Keeping the life-blood flowing
Cardiovascular health is influenced not only by blood cholesterol, cholesterol transporters known as lipoproteins, and antioxidants, but also by the tendency of blood to coagulate or clot.,,,
All of us have clotting factors in our blood to ensure we do not bleed to death if we cut ourselves – and that’s a good thing! But conditions such as metabolic syndrome, hypothyroidism, hypertension, and atherosclerosis – and even “normal” aging – can cause problems with blood flow, resulting in the development of a blood clot inside an artery or vein, and that’s a bad thing.,,,,
In the lungs, a blood clot causes chest pain, elevated heart rate, shortness of breath, and low-grade fever. In an arm or leg, a blood clot can cause pain, swelling, and discoloration of the affected area. When a clot blocks the blood flow to the heart or the brain, a heart attack or stroke can follow.
Ideally there will be a balance between the pro-coagulant (pro-blood clotting) and anticoagulant (anti-blood clotting) factors in the blood to maintain healthy blood flow. A healthy diet, including sufficient omega-3 fatty acids, fruits, and vegetables, can help maintain this balance.
Other than diet, how can we reduce the risk of clotting and support cardiovascular health?
Enzymes that dissolve fibrin
Blood clots are composed primarily of cells known as platelets and a protein called fibrin, which provides the structural backbone for clots. The amount of fibrin is influenced in part by levels of its precursor (fibrinogen), and by thrombin, an enzyme in blood that converts fibrinogen to fibrin., Elevated levels of thrombin and fibrinogen make a significant contribution to heart disease.,,
A process known as fibrinolysis (fibrin breakdown) prevents excess fibrin from piling up and helps dissolve newly formed clots. Fibrinolysis begins with tissue plasminogen activator (tPA), an enzyme that cleaves plasminogen to produce plasmin, which in turn breaks down fibrin and helps eliminate clots.
Drugs such as alteplase (recombinant tPA) are known as “clot buster” drugs, since they are often used to break up blood clots after a heart attack (a clot that cuts off blood supply to the heart), stroke (a blood clot in the brain), or pulmonary embolism (a blockage in an artery of the lungs).,, However, clot buster drugs are not suitable for prevention: they must be administered intravenously, and are associated with significant side effects including an increased risk of stroke.,,
Amazingly, certain edible bacteria and invertebrates like earthworms produce fibrinolytic enzymes that are bioavailable when taken orally and have a history of safe use. When they are ingested, the enzymes help break down excess fibrin in the bloodstream.,, Lumbrokinase is found in earthworm powder (“dilong”), and nattokinase – from the Japanese food natto – is made by a bacterium found in soil. These “enzymes from the earth” have been used for centuries to support heart health.
A one-year controlled clinical trial of lumbrokinase supplementation in 192 patients showed a reduction in arterial plaque and a 4.7% reduction in the risk of stroke with no significant adverse effects.
Earthworm powder from species such as Lumbricus rubellus and Eisenia fetida has long been used as a traditional medicine in East Asia., Enzymes isolated from L. rubellus were shown in 1991 to have fibrinolytic properties, and the enzyme complex was named lumbrokinase (LK)., Earthworm enzymes have dual beneficial effects: they not only help dissolve blood clots but also have anticoagulant properties.,
In animal models of heart attack damage (myocardial ischemia-reperfusion injury), LK supplementation reduced heart muscle damage and improved cardiac function compared to a control., LK also was shown to facilitate peripheral nerve regeneration in diabetic rats, and to ameliorate cardiac fibrosis (a scarring process of the heart) induced by secondhand smoke in an animal model.,
In a placebo-controlled study of healthy human volunteers, LK was shown to exert fibrinolytic activity without harmful side effects or allergic reactions. A one-year controlled clinical trial of LK supplementation in 192 patients showed a reduction in arterial plaque and a 4.7% reduction in the risk of stroke with no significant adverse effects.
“The overall data suggest that the oral consumption of nattokinase supports healthy blood pressure in both sexes.”
The traditional Japanese food called natto is made from steamed soybeans covered with rice straw and left to ferment for 20 hours, although nowadays bacterial spores are used to speed up the fermentation process., The active bacterium is designated Bacillus subtilis (subspecies natto), which can be found in soil and grows on rice straw.
The natto bacterium secretes a fibrinolytic enzyme known as nattokinase (NK). Extensive animal studies show that NK can break down fibrin, reduce blood viscosity (thickness), and improve arterial blood flow.,,,,,,,
Fermented natto is known to be slimy and sticky, with a pungent odor that reminds some of limburger cheese (or smelly socks!). Fortunately, purified NK is available in capsule or softgel forms, free of the food’s typical undesirable odor.
In humans, a single oral dose of 2,000 fibrinolytic units (FU, the standard measurement used to quantify NK dosage) of NK was shown to enhance fibrinolysis within four hours of ingestion, validating its oral bioavailability and rapid efficacy. Twice-daily consumption of 2,000 FU of NK for eight weeks was shown to lower plasma levels of fibrinogen, factor VII, and factor VIII, all of which are associated with cardiovascular disease (CVD) risk. These beneficial effects were seen both in healthy human volunteers and in individuals with two or more of the following: hypertension, smoking, diabetes mellitus, atrial fibrillation, lipid disorder, overweight, and/or physical inactivity.
In two different studies of hypertensive subjects who consumed 2,000 FU of NK daily for four or eight weeks, NK supplementation was associated with a decrease in systolic and diastolic blood pressure., The authors of the North American study concluded, “The overall data suggest that the oral consumption of nattokinase supports healthy blood pressure in both sexes… In addition, the reduction in elevated von Willebrand factor [a CVD risk marker] in the female subgroup suggests a possible reduction of risk for stroke.”
A history of safe use
Earthworms have been used as a traditional Chinese medicine for at least 2,000 years, while the first mention of natto was in 1405 AD, over six hundred years ago. The consumption of LK and NK has been shown to be well tolerated in humans.,,, Despite the excellent safety profile of LK and NK, caution is warranted in individuals with bleeding disorders and in those taking blood thinning medications such as aspirin, and use should occur only under the guidance of a qualified practitioner.
Certain food-grade bacteria and invertebrates produce orally-available fibrinolytic enzymes that have beneficial system-wide effects. The best-characterized fibrinolytic enzymes are nattokinase, from the Japanese food called natto, and lumbrokinase, from earthworm powder. These natural products have a long history of safe use in food and traditional medicine. Pre-clinical and clinical studies have shown beneficial effects of LK and NK on numerous measures of cardiovascular system health.
Click here to see References
 Koenig W. Fibrin(ogen) in cardiovascular disease: an update. Thromb Haemost. 2003 Apr;89(4):601-9.
 Russo I. The prothrombotic tendency in metabolic syndrome: focus on the potential mechanisms involved in impaired hemostasis and fibrinolytic balance. Scientifica (Cairo). 2012;2012:525374.
 Reddel CJ, et al. Detection of hypofibrinolysis in stable coronary artery disease using the overall hemostatic potential assay. Thromb Res. 2013 May;131(5):457-62.
 Uner AG, et al. Mice with diet-induced obesity demonstrate a relative prothrombotic factor profile and a thicker aorta with reduced ex-vivo function. Blood Coag Fibrinol. 2018 Apr 1;29(3):257-66.
 Favaloro EJ, et al. Aging hemostasis: changes to laboratory markers of hemostasis as we age – a narrative review. Semin Thromb Hemost. 2014 Sep;40(6):621-33.
 Eren M, et al. Role of plasminogen activator inhibitor-1 in senescence and aging. Semin Thromb Hemost. 2014 Sep;40(6):645-51.
 Previtali E, et al. Risk factors for venous and arterial thrombosis. Blood Transfus. 2011 Apr;9(2):120-38.
 Mazur P, et al. Prothrombotic alterations in plasma fibrin clot properties in thyroid disorders and their post-treatment modifications. Thromb Res. 2014;134(2):510–7.
 Chapin JC, Hajjar KA. Fibrinolysis and the control of blood coagulation. Blood Rev. 2015 Jan;29(1):17-24.
 Sanchez C, et al. Diet modulates endogenous thrombin generation, a biological estimate of thrombosis risk, independently of the metabolic status. Arterioscler Thromb Vasc Biol. 2012 Oct;32(10):2394-404.
 Rajaram S. The effect of vegetarian diet, plant foods, and phytochemicals on hemostasis and thrombosis. Am J Clin Nutr. 2003 Sep;78(3 Suppl):552S-8S.
 Furie B. Pathogenesis of thrombosis. ASH Education Program Book. 2009 Jan 1;2009(1):255-8.
 Bridge KI, et al. Clot properties and cardiovascular disease. Thromb Haemost. 2014 Nov;112(5):901-8.
 Dawson TM, Dawson VL. Taming the clot-buster tPA. Nat Med. 2006 Sep;12(9):993-4.
 Hao Q, et al. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev. 2015 Sep 30;(9):CD004437.
 Kunadian V, Gibson CM. Thrombolytics and myocardial infarction. Cardiovasc Ther. 2012 Apr;30(2):e81-8.
 Martin C, et al. Systemic thrombolysis for pulmonary embolism: a review. P T. 2016 Dec;41(12):770-5.
 Fujita M, et al. Transport of nattokinase across the rat intestinal tract. Biol Pharm Bull. 1995;18:1194-6.
 Ero MP, et al. A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose. Altern Ther Health Med. 2013;19:16-9.
 Fan Q, et al. Some features of intestinal absorption of intact fibrinolytic enzyme III‐l from Lumbricus rubellus. Biochem Biophys Acta. 2001;1526(3):286-92.
 Cooper EL, et al. Dilong: food for thought and medicine. J Tradit Complement Med. 2012 Oct;2(4):242-8.
 Wang KY, et al. Recombinant protein production of earthworm lumbrokinase for potential antithrombotic application. Evid Based Complement Alternat Med. 2013;2013:783971.
 Mihara H, et al. A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. Jpn J Physiol. 1991;41(3):461-72.
 Nakajima N, et al. Characterization of potent fibrinolytic enzymes in earthworm, Lumbricus rubellus. Biosci Biotechnol Biochem. 1993 Oct;57(10):1726-30.
 Trisina J, et al. DLBS1033, a protein extract from Lumbricus rubellus, possesses antithrombotic and thrombolytic activities. J Biomed Biotechnol. 2011;2011:519652.
 Hrzenjak T, et al. Fibrinolytic and anticoagulative activities from the earthworm Eisenia foetida. Comp Biochem Physiol B Biochem Mol Biol. 1998 Apr;119(4):825-32.
 Wang YH, et al. Sirt1 activation by post-ischemic treatment with lumbrokinase protects against myocardial ischemia-reperfusion injury. Front Pharmacol. 2018 Jun 15;9:636.
 Wang YH, et al. Lumbrokinase attenuates myocardial ischemia-reperfusion injury by inhibiting TLR4 signaling. J Mol Cell Cardiol. 2016 Oct;99:113-22.
 Lee HC, et al. Improved peripheral nerve regeneration in streptozotocin-induced diabetic rats by oral lumbrokinase. Am J Chin Med. 2015;43(2):215-30.
 Liao HE, et al. Cardio protective effects of lumbrokinase and dilong on second-hand smoke-induced apoptotic signaling in the heart of a rat model. Chin J Physiol. 2015 Jun 30;58(3):188-96.
 Lai CH, et al. Lumbrokinase from earthworm extract ameliorates second-hand smoke-induced cardiac fibrosis. Environ Toxicol. 2015 Sep;30(10):1216-25.
 Tjandrawinata RR, et al. The safety and tolerability of lumbrokinase DLBS1033 in healthy adult subjects. Drug Res (Stuttg). 2016 Jun;66(6):293-9.
 Cao YJ, et al. 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 Nov;126(21):4060-5.
 Sumi H, et al. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet. Experientia. 1987;43:1110-1.
 Murooka Y, Yamshita M. Traditional healthful fermented products of Japan. J Ind Microbiol Biotechnol. 2008 Aug;35(8):791-8.
 Sumi H, et al. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol. 1990;84:139-43.
 Fujita M, et al. Purification and characterization of a strong fibrinolytic enzyme (nattokinase) in the vegetable cheese natto, a popular soybean fermented food in Japan. Biol Pharm Bull. 1995;18:1387-91.
 Park KJ, et al. The antithrombotic and fibrinolytic effect of natto in hypercholesterolemia rats. Prev Nutr Food Sci. 2012;17:78-82.
 Pais E, et al. Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity. Clin Hemorheol Microcirc. 2006;35:139-42.
 Jang JY, et al. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation. Lab Anim Res. 2013;29:221-5.
 Omura K, et al. A newly derived protein from Bacillus subtilis natto with both antithrombotic and fibrinolytic effects. J Pharmacol Sci. 2005 Nov;99(3):247-51.
 Kurosawa Y, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.
 Hsia CH, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009;29:190-6.
 Kim JY, et al. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens Res. 2008;31:1583-8.
 Jensen GS, et al. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial. Integr Blood Press Control. 2016;9:95-104.
 Sun Z, Jiang H. Nutritive evaluation of earthworms as human food [Internet]. London: IntechOpen; 2017. Available from: https://www.intechopen.com/books/future-foods/nutritive-evaluation-of-earthworms-as-human-food
 Shurtleff W, Aoyagi A. History of Natto and Its Relatives (1405-2012). Lafayette, California: Soyinfo Center; 2012. Available from: http://agris.fao.org/agris-search/search.do?recordID=US201300005952
 Lampe BJ, English JC. Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. Food Chem Toxicol. 2016;88:87-99.
 Chang YY, et al. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47:467-9.