Why Women Taking Birth Control Should Consider Nattokinase

While sitting having breakfast with her award-winning singer husband Justin, model Hailey Bieber suddenly felt a weird sensation going down her arm and into her fingertips, and then her face drooped. Although only in her 20s, she was having a stroke. Among other factors such as lack of sufficient hydration, one culprit, said her doctors, was likely her birth control.

At least 248 million women globally are using hormonal contraception, according to the World Health Organization. Using birth control pills and other hormone-based contraceptives is known to elevate the risk of blood clot development. Although the risk may be small, it should not be ignored.

The most common hormone contraceptive prescribed for women is the combination of estrogen and progestin, which has been identified as creating a greater risk of ischemic stroke and myocardial infarction, according to a study of more than 2 million women aged 15 to 49. After five years of follow-up (22,209,697 person-years), 4,730 ischemic strokes were recorded.

Birth Control and Clotting

Overall, there is substantial published data comparing blood clot prevalence between women taking birth control pills and those not taking them. It appears that estrogen is the villain in hormonal birth control, as the data consistently show that combined hormonal contraceptives containing estrogen increase the risk of venous thromboembolism (VTE). And in the previously mentioned study, non-oral combined estrogen-progestin contraception methods, including the vaginal ring and the transdermal patch, had higher associated risks.

A 1990 study found that 30 mcg or more of estrogen has a dose-dependent effect on clotting factors.

Women of childbearing age who are not taking oral contraceptives have a baseline VTE incidence of up to 5 per 10,000 women each year. In contrast, women taking birth control pills experience a rate of 3 to 9 per 10,000 women per year. FDA research found that out of every 10,000 women taking birth control pills, 3-9 will develop a blood clot, compared to 1-5 per 10,000 women not using birth control. Over a 10-year period, the rate for clots is about 0.3% to 1% for women on the pill.

The risk is reduced after the birth control is stopped. Researchers analyzed coagulation biomarkers associated with combined hormonal contraceptives and clotting activity in 66 women while taking birth control and several weeks after the last dose.

Women exhibited elevated levels of clotting markers while taking birth control. After stopping their contraceptives, these coagulation markers plummeted within two weeks, and by week 12, all markers were similar to the control group of women not using hormone-based birth control. Overall, around 80% of the total drop in clotting markers seen in these women occurred within two weeks of stopping their birth control.

The thrombogenicity of estrogen-progestin birth control is believed to be caused largely by changes in clotting factors and vasculature induced by the contraceptive. 

The Role of Fibrin in Coagulation

Fibrin can be beneficial and, conversely, potentially dangerous by increasing clot formation. Regulating fibrin production is key to ensuring proper blood coagulation (such as when the skin is cut).

Fibrinogen, a soluble protein in blood plasma, produces fibrin. Injury activates the enzyme thrombin which converts fibrinogen into insoluble fibrin strands. These strands form a mesh, trapping red blood cells and platelets, thus beginning the clotting process to stop bleeding and support tissue repair.

Excess fibrin tends to create rogue blood clots that may trigger potentially fatal events such as heart attacks and stroke. The stopgap in this situation is the enzyme plasmin which is involved in fibrinolysis, the process that destroys dangerous excess fibrin.

The key to reducing risk of unnecessary clot production is the ability to regulate fibrin production. This is where nattokinase, a well-studied serine proteinase from Bacillus subtilis, can be most beneficial.

The Role of Nattokinase in Fibrin Regulation

Research shows that nattokinase regulates fibrin through three key mechanisms:

Enhances Plasmin Activity: Nattokinase indirectly generates fibrinolysis by stimulating plasminogen activators, specifically tissue plasminogen activator, accelerating conversion of plasminogen to plasmin.

Reduces Fibrinogen Levels: Research suggests that nattokinase may reduce circulating fibrinogen in the blood, reducing the raw material available for excessive clot formation.

Inhibits Platelet Aggregation: Nattokinase has been shown to inhibit clumping of platelets, another mechanism by which clots may form. A review of human studies suggests that nattokinase helps decrease blood viscosity and boost blood flow, reduce the stickiness of red blood cells, thereby inhibiting platelet aggregation.

After two months of supplementation with nattokinase, researchers observed that plasma levels of three coagulation factors declined: fibrinogen by 9%, factor VII by 14%, and factor VIII by 17%. 

NSK-SD nattokinase has been shown in more than 30 pre-clinical and human studies to degrade fibrin clots both directly and indirectly. Clot lysis assays indicate NSK SD dissolves fibrin six times more effectively than plasmin, which is involved in clot degradation and removal. NSK-SD also targets fibrin indirectly by affecting plasminogen activator activity (the first step of plasmin production).

A single dose of 2000FU nattokinase (as NSK-SD) induced fibrinolysis through cleavage of cross-linked fibrin. Specifically, the antithrombin concentration in participants’ blood increased significantly only two hours after supplementation. Fibrinogen degradation product fragments and d-dimers (indicators of clot degradation) were observed four and six hours after nattokinase consumption, respectively, and factor VIII activity declined four hours after NK ingestion. The results of this study indicated that multiple pathways may be involved in NK fibrinolysis and anti-coagulation activity. 

Supplementation with 8000FU nattokinase (NSK-SD) for 90 days was significantly correlated with the improvement of platelet function, D-dimer (a protein fragment indicative of clot degradation) and whole blood viscosity in a high-risk population of cardiovascular and cerebrovascular diseases, and the effect was more discernible through time (Qian 2024).

In a rat model of thrombosis in the common carotid artery, those administered nattokinase (NSK-SD) recovered 62% of arterial blood flow.

The evidence strongly suggests that nattokinase supplementation helps reduce risk of clot formation through regulating fibrin production.

Conclusion

Although the risk for stroke caused by unnecessary clot development among women taking estrogen-progestin birth control is small, women who are proactive with a preventative health mindset will appreciate the ability to reduce their risk even further.