Lumbrokinase

Lumbrokinase

1. Identity: Names, Source, and Preparations

Nomenclature and Classification

Lumbrokinases are a group of enzymes isolated and purified from different species of earthworms, recognized as fibrinolytic agents that can be used to treat various conditions associated with thrombosis. They belong to the group of serine proteases capable of preventing thrombosis through the proteolysis of both plasminogen-bound and plasminogen-free fibrin molecules. The enzymes were collectively named lumbrokinase after the genus name for earthworm, Lumbricus.

Lumbrokinase exists as a complex of six serine protease isoforms, each isoform having different molecular weights ranging from 14 to 33 kDa, with variety in fibrinolytic activity. LKs can maintain activity under both acidic and basic conditions, with a wide pH range of 1–11. Their protein molecular mass is between 20 to 35 kDa, and the isoelectric points (pI) range from 3 to 5. Some LKs are also resistant to high temperatures (up to 60°C).

Since each fibrinolytic enzyme was independently isolated and named by different research groups, the same enzyme may have multiple names. Therefore, the total number of LKs is not clear, and LK nomenclature needs to be standardized based on proteinase function, property, and source. One commercially standardized formulation is designated DLBS1033, derived from Lumbricus rubellus, used extensively in Indonesian and Chinese clinical research.

Natural Source Species

Earthworms such as Lumbricus rubellus and Eisenia fetida produce lumbrokinase, a fibrin-specific protease which can lower blood viscosity, minimize platelet accumulation, and promote thrombus dissolution by transporting it into the blood via the intestinal epithelium. Seven fibrinolytic enzymes were purified from E. fetida by Zhou et al. in 1988. Isozymes of LK have also been isolated from L. bimastus and E. andrei.

Commercial Preparations and Dosage Forms

Lumbrokinase has been manufactured into enteric capsules or enteric-coated tablets since the 1990s. The most common side effect is hypersensitivity caused by heterogeneous proteins. In China, there are five manufacturers producing lumbrokinase drug substances and enteric capsules; the substances are extracted from the cultured earthworm Eisenia fetida. The extraction process of lumbrokinase generally consists of three major steps: the bodies of the earthworm are milled and centrifuged to produce a supernatant, which is then purified with a DEAE (diethylaminoethyl) column and powdered through filtration, ultrafiltration, and lyophilization.

EFEs (earthworm fibrinolytic enzymes) demonstrate high-temperature stability, strong tolerance to organic solvents, a broad pH range, and some of them can be absorbed in intact form into the bloodstream through the intestinal epithelium. All these superior properties make these enzymes attractive as oral thrombolytic agents.

In clinical practice, LK can only be administered orally because of its antigenicity, immunogenicity, and potential to produce anaphylactic reactions after injection. Researchers have also investigated PEGylated (polyethylene glycol-modified) forms and recombinant expression systems — including yeast (Pichia pastoris) and transgenic plants — as approaches to enable injectable use and reduce production costs, though none are yet in routine clinical use.

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2. Traditional and Historical Use

Earthworms, also called Dilong (Earth Dragon) in Chinese, have been used as a traditional medicine and food resource in China, Japan, and other Far East countries for thousands of years. Earthworms contain many compounds with potential medicinal properties and have been administered to treat inflammatory, hematological, oxidative, and nerve diseases. Earthworms also exhibit antimicrobial, antiviral, and anticancer properties.

Earthworm (Lumbricus terrestris) is well known for its pharmaceutical value in Traditional Chinese Medicine. The written history of its application for medicinal usage can be traced back to 1578 AD, when the ancient physician Shizhen Li detailed the medical uses of earthworms in The Compendium of Materia Medica.

In traditional Chinese medicine, earthworm extracts (known as Dilong) have long been used to activate blood circulation, remove blood stasis, and address issues related to the liver, spleen, lung, and various neurological disorders, including as anticonvulsants, analgesics, and sedatives.

Earthworms have been used as a traditional medicine in China, Japan, and other Far East countries for thousands of years. Oral administration of dry earthworm powder is considered a potent and effective supplement for supporting healthy blood circulation.

Historically, North American Cherokee Indians used earthworm poultices to remove thorns, and the Nanticoke Tribe of Delaware used earthworms to treat rheumatic pain. Many alternative and traditional disciplines of medicine, such as those in China, Japan, and Korea, developed medicinal uses of Dilong from an initial utilization as nutrition.

In 1991, Dr. Mihara and other scientists in Japan successfully extracted and characterized a group of fibrinolytic enzymes from the earthworm species Lumbricus rubellus. These enzymes are capable of degrading both plasminogen-rich and plasminogen-free fibrin. This formal scientific characterization marked the transition from traditional empirical use to evidence-based investigation.

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3. Key Constituents and Mechanisms of Action

Biochemical Identity

Lumbrokinase is the name of a group of bioactive proteolytic enzymes including plasminogen activator and plasmin. The purified fractions contain five protein bands (F25-1, F25-2, F85-1, F85-2, and F85-3), which displayed strong fibrinogenolytic activity. F85-1, F85-2, and F85-3 showed molecular weights of 42.6 kDa, 27.03 kDa, and 14 kDa, respectively, and were identified as lumbrokinase isoenzymes. This study indicates that the F25 and F85 fractions are similar to published fibrinolytic protease-1 and lumbrokinase, respectively, in terms of their amino acid sequence.

In its direct mode of action, lumbrokinase hydrolyzes fibrin and fibrinogen by cleaving specific peptide bonds, primarily those involving basic amino acids such as arginine and lysine, owing to its trypsin-like serine protease nature. For instance, the isoform known as earthworm fibrinolytic enzyme II (EFE-II) from Eisenia fetida degrades the Aα chain of fibrinogen in both the N-terminal and C-terminal regions, facilitating the dissolution of mature, cross-linked clots.

Dual Mechanism of Fibrinolysis

Lumbrokinase has a dual mechanism in clot degradation: it acts on fibrin directly and activates plasminogen, converting it into plasmin, which subsequently induces plasmin-based clot dissolution. Lumbrokinase has the capability of directly dissolving fibrinogen and fibrin clots, inhibiting platelet activation and aggregation, converting plasminogen into plasmin, and increasing native tissue plasminogen activator (t-PA) activity to dissolve fibrin clots.

Fibrin Selectivity

Lumbrokinase has fibrinolytic and fibrinogenolytic activities, reduces blood viscosity, and reduces platelet aggregation. Lumbrokinase thrombolytic activity can only occur in the presence of fibrin; this indicates that treatment with lumbrokinase greatly reduces hemorrhage due to hyperfibrinolysis, in contrast with either streptokinase or urokinase. One key, remarkable property of lumbrokinase is that, unlike the medications streptokinase and urokinase, it is only active in the presence of fibrin.

Hemorheological Effects

Lumbrokinase reduces fibrinogen, prolongs prothrombin time (PT) and activated partial thromboplastin time (APTT), reduces plasma viscosity, and inhibits platelet aggregation. In vitro studies showed that DLBS1033 has fibrinogenolytic activities on fibrinogen α, β, and γ chains, decreasing platelet aggregation and prolonging clotting time.

Anti-inflammatory Properties

In animal research, lumbrokinase inhibited ischemia-reperfusion-induced arrhythmias and reduced mortality, as well as decreased lactate dehydrogenase levels in carotid blood. Lumbrokinase also inhibited the enhancement of ischemia-reperfusion-induced expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), and matrix metalloproteinases. These findings, from a rat model of myocardial ischemia-reperfusion injury, suggest cardioprotective effects beyond simple fibrinolysis — though they have not yet been replicated in human clinical trials.

Amyloid-Degrading Potential

Lumbrokinase is a 25–32 kDa fibrinolytic enzyme extracted from earthworms. Due to its effective fibrinolytic activity and inhibitory effects on platelet aggregation, lumbrokinase has been clinically proven to prevent and treat cardiovascular disease, and its amyloid-degrading potential has also been recently reported. This latter property is the basis for emerging investigation into post-viral and chronic illness applications (see below).

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4. Scientific Evidence by Area of Use

4.1 Acute Ischemic Stroke

Lumbrokinase has been widely used for patients with acute ischemic stroke (AIS) in China; however, because rigorously designed studies are lacking, safety and efficacy of lumbrokinase in the treatment of acute ischemic stroke remains largely unknown.

A 2025 meta-analysis published in a peer-reviewed journal provides the most comprehensive synthesis to date. A total of 64 studies were included in the analysis, selected after a comprehensive screening process that involved the identification of 1,836 records through database searches and manual reviews, followed by the exclusion of 1,773 duplicates and irrelevant studies. The final dataset comprised randomized controlled trials evaluating the efficacy and safety of the intervention across various clinical and laboratory outcomes.

A total of 35 RCTs published between 2010 and 2024 were included. Compared with supportive care alone, lumbrokinase adjunct therapy significantly improved Barthel Index scores (MD = 15.17; 95% CI: 14.60 to 15.74) and reduced NIHSS scores (MD = −2.01; 95% CI: −2.06 to −1.97). Safety analyses revealed no significant increase in adverse events including gastrointestinal discomfort (OR = 1.00; 95% CI: 0.32 to 3.16) and GI bleeding (OR = 1.42; 95% CI: 0.55 to 3.67).

An earlier meta-analysis of 4,751 patients from 33 randomized controlled studies found complementary results. You et al. found that lumbrokinase could facilitate the recovery of neurological functions and improve the activity of daily living, with mild side effects including nausea and vomiting, black stool (but stable hemoglobin levels), dizziness, and other symptoms at a low frequency.

Zuo found that lumbrokinase plus aspirin decreased plasma fibrinogen concentration, whole blood viscosity, and plasma viscosity. Patients treated with lumbrokinase plus aspirin had lower NIHSS scores 12 months later. Nonetheless, available studies were usually of poor quality with various methodological limitations.

In response to these limitations, a prospective multicenter double-blind placebo-controlled RCT (LUCENT trial) was designed. This multicenter, randomized, and controlled trial aims to compare lumbrokinase plus aspirin versus aspirin alone in patients with acute ischemic stroke. A total of 220 eligible participants are to be randomized in a 1:1 ratio. Participants must be diagnosed with acute ischemic stroke for the first time, with symptoms appearing within 72 hours, NIHSS scores between 5 and 15, and aged between 35 and 85 years. They must not have received intravenous thrombolysis, arterial thrombolysis, or intravascular intervention. This trial's results are awaited to determine lumbrokinase's standing in contemporary stroke care.

Evidence strength — Acute ischemic stroke: Moderate to preliminary. Multiple RCTs and meta-analyses exist showing neurological benefit and fibrinogen reduction; however, most component studies are of poor-to-moderate methodological quality, conducted predominantly in China, and rigorous Western double-blind placebo-controlled trials remain ongoing.

4.2 Secondary Prevention of Ischemic Stroke

For secondary prevention of ischemic stroke, a 2013 multicenter, randomized, parallel-group controlled trial published in the Chinese Medical Journal enrolled 310 patients with ischemic stroke. Adding one-year oral lumbrokinase enteric-coated capsules to standard therapy significantly reduced the incidence of total vascular events (2.08% vs. 6.78% in controls) and cerebral vascular events (1.04% vs. 5.93%), including recurrent ischemic stroke or transient ischemic attack. The intervention also lowered plasma fibrinogen levels, improved carotid plaque status (including reduced intima-media thickness and lower detection rate of vulnerable plaques), and reduced NIHSS scores compared to controls.

The study design was described as follows: this multicenter, randomized, parallel group and controlled study began treatment in hospitalized patients with ischemic stroke and continued for 12 months. Patients were randomized to either the control group receiving standard stroke treatment or the fibrinogen-depleting group receiving standard stroke treatment plus enteric-coated lumbrokinase capsules. NIHSS scores and plasma fibrinogen levels were recorded; carotid artery intima-media thickness and plaque status were examined through carotid ultrasound. Primary outcomes included all-cause mortality, any event of recurrent ischemic stroke/TIA, hemorrhagic stroke, myocardial infarction and angina, and other noncerebral ischemia or hemorrhage.

Evidence strength — Secondary stroke prevention: Preliminary positive. One well-described multicenter RCT shows significant reductions in vascular events over 12 months, but independent replication in other populations is absent.

4.3 Coronary Artery Disease and Myocardial Perfusion

Currently, LKs are widely used clinically as a thrombolytic agent in China to treat cerebral infarction, coronary heart disease, pulmonary heart disease, and deep vein thrombosis. Lumbrokinase has been used to treat patients with cardiovascular disease, to prevent secondary ischemic stroke, and to improve myocardial perfusion in patients with stable angina.

In animal models, the signaling pathways involved in lumbrokinase-inhibited expressions of inflammation mediators were investigated in rats subjected to myocardial ischemia-reperfusion injury. The left main coronary artery of anesthetized rats was subjected to 1 hour occlusion and 3 hours reperfusion. Lumbrokinase inhibited ischemia-reperfusion-induced arrhythmias and reduced mortality, as well as decreased lactate dehydrogenase levels in carotid blood.

Evidence strength — Coronary artery disease: Preliminary. Clinical use is documented in China; however, high-quality independent RCT evidence from well-designed trials focusing specifically on coronary artery disease endpoints is limited.

4.4 Peripheral Arterial Disease (PAD)

Lumbrokinase, an oral anti-thrombotic and fibrinolytic agent, was not yet part of the recommendations of any guidelines but had shown in two studies that it could increase the Ankle Brachial Index (ABI), which was used to evaluate drug efficacy for PAD.

A meta-analysis appraised two randomized control trials that evaluated the safety and efficacy of lumbrokinase compared to placebo with the standard regimen, and another study of lumbrokinase compared to placebo versus lumbrokinase with Prostaglandin E1 (PGE1) among adult patients for the reduction of symptoms of PAD and increase in ABI. Lumbrokinase at 460 to 490 mg three times a day for 2 weeks to 3 months showed no significant relationship but had a trend in increasing the ankle-brachial index to a borderline level compared to placebo. Additional studies with larger sample sizes must be done; further research is needed to illuminate whether a longer duration of treatment can increase the ABI more.

Evidence strength — PAD: Very preliminary. A borderline trend in ABI was observed in a small meta-analysis of just two RCTs; no strong conclusion is possible.

4.5 Post-Surgical and Intra-Abdominal Adhesion Prevention

Lumbrokinase treatment significantly decreased the severity and the area of intra-abdominal adhesion in vivo in a dose-dependent manner compared with controls (untreated and hyaluronate-treated). Lumbrokinase-associated adverse effects were not observed. Immunohistochemical analysis of adhesion tissues revealed a loosened adhesive band between tissues, coupled with significantly decreased peritoneal thickening in the lumbrokinase-treated group versus the control group.

Three-dimensional spheroid, MTT, and scratch wound migration assays using the IMR-90 human fibroblast cell line demonstrated that lumbrokinase significantly attenuated the migration and adhesive activity of fibroblasts without compromising cell proliferation.

Evidence strength — Post-surgical adhesion: Preclinical only (animal models and cell-line data). No clinical trials in human subjects have been published in this specific indication.

4.6 Diabetic Foot Ulcers and Peripheral Vascular Complications of Diabetes

Rey conducted a study on 28 diabetic foot ulcer subjects who were given three times 500 mg lumbrokinase or placebo per day (n=14) for seven days. In the treatment group, D-dimer was elevated, suggesting increased fibrinolytic activity. Based on its composition as a serine protease enzyme, lumbrokinase's mechanism of action as a fibrinolytic and antithrombotic is implicated in such effects.

Evidence strength — Diabetic complications: Extremely preliminary. A very small short-duration study exists; no definitive clinical conclusions are possible.

4.7 Long COVID, ME/CFS, and Post-Treatment Lyme Disease Syndrome

Early research showed that people with long COVID and ME/CFS have microclots. This points to a possible shared problem with blood flow in both conditions. Small fibrin/amyloid microclots have been identified in long COVID blood. The SARS-CoV-2 S1 protein may "seed" their formation by inducing a type of fibrinogen resistant to breakdown that becomes part of clot structure.

A clinical trial has been initiated to test if the fibrinolytic enzyme lumbrokinase improves symptoms and mitigates blood clotting issues or platelet hyperactivation in patients with long COVID, ME/CFS, and long Lyme disease. Small microclot deposits previously identified in long COVID and ME/CFS blood will be measured before and after treatment to determine if lumbrokinase disrupts their formation. The long Lyme arm of the trial is supported via the Steve & Alexandra Cohen Foundation's Clinical Trials Network Coordinating Center for Lyme and other Tick-Borne Diseases.

This second clinical trial, funded by the PolyBio Research Foundation at Mount Sinai, will test whether the enzyme lumbrokinase can help reduce the formation of microclots in patients with long COVID and/or ME/CFS. Past studies suggest the formation of microclots in the blood may contribute to overall symptom severity in these conditions. Researchers will test patients for microclots before taking lumbrokinase, then test them after taking the supplement to see if this enzyme breaks down microclots, and will also evaluate whether symptoms improve for patients while taking the supplement.

This trial (NCT06511050), being conducted by the Icahn School of Medicine at Mount Sinai, is currently recruiting as of early 2026, with an estimated primary completion date of December 2026.

Although research in long COVID and ME/CFS is still in early stages, the mechanisms of these enzymes are compelling. Until large-scale trials are completed, lumbrokinase remains a promising but experimental tool in managing microclot-related symptoms.

Evidence strength — Long COVID/ME/CFS/Lyme: Investigational only. Clinical trials are currently in progress; no efficacy or safety data from completed human trials in these populations have yet been published.

4.8 Nerve Regeneration

Wei et al. (2009) used Lumbricus, a widely known earthworm in traditional Chinese medicine, to show increased nerve cell regeneration in damaged nerves in rats, noting the earthworm's ability to regenerate severed body members. Studies in animal models have suggested benefits for peripheral nerve regeneration in streptozotocin-induced diabetic rats through improved circulatory blood flow and axonal regeneration.

Evidence strength — Nerve regeneration: Preclinical only. No human trials exist in this indication.

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5. Body Systems and Health Areas of Association

• Cardiovascular system: Thrombus dissolution, fibrinogen reduction, platelet aggregation inhibition; applied clinically in China for cerebral infarction, coronary heart disease, angina, and pulmonary heart disease. LKs are widely used clinically as a thrombolytic agent in China to treat cerebral infarction, coronary heart disease, pulmonary heart disease, and deep vein thrombosis.
• Cerebrovascular system: Acute ischemic stroke treatment and secondary stroke prevention; modulation of post-ischemia neurological outcomes. Lumbrokinase significantly attenuated infarct volume and improved neurological dysfunction in animal models of permanent middle cerebral artery occlusion.
• Peripheral vascular system: Peripheral arterial disease with evidence for borderline improvement in ankle-brachial index; also relevant for deep vein thrombosis and peripheral embolism.
• Coagulation and fibrinolytic system: Modulation of fibrinogen levels, PT/APTT, D-dimer, and platelet function. The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis.
• Connective tissue / post-surgical: Prevention of intra-abdominal fibrous adhesion formation via attenuation of fibroblast migration and AP-1/ICAM-1 signaling. Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix.
• Immune and inflammatory system: Earthworms have been administered to treat inflammatory, hematological, oxidative, and nerve diseases. Lumbrokinase specifically has shown inhibition of COX-2, iNOS, and matrix metalloproteinase expression in animal studies.
• Microcirculatory/post-viral: Investigational interest in fibrin/amyloid microclot dissolution in long COVID and ME/CFS.

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6. Dosage Forms and Dosages Reported in Studies

In the current Chinese guidelines for the treatment of acute ischemic stroke, lumbrokinase is listed as a defibrinogenating agent with strong recommendation. The specific dosage protocols reported in published research are as follows:

• Acute ischemic stroke (Chinese clinical practice): Enteric-coated capsules used in the LUCENT trial protocol and comparable RCTs, given orally in divided doses; the formulation, specific per-capsule dose in mg of active enzyme, and interval vary by study. Jin et al. conducted a study on 51 cerebral infarct subjects who were given oral lumbrokinase for 28 days. A separate study by Rey used three times 500 mg lumbrokinase or placebo per day (n=14) for seven days in diabetic foot ulcer subjects.
• Secondary stroke prevention (Cao et al., 2013): One-year therapy with oral lumbrokinase enteric-coated capsules; the multicenter, randomized, parallel group study began treatment in hospitalized patients with ischemic stroke and continued for 12 months.
• Peripheral arterial disease: Lumbrokinase at 460 to 490 mg three times a day for 2 weeks to 3 months.
• Healthy volunteer safety trial: Enteric-coated lumbrokinase at 490 mg taken three times daily was well tolerated in healthy adults over 14 days, with no significant adverse effects reported.
• Supplement product guidance (Boluoke formulation): For most chronic conditions and maintenance, 1 capsule once to three times daily on an empty stomach is suggested. In acute conditions, Boluoke can be taken at a dose of 2 capsules three times daily on an empty stomach for 3 to 6 weeks or as long as a doctor recommends.

Lumbrokinase dosing in research is typically measured in units (U) rather than milligrams, and the specific doses vary across studies. Supplement manufacturers commonly sell products in the range of 20,000 to 40,000 units per capsule, with labels suggesting one to three capsules daily.

It should be noted that activity units used for lumbrokinase (LKUs, FUs, IUs) are not interchangeable across products or studies, and the lack of a standardized international unit makes cross-study dosage comparisons difficult.

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7. Safety Considerations and Drug Interactions

Overall Safety Profile

Lumbrokinase appears to be safe for most people based on the available clinical evidence. A meta-analysis of multiple trials found no significant increase in adverse events compared to standard therapy, including no meaningful difference in rates of gastrointestinal discomfort, vomiting, rash, or GI bleeding. That said, lumbrokinase is a fibrinolytic enzyme, and that mechanism carries inherent risks in certain situations.

Lumbrokinase has not shown any adverse effects on the functions of the nervous system, respiratory system, cardiovascular vessels, or the liver and kidney.

Known and Documented Adverse Effects

A meta-analysis of 4,751 patients from 33 randomized controlled studies found mild side effects including nausea and vomiting, black stool (but stable hemoglobin levels), dizziness, and other symptoms at a low frequency.

The final product may also contain other earthworm contaminants that can induce adverse side effects, such as an upset stomach or vomiting. The most common side effect reported with conventional preparations is hypersensitivity caused by heterogeneous proteins.

Route-Specific Safety Issue

In clinical practice, LK can only be administered orally because of its antigenicity, immunogenicity, and potential to produce anaphylactic reactions after injection. This is a clinically significant consideration distinguishing lumbrokinase from conventional injectable thrombolytics such as tPA or streptokinase.

Drug Interactions

Major clinical trials have excluded participants who were already taking anticoagulants, antiplatelet drugs, or nonsteroidal anti-inflammatory drugs like ibuprofen within seven days of starting lumbrokinase.

Anticoagulant drugs like warfarin, heparin, or direct oral anticoagulants (DOACs) may have an additive effect when taken with lumbrokinase, increasing the risk of bleeding. Similarly, antiplatelet medications such as aspirin or clopidogrel can also interact with lumbrokinase, potentially enhancing their blood-thinning effects and leading to an elevated risk of bleeding complications. Conversely, medications that promote clot formation or inhibit fibrinolysis might reduce the effectiveness of lumbrokinase.

Some commercially available lumbrokinase products have been used concomitantly with anticoagulants in clinical studies with a reported acceptable profile, reflecting a property of lumbrokinase distinct from conventional anticoagulants — its mechanism acts on fibrin directly rather than primarily on the clotting cascade. Boluoke has been shown not to significantly affect PT and aPTT (thus it does not affect INR).

Perioperative Considerations

Because lumbrokinase is a fibrinolytic enzyme, perioperative management is an important concern. Product guidance based on clinical practice indicates that the conservative approach is to discontinue lumbrokinase prior to elective surgery and to delay reinstatement postoperatively, though no formal guideline from a major international health body currently addresses this specifically for lumbrokinase.

Pregnancy and Lactation

There is no published safety data on lumbrokinase use during pregnancy or breastfeeding, which means the risk is simply unknown rather than established as safe.

Contraindications Noted in Research Protocols

Based on design criteria used in clinical trials and formulation documentation, contraindications consistently cited include known allergy to lumbrokinase or earthworm protein, recent surgical procedure, active hemorrhage, and pre-existing bleeding disorders. Lumbrokinase-associated adverse effects were not observed in the intra-abdominal adhesion animal studies, and enteric-coated lumbrokinase at 490 mg three times daily was well tolerated in healthy adults over 14 days.

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8. Regulatory and Research Context

In the current Chinese guidelines for the treatment of acute ischemic stroke, lumbrokinase is listed as a defibrinogenating agent with strong recommendation. Lumbrokinase has not been approved by the U.S. Food and Drug Administration (FDA) as a drug and is sold in North America, Europe, and Australia as a dietary supplement. No entry exists in the European Medicines Agency, WHO monographs, or the German Commission E for lumbrokinase specifically, though the ingredient is in active academic and clinical investigation globally.

Many lumbrokinase genes have been cloned and characterized. Advances in genetic technology have provided the ability to produce recombinant LK and have made it feasible to purify a single lumbrokinase enzyme for potential antithrombotic application. Recombinant production platforms — including Pichia pastoris, Escherichia coli, and transgenic tobacco plant systems — are under development to address quality standardization, production scalability, and the elimination of co-purified earthworm allergens that complicate conventional preparations.

References

• Stephani L et al. "Purification and proteomic analysis of potent fibrinolytic enzymes extracted from Lumbricus rubellus." Proteome Science, 2023. PMC10165752
• Nguyen QTT et al. "Lumbrokinase, a Fibrinolytic Enzyme, Prevents Intra-Abdominal Adhesion by Inhibiting the Migrative and Adhesive Activities of Fibroblast via Attenuation of the AP-1/ICAM-1 Signaling Pathway." BioMed Research International, 2023. PMC9851794
• Wang KY et al. "Recombinant Protein Production of Earthworm Lumbrokinase for Potential Antithrombotic Application." Evidence-Based Complementary and Alternative Medicine, 2013. PMC3876685
• Therapeutic Potential of Lumbrokinase in Acute Ischemic Stroke: A Meta-Analysis of Efficacy and Safety. PubMed Central, 2025. PMC12417717
• Efficacy and safety of lumbrokinase plus aspirin versus aspirin alone for acute ischemic stroke (LUCENT): study protocol for a multicenter randomized controlled trial. Trials, 2022. PubMed 35410433
• Cao Y-J et al. "Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a multicenter, randomized, parallel-group and controlled clinical trial." Chinese Medical Journal, 2013. PubMed 24229674
• LUCENT Trial Protocol. "Efficacy and safety of lumbrokinase plus aspirin versus aspirin alone for acute ischemic stroke." Trials, 2022. PMC8996506
• Agoncillo A. "Meta-analysis on the safety and efficacy of Lumbrokinase in peripheral arterial disease." European Heart Journal. Acute Cardiovascular Care, 2021. PMC8263976
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• Dilong: Food for Thought and Medicine. PMC, 2014. PMC3942902
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• Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review. PMC, 2024. PMC11528390
• NCT06511050: Lumbrokinase for Adults With Long Covid, Post-treatment Lyme Disease Syndrome, and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. ClinicalTrials.gov, Icahn School of Medicine at Mount Sinai.
• PolyBio Research Foundation: Lumbrokinase LongCOVID & ME/CFS Clinical Trial.
• Mount Sinai News: Mount Sinai Receives $2.6 Million Grant From PolyBio Research Foundation for Long COVID Clinical Trials, 2024.
• Cloning of thrombolytic enzyme (lumbrokinase) from earthworm and its expression in the yeast Pichia pastoris. ScienceDirect, 2005.
• Preparation of pegylated lumbrokinase and an evaluation of its thrombolytic activity both in vitro and in vivo. ScienceDirect, 2013.
• A Clinical Trial on Biological Half Life of Bioactive Protein DLBS1033. International Journal of Integrated Medicine.