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byNicolas Hulscher, MPHWe have just assembled decades of evidence to evaluate the remarkable multi-target effects of nattokinase, an orally administered fibrinolytic enzyme derived from natto, the traditional Japanese fermented soybean food. Across the literature, nattokinase shows activity spanning spike protein, amyloid, abnormal microclots, fibrin, coagulation, blood pressure, platelet activity, and atherosclerotic plaque.Our new paper,“Proteolytic Targets and Clinical Benefits of Oral Nattokinase: Spike Protein and Amyloid Degradation, Fibrinolysis, and Cardiovascular Risk Reduction,”was produced through a collaboration between The Wellness Company and the McCullough Foundation. It represents one of the most comprehensive evaluations of nattokinase to date, uniquely integrating its proteolytic, cardiovascular, pharmacokinetic, amyloid, and spike-protein literature into a single review.The paper brings together the evidence across eight major domains:SPIKE PROTEIN DEGRADATIONThree independent laboratories have reported that natto-derived or related serine proteases can degrade SARS-CoV-2 spike protein in vitro.Most importantly,purified nattokinase itselfproduced dose- and time-dependent degradation of full-length spike protein and the S2 subunit across a broad concentration range. Researchers also demonstrated degradation of spike expressed on the surface of cells.Different preparations, different model systems, same basic conclusion: spike protein is susceptible to degradation by this class of proteolytic enzymes.AMYLOID DEGRADATIONNattokinase has also demonstrated activity against several structurally distinct amyloid proteins.Published studies report degradation ofAβ40, Aβ42, human prion peptide fibrils, insulin fibrils, and β2-microglobulin fibrils. This broad activity suggests that nattokinase can attack abnormal cross-β protein structures rather than acting on only one specific amyloid protein.AMYLOID MICROCLOT DISSOLUTIONRecombinant nattokinase has directly degradedfibrinaloid amyloid microclots in vitro.These abnormal structures are composed largely of misfolded fibrin(ogen) and have been reportedin persistent illness following COVID-19 mRNA injection. Because spike protein itself can drive fibrin(ogen) into a fibrinolysis-resistant amyloid state, nattokinase is particularly relevant: it may targetboththe abnormal clot structure and, experimentally, the spike protein involved in its formation.BLOOD CLOT BREAKDOWNFibrinolysis remains nattokinase’s best-established biological activity.Nattokinase can directly cleave fibrin independently of plasminogen. Experimental work also found that it cleaved cross-linked fibrin with roughlysix-fold the catalytic efficiency of plasmin in vitroand dissolved thrombus aboutfour times as effectively at an equivalent molar dose in an animal model.BOOSTING THE BODY’S NATURAL CLOT-DISSOLVING SYSTEMNattokinase does not only attack fibrin directly.It can also cleave and inactivatePAI-1, one of the body’s major brakes on fibrinolysis, while promoting release oftissue plasminogen activator (tPA). This gives nattokinase two potential routes to the same endpoint: direct clot breakdown and enhancement of the body’s endogenous fibrinolytic machinery.SHRINKING ARTERIAL PLAQUEThe human carotid imaging findings are among the most striking observations in the review.At2,000 FU/day, a long-term randomized placebo-controlled trial found no significant plaque effect. A lower-dose arm at3,600 FU/daywas also ineffective.But at6,000 FU/day, carotid plaque area fell by36.6% over 26 weeks.At10,800 FU/day, another study reported an approximately36% reduction over 12 months, together with a decline in carotid intima-media thickness from 1.33 to 1.04 mm.That dose pattern raises the possibility of a therapeutic threshold around6,000 FU/day.LOWERING BLOOD PRESSURERandomized human evidence also supports a modest blood-pressure effect.A meta-analysis of six randomized trials involving 546 participants found average reductions of approximately3.45 mmHg systolicand2.32 mmHg diastolicblood pressure.REDUCING COAGULATION AND PLATELET CLUMPINGHuman studies have reported reductions in several important coagulation markers, includingfibrinogen, factor VII, factor VIII, and von Willebrand factor.Nattokinase has also been shown experimentally to inhibitplatelet aggregation and thrombus formation, adding another pathway through which it may influence cardiovascular risk.THIS ISN’T JUST A TEST-TUBE STORYAfter oral dosing, nattokinase-related material has been detected in human blood, with peak serum immunoreactivity occurring at roughly13 hours.In a randomized, double-blind, placebo-controlled crossover study, a single oral dose also changed multiple clotting and clot-breakdown markers within hours, including increased D-dimer and fibrin degradation products, reduced factor VIII activity, increased antithrombin, and prolonged aPTT.LOWER CARDIOVASCULAR AND STROKE MORTALITY WITH NATTO INTAKELong-term population data point in the same direction.In prospective Japanese cohorts, higher natto intake was associated with a25% lower risk of cardiovascular mortalityand a32% lower risk of stroke mortality.SAFETYNattokinase has beenwell tolerated across human studies, with no notable adverse events reported across six randomized trials. Even10,800 FU/day for 12 monthswas used in a large observational cohort without reported excess bleeding.Its main precaution is predictable from its clot-dissolving effects: people taking blood thinners or antiplatelet medications should use it only with medical supervision, and pregnant women should avoid nattokinase because its safety in pregnancy has not been established.CONCLUSIONNattokinase is inexpensive, orally available, already widely used, and holds immense promise for cardiovascular risk reduction in the post-COVID era.The major unanswered question is no longer whether nattokinase can degrade these targets under experimental conditions. It can.The critical translational question is whether orally administered nattokinase reaches circulating or tissue spike protein, fibrinaloid microclots, and other pathological protein targets at concentrations high enough to reproduce these effects in humans.It now deserves large-scale clinical testing for cardiovascular risk reduction and other post-vaccination injury applications.We plan to launch some of these studies shortly. In particular, we will be studying the potential spike-reducing effects ofUltimate Spike Detox(8,000 FU nattokinase) in a large cohort of participants.Nicolas Hulscher, MPHEpidemiologist and Foundation Administrator, McCullough FoundationSupport our mission:mcculloughfnd.orgPlease consider following both theMcCullough Foundationandmy personal accountonX(formerly Twitter) for further content.FOCAL POINTS (Courageous Discourse™) is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.