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Nattokinase

  • Dear Readers,

    Welcome to a new decade and the January 2020 issue of TotalHealth Magazine.

    Carmen V. Russoniello, PhD, LPC, LRT/CTRS, BCB, BCN, Professor and Director, Center for Applied Psychophysiology East Carolina University, brings us, Mobile Stress Assessments and Biofeedback: Modern Tools For Managing Health. Dr. Russoniello discusses it is possible to use modern apps to assess stress and apply mobile-accessed biofeedback to improve health. Most smartphones only provide low-to-medium levels of accuracy and functionality; read on for news on SAB systems that will revolutionize health care.

    Sherrill Sellman, ND, presents, Hygeena; The Ultimate Vaginal Healing And Rejuvenation Solution. While this a sensitive issue for many women it is important to discuss with your health practitioner. The article discusses “old school” remedies that women need to beware of, and new healthful solutions for restoration and rejuvenation.

    Professor Gene Bruno, MS, MHS, Rh(Ahg), starts the year off with, Nattokinase: An Enzyme For Cardiovascular Health And More. Nattokinase is an enzyme that has proven efficacy in reducing blood clotting factors. It is also effective for reducing hypertension and in general shows benefits for cardiovascular health and more.

    Ann Louise Gittleman, PhD, CNS, begins a series on Smart Recipes. Over the next several months she’ll provide Smart recipes for breakfast, lunch and dinner; along with starters and snacks. Be sure to check out this month for yummy smoothie recipes to start the new year.

    Gloria Gilbère, CDP, DAHom, PhD, begins the year with, A New Year, A New You, The Making Of A Detox Smoothie And Soup. Dr. Gloria starts with variations on fruit smoothies that include a green apple smoothie and a cilantro smoothie. She also provides us with a delectable Cucumber Avocado Soup that can be eaten hot or cold. Also, she lists the healthy benefits of each ingredient.

    This month Shawn Messonnier, DVM, begins a four-part series on Inflammatory Bowel Disease In Pets. He’ll discuss ways to help your pet with severe symptoms, bouts of diarrhea, and leaky gut, with the use of natural diets, pro- and pre-biotics, antioxidants, and plant enzymes.

    Thank you to our authors, readers and advertisers for making TotalHealth Online possible.

    Wishing you a Happy New Year from all of us at TotalHealth, and best in health.

    TWIP—The Wellness Imperative People

    Click here to read the full January 2020 issue.

    Click here to read the full January 2020 issue.

  • Nattokinase is a fibrinolytic (i.e., fibrin degrading) enzyme derived from a Japanese food called natto. Nattokinase is produced during the very fermentation process which creates natto, involving boiled soybeans fermented with the bacteria Bacillus natto.1,2 Nattokinase has fibrinolytic activity that is 4-times more potent than plasmin3 (a blood enzyme that degrades many blood plasma proteins, most notable, fibrin clots).4 Nattokinase works by inactivating plasminogen activator inhibitor 1 (PAI-1).5,6 PAI-1 would otherwise inactivate plasminogen and hence fibrinolysis (the breakdown of fibrin clots). Its average activity is about 40 CU (plasmin units)/gram.7 Also, Nattokinase is orally available as a dietary supplement. This has been demonstrated in both human and animal research.8,9

    Nattokinase And Blood Clotting Factors
    Accumulation of fibrin in the blood vessels usually results in thrombosis (the formation of blood clots), leading to myocardial infarction (heart attack) and other cardiovascular diseases. For thrombolytic therapy, microbial fibrinolytic enzymes have now attracted much more attention than typical thrombolytic agents because of the expensive prices and the undesirable side effects of the latter. The fibrinolytic enzymes were successively discovered from different microorganisms, the most important among which is the genus Bacillus from traditional fermented foods. Perhaps the most significant of the enzymes is nattokinase, which has been shown thrombolysis (the breakdown of blood clots).10

    Nattokinase An Enzyme for Cardiovascular Health

    In an open-label, self-controlled clinical trial11, researchers hypothesized that nattokinase could reduce certain blood clotting factors that are associated with an increased risk for cardiovascular disease. The subjects in the study were divided into the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested two capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for two months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. After two months, the results were a significant time effect was observed in the change from baseline of fibrinogen, factor VII, and factor VIII, suggesting that the plasma levels of the three coagulation factors continuously declined during intake: No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a cardiovascular disease nutraceutical by decreasing plasma levels of the blood clotting factors: fibrinogen, factor VII, and factor VIII.

    The development of edema, and superficial and deep vein thrombosis (DVT) is not uncommon in long-haul flights (seven to eight hours), particularly in high-risk subjects. In a randomized, controlled trial12, high-risk subjects on longhaul flights were supplemented with a combination product containing nattokinase plus pycnogenol. Two capsules were taken two hours before the flight and then again six hours later. The results were that the nattokinase combination product was effective in reducing thrombotic events and in controlling edema in high-risk subjects in long flights. Furthermore, the difference between the control group and the nattokinase group was statistically significant.

    In addition to human research, nattokinase has also been investigated in animal studies. In one such study, nattokinase was administered to rats with a thrombus in the common carotid artery. The results were that the thrombolytic properties of nattokinase were stronger than that of plasmin or elastase.13 Likewise, other animal research has also demonstrated the fibrinolytic effect of nattokinase.14,15

    In-vitro and in-vivo studies have consistently demonstrated the potent fibrinolytic effect of nattokinase. Additional invitro research16 has also shown a significant, dose-dependent decrease of red blood cell aggregation, with these beneficial effects evident at concentrations similar to those achieved in previous in-vivo animal trials. This additional research data also suggests value for nattokinase as a therapeutic blood-thinning agent.

    Nattokinase And Hydrolyzing Amyloid Fibrils
    More than 20 unrelated proteins can form amyloid fibrils, which are related to various diseases, such as Alzheimer’s disease, prion disease (e.g. “mad cow” disease), and systematic amyloidosis. Amyloid fibrils are an insoluble fibrous protein aggregates. Enhancing amyloid clearance is one of the targets of the therapy of these amyloid-related diseases. Although there is debate on whether the toxicity is due to amyloids or their precursors, research on the degradation of amyloids may help prevent or alleviate these diseases. In one study17, researchers explored the amyloid-degrading ability of nattokinase. Results demonstrated that nattokinase was effective in hydrolyzing amyloid fibrils. In fact, it was effective in hydrolyzing three different amyloid fibrils. These included Aβ40 fibrils (found in Alzheimer’s disease), insulin fibrils (caused by repeated insulin injection of diabetes patients) and prion peptide fibrils. The researchers concluded that this, “amyloid-degrading ability of nattokinase suggests that it may be useful in the treatment of amyloid-related diseases.”

    Nattokinase And Hypertension
    In a randomized, double-blind, placebo-controlled trial18, 86 participants ranging from 20 to 80 years of age with an initial untreated systolic blood pressure (SBP) of 130 to 159 mmHg received nattokinase (2,000 FU/capsule) or a placebo capsule for eight weeks. The objective of this study was to examine the effects of nattokinase supplementation on blood pressure in subjects with pre-hypertension or stage 1 hypertension. Seventy-three subjects completed the protocol. Compared with the control group, the statistically significant changes in SBP and diastolic blood pressure (DBP) were -5.55 mmHg and -2.84 mmHg, respectively, after the 8-week intervention. The corresponding net change in renin activity was -1.17 ng/mL/h for the nattokinase group compared with the control group. In conclusion, nattokinase supplementation resulted in a reduction in SBP and DBP. These findings suggest that increased intake of nattokinase may play an important role in preventing and treating hypertension.

    Nattokinase And Artery Intimal Thickening
    As the internal diameter of an artery, or intima, thickens, so does the risk for atherosclerosis and stroke. The thickening process is characterized by a remodeling of arteries involving the concomitant accumulation of fatty plaque formations. This is then complicated by the formation of blood clots involving fibrin. As the blood clots accumulate around the plaque, blood flow is cut off and a heart attack or stroke can result. It was previously noted how nattokinase can help reduce blood lotting factors. In addition, this enzyme can also help reduce the thickening of the arterial intima.

    In animal research, intimal thickening occurs following endothelial injury to the artery. However, the administration of nattokinase was successful at inhibiting intimal thickening.19 In other animal research nattokinase also suppressed intimal thickening produced by endothelial injury in the artery. Apparently, nattokinase causes lysis (breakdown) of thrombi (blood clots) that form at the vessel wall.20,21

    Conclusion
    Nattokinase is a fibrinolytic enzyme with demonstrated efficacy in reducing blood clotting factors. It has also demonstrated effectiveness in hydrolyzing amyloid fibrils, reducing hypertension and reducing artery intimal thickening. Collectively, these functions have benefits for cardiovascular health and more.

    References:

    1. 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;43:1110–1.
    2. Fujita M, Nomura K, Hong K, et al. Purification and characterization of a strong fibrinolytic enzyme (nattokinase) in the vegetable cheese natto, a popular soybean fermented food in Japan. Biochem Biophys Res Commun 1993;197:1340–7.
    3. Fujita M, Hong K, Ito Y, et al. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in a rat. Biol Pharm Bull. 1995;18:1387–91.
    4. 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;43:1110–1.
    5. 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 Sci2003;73:1289–98.
    6. Urano T, Ihara H, Umemura K, Suzuki Y, Oike M, Akita S, Tsukamoto Y, Suzuki I, Takada A. The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis Cleaves and inactivates plasminogen activator inhibitor type 1. J Biol Chem 2001;276(27):24690–6.
    7. 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;54:531–9.
    8. Fujita M, Hong K, Ito Y, Misawa S, Takeuchi N, Kariya K, Nishimuro S. Transport of nattokinase across the rat intestinal tract. Biol Pharm Bull. 1995;18(9):1194–6.
    9. Sumi H, Hamada H, Nakanishi K, Hiratani H. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84(3):139–43.
    10. Peng Y, Yang X, Zhang Y. Microbial fibrinolytic enzymes: an overview of source, production, properties, and thrombolytic activity in vivo. Appl Microbiol Biotechnol 2005;69(2):126–32.
    11. Hsia CH, Shen MC, Lin JS, Wen YK, Hwang KL, Cham TM, Yang NC. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res 2009;29(3):190–6.
    12. 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;54:531–9.
    13. Fujita M, Hong K, Ito Y, Fujii R, Kariya K, Nishimuro S. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat. Biol Pharm Bull. 1995;18(10):1387–91.
    14. Fujita M, Hong K, Ito Y, Misawa S, Takeuchi N, Kariya K, Nishimuro S. Transport of nattokinase across the rat intestinal tract. Biol Pharm Bull. 1995;18(9):1194–6.
    15. Sumi H, Hamada H, Nakanishi K, Hiratani H. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84(3):139–43.
    16. Pais E, Alexy T, Holsworth RE Jr, Meiselman HJ. Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity. Clin Hemorheol Microcirc 2006;35(1-2):139–42.
    17. Hsu RL, Lee KT, Wang JH, Lee LY, Chen RP. Amyloid-degrading ability of nattokinase from Bacillus subtilis natto. J Agric Food Chem 2009;57(2):503–8.
    18. Kim JY, Gum SN, Paik JK, Lim HH, Kim KC, Ogasawara K, Inoue K, Park S, Jang Y, Lee JH. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens Res 2008;31(8):1583–8.
    19. Gong M, Lin HB, Wang Q, Xu JP. [Effect of nattokinase on restenosis after percutaneous transluminal angioplasty of the abdominal artery in rabbits] Nan Fang Yi Ke Da Xue Xue Bao 2008;28(9):1538–41.
    20. 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;73:1289–98.
    21. Suzuki Y, Kondo K, Ichise, H, et al. Dietary supplementation with fermented soybeans suppresses intimal thickening. Nutrition 2003;19:261–4.