Does Nattokinase Increase Estrogen Levels?

Nattokinase is an enzyme derived from natto, a traditional Japanese food consisting of fermented soybeans. Because soybeans contain compounds that can interact with the endocrine system, a common question is whether this enzyme, often taken as a supplement, influences the body’s delicate balance of hormones. This article investigates the current scientific understanding of Nattokinase’s mechanism and directly addresses whether it increases or affects estrogen levels in the human body.

The Nature of Nattokinase and Its Enzymatic Action

Nattokinase is classified as a serine protease, an enzyme that specializes in breaking down proteins. It is produced by the bacterium Bacillus subtilis natto during the fermentation process of boiled soybeans. Nattokinase is a protein composed of 275 amino acids, and its function is highly specific.

The primary function of Nattokinase is its potent fibrinolytic activity, meaning it acts as a clot-dissolving agent. It works by directly hydrolyzing fibrin, the protein structure that forms the mesh of a blood clot. This enzymatic action enhances the body’s natural ability to dissolve clots by converting prourokinase into urokinase and degrading plasminogen activator inhibitor-1.

How Estrogen Levels Are Regulated

Estrogen, a steroid hormone, is regulated through two primary biological processes: synthesis and metabolism. Estrogen production occurs through aromatization, which relies on the cytochrome P-450 enzyme known as aromatase. Aromatase converts precursor hormones, specifically androgens, into estrogens. This enzyme is present in various tissues, including the ovaries, adrenal glands, fat tissue, and the liver.

The second stage of regulation involves the breakdown and deactivation of circulating estrogen, which takes place predominantly in the liver. Liver enzymes perform Phase I hydroxylation, modifying the estrogen molecule. The modified estrogen is then prepared for excretion during Phase II metabolism, often through methylation and glucuronidation, which makes the hormone water-soluble for elimination. This complex, two-phase system ensures that estrogen levels are tightly controlled.

Scientific Evidence on Nattokinase and Estrogen Levels

The question of Nattokinase affecting estrogen levels stems from its source, the soybean, which contains isoflavones, a class of compounds known as phytoestrogens. Phytoestrogens can weakly bind to estrogen receptors, potentially mimicking or modulating estrogenic activity. However, Nattokinase itself is a purified enzyme, a large protein molecule, and not a phytoestrogen.

Mechanistically, Nattokinase is a protein-cleaving enzyme and acts solely on protein substrates like fibrin. Estrogen is a small, lipid-soluble steroid hormone, and its synthesis and metabolism are controlled by other classes of enzymes, specifically the steroidogenic enzyme aromatase and the liver’s Cytochrome P450 enzymes. There is no known biological pathway for a protease like Nattokinase to interact with these steroid-modulating enzymes or to physically bind to estrogen receptors.

Clinical research on Nattokinase has focused almost entirely on its effects on cardiovascular markers, such as blood pressure, cholesterol, and clotting factors. The safety studies conducted have not typically included comprehensive hormonal panels because a direct interaction is chemically implausible. Furthermore, the few clinical trials that involve Nattokinase and hormones are designed to test its safety when used alongside established Hormone Replacement Therapy (HRT), suggesting researchers do not consider it a hormone modulator.

Therefore, the scientific evidence indicates Nattokinase does not function as an endocrine disruptor or a hormone-mimicking substance. Its mechanism is highly specific to protein degradation within the circulatory system, a function entirely separate from the synthesis, metabolism, or receptor binding of estrogen. Any effects on hormones would be attributed to residual isoflavones in unpurified natto products, not the Nattokinase enzyme itself.

Conclusion on Clinical Relevance

Based on its specific biochemical action, Nattokinase is highly unlikely to impact endogenous estrogen levels. The enzyme’s role as a potent protease is limited to breaking down protein structures, such as fibrin, a function distinct from the processes that regulate steroid hormones. It does not interfere with the aromatase enzyme responsible for estrogen synthesis, nor does it interact with the liver’s complex metabolic pathways that break down and excrete estrogen.

For the average consumer, taking a Nattokinase supplement for its circulatory benefits does not carry the same concerns regarding hormonal activity as consuming large amounts of unfermented soy products. Individuals with pre-existing hormone-sensitive conditions, such as certain cancers or endometriosis, should always consult a healthcare provider before introducing any new supplement. This consultation ensures that any potential interactions with current medications or specific health risks are properly assessed.