Nattokinase
Research reviewed: Added 06/11
Nattokinase is a dietary supplement with 16 published peer-reviewed studies involving 15,374 participants, researched for Reduced cholesterol levels, Reduced artery plaque, Reduced risk of cardiovascular mortality and 3 more areas.
Evidence at a Glance
Strength is scored by study design, sample size, study type, and outcomes
Reduced cholesterol levels
StrongReduced artery plaque
ModerateReduced risk of cardiovascular mortality
ModerateOther Cardiovascular Diseases
StrongCOVID-19
WeakNeuroprotective effects
WeakResearch Visualised
Visual breakdown of the clinical data.
Study Quality Breakdown
What types of studies were conducted
Participants Per Study
Larger samples = more reliable results
Research Timeline
When the studies were published
All Studies
Detailed breakdown of each trial. Click to expand.
Reduced cholesterol levels
To examine the effects of nattokinase on heart health indicators in people with dyslipidemia (abnormal levels of fats in the blood).
Study Type
Randomised, double-blind, placebo-controlled trial
Purpose
To examine the effects of nattokinase on heart health indicators in people with dyslipidemia (abnormal levels of fats in the blood).
Dose
5000 FU/day
Participants
113 men and women with an average age of 59 years
Duration
120 days
Results
The researchers observed a significant reduction in total cholesterol of −13.75 mmol/L in the nattokinase group after 120 days of treatment, while the placebo group saw a small decrease −4.16 mmol/L. Similarly, for LDL “bad” cholesterol, the nattokinase group demonstrated a significant decrease of −12.82 mmol/L, whereas the placebo group experienced an increase of 1.83 mmol/L. This suggests that this natural supplement could be a helpful addition to managing high cholesterol.
To investigate the effects of nattokinase combined with red yeast rice in patients with coronary artery disease.
Study Type
Randomised, double-blind, placebo-controlled trial
Purpose
To investigate the effects of nattokinase combined with red yeast rice in patients with coronary artery disease.
Dose
1. Nattokinase + Red Yeast Rice Group: 3661.8 FU/day nattokinase and 9mg monacolins 2. Nattokinase Only Group: 3615.0 FU/day 3. Red Yeast Rice Only Group: 9 mg monacolins (6 x 1.5 mg capsules) 4. Placebo Group
Participants
178 men and women with an average age of 62 years
Duration
90 days
Results
The group taking nattokinase combined with red yeast rice showed the largest significant reductions in triglycerides (−0.39 mmol/L), total cholesterol (−0.66 mmol/L), and diastolic blood pressure (−7.39 mmHg), along with a significant increase in HDL “good” cholesterol (+0.195 mmol/L) compared to other groups.
To demonstrate the effects of nattokinase in the management of stroke.
Study Type
Randomised, single-blind, placebo-controlled trial
Purpose
To demonstrate the effects of nattokinase in the management of stroke.
Dose
1200 FU/d or control (standard care treatment)
Participants
61 men and women patients in the subacute stage of ischemic stroke with an average age of 60 years
Duration
60 days
Results
After 60 days of treatment, 61.3% of patients taking nattokinase demonstrated the highest level of recovery based on a measure of disability, compared to only 13.3% in the control group. Additionally in the nattokinase group, researchers observed that the cholesterol levels—a significant factor in stroke risk—significantly dropped from 5.5 mmol/L to 4.64 mmol/L, while the control group saw a smaller decrease from 5.53 mmol/L to 4.79 mmol/L. Common symptoms like headache, dizziness, fatigue, and poor sleep improved in both groups, though the nattokinase group reported greater relief. Some patients in both groups still reported numbness, back pain, knee weakness, speech difficulties, and memory issues, with the nattokinase group generally performing better. Overall, the results suggest the potential of nattokinase as a potential alternative to conventional interventions in stroke management.
Reduced artery plaque
To evaluate the effect of nattokinase in reducing carotid artery thickness and carotid plaque (fatty deposits) size. The carotid arteries are two major blood vessels on each side of the neck that supply oxygen-rich blood to the brain, face, and head. Plaque buildup in these artery walls can thicken them, leading to blockages and raising the risk of heart disease and stroke.
Study Type
Randomised controlled trial
Purpose
To evaluate the effect of nattokinase in reducing carotid artery thickness and carotid plaque (fatty deposits) size. The carotid arteries are two major blood vessels on each side of the neck that supply oxygen-rich blood to the brain, face, and head. Plaque buildup in these artery walls can thicken them, leading to blockages and raising the risk of heart disease and stroke.
Dose
6000 FU/day of nattokinase or 20 mg/day of simvastatin (common medication to lower bad cholesterol levels)
Participants
86 men and women
Duration
26 weeks
Results
After 26 weeks of treatment, the nattokinase group demonstrated a significant reduction in plaque area and artery wall thickness. The plaque area decreased from 0.25 to 0.16 cm², and artery thickness dropped from 1.13 to 1.01 mm. This reduction was much greater than in the control group, with a decrease of -36.6% in the nattokinase group compared to -11.5% in the control group. A reduction in plaque area and artery wall thickness means that the buildup of fatty deposits (plaque) within the artery walls has decreased, and the artery walls themselves have become thinner. This improvement increases blood flow, lowers the risk of blockages, and reduces the chances of heart attack and stroke.
To evaluate the clinical effects of nattokinase on the management of atherosclerosis (a condition where fatty deposits build up inside the arteries) and hyperlipidemia (high levels of fats in the blood).
Study Type
Retrospective observational study
Purpose
To evaluate the clinical effects of nattokinase on the management of atherosclerosis (a condition where fatty deposits build up inside the arteries) and hyperlipidemia (high levels of fats in the blood).
Dose
Two doses compared: 3,600 FU/day (low dose) vs 10,800 FU/day (high dose) of nattokinase
Participants
1,062 men and women with an average age of 68 years
Duration
12 months
Results
Data demonstrate that atherosclerosis progression and hyperlipidemia can be effectively managed with nattokinase at a dose of 10,800 FU/day, while the lower dose of 3,600 FU/day was found to be ineffective. The dose of 10,800 FU/day was safe and well tolerated. Some lifestyle factors and the coadministration of vitamin K2 and aspirin led to improved outcomes. After 12 months of daily nattokinase supplementation at the effective dose, 95.4% of participants demonstrated significant improvement in total cholesterol, 85.2% in triglycerides, 84.3% in LDL "bad" cholesterol, and 89.1% in HDL "good" cholesterol. Additionally, the researchers observed that the thickness of the carotid artery wall and the size of artery plaque were significantly reduced. The average artery wall thickness dropped from 1.33 mm to 1.04 mm, and plaque size decreased by up to 36%. These findings provide clinical evidence on the effective dose of nattokinase in the management of cardiovascular disease and challenge the commonly recommended dose of 2,000 FU per day, suggesting it may be too low.
To investigate the effects of dietary supplements with natto extracts, on the growth of new tissue (neointima) in blood vessels and the breakdown of clots where the blood vessel lining is damaged.
Study Type
Animal study (Rats)
Purpose
To investigate the effects of dietary supplements with natto extracts, on the growth of new tissue (neointima) in blood vessels and the breakdown of clots where the blood vessel lining is damaged.
Dose
Dietary natto-extracts supplementation containing nattokinase of 50 or 100 CU/body
Duration
6 weeks
Results
The researchers observed that when rats were given natto extracts before and after the injury, the thickening of the inner layer of their blood vessels (known as intimal thickening) was significantly reduced compared to those that did not receive the supplements. Specifically, the intima/media ratio, which indicates the thickness of the inner layer relative to the middle layer of the blood vessel, was much lower in the natto-treated groups. Additionally, while both groups had their blood vessels reopen after injury, the natto-treated rats showed that the clots (thrombi) formed at the injury site were breaking down more effectively and detaching from the vessel walls. This suggests that natto extracts may help improve blood flow and reduce the risk of complications after blood vessel injuries by promoting the breakdown of clots and preventing excessive thickening of the vessel walls
To investigate the effects of nattokinase in combination with Korean red ginseng on aortic plaques in rabbits fed a high cholesterol diet.
Study Type
Animal study (Rabbits)
Purpose
To investigate the effects of nattokinase in combination with Korean red ginseng on aortic plaques in rabbits fed a high cholesterol diet.
Dose
500 FU nattokinase per treatment and combined with Korean red ginseng, which was added to the rabbits' diet at a ratio of 1:1 (w/w)
Duration
8 weeks
Results
The rabbits that received red ginseng and nattokinase showed a significant reduction in the area of aortic plaques. Aortic plaques are fatty deposits that can lead to atherosclerosis, a condition that narrows the arteries and can cause heart problems. In addition, nattokinase with red ginseng significantly lowered the levels of triglycerides in the blood of the rabbits that were on a high cholesterol diet. This is important because high triglyceride levels can lead to heart disease. Overall, the findings suggest that the combination of Korean red ginseng and nattokinase could be a promising approach to improve lipid profiles and reduce aortic plaque formation in conditions of high cholesterol.
Reduced risk of cardiovascular mortality
To examine the association of cardiovascular disease mortality with the intake of natto, soy protein, and soy isoflavones.
Study Type
Cohort study
Purpose
To examine the association of cardiovascular disease mortality with the intake of natto, soy protein, and soy isoflavones.
Dose
Approximately 0, 1.4, 2.7, or 7.3 g/day of natto (median values)
Participants
13,355 male and 15,724 female participants with an average age of 55 years
Duration
16 years of follow-up
Results
The study found that higher intake of natto was significantly associated with a reduced risk of death from cardiovascular disease and stroke. Those in the highest natto intake had a 25% lower risk of cardiovascular disease mortality compared to those with the lowest intake. Additionally, high intake of natto was associated with a 32% lower risk of death from all types of stroke. For ischemic stroke specifically, the highest natto consumers had a 33% lower risk of death.
Other Cardiovascular Diseases
To examine the effects of nattokinase supplementation on blood pressure in subjects with borderline high blood pressure or early-stage high blood pressure.
Study Type
Randomised, double-blind, placebo-controlled trial
Purpose
To examine the effects of nattokinase supplementation on blood pressure in subjects with borderline high blood pressure or early-stage high blood pressure.
Dose
2000 FUs/day of nattokinase or placebo
Participants
86 men and women with an average age of 47 years
Duration
8 weeks
Results
The study found a significant association between 8 weeks of nattokinase supplementation and reduced blood pressure compared to the control group. In the nattokinase group, systolic blood pressure significantly decreased by an average of 13.26 mmHg, while the control group saw a smaller reduction of 7.7 mmHg. Diastolic blood pressure also dropped significantly in the nattokinase group by 5.67 mmHg, compared to 2.82 mmHg in the control group. These findings suggest that nattokinase could be beneficial for lowering blood pressure,
To explore the effects of nattokinase on blood pressure and other cardiovascular risk markers in adults with high blood pressure.
Study Type
Randomised, double-blind, placebo-controlled trial
Purpose
To explore the effects of nattokinase on blood pressure and other cardiovascular risk markers in adults with high blood pressure.
Dose
100 mg/2000 FUs/day nattokinase or placebo
Participants
79 hypertensive men and women with an average age of 53 years
Duration
8 weeks
Results
The study found that 8 weeks of nattokinase supplementation significantly reduced diastolic blood pressure, especially in males. Overall, diastolic blood pressure decreased from 87 mmHg to 84 mmHg in the nattokinase group, and from 86 mmHg to 81 mmHg in males. Notably, among participants with low blood renin levels—an enzyme that helps regulate blood pressure by controlling the balance of salt and water in the body—66% showed improvement with nattokinase, compared to only 8% in the placebo group. These findings suggest that nattokinase may be a useful alternative for managing high blood pressure.
To investigate the effects of nattokinase on blood clotting and lipids (fats) that are associated with an increased risk for cardiovascular disease.
Study Type
Open-label clinical trial (uncontrolled)
Purpose
To investigate the effects of nattokinase on blood clotting and lipids (fats) that are associated with an increased risk for cardiovascular disease.
Dose
4000 FU/day of nattokinase
Participants
Healthy group: 15 healthy men and women with an average age 51 years Cardiovascular group: 15 men and women with an average age of 57 years Dialysis group: 15 men and women undergoing dialysis with an average age of 61 years
Duration
2 months
Results
Researchers observed that after two months of taking nattokinase, three key blood-clotting proteins—fibrinogen, factor VII, and factor VIII—were significantly reduced, which could lower heart disease risk. Fibrinogen, which helps form blood clots but can increase heart disease risk if too high, dropped by about 9% in healthy people, 7% in those at cardiovascular risk, and 10% in dialysis patients. Factor VII, a protein that starts the clotting process and is linked to clots in blood vessels, fell by 14% in healthy individuals, 13% in the cardiovascular group, and 7% in dialysis patients. Factor VIII, another clot-stabilising protein associated with heart risks, saw the largest decrease, with reductions of 17% in healthy people and 19% in both the cardiovascular and dialysis groups. These consistent reductions across all groups suggest that nattokinase could be beneficial for heart health by lowering these clotting factors.
To investigate the effects of nattokinase on deep vein thrombosis during long flights, particularly focusing on high-risk individuals. Deep vein thrombosis is a condition where blood clots form in deep veins, often in the legs.
Study Type
Randomised placebo-controlled trial
Purpose
To investigate the effects of nattokinase on deep vein thrombosis during long flights, particularly focusing on high-risk individuals. Deep vein thrombosis is a condition where blood clots form in deep veins, often in the legs.
Dose
150 mg/capsule proprietary blend of nattokinase and pycnogenol or placebo Subjects took 2 capsules 2 hours before flights and 2 capsules 6 hours later
Participants
186 men and women at high risk of deep vein thrombosis, with an average age of 49 years.
Duration
Short term: Treatment taken within 2 hours before and 6 hours after the flight.
Results
The study reported that in the treatment group, only 7 out of 94 subjects experienced thrombotic events, compared to 19 out of 92 in the control group, indicating a significant reduction in deep vein thrombosis occurrences. Additionally, Flite Tabs helped control edema, which is swelling that can lead to vein compression and increase the risk of deep vein thrombosis. Overall, the results suggest that Flite Tabs are a valuable preventive option for individuals at high risk of developing deep vein thrombosis during long-haul flights.
To evaluate the effects and safety of nattokinase in patients admitted to vascular surgery. Pain after vascular surgery is common because the procedure involves repairing or reconstructing blood vessels, which can disturb nerves and tissues around them. Managing pain after vascular surgery is essential for patient comfort and recovery, often involving medications and gradual movement to support healing and restore normal blood flow.
Study Type
Clinical trial (uncontrolled)
Purpose
To evaluate the effects and safety of nattokinase in patients admitted to vascular surgery. Pain after vascular surgery is common because the procedure involves repairing or reconstructing blood vessels, which can disturb nerves and tissues around them. Managing pain after vascular surgery is essential for patient comfort and recovery, often involving medications and gradual movement to support healing and restore normal blood flow.
Dose
Group 1: Patients with deep vein thrombosis, treated with an anticoagulant medication plus 100 mg/2000 FU/day nattokinase. Group 2: Patients with phlebitis (inflammation of a vein), treated with an anticoagulant medication plus 100 mg/2000 FU/day nattokinase. Group 3: Patients with venous insufficiency a condition in which the flow of blood through the veins is blocked, causing blood to pool in the legs) after classical surgery, treated with nattokinase 100 mg/2000 FU/day one day later.
Participants
153 men and women patients with an average age of 56 years
Duration
30 days
Results
The study showed significant symptom improvements for patients treated with nattokinase for blood vessel conditions. In Group 1, those treated with an anticoagulant followed by nattokinase reported reduced pain, while Group 2, treated with another anticoagulant followed by nattokinase, experienced complete symptom relief. Group 3, who had surgery and then started nattokinase, also had full relief, indicating nattokinase’s effectiveness in reducing pain and supporting blood vessel health. No side effects or new blood vessel issues were observed, suggesting nattokinase is a safe treatment option.
COVID-19
To examine the effect of nattokinase on COVID-19 virus
Study Type
Cellular study
Purpose
To examine the effect of nattokinase on COVID-19 virus
Dose
Nattokinase concentrations tested included 32 µg/mL, 8 µg/mL, 2 µg/mL, 500 ng/mL, 125 ng/mL, 31.25 ng/mL, and 7.8125 ng/mL. More technical summary: The researchers observed that nattokinase could break down the spike protein of the COVID-19 virus, an essential part of the virus to enter human cells. They found that nattokinase reduced the spike protein on cells without harming them, and its effectiveness increased with both higher doses and longer exposure times. Further laboratory tests confirmed this effect, and its protein-breaking activity was essential, as it didn’t work when heated or blocked by inhibitors. Given its ability to reduce the spike protein, nattokinase could potentially be developed as a treatment to support COVID-19 prevention and complement vaccination efforts, especially for new virus variants.
Results
The researchers found that nattokinase could break down a key protein on the surface of the COVID-19 virus, which the virus needs to enter human cells. By breaking down this protein, nattokinase could reduce the virus's ability to infect cells. Importantly, the enzyme was effective at safe levels and did not harm healthy cells, and the effectiveness of nattokinase increased as the dosage increased.These results suggest that nattokinase could have potential as a natural way to help prevent COVID-19 infections.
Neuroprotective effects
To investigate the neuroprotective effects of nattokinase on ischemic stroke, which occurs when a blood vessel supplying blood to the brain becomes blocked, usually by a blood clot.
Study Type
Rodent and cellular study
Purpose
To investigate the neuroprotective effects of nattokinase on ischemic stroke, which occurs when a blood vessel supplying blood to the brain becomes blocked, usually by a blood clot.
Dose
5000, 10000, 20000 FU/kg of nattokinase
Duration
7 days
Results
The results showed that nattokinase reduced brain damage and improved the rats' recovery in a dose-dependent way (higher doses led to better results). Further cellular studies showed that nattokinase helped prevent brain cell death under stressful conditions, like lack of oxygen and nutrients. This suggests that nattokinase could potentially protect brain cells from damage during a stroke.
To investigate the effects of nattokinase on the breakdown of harmful proteins (amyloid fibrils) which are linked to diseases like Alzheimer's.
Study Type
In-vitro study
Purpose
To investigate the effects of nattokinase on the breakdown of harmful proteins (amyloid fibrils) which are linked to diseases like Alzheimer's.
Results
The study investigated how well nattokinase can break down harmful protein clumps called amyloid fibrils, which are linked to Alzheimer’s disease. The results showed that nattokinase effectively breaks down these fibrils under body-like conditions, making it potentially helpful for clearing these clumps in the body. This suggests that nattokinase could be a safe and promising option for treating diseases like Alzheimer’s.
Frequently Asked Questions
Common questions about Nattokinase research
There are currently 16 peer-reviewed studies on Nattokinase, involving 15,374 total participants. Research covers Reduced cholesterol levels, Reduced artery plaque, Reduced risk of cardiovascular mortality and 3 more areas. The overall evidence strength is rated as Very Strong.
The evidence is currently rated as "Very Strong Evidence". This rating is based on study design quality (randomisation, blinding, placebo controls), sample sizes, study types (11 human studies, 3 animal studies), and reported outcomes.
Nattokinase has been researched for: Reduced cholesterol levels, Reduced artery plaque, Reduced risk of cardiovascular mortality, Other Cardiovascular Diseases, COVID-19, Neuroprotective effects. Each area has its own body of evidence which you can explore in the study breakdowns above.
Yes, 11 out of 16 studies are human trials. The remaining 3 are animal studies. Human trials carry more weight in our evidence scoring system.
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