Nattokinase and Blood Pressure Reduction in Cardiovascular Disease
Direct Evidence-Based Answer
Yes, nattokinase does reduce blood pressure in adults, including those with cardiovascular disease history, though the effect is modest and should not replace guideline-directed medical therapy.
Blood Pressure Reduction Evidence
The most robust evidence comes from randomized controlled trials demonstrating consistent blood pressure reductions:
In North American populations with hypertension, nattokinase 100 mg daily for 8 weeks reduced systolic BP by approximately 5-6 mmHg and diastolic BP by 3 mmHg compared to placebo, with more pronounced effects in males (diastolic BP dropped from 86 to 81 mmHg, p<0.006) 1.
In Asian populations with prehypertension or stage 1 hypertension, nattokinase 2,000 FU daily for 8 weeks produced net reductions of -5.55 mmHg in systolic BP (95% CI: -10.5 to -0.57 mmHg, p<0.05) and -2.84 mmHg in diastolic BP (95% CI: -5.33 to -0.33 mmHg, p<0.05) compared to placebo 2.
The mechanism appears related to reduced renin activity, with a net change of -1.17 ng/mL/h in the nattokinase group compared to controls (p<0.05) 2.
Critical Limitation: Atherosclerosis Progression
However, the most recent and highest-quality long-term study contradicts any cardiovascular benefit:
In a 3-year randomized controlled trial of 265 individuals (median age 65.3 years) without clinical CVD, nattokinase 2,000 FU daily had no effect on subclinical atherosclerosis progression measured by carotid intima-media thickness or arterial stiffness 3.
Nattokinase had no significant effect on blood pressure in this longer-term study, contradicting the shorter-term trials 3.
No effects were observed on metabolic factors, inflammatory markers, or coagulation parameters 3.
Clinical Context for Cardiovascular Disease Patients
For adults with established cardiovascular disease, guideline-directed medical therapy remains the evidence-based standard:
ACE inhibitors or ARBs are recommended as first-line therapy for patients with CVD and hypertension (systolic BP ≥130 or diastolic BP ≥80 mmHg), with additional agents added as needed 4.
Beta blockers are particularly effective in patients with chronic coronary disease, especially those with ongoing angina, reducing angina, improving exercise tolerance, and reducing cardiovascular events 4.
The 2017 ACC/AHA guidelines recommend nonpharmacological interventions including weight loss, DASH diet, sodium reduction, potassium supplementation, and structured exercise programs as Class I recommendations with Level A evidence 4.
Reconciling the Contradictory Evidence
The discrepancy between short-term BP reduction studies and the long-term null atherosclerosis study suggests:
Short-term BP reductions (5-6 mmHg systolic) may occur but do not translate into meaningful cardiovascular outcomes 2, 1, 3.
The 3-year trial is the highest quality evidence (longest duration, largest sample, objective atherosclerosis endpoints) and should be prioritized when assessing cardiovascular benefit 3.
Nattokinase's theoretical fibrinolytic, antiplatelet, and lipid-lowering effects described in reviews 5 were not confirmed in the rigorous long-term trial 3.
Clinical Recommendation
Nattokinase should not be used as a substitute for proven antihypertensive medications in patients with cardiovascular disease. While modest short-term BP reductions have been demonstrated, the lack of effect on atherosclerosis progression and the absence of long-term cardiovascular outcome data mean it cannot be recommended as primary therapy 3.
If a patient with CVD wishes to use nattokinase as an adjunct, they must:
- Continue all guideline-directed medical therapy (ACE inhibitors/ARBs, beta blockers, statins, antiplatelet agents) 4.
- Achieve target BP <130/80 mmHg with proven medications 4.
- Monitor for potential drug interactions, particularly with anticoagulants given nattokinase's fibrinolytic properties 5, 6.
Common Pitfalls to Avoid
Do not discontinue or reduce proven antihypertensive medications in favor of nattokinase, as this would contradict all major hypertension guidelines 4.
Do not assume cardiovascular benefit based solely on BP reduction, as the long-term atherosclerosis study demonstrated no clinical benefit despite theoretical mechanisms 3.
Do not overlook lifestyle modifications (sodium restriction <2g/day, DASH diet, weight loss, exercise) which have stronger evidence for cardiovascular benefit than nattokinase 4.