Nattokinase and Blood Pressure

Introduction

Blood pressure effects represent one of the more promising areas of nattokinase research. Unlike the atherosclerosis evidence, where the largest trial was negative, blood pressure trials have consistently shown modest reductions in both systolic and diastolic pressure. The question is whether these effects are clinically meaningful and how they compare to established antihypertensive therapies.

This article examines the proposed mechanism for blood pressure reduction, the magnitude of effects observed in clinical trials, whether nattokinase adds to standard treatment, and how quickly effects manifest. The evidence supports a real but modest antihypertensive effect that falls short of what prescription medications achieve.

For context on nattokinase mechanisms, see the fundamentals article. Patients considering nattokinase alongside blood pressure medications should review the drug interactions section carefully.

What is the proposed mechanism for blood pressure reduction?

Nattokinase may lower blood pressure through effects on the renin-angiotensin system. Research suggests the enzyme inhibits angiotensin-converting enzyme, similar to the mechanism of ACE inhibitor medications like lisinopril. This would explain both the blood pressure reduction and the potential for additive effects when combined with other antihypertensive classes (Chen et al., 2018).

Additional mechanisms may contribute. Nattokinase reduces blood viscosity by degrading fibrinogen and reducing red blood cell aggregation. Thicker blood requires higher pressure to circulate. By improving blood rheology, nattokinase may reduce peripheral vascular resistance independently of direct effects on the renin-angiotensin system (Kurosawa et al., 2015).

Anti-inflammatory effects could also play a role. Chronic inflammation contributes to endothelial dysfunction and elevated blood pressure. Research showing that nattokinase interrupts inflammatory pathways suggests an indirect contribution to blood pressure lowering, though this remains speculative in humans (Wu et al., 2020).

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How large are the observed effects in trials?

The most cited blood pressure trial randomized 86 participants with pre-hypertension or stage 1 hypertension to nattokinase 2,000 FU daily or placebo for eight weeks. The nattokinase group showed reductions of approximately 5 mmHg in systolic and 3 mmHg in diastolic blood pressure compared to placebo. These effects reached statistical significance (Kim et al., 2008).

A 2023 meta-analysis pooled six randomized controlled trials with 546 total participants. The analysis found statistically significant reductions in both systolic and diastolic blood pressure with nattokinase supplementation, confirming the direction of effect seen in individual trials. Effect sizes were modest but consistent across studies (Li et al., 2023).

To put these numbers in perspective, a 5 mmHg reduction in systolic blood pressure would be considered clinically meaningful if sustained, as epidemiological data links this magnitude of reduction to lower cardiovascular risk. However, first-line antihypertensive medications typically produce larger reductions, often 10-15 mmHg systolic in hypertensive patients.

Is the effect additive to standard antihypertensives?

This question has not been rigorously answered. Most nattokinase blood pressure trials enrolled participants who were either medication-naive or required washout periods before randomization. Whether nattokinase provides additional benefit on top of ACE inhibitors, ARBs, calcium channel blockers, or diuretics is unknown.

A recent trial evaluated nattokinase combined with red yeast rice in patients with stable coronary artery disease, many of whom were on standard cardiovascular medications. The combination showed antihypertensive effects, but the study design does not allow attribution of blood pressure changes specifically to nattokinase (Liu et al., 2024).

The theoretical case for additivity is mixed. If nattokinase works primarily through ACE inhibition, combining it with an ACE inhibitor would likely show diminishing returns. Combining with a calcium channel blocker or diuretic might produce more complementary effects. These pharmacological hypotheses remain untested in controlled trials.

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How quickly does any blood pressure effect manifest?

The Kim et al. trial showed blood pressure differences emerging over the eight-week study period. Whether effects occur within days or require weeks to manifest was not specifically addressed in most trial designs (Kim et al., 2008).

Acute pharmacokinetic studies provide some insight. A single dose of nattokinase produces measurable changes in coagulation and fibrinolysis parameters within hours, peaking at approximately 13 hours and persisting for at least 48 hours. If blood pressure effects depend on these hemostatic changes, some benefit might occur relatively quickly (Kurosawa et al., 2015).

Chronic effects likely differ from acute responses. Blood viscosity reduction, ACE inhibition, and anti-inflammatory effects may require sustained supplementation to translate into measurable blood pressure changes. Patients starting nattokinase for blood pressure should not expect immediate results and should monitor response over weeks to months.

Conclusion

Nattokinase appears to lower blood pressure modestly, with trial data supporting reductions of approximately 5 mmHg systolic and 3 mmHg diastolic. The mechanism may involve ACE inhibition, blood viscosity reduction, and anti-inflammatory effects. These effects are real but smaller than what prescription antihypertensives achieve.

For patients with mildly elevated blood pressure who prefer to try non-pharmacological approaches first, nattokinase represents one option supported by reasonable evidence. For patients with established hypertension requiring tight control, nattokinase cannot substitute for proven medications. Whether it adds meaningful benefit to standard therapy remains unknown.

The next article addresses the critical safety question of how nattokinase interacts with anticoagulants, antiplatelet agents, and other cardiovascular medications.