Enhancing Cardiovascular Health: The Role of Nattokinase

Introduction to Nattokinase and Its Benefits

Nattokinase is a potent enzyme extracted from natto, a traditional Japanese food made from fermented soybeans. It has gained popularity in recent years due to its potential health benefits, particularly in enhancing cardiovascular health. Nattokinase’s lipid-lowering properties play a crucial role in its cardiovascular benefits, making it an attractive alternative for individuals seeking natural methods to manage their lipid levels and overall heart health.

According to research, nattokinase is a serine protease that exhibits fibrinolytic activity, which means it can dissolve blood clots by breaking down fibrin, a protein involved in clot formation. This action helps improve blood flow, reduce blood viscosity, and lower the risk of cardiovascular diseases (Wei et al., 2025). Furthermore, nattokinase has been shown to exert lipid-lowering effects by modulating lipid metabolism and lowering total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, while potentially increasing high-density lipoprotein cholesterol (HDL-C) levels (Chen et al., 2024).

The multifaceted benefits of nattokinase make it a promising natural remedy for individuals looking to enhance their cardiovascular health. Its safety profile, coupled with clinical evidence supporting its efficacy, further reinforces its potential role in lipid management and cardiovascular disease prevention.

Mechanisms of Action for Lipid Reduction by Nattokinase

Nattokinase’s lipid-lowering effects are achieved through several mechanisms that target key processes in lipid metabolism. These mechanisms include:

1. Activation of Hormone-Sensitive Lipase (HSL): Nattokinase enhances the activity of HSL, which is crucial for the hydrolysis of triglycerides, leading to the release of free fatty acids and glycerol. This process promotes the breakdown of stored fats in adipose tissue, reducing overall lipid levels in the bloodstream (Wei et al., 2025).

2. Enhancement of Lipoprotein Lipase (LPL) Activity: Nattokinase has been shown to stimulate LPL, an enzyme responsible for the hydrolysis of triglycerides in lipoproteins. By increasing LPL activity, nattokinase facilitates the breakdown of triglycerides from chylomicrons and very low-density lipoproteins (VLDL), thereby decreasing plasma triglyceride levels (Chen et al., 2024).

3. Inhibition of HMG-CoA Reductase: One of the critical enzymes in cholesterol synthesis, HMG-CoA reductase, is inhibited by nattokinase. This inhibition reduces the endogenous production of cholesterol in the liver, resulting in lower levels of LDL-C in circulation (Wei et al., 2025).

4. Promotion of Antithrombotic Effects: By promoting fibrinolysis through its action on fibrin, nattokinase helps maintain healthy blood flow and circulation. This effect is beneficial for reducing the risk of thromboembolic events, which are often associated with elevated lipid levels and cardiovascular diseases (Chen et al., 2024).

These mechanisms collectively contribute to the lipid-lowering effects of nattokinase, making it a valuable addition to cardiovascular health management.

Clinical Evidence Supporting Nattokinase for Cardiovascular Health

Numerous clinical studies have investigated the efficacy of nattokinase in managing lipid levels and improving cardiovascular health. A comprehensive review of the literature reveals several key findings:

1. Reduction in Total Cholesterol and LDL-C: A randomized controlled trial involving 60 patients with primary hyperlipidemia demonstrated that participants receiving nattokinase showed a significant reduction in total cholesterol and LDL-C levels compared to the placebo group (Chen et al., 2024). The study reported a decrease of approximately 10% in TC and 11% in LDL-C, indicating nattokinase’s effectiveness in lipid management.

2. Improvement in Carotid Intima-Media Thickness (IMT): Another clinical study involving patients with carotid artery disease indicated that nattokinase supplementation resulted in a significant reduction in carotid IMT, an important marker of atherosclerosis. Patients taking nattokinase alongside conventional lipid-lowering medications exhibited a 36.6% reduction in carotid plaque size, compared to a mere 11.5% reduction in the control group (Chen et al., 2024).

3. Long-Term Cardiovascular Benefits: A large-scale study involving over 1,000 participants took a nattokinase preparation for 12 months and observed a 21.7% reduction in carotid intima-media thickness along with significant improvements in lipid profiles. Participants demonstrated a 15.9% reduction in total cholesterol, 15.7% reduction in triglycerides, and a 15.8% increase in HDL-C (Chen et al., 2024). The study concluded that nattokinase is a safe and effective adjunct therapy for managing cardiovascular diseases.

These clinical findings support the use of nattokinase as a viable alternative or adjunct to traditional lipid-lowering therapies, particularly for patients who may experience side effects from conventional medications.

Comparative Analysis: Nattokinase vs. Traditional Lipid-Lowering Drugs

When evaluating nattokinase in the context of traditional lipid-lowering drugs such as statins and fibrates, several distinctions become evident:

1. Mechanism of Action

• Statins: Statins primarily inhibit HMG-CoA reductase to reduce cholesterol synthesis in the liver, effectively lowering LDL-C levels. However, they can also have adverse effects, including muscle pain, liver enzyme elevation, and increased risk of diabetes.
• Fibrates: Fibrates activate PPAR-α to enhance the breakdown of triglycerides and increase HDL-C levels. They are effective for hypertriglyceridemia but have limited impact on LDL-C and may induce gastrointestinal side effects.

2. Safety and Tolerance

Nattokinase is derived from natural sources and has a favorable safety profile, with few reported adverse effects. It is particularly beneficial for patients who are intolerant to traditional lipid-lowering agents. In contrast, statins and fibrates are associated with a range of side effects, which can lead to discontinuation of therapy (Wei et al., 2025).

3. Efficacy

While statins demonstrate rapid and significant LDL-C reduction, nattokinase shows a more gradual but multifaceted lipid-lowering effect, addressing triglycerides, cholesterol synthesis, and overall cardiovascular health. Research suggests that nattokinase may provide additive effects when combined with traditional medications, enhancing lipid regulation without the added risk of adverse reactions (Chen et al., 2024).

Safety Profile and Considerations for Nattokinase Use

Nattokinase is generally regarded as safe for most individuals when taken at recommended doses. Clinical trials have confirmed low rates of adverse effects, with occasional reports of mild gastrointestinal discomfort (Wei et al., 2025). However, some considerations should be noted:

1. Potential Bleeding Risk: Due to its fibrinolytic properties, nattokinase may increase the risk of bleeding, particularly in individuals taking anticoagulant medications. It is essential for patients to consult healthcare providers before initiating nattokinase supplementation.

2. Interaction with Other Medications: Nattokinase may interact with other medications that affect blood clotting or lipid levels. Patients should disclose all medications and supplements they are taking to their healthcare provider to avoid potential interactions.

3. Quality of Supplements: The market offers various nattokinase formulations; choosing high-quality products with standardized activity levels is crucial for ensuring efficacy and safety.

4. Population Considerations: While nattokinase is generally safe, individuals with specific health conditions, such as liver disease, should exercise caution and consult healthcare professionals before use.

FAQ

What is nattokinase?

Nattokinase is an enzyme derived from natto, a traditional Japanese fermented soybean dish. It is known for its fibrinolytic activity, which helps dissolve blood clots and improve cardiovascular health.

How does nattokinase lower lipid levels?

Nattokinase lowers lipid levels by activating enzymes involved in lipid metabolism, inhibiting cholesterol synthesis, and enhancing the breakdown of triglycerides.

Is nattokinase safe to use?

Generally, nattokinase is considered safe for most individuals. However, it may increase bleeding risk and should be used cautiously, especially in individuals on anticoagulant medications.

How does nattokinase compare to statins?

While statins provide significant and rapid LDL-C reduction, nattokinase offers a multifaceted approach to lipid management with fewer side effects, making it suitable for those intolerant to statins.

Can I take nattokinase with my current medications?

Before taking nattokinase, it is essential to consult a healthcare provider to ensure there are no potential interactions with current medications.

References

1. Wei, C., Cai, R., Song, Y., Liu, X., & Xu, H.-L. (2025). Research Progress of Nattokinase in Reducing Blood Lipid. Nutrients, 17(11), 1784

2. Chen, H., McGowan, E. M., Ren, N., Lal, S., Nassif, N., Shad-Kaneez, F., & Qu, X. (2024). Effective Management of Atherosclerosis Progress and Hyperlipidemia with Nattokinase: A Clinical Study with 1062 Participants. Frontiers in Cardiovascular Medicine, 9. Retrieved from https://pubmed.ncbi.nlm.nih.gov/12152994/

3. Zhang, H. X. (2025). Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects. MedComm, 2020. Retrieved from https://pubmed.ncbi.nlm.nih.gov/12152427/

4. Péntek, L., Szarka, G., Ross, L., Balogh, B., Telkes, I., & Völgyi, B. (2025). Eyes Are the Windows to the Soul: Reviewing the Possible Use of the Retina to Indicate Traumatic Brain Injury. Int J Mol Sci, 26(11), 5171

5. Medoro, A., Davinelli, S., Scuderi, L., Scuderi, G., & Scapagnini, G. (2025). Targeting Senescence, Oxidative Stress, and Inflammation: Quercetin-Based Strategies for Ocular Diseases in Older Adults. Clinical Interventions in Aging, 15, 1-12. Retrieved from https://doi.org/10.2147/CIA.S516946

6. Ghosh, S. (2025). Nail the diagnosis: Lamivudine-induced periungual pyogenic granulomas in PLHIV. IDCases, 12, e02270. Retrieved from https://doi.org/10.1016/j.idcr.2025.e02270