Summary
Highlights
Dr. Lily Johnston introduces herself as a vascular surgeon specializing in cardiometabolic prevention and explains that she no longer uses Nattokinase, despite frequent patient inquiries. She recounts the case of Susan, a patient with established carotid plaque and a family history of high cholesterol, who was motivated to try Nattokinase as an alternative to statins.
Nattokinase is an enzyme from fermented soybeans, widely sold as a cardiovascular supplement. Its purported benefits include breaking up existing clots by cleaving fibrin bonds, enhancing the body's natural clot-busting system (fibrinolysis), increasing TPA (tissue plasminogen activator), lowering blood pressure by inhibiting ACE, and preventing platelet aggregation.
A key question is Nattokinase's bioavailability, as stomach acid can degrade enzymes. While some studies suggest it makes it into the bloodstream, the exact amount is unknown and possibly variable. The most replicated and confident finding for Nattokinase is its modest effect on blood pressure control, with meta-analyses showing a small but statistically significant decrease (e.g., 3 mmHg systolic, 2 mmHg diastolic). While not a primary choice for blood pressure management, it's considered a reasonable option if conventional medications are avoided.
The video delves into the controversial claims regarding Nattokinase's effect on atherosclerosis (plaque) and LDL cholesterol. A 2022 study, widely discussed online, suggested significant plaque and LDL reduction. However, Dr. Johnston identifies major flaws in this study, including its retrospective, non-randomized design, lack of a control group, unclear dosing, potential confounding factors (co-administered Vitamin K2 and aspirin), and conflict of interest (authors affiliated with Nattokinase manufacturers).
Further concerns are raised about the 2017 study from the same research group, which was published primarily in Chinese, had questionable randomization methods, and lacked blinding for ultrasound technicians. The claimed 36% plaque reduction is considered unrealistic given that even aggressive medical management typically yields less than 5% regression. Regarding lipid reduction, studies on Nattokinase show mixed results, with randomized trials often finding no significant change in atherogenic lipid particles like APOB. The observed lipid changes in some studies could be due to co-administered supplements like red yeast rice.
While lower doses of Nattokinase (2000 FU) appear safe in randomized trials, the impact of higher doses on clotting factors is unclear. Case reports highlight potential adverse events, including bleeding when combined with aspirin or taken alone, and a patient who developed clots after substituting Nattokinase for prescribed blood thinners. The unregulated nature of supplements is also emphasized, with studies showing significant variability in actual Nattokinase content compared to label claims, raising concerns about both efficacy and safety.
The Nattokinase Atherothrombotic Prevention Study (NAPS) by Dr. Howard Hodis, a well-designed, blinded, and placebo-controlled trial over three years with over 250 patients, found no change in CINT (carotid intimal medial thickness), arterial stiffness, blood pressure, or coagulation factors at the standard 2000 FU dose. This robust study contradicts claims of plaque regression and highlights the need for a clear dose-response curve for Nattokinase's effects on plaque.
Despite initial enthusiasm based on the 2022 study, Susan, after a year on a high dose of Nattokinase (10,000-12,000 FU), showed progression in her CINT, leading to an almost decade increase in her arterial age, while her plaque burden remained unchanged. This N=1 experiment, combined with the critical evaluation of the literature, led Dr. Johnston to stop recommending Nattokinase for plaque. She encourages patients who choose to use it to test and monitor their progress, rather than relying on anecdotal evidence or flawed studies, emphasizing the importance of evidence-based intervention in managing cardiovascular disease.