Nattokinase for Heart Health: Does It Really Work?

randomized-controlled-trial PMID: 33843667

Quick Summary: A recent study looked at whether nattokinase could prevent the buildup of plaque in arteries. The results showed that taking nattokinase for three years didn't slow down this process in healthy adults.

What The Research Found

This study found that taking nattokinase didn't help prevent the early stages of atherosclerosis (hardening of the arteries) in people who were already healthy. The study looked at how much the arteries thickened over time and found no difference between those taking nattokinase and those taking a placebo (a sugar pill).

Study Details

Who was studied: 265 adults, average age 65, who didn't have any signs of heart disease.

How long: The study lasted for about 3 years.

What they took: Participants took either 2,000 fibrinolytic units (FU) of nattokinase daily or a placebo.

What This Means For You

If you're a healthy adult looking to prevent heart disease, this study suggests that nattokinase might not be the answer. It doesn't appear to offer any benefit in preventing the early stages of artery hardening. Always talk to your doctor before starting any new supplements.

Study Limitations

The study only included healthy, older adults, so the results might not apply to people with existing heart problems or younger individuals.

The study used a specific dose of nattokinase, and other doses might have different effects.

The study focused on early signs of heart disease, so it's possible that longer-term studies might show different results.

Key Findings

This randomized controlled trial found no significant benefit of nattokinase supplementation on subclinical atherosclerosis progression or cardiovascular biomarkers. After a median 3 years, nattokinase (2,000 FU/day) showed null effects on the primary outcomes: annualized change in carotid intima-media thickness (CIMT; p=0.17) and carotid arterial stiffness (CAS; p=0.29). No statistically significant differences were observed for secondary outcomes, including blood pressure, coagulation/fibrinolysis markers, inflammatory markers, or metabolic parameters (all p>0.05). The study concludes nattokinase does not prevent atherosclerosis progression in low-risk, asymptomatic individuals.

Study Design

This was a double-blinded, placebo-controlled randomized trial conducted over a median duration of 3 years. The study enrolled 265 participants with a median age of 65.3 years, all without clinical cardiovascular disease (CVD) and classified as low CVD risk. Primary outcomes were measured via serial carotid ultrasound (CIMT and CAS) every 6 months. Secondary outcomes included blood pressure, metabolic panels, coagulation/fibrinolysis factors (e.g., D-dimer, fibrinogen), inflammatory markers (e.g., CRP), and cellular activation markers, assessed at least every 6 months.

Dosage & Administration

Participants received oral nattokinase at 2,000 fibrinolytic units (FU) daily in capsule form, compared to an identical placebo. The dose was administered consistently throughout the median 3-year intervention period.

Results & Efficacy

Nattokinase supplementation did not significantly alter the annualized rate of change in CIMT (difference: −0.002 mm/year; 95% CI: −0.005 to 0.001; p=0.17) or CAS (difference: −0.03 m/s/year; 95% CI: −0.09 to 0.03; p=0.29) versus placebo. No meaningful effects were detected for systolic/diastolic blood pressure (mean differences: −0.8/−0.5 mmHg; p=0.42 and p=0.58), coagulation markers (e.g., D-dimer: p=0.61), inflammatory markers (e.g., CRP: p=0.74), or other laboratory parameters. All p-values exceeded 0.05, indicating no statistical significance.

Limitations

The study exclusively enrolled low-CVD-risk, asymptomatic older adults (median age 65.3), limiting generalizability to high-risk populations or younger individuals. The 2,000 FU dose may not reflect higher doses used in other contexts. While the 3-year duration is robust for subclinical atherosclerosis research, longer follow-up might be needed to detect subtle effects. The null findings could also reflect insufficient statistical power for rare clinical endpoints, though the sample size (n=265) was adequate for primary imaging outcomes.

Clinical Relevance

For supplement users, this high-quality trial provides strong evidence against nattokinase for preventing early atherosclerosis in healthy, low-risk older adults. It challenges common claims about nattokinase’s cardiovascular benefits, indicating it does not slow arterial thickening or improve thrombosis-related biomarkers in this demographic. Individuals using nattokinase for CVD prevention should note no measurable benefit was observed over 3 years. Future research should target high-risk cohorts (e.g., hypertension, diabetes) and explore higher doses, but current evidence does not support routine use for atherosclerosis prevention in asymptomatic populations.