inflammatory mediators in rats.. Environ Sci Pollut Res Int. 2026. PMID:41703370.PMID 41703370 ↗Journal Environ Sci Pollut Res IntYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41703370/
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Observational / other LOW evidence YELLOWProcess Analysis of Millet Bran Fermentation by Bacillus natto: Dynamic Changes in Enzyme Activities and Bioactive Components. ↗Zhang S et al.. Process Analysis of Millet Bran Fermentation by Bacillus natto: Dynamic Changes in Enzyme Activities and Bioactive Components.. Foods. 2026. PMID:41683071.PMID 41683071 ↗Journal FoodsYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41683071/
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Observational / other LOW evidence YELLOWDiscovery of age and blood group associated variability in nattokinase mediated thrombolysis and its relevance to cardiovascular management. ↗Bhatt TC et al.. Discovery of age and blood group associated variability in nattokinase mediated thrombolysis and its relevance to cardiovascular management.. Sci Rep. 2026. PMID:41654604.PMID 41654604 ↗Journal Sci RepYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41654604/
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Observational / other LOW evidence YELLOWDifferences in Nutrition and Sensory Quality Between Cooked Soybeans, Fermented Natto, and Post-Ripening Natto. ↗He Y et al.. Differences in Nutrition and Sensory Quality Between Cooked Soybeans, Fermented Natto, and Post-Ripening Natto.. Foods. 2026. PMID:41596835.PMID 41596835 ↗Journal FoodsYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41596835/
Score Transparency
0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.
Method: Q = number of approved references ÷ 10 (capped at 1.0)
Limited — mostly case reports or animal studies
Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.
Mixed or neutral — roughly equal benefit and risk signals
Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.
One or more monitoring-level safety signals active
Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.
Final GIRI Score for Nattokinase. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
Full methodology & data sources
The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.
- References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
- Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
- Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
- Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.
Risk Level Classification
Based on available regulatory signals and scientific evidence, this ingredient presents a high safety concern. Its use in dietary supplements is associated with documented adverse events.
0–3.0
3.0–5.5
5.5–7.5
7.5–10
The score pin shows exactly where this ingredient falls on the fixed risk scale.
What drove the High classification for Nattokinase
A score of 6.0 places this ingredient in the High band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
0 approved references.
Limited — mostly case reports or animal studies (Level 4–5).
Neutral or mixed — benefit and risk signals roughly balanced.
No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.
No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).
How are the Low / Moderate / High / Critical thresholds defined?
The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:
| Level | Score | Meaning |
|---|---|---|
| LOW | 0.0 – 2.9 | Sparse or predominantly beneficial evidence. No active safety alerts. |
| MODERATE | 3.0 – 5.4 | Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups. |
| HIGH | 5.5 – 7.4 | Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended. |
| CRITICAL | 7.5 – 10 | Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision. |
Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.