Is nattokinase effective for treating atherosclerosis in an adult patient with hypertension, hyperlipidemia, and a history of smoking?

Nattokinase for Atherosclerosis

Nattokinase at a dose of 10,800 FU/day can effectively reduce carotid artery plaque size and intima-media thickness in patients with atherosclerosis, but lower doses (2,000-3,600 FU/day) are ineffective, and no major cardiovascular guidelines currently recommend it as standard therapy.

Evidence Quality and Guideline Position

Major cardiovascular guidelines from the ACC/AHA, ESC/ESH, and other authoritative bodies do not include nattokinase in their recommendations for atherosclerosis management 1. These guidelines consistently recommend proven therapies including:

• Antihypertensive medications (thiazide diuretics, ACE inhibitors, ARBs, calcium channel blockers) targeting BP <130/80 mmHg 1
• Statins for lipid management in patients with atherosclerotic disease 1
• Antiplatelet therapy (aspirin) for secondary prevention 1
• Smoking cessation as the single most effective lifestyle intervention 1

Research Evidence on Nattokinase

High-Dose Efficacy (10,800 FU/day)

The most compelling evidence comes from a 2022 study with 1,062 participants showing that nattokinase at 10,800 FU/day significantly reduced carotid intima-media thickness and plaque size with improvement rates of 66.5-95.4% over 12 months 2. This dose was well-tolerated with no significant adverse effects 2.

A smaller 2017 Chinese study (76 patients) using 6,000 FU/day demonstrated a 36.6% reduction in carotid plaque size compared to 11.5% with simvastatin, though statins showed greater lipid-lowering effects 3. The mechanism appeared independent of lipid reduction 3.

Low-Dose Inefficacy (2,000-3,600 FU/day)

Critical limitation: The same 2022 study found nattokinase at 3,600 FU/day was completely ineffective for lipid lowering or atherosclerosis suppression 2.

A rigorous 2021 randomized controlled trial (265 participants, median 3 years follow-up) using the commonly recommended dose of 2,000 FU/day showed null effects on carotid intima-media thickness, arterial stiffness, blood pressure, and all laboratory parameters 4. This challenges the widely cited 2,000 FU/day recommendation 2, 4.

Safety Profile

Nattokinase demonstrated good safety in vascular surgery patients when combined with anticoagulants (fondaparinux, enoxaparin), though this requires careful INR monitoring 5. No significant adverse effects were reported at 10,800 FU/day 2.

Clinical Algorithm for Your Patient

For an adult with hypertension, hyperlipidemia, smoking history, and atherosclerosis:

1. First-line evidence-based therapy (Class I recommendations):

   • Initiate or optimize antihypertensive medication targeting BP <130/80 mmHg 1
   • Start high-intensity statin therapy 1
   • Prescribe aspirin for secondary prevention 1
   • Implement aggressive smoking cessation interventions 1

2. If considering nattokinase as adjunctive therapy:

   • Only use 10,800 FU/day (not the commonly cited 2,000 FU/day) 2
   • Avoid doses ≤3,600 FU/day as they are ineffective 2, 4
   • Consider co-administration with vitamin K2 and aspirin for synergistic effects 2
   • Monitor INR if patient is on anticoagulants 5

3. Enhanced efficacy factors:

   • Encourage regular exercise (improves nattokinase effects) 2
   • Address modifiable factors: smoking cessation, alcohol moderation, weight management 2

Critical Caveats

• Nattokinase cannot replace guideline-directed medical therapy for atherosclerosis 1
• The dose matters critically—most commercial preparations and prior recommendations use ineffective doses 2, 4
• Long-term cardiovascular outcome data (MI, stroke, mortality) are lacking for nattokinase 4
• The 2022 study showing efficacy was not placebo-controlled, limiting strength of conclusions 2

Bottom line: While high-dose nattokinase (10,800 FU/day) shows promise for reducing atherosclerotic plaque burden, it should only be considered as an adjunct to proven guideline-directed therapies, not as a replacement 1, 2.