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Updated 18 February 2013

Nattokinase

Natto is a traditional Japanese food, prepared by fermenting boiled soybeans with the bacterium Bacillus subtilis. Nattokinase is an enzyme, which breaks down protein, and is purified from the cheese-like natto. Nattokinase was discovered in 1980 by a researcher who was trying to identify a natural agent that could successfully dissolve clots.

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RELATED TERMS

Fermented soybeans, Flite Tabs, natto, natto extract, nattokinase, NK, NSK II, NSK-SD, subtilisin NAT.

BACKGROUND

Natto is a traditional Japanese food, prepared by fermenting boiled soybeans with the bacterium Bacillus subtilis. Nattokinase is an enzyme, which breaks down protein, and is purified from the cheese-like natto. Nattokinase was discovered in 1980 by a researcher who was trying to identify a natural agent that could successfully dissolve clots.

People throughout Asia have consumed soybeans in a variety of traditional foods (including natto) for over 1,000 years. Due to their possible contribution to the observed low rates of heart disease in Asian countries, soy products such as natto have recently attracted attention in the West. As a result, nattokinase is a popular health food supplement.

Nattokinase has been reported to have blood-thinning effects. Recently, research has indicated that nattokinase may have potential in the treatment of vein clots, or deep venous thrombosis (DVT), and high blood pressure, when used in combination with the standard therapies for these conditions.

EVIDENCE TABLE

Conditions

Uses
disclaimer: These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Grade*

High blood pressure

Nattokinase has traditionally been used as a blood pressure-lowering agent in Asia. Results of clinical studies support this use. Future studies will provide additional valuable information on the use of nattokinase to treat high blood pressure.

B

Vein clots (deep venous thrombosis)

Evidence suggests that the combination product Flite Tabs, containing nattokinase and Pycnogenol©, may reduce the frequency of clotting effects and swelling in high-risk individuals on long air flights. Further research on the effect of nattokinase alone is needed before a conclusion can be made.

C

*Key to grades: A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).

TRADITION

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below. Angina (chest pain), atherosclerosis (clogged arteries), bone loss, cholesterol (lowering), chronic fatigue syndrome, endometriosis, eye disorders (pharmacologic vitreolysis, posterior vitreous detachment (PVD)), fibromyalgia, hemorrhoids, infertility, inflammation (chronic), muscle spasm, pain, peripheral vascular disease, rheumatism (soft tissue), stroke (noncardiac origin), tissue oxygenation, uterine fibroids, varicose veins, vision problems, wound healing.

DOSING

disclaimer: The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

Manufacturers recommend that nattokinase be given by mouth at a dose of 100 milligrams three times daily. Other recommended doses range from 2,000 to 6,000 fibrinolytic units (FU). A fibrinolytic unit is a measure of the ability to break down the protein fibrin, a component of blood clots.

For high blood pressure, the following has been taken: one capsule of NSK-II (Japan Bio Sciences Laboratories Company Ltd., Japan; containing 2,000 FU/capsule) by mouth daily for eight weeks; two capsules of NSK-II by mouth daily for four weeks; a freeze-dried extract (80% ethanol; equivalent to 200 grams of natto and 6,400 FU) by mouth daily for four consecutive days.

For vein clots (deep venous thrombosis (DVT)), two capsules of Flite Tabs (Aidan, Tempe, AZ; containing 150 milligrams of pinokinase (Pycnogenol© and nattokinase)) has been taken by mouth with 250 milliliters of water, two hours before a flight and six hours later.

Children (under 18 years old)

There is no proven safe or effective dose for nattokinase in children.

SAFETY

disclaimer: The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Avoid with known allergy or hypersensitivity to natto, nattokinase, soybean (Glycine max), or soy-based products.

Side Effects and Warnings

Natto has been consumed in regions of Japan for over 1,000 years, suggesting that it and nattokinase are likely safe when consumed in food amounts.

Nattokinase may increase the risk of bleeding. Caution is advised in patients with bleeding disorders, such as cerebral microangiopathy, or in those taking drugs, herbs, or supplements that may increase the risk of bleeding. Dosing adjustments may be necessary.

A single case of brain hemorrhage has been reported. Although not well studied in humans, hemorrhage in the retina of the eye has been reported in experimental studies.

Some nattokinase supplements contain vitamin K, which may work against the effects of blood thinners like warfarin (Coumadin©).

Nattokinase may cause easy bruising and changes in the retina.

Nattokinase may cause low blood pressure. Caution is advised in patients taking drugs, herbs or supplements that lower blood pressure.

Avoid in pregnant or breastfeeding women due to a lack of available scientific evidence.

Avoid with known allergy or hypersensitivity to natto, nattokinase, soybean (Glycine max), or soy-based products.

Pregnancy and Breastfeeding

Avoid in pregnant or breastfeeding women due to a lack of available scientific evidence.

INTERACTIONS

disclaimer: Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

Nattokinase may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin©) or heparin, antiplatelet drugs such as clopidogrel (Plavix©), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin©, Advil©) or naproxen (Naprosyn©, Aleve©). Some natto and nattokinase supplements contain vitamin K, which may work against the effects of anticoagulants ("blood thinners") such as warfarin (Coumadin©) or heparin.

Nattokinase may cause low blood pressure. Caution is advised in patients taking drugs that lower blood pressure.

Interactions with Herbs and Dietary Supplements

Nattokinase may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases. Some natto and nattokinase supplements contain vitamin K, which may work against the effects of some agents that increase the risk of bleeding.

Nattokinase may cause low blood pressure. Caution is advised in patients taking herbs or supplements that lower blood pressure.

ATTRIBUTION

This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

  • Cesarone MR, Belcaro G, Nicolaides AN, et al. Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial. Angiology 2003;54(5):531-539. View abstract
  • Chang YY, Liu JS, Lai SL, et al. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med 2008;47(5):467-469. View abstract
  • Fujita M, Hong K, Ito Y, et al. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat. Biol Pharm Bull 1995;18(10):1387-1391. View abstract
  • Kazuya O, Shigeo I, Kenichim S. Report of research: an oral safety study of nattokinase containing food, Natural Super Kinase II: a randomized placebo controlled double-blind study. Progress in Medicine 2006;26(5):5.
  • Kim JY, Gum SN, Paik JK, et al. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens Res 2008;31(8):1583-1588. View abstract
  • Law D, Zhang Z. Stabilization and target delivery of Nattokinase using compression coating. Drug Dev Ind Pharm 2007;33(5):495-503. View abstract
  • Maruyama and Sumi. Effect of Natto Diet on Blood Pressure. 1998.
  • Pais E, Alexy T, Holsworth RE Jr., et al. Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity. Clin Hemorheol Microcirc 2006;35(1-2):139-142. View abstract
  • Sumi H, Hamada H, Nakanishi K, et al. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol. 1990;84(3):139-143. View abstract
  • Sumi H, Hamada H, Tsushima 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(10):1110-1111. View abstract
  • Suzuki Y, Kondo K, Ichise H, et al. Dietary supplementation with fermented soybeans suppresses intimal thickening. Nutrition 2003;19(3):261-264. View abstract
  • Suzuki Y, Kondo K, Matsumoto Y, et al. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery. Life Sci 2003;73(10):1289-1298. View abstract
  • Tai MW, Sweet BV. Nattokinase for prevention of thrombosis. Am J Health Syst Pharm 6-15-2006;63(12):1121-1123. View abstract
  • Takano A, Hirata A, Ogasawara K, et al. Posterior vitreous detachment induced by nattokinase (subtilisin NAT): a novel enzyme for pharmacologic vitreolysis. Invest Ophthalmol Vis Sci 2006;47(5):2075-2079. View abstract
  • Urano T, Ihara H, Umemura K, et al. The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis Cleaves and inactivates plasminogen activator inhibitor type 1. J Biol Chem 2001;276(27):24690-24696. View abstract
disclaimer: Natural Standard Bottom Line Monograph, Copyright © 2011 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions. disclaimer: While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy. disclaimer: The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

Copyright © 2011 Natural Standard (www.naturalstandard.com)



Copyright © 2011 Natural Standard (www.naturalstandard.com)
 
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