Nattokinase: New Biological Activities, Clinical Applications, and Emerging Manufacturing Technologies

Nattokinase (NK) is a serine protease enzyme originally isolated from natto, a traditional Japanese fermented soybean food. Produced by the bacterium Bacillus subtilis during fermentation, NK is renowned for its potent fibrinolytic activity – it directly dissolves fibrin blood clots and enhances the body's natural thrombolysis. It has gained attention as a natural nutraceutical for cardiovascular health, with studies indicating benefits such as improved blood flow and mild blood pressure reduction. Beyond these well-established antithrombotic effects, emerging research reveals that NK may exert diverse biological activities. These include antihypertensive and anti-atherosclerotic effects (improving lipid profiles and reducing arterial plaque formation), anti-platelet aggregation, anti-inflammatory properties, and even neuroprotective potential (for example, the degradation of amyloid-beta plaques in models of Alzheimer’s disease). NK has also demonstrated benefits in ocular health by reducing pathological retinal neovascularization in disease models. These multifaceted functions underscore the broad relevance of NK to human health across cardiovascular, metabolic, and neurological domains. As a food-derived enzyme with therapeutic potential, nattokinase exemplifies the intersection of nutrition and medicine, making it a compelling subject for research in clinical nutrition, food science technology, and metabolism.

This Research Topic aims to consolidate state‑of‑the‑art knowledge on nattokinase from manufacturing to clinical application. We seek contributions that (i) clarify established and emerging biological activities of NK and their mechanisms of action; (ii) evaluate the current clinical evidence in human health, with an emphasis on cardiovascular and related cardiometabolic or neurovascular outcomes; and (iii) advance the field’s understanding of pharmacokinetics, bioavailability, and appropriate dosing strategies. In parallel, we will also highlight next‑generation production, purification, formulation, and delivery technologies that improve enzyme yield, purity, stability, and product consistency. A further objective is to critically examine safety, including drug–nutrient interactions, contraindications, and adverse event reporting, to support more rational and responsible use of NK in nutrition and healthcare settings.

This Research Topic welcomes submissions of Original Research, Reviews, Mini Reviews, Perspectives, and Clinical Trial articles focused on nattokinase in human nutrition and health. Manuscripts may address (but are not limited to):
● Pharmacological and nutritionally relevant mechanisms of NK (fibrinolytic, vascular, metabolic, neurovascular/neuroprotective, anti-inflammatory, and other emerging effects)
● Pharmacokinetics/pharmacodynamics, oral bioavailability, metabolism, biomarkers of exposure/response, and dose–response relationships
● Human studies (interventional or observational), including pragmatic and real world evidence, with rigorous reporting of endpoints and adverse events
● Drug–nutrient and nutraceutical–nutraceutical interactions, particularly with anticoagulants/antiplatelet agents and commonly used cardiometabolic therapies
● Safety and risk assessment (bleeding risk, contraindications, special populations, long term use, and post market surveillance)
● Manufacturing and enabling technologies (fermentation optimization, strain improvement/recombinant production, purification, quality control/standardization, and novel formulations or delivery systems)