Nattokinase use in DVT prophylaxis

Samad Tirmizi, Pharm. D. Candidate c/o 2014

Deep vein thrombosis (DVT) is a clot formation that occurs within deep veins, generally in the legs. This can cause swelling and pain due to the engorged vessels, and can eventually result in further complications such as a pulmonary embolism. Patients at high risk for DVT are given prophylactic treatment to prevent such an occurrence. Some people at high risk include long term hospitalized patients, post-surgical patients, pregnant women, and people who fly for extended periods of time.1 Prophylactic treatment generally involves use of anticoagulants such as heparin, warfarin, or thrombolytic medications, but there is a fairly high risk of bleeding associated with these drugs. Currently, there are very few known homeopathic options available for patients who would fit the need for DVT prophylaxis.1

It is theorized that a product called Nattokinase can be used for prevention of deep vein thrombosis (DVT). Nattokinase is a serine protease found in soybeans that contains fibrinolytic properties. It is known to be stable in a pH range from 6 to 12, but inactive in acidic environments.2,3,4 Studies have demonstrated that Nattokinase is absorbed across the intestinal tract of rats.5

Nattokinase lacks clinical studies to show safe and effective dosing. There is neither pregnancy information, nor any interaction information currently available.6 Additionally, no reports of adverse reactions have been documented in the trials evaluating nattokinase. However, an acute cerebellar hemorrhage case report in a patient with history of ischemic stroke results in a theoretical risk of bleeding.6 Nattokinase should also be avoided in patients with peptic ulcer disease or coagulation disorder, pre- or post- surgery patients, and in patients on concomitant anticoagulation therapy.6

A study published in Nutrition in 2009 by Dr. Hsia showed that Nattokinase was shown to decrease factors VII, VIII, and plasma fibrinogen levels.7 The study was an open-label, self-controlled clinical trial on 15 healthy volunteers, 15 dialysis patients, and 15 cardiovascular risk factor patients. The patients took two capsules of Nattokinase by mouth for two months. The primary outcome was decreased clotting factors. Compared to baseline, the healthy patients were shown to have decreased factor VIII by 17%, factor VII by 14%, and fibrinogen by 9%; dialysis patients were shown to have decreased factor VIII by 19%, factor VII by 7%, and fibrinogen by 10%; cardiovascular risk factor patients were shown to have decreased factor VIII by 19%, factor VII by 13%, and fibrinogen by 7%. 7 Although the study sounds assuring, it was performed on a small sample of the population.  The study design is also a weakness to note, as it was not randomized and had no placebo-control group.

The LONFLIT-FLITE study in 2003 is the only randomized, parallel placebo-controlled trial that has been published, consisting of 186 subjects: 92 subjects in the control group and 94 subjects in the treatment group. Patients at high risk for DVT were given Flite Tabs® during long 7-8 hour flights.8 Flite Tabs® contain nattokinase for its fibrinolytic function, and pycnogenol, a natural plant-based product which may help reduce edema.9 Inclusion criteria were patients at high risk for episodes of DVT, including previous superficial vein thrombosis or DVT episode, coagulation disorders, severe obesity or limitation of mobility due to bone or joint problems, neoplastic disease within 2 years, clinical cardiovascular disease, and large varicose. Exclusion criteria were patients who used anticoagulants, had any recent treatments done (time range not defined), and possible low compliance (compliance risk assessment not defined). Of the 92 control group subjects, 5 had a DVT, and 2 had superficial thrombosis. In the treatment group of 94, there was no thrombotic event observed.[8]

This study shows the potential of nattokinase. However, since a combination product was used, it is difficult to assess whether DVT prevention was caused by the nattokinase or the pycnogenol. The study sets a course for potential research on nattokinase alone, or even in the combination Flite Tabs® formulation for its fibrinolytic activities.

Though studies show that this natural medicine may work, there have been no comparative studies of Nattokinase to Warfarin or other anticoagulants in humans. Thus, a specific dose for a patient cannot be recommended. Currently there are no reports of adverse effects and potential drug interactions, however this is another limitation due to limited data on this natural product. Additionally, the general efficacy studies done had very small populations and most concluded that there is potential for this product. However, further studies need to be conducted.


  1. Alldredge BK, Corelli RL, Ernst ME, et al, eds. Applied Therapeutics: The Clinical Use of Drugs. 10th ed. Philadelphia, PA: Wolters Kluwer and Lippincott Williams & Wilkins;2013:345-376.
  2. Fujita M, Nomura K, Hong K et al. Purification and characterization of a strong fibrinolytic enzyme (nattokinase) in the vegetable cheese nato, a popular soybean fermented food in Japan. Biochem Biophys Res Commun. 1993; 197:1340-7.
  3. Sumi H, Hamada H, Tsushima Het 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.
  4. Yoshimoto T, Fukomoto J, Tsuro D. Studies on bacterial proteases: some enzymatic and physicochemical properties of the alkaline protease from Bacillus natto. Int J Protein Res. 1971; 3:285-95
  5. Fujita M,  Hong K, Ito Y et al. Transport of nattokinase across the rat intestinal tract. Biol Pharma Bull. 1995; 18:1194-6.
  6. Lexicomp Online, Natural Products Database, Hudson, Ohio: Lexi-Comp, Inc.; 2013; August 04, 2013.
  7. Hsia C, Shen M, Lin J et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutrition Research. 2009; 29:190-196
  8. Cesarone M, Belcaro G, Nicolaides A et al. Prevention of Venous Thrombosis in Long-Haul Flights with Flite Tabs: The LONFLIT-FLITE Randomized, Controlled Trial. Angiology 2003; 54:531-239.
  9. Cesarone M, Belcaro G, Rohdewal P et al.Prevention of edema in long flights with Pycnogenol. Clin Appl Thromb Hemost. 2005;11(3):289-94.
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