Lumbrokinase (Earthworm Fibrinolytic Enzyme)

Lumbricus rubellus (earthworm) — six fibrinolytic serine proteases
Evidence Level
Limited
3 Clinical Trials
7 Documented Benefits
2/5 Evidence Score

A group of six fibrinolytic serine-protease enzymes extracted from the earthworm Lumbricus rubellus. Used in Traditional Chinese Medicine for centuries as 'di long' (earth dragon) for circulatory conditions. Almost all of its human research was done in hospital patients being treated for stroke, not in people buying a supplement, and that research is weak. A 2025 meta-analysis pooled 35 trials whose own reviewers describe many as carrying a moderate to high risk of bias, with heterogeneity of 97 percent and 94 percent on its two main outcomes and limited generalizability. None of the 35 trials used a placebo or blinded its patients, nearly all were published in Chinese local journals, and none compared lumbrokinase directly with alteplase. The one placebo controlled study in healthy adults was a 20 person safety trial of 490 mg three times daily for 14 days, and it found no change in any clotting measurement versus placebo. Because lumbrokinase breaks down fibrin, the practical issue for most readers is bleeding risk and interaction with blood thinners rather than benefit. It is extracted from earthworms, so it is not vegetarian or vegan. Stroke and clotting disorders are medical conditions treated by a doctor, and nothing on this page is a substitute for prescribed treatment.

Studied Dose No dose has been established for healthy people; the only placebo controlled study used 490 mg three times daily for 14 days and produced no change in clotting versus placebo.
Active Compound Six fibrinolytic serine-proteases collectively named lumbrokinase (abundant asparagine/aspartic acid, minimal proline/lysine).

Benefits

What the pooled hospital research actually shows

The largest evidence summary is a 2025 meta-analysis of 35 trials in hospital patients receiving supportive care after a stroke. It reported better Barthel Index and NIHSS scores and an overall curative effect (odds ratio 2.77, 2.33 to 3.29), but heterogeneity was 97 percent and 94 percent for those two functional outcomes, none of the 35 trials used a placebo or blinded its patients, and the reviewers state that many carried a moderate to high risk of bias. When the pooled response was broken into specific grades, most were not significant, including cured (odds ratio 1.12, 0.83 to 1.52) and markedly effective or effective (0.92, 0.62 to 1.38). None of this describes a healthy person taking a capsule at home, and none of it is a reason to use lumbrokinase instead of medical care.

One year hospital trial of fibrinogen lowering

In a Chinese multicenter trial, 310 hospitalized stroke patients were assigned to standard stroke treatment alone (118 people) or standard treatment plus enteric coated lumbrokinase (192 people) for 12 months. There was no placebo group, blinding is not reported, and the two groups were of very unequal size. Plasma fibrinogen, carotid intima media thickness and NIHSS scores were better in the lumbrokinase group, and the incidence of total vascular endpoints was 2.08 percent versus 6.78 percent over the year. The authors concluded only that such therapy may be beneficial. This was hospital care for people who had already had a stroke. Anyone in that situation is under a doctor's management and must not swap prescribed treatment for a supplement.

Measured changes in clotting tests (small hospital study)

In a small single blind study of 51 hospitalized patients with cerebral infarction (31 given lumbrokinase, 20 controls), kaolin partial thromboplastin time was prolonged, tPA activity and D-dimer rose, and fibrinogen fell in the lumbrokinase group. Prothrombin time and plasminogen activator inhibitor activity did not change in either group. Stroke scores fell in BOTH groups, and the report gives no between group statistical test for that difference. The paper states neither the dose nor the duration of treatment. What this study shows is that lumbrokinase can move clotting measurements, which is also the reason it can add to bleeding risk.

A cited study that cannot be located

This card's source is a study attributed to Rey, reported as 500 mg three times daily for 7 days in people with diabetic foot ulcers. Searches of PubMed, Europe PMC and the open literature return no such published paper, and no author named Rey appears on any lumbrokinase publication. Until a real citation exists there is nothing here a reader can rely on.

In healthy adults, no measurable change in clotting tests

The fibrinogen chain degradation, reduced platelet aggregation and prolonged clotting time attributed to the Indonesian product DLBS1033 came from laboratory assays on blood samples, not from a trial in volunteers. When the same product was actually given to people, in a randomized double blind placebo controlled crossover study of 20 healthy adults taking 490 mg three times daily for 14 days, there were no significant differences from placebo in hemostasis parameters, hematology, blood chemistry, urine testing, stool occult blood or ECG, and no bleeding symptoms. That study was designed to test safety rather than benefit, and 20 people is small, but it is the only placebo controlled human trial of any lumbrokinase product and nothing measurable changed.

A different branded product, open label, company author

An Indonesian randomized trial of 180 stroke inpatients compared standard therapy (aspirin, atorvastatin and vitamin B12) with the same therapy plus DLBS1033, and reported larger NIHSS and Barthel Index improvements in the DLBS1033 arm. The trial was open label with no placebo, the difference in favorable modified Rankin outcome at day 30 was not significant (86.7 versus 80 percent, p = 0.302), it tested one company's branded protein fraction rather than lumbrokinase supplements in general, and one of its authors is an employee of the company that makes it. This does not extend the findings to healthy people.

Preclinical cardioprotection

Preclinical models show Sirt1 activation with post-ischemic cardioprotection and TLR4 signaling inhibition with cardioprotective effects. Preclinical mechanistic findings, not yet translated to clinical cardiovascular endpoints.

Mechanism of action

1

Direct fibrinolysis (fibrin-specific)

Lumbrokinase degrades fibrin directly, acting on fibrin plates even when no plasminogen is present. It is often described as more fibrin specific than nattokinase, but no head to head human comparison of the two has been published. Fibrin specificity is not a safety guarantee: anything that dissolves fibrin can also dissolve a clot you need.

2

Indirect fibrinolysis via tPA / plasminogen activation

Lumbrokinase enhances endogenous fibrinolysis by promoting tissue plasminogen activator (tPA) activity and plasminogen-to-plasmin conversion. Indirect mechanism amplifying the body's own fibrinolytic system.

3

Six-enzyme group (Cho 2004 + Mihara 1991 characterization)

Foundational characterization work purified and characterized six fibrinolytic serine proteases - abundant asparagine/aspartic acid and minimal proline/lysine, distinguishing the compositional profile from typical serine proteases.

4

Higher thermal stability and alkali resistance

The purified enzymes tolerate heat and a wide pH range in the test tube. That does not mean they survive a stomach. Formulation work on the Lumbricus rubellus protein fraction DLBS1033 found it unstable at low pH and in gastric fluid, which is why the products that have been tested are enteric coated. Evidence that intact enzyme crosses the gut wall comes from rat intestine and rat plasma, not from humans.

5

Plasminogen activation: the claim is not settled

Lumbrokinase is often said not to activate plasminogen. The study that purified and characterised the six enzymes reported the opposite, that plasminogen was activated into plasmin by them, and the human trials that measured it found tPA activity and D-dimer rose during use. Do not treat this as a reason to assume a lower bleeding risk.

6

TLR4 signaling inhibition (preclinical)

Preclinical evidence that lumbrokinase inhibits TLR4 signaling, contributing to anti-inflammatory and cardioprotective effects in animal models. Mechanistic rationale that has not yet been confirmed in clinical trials.

7

Sirt1 activation (preclinical)

Preclinical evidence of Sirt1 pathway activation contributing to post-ischemic cardioprotection. Animal-model finding pending human translation.

Clinical trials

1
META-ANALYSIS, NOT A TRIAL: 35 unblinded stroke trials pooled
PubMed

Meta-analysis of 35 randomized trials, 2010 to 2024, in stroke inpatients, none of them placebo controlled or blinded. Not a trial in its own right.

Hospital inpatients being treated for acute ischemic stroke, pooled across 35 trials, nearly all conducted in China.

Wiyarta E and colleagues, Ther Clin Risk Manag 2025;21:1319 to 1331. This is a meta-analysis, not a trial. It pooled 35 randomized trials published between 2010 and 2024, nearly all in Chinese local journals, in hospital patients receiving supportive care after a stroke. Reported results: Barthel Index mean difference 15.17 with heterogeneity 97 percent, NIHSS mean difference minus 2.01 with heterogeneity 94 percent, and an overall curative effect odds ratio of 2.77 (2.33 to 3.29). Broken into specific response grades, most were not significant, including cured, odds ratio 1.12 (0.83 to 1.52) and markedly effective or effective, 0.92 (0.62 to 1.38). The reviewers report that many included trials carried a moderate to high risk of bias, that heterogeneity was substantial, that generalizability is limited, and that alteplase remains the standard therapy. No included trial used a placebo or blinded its patients.

2
12 month hospital trial after stroke, no placebo (Cao 2013)
PubMed

Multicenter randomized controlled trial in China, 310 hospitalized stroke patients, 12 months, control group received standard treatment.

310 adults hospitalised in China after an ischemic stroke: 192 given lumbrokinase plus standard treatment, 118 given standard treatment alone.

Cao YJ and colleagues, Chin Med J (Engl) 2013;126(21):4060 to 4065. Patients were randomized to standard stroke treatment alone or to standard stroke treatment plus enteric coated lumbrokinase capsules for 12 months. There was no placebo group, blinding is not reported, and the arms were unequal (192 versus 118). Plasma fibrinogen, carotid intima media thickness, vulnerable plaque detection and NIHSS scores were better with lumbrokinase, and the incidence of total vascular endpoints was 2.08 percent versus 6.78 percent over the year. The paper does not state the dose. The authors' own conclusion is that this therapy may be beneficial.

3
Single blind study of 51 stroke inpatients (Jin 2000)
PubMed

Randomized single blind study in China, 51 hospitalized cerebral infarction patients, coagulation and fibrinolysis laboratory measures.

51 adults hospitalized in China with cerebral infarction: 31 given lumbrokinase, 20 controls.

Jin L, Jin H, Zhang G, Xu G, Clin Hemorheol Microcirc 2000;23(2 to 4):213 to 218. Randomized, single blind, 31 treated and 20 control. In the lumbrokinase group kaolin partial thromboplastin time was prolonged, tPA activity and D-dimer rose, and fibrinogen fell. Prothrombin time and plasminogen activator inhibitor activity did not change in either group. Stroke scores fell in both groups, more so with lumbrokinase, and no between group statistical comparison is reported. The paper states neither the dose nor the treatment duration.

Side effects and drug interactions

Common Potential side effects

Bleeding is the main concern. Lumbrokinase degrades fibrin, the protein that holds clots together, and in the stroke trials it prolonged clotting times, raised D-dimer and lowered fibrinogen. Pooled trial data did not show a significant increase in gastrointestinal bleeding, but only three trials reported it, which is far too few to rule it out. Watch for unusual bruising, nosebleeds, bleeding gums, blood in urine or stool, or a cut that will not stop.
GI upset (occasional).
Stop and seek medical help for any unexplained or heavy bleeding, black or tarry stools, coughing or vomiting blood, or a sudden severe headache.
Allergic reactions (rare; earthworm-derived).
Pregnancy/lactation: avoid (limited safety data).
Bleeding disorders: avoid.
Surgery and dental work: stop at least 1 to 2 weeks before any planned operation, dental extraction, deep cleaning, biopsy, colonoscopy with polyp removal, or spinal or epidural injection, and tell the surgeon, anaesthetist or dentist you have been taking it.
Anyone who has had a stroke, a TIA or a blood clot, or who takes an anticoagulant, is under medical care: do not substitute lumbrokinase for prescribed treatment and do not stop prescribed treatment in order to take it. The longest published use is 12 months, in a hospital trial that had no placebo group.
Ethical/religious: derived from earthworms — concern for vegetarians/vegans + certain religious practices.

Important Drug interactions

Anticoagulants (warfarin, apixaban, rivaroxaban, edoxaban, dabigatran, heparins): do not combine without your prescriber's agreement. Lumbrokinase measurably prolongs clotting times and lowers fibrinogen in human trials, so the added bleeding risk is not theoretical. Warfarin is dosed against INR, and adding an unmeasured fibrinolytic on top of it is unsafe.
Antiplatelets (aspirin, clopidogrel, ticagrelor, prasugrel, dipyridamole): additive bleeding risk. Most published lumbrokinase trials gave it on top of antiplatelet therapy in hospital, under supervision, which is not the same as taking it alongside your own aspirin at home.
Fibrinolytics (tPA, urokinase, streptokinase): theoretical synergistic effects — avoid concurrent use.
NSAIDs (ibuprofen, naproxen, diclofenac, high dose aspirin): additive bleeding risk, particularly gastrointestinal bleeding.
Other supplements taken for blood flow, including nattokinase, serrapeptase, high dose fish oil, high dose vitamin E and ginkgo: stacking fibrinolytic and antiplatelet supplements has not been tested and can only add to bleeding risk.
Surgery and dental procedures: discontinue at least 1 to 2 weeks beforehand and tell the surgeon, anaesthetist or dentist. This includes extractions, deep scaling, biopsies, and spinal or epidural injections.

Frequently asked questions about Lumbrokinase (Earthworm Fibrinolytic Enzyme)

What is lumbrokinase?

Lumbrokinase is a set of six enzymes extracted from the earthworm Lumbricus rubellus. It is an animal derived product made from earthworms, so it is not vegetarian or vegan and may not be acceptable under some religious dietary rules. In the laboratory these enzymes break down fibrin, the protein that holds clots together.

What is lumbrokinase used for?

Nearly all the human research was done in hospital patients being treated for stroke, and those trials were unblinded and mostly published in Chinese local journals. In the one placebo controlled trial in healthy adults, a 20 person safety study, 14 days of dosing changed no clotting measurement compared with placebo. There is no established use in healthy people.

When should I take lumbrokinase?

Products are sold as enteric coated capsules because the enzyme is destroyed by stomach acid, and they are usually taken away from food. How much intact enzyme reaches the bloodstream in people has never been measured: the absorption data come from rat intestine and rat plasma, and the one human study could detect activity only indirectly, through a downstream clotting marker, and only after three days of repeated dosing.

Is lumbrokinase safe?

Because it breaks down fibrin, lumbrokinase adds to bleeding risk. Do not combine it with warfarin, direct oral anticoagulants, heparin, aspirin, clopidogrel or other antiplatelets unless your doctor agrees, and stop it 1 to 2 weeks before surgery or dental procedures. Avoid it in pregnancy and breastfeeding, and with a bleeding disorder, a recent bleed or an active ulcer. If you have had a stroke, a TIA or a clot, you are under medical care and must not swap prescribed treatment for a supplement.

What is the recommended dosage of Lumbrokinase?

The clinically studied dose is No dose has been established for healthy people; the only placebo controlled study used 490 mg three times daily for 14 days and produced no change in clotting versus placebo. Always follow the product label and check with a healthcare provider for personal advice.

Is Lumbrokinase safe, and does it have side effects?

For most healthy adults, Lumbrokinase is well tolerated at studied doses. Reported effects can include: Bleeding is the main concern. Lumbrokinase degrades fibrin, the protein that holds clots together, and in the stroke trials it prolonged clotting times, raised D-dimer and lowered fibrinogen. It may also interact with some medications. Lumbrokinase is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Lumbrokinase interact with any medications?

Possible interactions include: Anticoagulants (warfarin, apixaban, rivaroxaban, edoxaban, dabigatran, heparins): do not combine without your prescriber's agreement. Lumbrokinase measurably prolongs clotting times and lowers fibrinogen in human trials, so the added bleeding risk is not theoretical. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Lumbrokinase?

NutraSmarts rates the evidence for Lumbrokinase as Limited (2 out of 5). It is backed by 3 clinical trials and 9 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(9 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Wiyarta E, Hidayat R, Kurniawan M, Saputro BIL, Maharani IL, Rampengan DDCH, Tanudharma LC, Tjandrawinata RR Therapeutic Potential of Lumbrokinase in Acute Ischemic Stroke: A Meta-Analysis of Efficacy and Safety Ther Clin Risk Manag. 2025;21:1319-1331. doi:10.2147/TCRM.S537232.PubMedUsed to support: Meta-analysis of 35 randomized trials published 2010 to 2024, nearly all in Chinese local journals, in hospital patients receiving supportive care after an acute ischemic stroke. Adjunctive lumbrokinase was associated with a better Barthel Index (mean difference 15.17) and NIHSS score (mean difference minus 2.01) and a higher overall curative effect (odds ratio 2.77, 2.33 to 3.29), but heterogeneity was 97 percent and 94 percent for the two functional outcomes, and when the response was broken into specific grades most were not significant, including cured (odds ratio 1.12, 0.83 to 1.52) and markedly effective or effective (0.92, 0.62 to 1.38). No included trial used a placebo or blinded its patients. The reviewers state that many included trials carried a moderate to high risk of bias, that heterogeneity was substantial, that generalizability is limited, and that alteplase remains the standard therapy. Adverse events including gastrointestinal bleeding did not differ significantly, but only three trials contributed to that estimate.
  2. Cao YJ, Zhang X, Wang WH, Zhai WQ, Qian JF, Wang JS, Chen J, You NX, Zhao Z, Wu QY, Xu Y, Yuan L, Li RX, Liu CF Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a multicenter, randomized, parallel-group and controlled clinical trial Chin Med J (Engl). 2013;126(21):4060-5.PubMedUsed to support: Multicenter randomized trial in China: 310 patients hospitalized after an ischemic stroke received standard stroke treatment alone (118 people) or standard treatment plus enteric coated lumbrokinase capsules (192 people) for 12 months. There was no placebo group, blinding is not reported, and the arms were unequal. Plasma fibrinogen, carotid intima media thickness, vulnerable plaque detection and NIHSS scores were better in the lumbrokinase arm, and total vascular endpoints occurred in 2.08 percent versus 6.78 percent over the year. The authors conclude only that long term oral fibrinogen depleting therapy may be beneficial. The dose is not stated in the published report.
  3. Jin L, Jin H, Zhang G, Xu G Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase Clin Hemorheol Microcirc. 2000;23(2-4):213-8.PubMedUsed to support: Randomized single blind study of 51 patients hospitalized in China with cerebral infarction (31 treated, 20 control). In the treated group kaolin partial thromboplastin time was prolonged, tPA activity and D-dimer rose and fibrinogen fell; prothrombin time and plasminogen activator inhibitor activity did not change in either group. The stroke score fell in both groups, more so in the treated group, and no between group statistical comparison is reported. The paper states neither the dose nor the duration of treatment.
  4. Mihara H, Sumi H, Yoneta T, Mizumoto H, Ikeda R, Seiki M, Maruyama M A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus Jpn J Physiol. 1991;41(3):461-72. doi:10.2170/jjphysiol.41.461.PubMedUsed to support: The original characterisation. Saline extracts of the earthworm Lumbricus rubellus were separated into six fibrinolytic enzymes, unusually rich in asparagine and aspartic acid and low in proline and lysine, which the authors named lumbrokinase collectively. The enzymes lysed fibrin plates both with and without plasminogen present and were heat stable. This is laboratory characterisation of the material, not evidence of any benefit in people.
  5. Cho IH, Choi ES, Lim HG, Lee HH Purification and characterization of six fibrinolytic serine-proteases from earthworm Lumbricus rubellus J Biochem Mol Biol. 2004;37(2):199-205. doi:10.5483/bmbrep.2004.37.2.199.PubMedUsed to support: Six lumbrokinase iso-enzymes of 24.6 to 33.1 kDa were purified from Lumbricus rubellus, active at an optimal 50 degrees C and across pH 4 to 12. The authors report that plasminogen was activated into plasmin by these enzymes, which runs against the common claim that lumbrokinase does not activate plasminogen. Laboratory work only, with no human outcome.
  6. Tjandrawinata RR, Trisina J, Rahayu P, Prasetya LA, Hanafiah A, Rachmawati H Bioactive protein fraction DLBS1033 containing lumbrokinase isolated from Lumbricus rubellus: ex vivo, in vivo, and pharmaceutic studies Drug Des Devel Ther. 2014;8:1585-93. doi:10.2147/DDDT.S66007.PubMedUsed to support: Laboratory and animal work showing that the earthworm protein fraction is unstable at low pH and in gastric fluid, so an enteric coating is needed to get it past the stomach. Intact protein absorption was demonstrated in small intestine, and a circulation half life of 70 minutes was measured using a radiolabelled preparation. No equivalent measurement of intact enzyme in human blood has been published.
  7. Tjandrawinata RR, Yunaidi DA, Susanto LW The Safety and Tolerability of Lumbrokinase DLBS1033 in Healthy Adult Subjects Drug Res (Stuttg). 2016;66(6):293-9. doi:10.1055/s-0035-1569406.PubMedUsed to support: Randomized, double blind, placebo controlled crossover study in 20 healthy adults taking the Lumbricus rubellus protein fraction DLBS1033 at 490 mg three times daily for 14 days. The study was designed to test safety and tolerability. There were no significant differences from placebo in hemostasis parameters, hematology, liver and renal function, lipids, fasting glucose, urine testing, stool occult blood or ECG, and no bleeding symptoms or allergic reactions. It is the only placebo controlled human trial of a lumbrokinase product, and nothing measurable changed in healthy people, although 20 subjects is too few to settle either benefit or harm. Two of the three authors work for the company that makes the product.
  8. Gayatri A, Nafrialdi N, Setiabudy RD, Tjandrawinata RR, Rachman A, Louisa M A Clinical Trial on Biological Half Life of Bioactive Protein from Lumbricus rubellus, DLBS1033 in Healthy Volunteers Acta Med Indones. 2018;50(3):208-214.PubMedUsed to support: Open label study in healthy adults given 490 mg three times daily. The enzyme itself was never measured in blood; the investigators tracked the downstream plasmin-antiplasmin complex instead. Activity could not be determined at all after a single dose. Only after three days of repeated dosing did the marker rise, giving a calculated biological half life of 8.6 hours. Prothrombin time and aPTT showed no significant change and there were no serious adverse events.
  9. Pinzon RT, Tjandrawinata RR, Wijaya VO, Veronica V Effect of DLBS1033 on Functional Outcomes for Patients with Acute Ischemic Stroke: A Randomized Controlled Trial Stroke Res Treat. 2021;2021:5541616. doi:10.1155/2021/5541616.PubMedUsed to support: Open label randomized trial of 180 stroke inpatients in Indonesia comparing standard therapy (aspirin 100 mg, atorvastatin 20 mg, vitamin B12) with the same therapy plus the branded earthworm protein fraction DLBS1033. NIHSS and Barthel Index improvements were larger in the DLBS1033 arm at discharge and at day 30. The proportion achieving a favorable modified Rankin score at day 30 did not differ significantly (86.7 versus 80 percent, p = 0.302). There was no placebo and no blinding, and one author is an employee of the company that manufactures the product.