Nattokinase is best known as a clot-dissolving, fibrinolytic enzyme, but a separate and growing body of preclinical research points to a distinct anti-inflammatory mechanism, one that may partly explain its broader cardiovascular effects. This research is real and mechanistically interesting, but it remains almost entirely preclinical, which matters for how it should be interpreted.
Key Takeaways
- A 2020 study found nattokinase suppressed LPS-induced activation of TLR4 and NOX2 signaling in macrophages, reducing downstream production of TNF-alpha and IL-6, and protected against LPS-induced acute kidney injury in mice.
- A 2024 study found nattokinase pretreatment reduced circulating adhesion molecules and vascular inflammation in TNF-alpha-treated mice, along with reduced aortic wall thickness, a marker relevant to atherosclerosis progression.
- Nattokinase has separately been shown in an eye disease model to downregulate VEGF and several pro-inflammatory cytokines, including IL-6 and TNF-alpha, alongside its known anti-angiogenic effects.
- No published human clinical trial has directly measured nattokinase’s effect on circulating CRP, TNF-alpha, or IL-6 levels; the anti-inflammatory research base is presently animal and cell-culture evidence, not confirmed in human trials.
- This anti-inflammatory mechanism is proposed as complementary to, not a replacement for, nattokinase’s established fibrinolytic and blood-pressure-related cardiovascular effects.
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The Cell-Level Mechanism
A 2020 study examined nattokinase’s effect on inflammation independent of its clot-dissolving activity. Researchers found that in macrophages, immune cells central to the body’s inflammatory response, nattokinase suppressed LPS (a bacterial toxin commonly used to trigger inflammation in lab models) from activating TLR4 and NOX2 signaling pathways. That suppression reduced downstream reactive oxygen species production, MAPK pathway activation, and NF-kB translocation, all of which are steps in the cellular chain of events that leads to producing pro-inflammatory mediators like TNF-alpha, IL-6, nitric oxide, and PAI-1. In the same study, nattokinase also protected mice from LPS-induced acute kidney injury and prevented xylene-induced ear swelling, a classic simple test for anti-inflammatory activity.
Why This Might Matter for Vascular Health Specifically
A separate 2024 study looked specifically at vascular endothelial cells, the layer lining blood vessel walls that plays a central role in both clotting regulation and atherosclerosis development. Nattokinase pretreatment in this study upregulated SRF and THBS1 gene expression, which was linked to increased protective autophagy and decreased necroptosis (a form of inflammatory cell death) and NLRP3 inflammasome activity in endothelial cells. In TNF-alpha-treated mice, nattokinase pretreatment reduced circulating adhesion molecule levels and reduced aortic wall thickness, a structural marker relevant to atherosclerosis progression. The researchers concluded this points toward nattokinase as a potentially useful nutraceutical adjunct for reducing vascular inflammation, alongside its established fibrinolytic role.
A Third Data Point From Eye Research
Separately, research into nattokinase’s effect on retinal neovascularization, new blood vessel growth associated with diseases like diabetic retinopathy, found that nattokinase administration downregulated VEGF, along with pro-inflammatory cytokines including IL-6, TNF-alpha, and IL-17, and the MCP-1 chemokine. This is a third, independent research context (ocular rather than cardiovascular or renal) showing a consistent pattern: nattokinase reducing the same family of inflammatory signaling molecules across different disease models.
What Has Not Been Shown
All three lines of evidence described above come from animal models or isolated cell cultures, not human clinical trials. No published study has directly measured nattokinase’s effect on circulating CRP, the most commonly used clinical marker of systemic inflammation, or on TNF-alpha and IL-6 blood levels in human subjects. That is a meaningful gap between a consistent, mechanistically plausible preclinical signal and a confirmed clinical effect people can rely on. The pattern across kidney, vascular, and ocular models is scientifically interesting and worth continued research attention, but it should be described as a proposed mechanism under investigation, not an established, clinically-proven anti-inflammatory benefit.
How This Fits With Nattokinase’s Other Research
This anti-inflammatory mechanism is best understood as a complementary hypothesis to nattokinase’s better-established cardiovascular effects, its fibrinolytic activity, modest blood pressure reduction, and reduced von Willebrand factor levels, rather than a separate headline claim. Chronic low-grade inflammation and coagulation are known to interact and reinforce each other in vascular disease, so a compound affecting both pathways has a coherent scientific rationale, even while the inflammation-specific human data remains to be generated.
Frequently Asked Questions
Does nattokinase lower CRP or other inflammation markers in humans?
This has not been directly tested in a published human clinical trial. The anti-inflammatory research on nattokinase, involving TNF-alpha, IL-6, and related pathways, currently comes from animal and cell-culture studies, not confirmed human blood-marker trials.
What is the proposed mechanism behind nattokinase’s anti-inflammatory effect?
Preclinical research suggests nattokinase can suppress TLR4/NOX2 signaling in immune cells, reducing downstream production of TNF-alpha, IL-6, and reactive oxygen species, and can reduce inflammatory adhesion molecules and inflammasome activity in vascular endothelial cells.
Is this anti-inflammatory research separate from nattokinase’s clot-dissolving effects?
Yes, though the two may be related. Nattokinase’s fibrinolytic activity and its anti-inflammatory signaling effects appear to work through distinct cellular mechanisms, and researchers propose they may work together to support vascular health, particularly in the context of atherosclerosis.
Should I take nattokinase specifically to reduce inflammation?
The current evidence for this specific use is preclinical (animal and cell-culture studies), not confirmed in human trials. It is reasonable to view this as a promising area of ongoing research rather than a proven, clinically established anti-inflammatory benefit at this time.
These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease. Always talk to your doctor before starting nattokinase, especially if you take blood thinners or have an upcoming surgery.
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease. Content is for informational purposes only and is not medical advice; consult a qualified healthcare provider before starting any supplement. As an Amazon Associate we earn from qualifying purchases.
