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, the trials compared lumbrokinase plus supportive care with supportive care alone, 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.
Fibrinogen and carotid artery wall thickness in a 12 month stroke trial
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 abstract 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.
Placebo-controlled trials we could not find in print
The maker of the Indonesian product DLBS1033 registered seven randomized, placebo-controlled trials, one withdrawn before enrolling anyone, and university teams ran two more that have finished. As far as we can find, only the 20-person healthy-volunteer study appears in PubMed. A completed 122-person diabetes trial, a 21-person healthy-volunteer trial and a 52-person stroke trial finished in 2025 have no results we could find; four others were stopped early, three for recruitment problems and one because the sponsor said the cases were no longer relevant after changes to the national healthcare system.
In healthy adults, no difference from placebo 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 published placebo controlled trial of a lumbrokinase product in healthy people that we found, and it found no significant difference from placebo.
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.
Heart findings in rats only
In rat experiments in which a heart artery was blocked and then reopened, lumbrokinase reduced heart damage and affected Sirt1 and TLR4 signaling. These are animal findings with no human heart outcomes, and they are not a reason to use a supplement for any heart condition.
Mechanism of action
Direct fibrinolysis (not fibrin-specific)
Lumbrokinase degrades fibrin directly, acting on fibrin plates even when no plasminogen is present. It is often marketed as fibrin-specific, but that is not supported: purified earthworm enzymes also break down fibrinogen in laboratory tests, the Chinese drug label says it lowers fibrinogen, and hospital studies found lower fibrinogen in treated patients. No head to head human comparison with nattokinase has been published. Anything that dissolves fibrin can also dissolve a clot you need.
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.
A family of six related enzymes
Foundational characterization work purified six fibrinolytic serine proteases that, compared with other serine enzymes, are unusually rich in asparagine or aspartic acid and contain very little proline or lysine.
Heat and pH stability in the test tube, not in the stomach
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.
Plasminogen activation: the marketing claim is contradicted
Lumbrokinase is often said not to activate plasminogen. A 2004 study that purified and characterized six of the enzymes reported the opposite: plasminogen was activated into plasmin by them. The Chinese drug label describes the product as containing a plasminogen activator, and in a hospital study of 51 stroke patients, tPA activity and D-dimer rose in those given lumbrokinase. Do not treat the marketing claim as a reason to assume a lower bleeding risk.
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.
Sirt1 activation (preclinical)
Preclinical evidence of Sirt1 pathway activation contributing to post-ischemic cardioprotection. Animal-model finding pending human translation.
Clinical trials
Meta-analysis of 35 randomized trials in stroke inpatients, comparisons of lumbrokinase added to supportive care with supportive care alone. Not a trial in its own right.
Hospital inpatients being treated for acute ischemic stroke, pooled across 35 trials, mostly from China, plus Indonesian trials of DLBS1033.
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, mostly from China, 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. The abstract also reports a pooled platelet aggregation change of minus 205.86, which is not plausible, and a 2024 conference version of the analysis lists its last author at Dexa Medica, maker of DLBS1033, while the journal version declares no conflicts.
Multicenter randomized controlled trial in China, 310 hospitalized stroke patients, 12 months, control group received standard treatment.
310 adults hospitalized 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 abstract does not state the dose. The authors' own conclusion is that this therapy may be beneficial.
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 abstract states neither the dose nor the treatment duration.