Can Nattokinase (nattokinase) be used to support heart health and reduce the risk of cardiovascular events?

Nattokinase and Heart Health: Evidence and Recommendations

Nattokinase is not recommended as a primary intervention for heart health or cardiovascular risk reduction as there are no established clinical guidelines supporting its use, and evidence for its cardiovascular benefits remains limited and preliminary. Instead, clinicians should focus on evidence-based interventions with proven cardiovascular benefits.

Current Evidence on Nattokinase

• Nattokinase is a serine protease derived from natto, a traditional Japanese fermented soybean food, with potential fibrinolytic, antithrombotic, and antihypertensive properties 1
• In small human studies, nattokinase has been shown to decrease plasma levels of fibrinogen (9-10%), factor VII (7-14%), and factor VIII (17-19%) after 2 months of administration (2000 fibrinolysis units twice daily) 2
• Pharmacokinetic studies have detected nattokinase in human blood following oral ingestion, with peak serum levels observed at approximately 13.3 ± 2.5 hours post-dose 3
• Preclinical safety studies indicate that nattokinase has a favorable safety profile with no evidence of mutagenic activity or potential to induce chromosome aberrations 4

Evidence-Based Cardiovascular Risk Reduction Strategies

Pharmacological Interventions with Proven Benefits

• For patients with established atherosclerotic cardiovascular disease or chronic kidney disease, sodium-glucose cotransporter 2 (SGLT2) inhibitors with proven cardiovascular outcomes benefit are recommended to reduce the risk of major adverse cardiovascular events 5
• In patients with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, SGLT2 inhibitors are recommended to reduce risk of worsening heart failure and cardiovascular death 5
• ACE inhibitors or angiotensin receptor blockers are recommended in patients with known atherosclerotic cardiovascular disease, particularly coronary artery disease, to reduce cardiovascular events 5
• For patients with prior myocardial infarction, β-blockers should be continued for 3 years after the event 5
• In patients with heart failure with reduced ejection fraction, β-blockers with proven cardiovascular outcomes benefit should be used unless contraindicated 5

Statin Therapy

• High-intensity statin therapy is recommended for patients with established cardiovascular disease, with evidence showing a 16% reduction in overall incidence of strokes compared to placebo over 4.9 years 6
• Achieving an LDL-C level of <70 mg/dL is associated with a 28% reduction in risk of stroke without increasing hemorrhagic stroke risk 6
• The number needed to treat (NNT) with statins varies based on patient risk factors, with an NNT of 28 for patients with coronary artery calcium score > 100 6

Lifestyle Interventions for Cardiovascular Health

• Healthy nutrition is important for preventing atherosclerotic cardiovascular disease and reducing major adverse cardiovascular events in high-risk patients 5
• Mediterranean diet supplemented with extra-virgin olive oil or nuts has been associated with lower risk of major adverse cardiovascular events and peripheral artery disease in high-risk patients 5
• Annual influenza vaccination is recommended for patients with cardiovascular disease, as observational studies have shown reduced cardiovascular event rates among vaccinated patients 5
• SARS-CoV-2 vaccination is recommended for patients with cardiovascular comorbidities who are at higher risk for hospitalization, thrombotic events, and death with infection 5

Limitations of Nattokinase Research

• Despite promising preclinical and small clinical studies, nattokinase is not mentioned in any major cardiovascular disease management guidelines 5
• Current research on nattokinase is limited by small sample sizes, short duration, and lack of clinical outcome data 2, 1
• While nattokinase is undergoing clinical trial studies for atherothrombotic prevention, results from these trials are not yet available to support clinical recommendations 7

Conclusion for Clinical Practice

• Focus on established, evidence-based interventions for cardiovascular risk reduction including SGLT2 inhibitors, GLP-1 receptor agonists, ACE inhibitors/ARBs, statins, and β-blockers as appropriate based on patient characteristics 5
• Emphasize lifestyle modifications including healthy diet patterns (such as Mediterranean diet), regular physical activity, smoking cessation, and appropriate vaccinations 5
• While nattokinase may have potential as a complementary approach based on its fibrinolytic properties, it should not replace established cardiovascular medications or preventive strategies with proven clinical outcomes benefits 1, 7
• If patients inquire about nattokinase, inform them that current evidence is preliminary and insufficient to recommend it as a primary intervention for cardiovascular disease prevention or treatment 1