Its Role in Heart Disease, IBS, Migraines, Fibromyalgia and Other Common Disorders
By Chris D. Meletis, ND
In the minds of many people, blood clots are often thought about in relation to cardiovascular concerns (in a detrimental sense) or in relation to wound healing (in a beneficial sense). However, research is beginning to emphasize an interesting fact—the process causing abnormal blood clotting (known as hypercoagulation) is linked not only to heart disease, stroke and hypertension but also to a wide range of conditions, including inflammatory bowel disease,1-2 migraines,3 fibromyalgia,4 diabetes and diabetic retinopathy,5-7 varicose veins,8-9 hemorrhoids,10 and dementia.11 Some research indicates that hypercoagulation may also be involved in chronic fatigue12 and Gulf War syndrome.12 Therefore, the implications of hypercoagulation stretch far beyond heart disease and stroke to also include many of the most common diseases of our time.
Furthermore, research shows that as we age, hypercoagulation increases, and that hypercoagulation becomes even more severe when subjects are under chronic stress.13 Many clinicians are reporting a widespread, subclinical chronic coagulation disorder even among patients in their 40s. Consequently, a large group of the population is at risk for not only heart disease, pulmonary embolism, hypertension, strokes and other cardiovascular conditions but also for any of the diseases mentioned above.
This article will describe an ideal way to reduce hypercoagulation and improve blood flow in order to help the body maintain healthy clotting levels. First, however, it will discuss the coagulation process, its role in cardiovascular health and further explain how abnormal coagulation is involved in many chronic disorders.
The Blood-Clotting Cascade
| Conditions Related to Hypercoagulation |
|---|
|
Fibrinogen is a plasma protein that plays a key role in blood clotting. Fibrinogen is converted into the coagulated protein fibrin by the action of thrombin in the presence of calcium, and it is this change that produces coagulation of the blood.14 When the body is wounded, this process is necessary and essential. However, infection, inflammation, aging and various diseases can trigger excess fibrinogen production. High fibrinogen levels and its conversion into fibrin are responsible for hypercoagulation. The body utilizes many natural methods of breaking down fibrin deposits, but as we age and in various disease states these fibrinolytic processes are often defective.
The Damage is Building in Our Vessels
The blood vessel lining is constantly subjected to free radical attack. Atherosclerosis is accelerated when free radicals cause the blood vessels to become inflamed. The body treats this damage like a wound, covering the damaged area with fibrin deposits and bringing in blood platelets in an attempt to heal the wounded area. Micro-thrombi accumulate on the vessels. At this stage, these micro-thrombi are still reversible. However, over time, with further damage, more fibrin is deposited. Arterial plaques produce chemicals that reduce the body’s ability to break down clots, further compounding the destructive process.
Heart attacks, pulmonary emboli and strokes often occur after a plaque’s cap ruptures. The body, acting as if needs to respond as it would to a wound, deposits fibrin over the rupture and a blood clot forms. This blocks blood flow even more, depriving the heart, lungs or brain of oxygen.
Because the fibrin deposits accumulate over time, the process can begin decades before the actual heart attack or other cardiovascular event occurs, indicating that even people in their forties may already be undergoing the first stages of this process.
Hypercoagulation and the Diseases of Our Time
In addition to cardiovascular disease, an increased state of hypercoagulation and the body’s weakened ability to dismantle abnormal fibrin deposits occurs in the following disorders.
Inflammatory Bowel Disease
Growing evidence recognizes inflammatory bowel disease (IBD) as being characterized by hypercoagulation and an increased tendency toward developing thrombi, blood clots that obstruct a blood vessel or a cavity of the heart. In Crohn’s disease and ulcerative colitis, the two major forms of IBD, patients have abnormalities in coagulation and fibrinolysis, the process by which the body breaks down fibrin. In these patients, abnormal clotting processes were linked to the severity of the Crohn’s Disease Activity Index.1
Recently, some studies have revealed that the poor mucosal healing, inflammatory ulcerations and damage in the IBD intestine could depend on microvascular dysfunction, resulting in diminished ability for the blood vessels to dilate. IBD also is associated with an increased risk of deep vein thrombosis and pulmonary embolism and these conditions happen at an earlier age in IBD patients compared to non-IBD patients.2
Due to the link between hypercoagulation and IBD, anticoagulants are now often given to these patients.15
Migraines
The proposal that a primary abnormality of platelet behavior causes migraine was first proposed in 1978. Further studies provide strong additional support for the platelet hypothesis in migraine. Platelets from people with migraines aggregate more readily, their platelet fibrinogen receptors have greater affinity, and their platelet membranes show altered viscosity.3
Fibromyalgia, Chronic Fatigue, Gulf War Syndrome
In chronic fatigue and/or fibromyalgia, patients have demonstrated enhanced platelet activation and fibrinogen and prothrombin activity.4
Researchers have also noted activation of the coagulation system in Gulf War Syndrome, which is similar to chronic fatigue syndrome and fibromyalgia.12 This finding led researchers to conclude, “This evidence of a hypercoagulable state suggests that symptoms may be due to poor blood flow and, therefore, a basis for the potential utility of anticoagulant therapy.”12
Varicose Veins, Venous Insufficiency
Varicose veins, venous insufficiency, venous thrombosis (a blood clot in the veins) and deep vein thrombosis (a blood clot in one or more of the veins in the deep venous system of the upper or lower extremities) are related conditions that involve abnormalities in coagulation and fibrinolysis. Defects in the body’s ability to degrade fibrinogen have been noted in cases where varicose veins progress to venous insufficiency with skin changes and venous ulcers.8 In venous thrombosis, researchers have noted hypercoagulability due to local accumulation of activated clotting factors and coagulation activation products.9Hemorrhoids, really varicose veins of the rectum, also are linked to the blood clotting process and studies have found that blood fibrinogen levels are increased in people with hemorrhoids.10, 16
Diabetes
The body naturally destroys clots through the formation of plasmin, a thrombolytic (clot-dissolving) enzyme. Plasmin is made from plasminogen through the action of an enzyme, tissue plasminogen activator (TPA). In obese patients with type 2 diabetes, the ability to break down fibrinogen is impaired by increased plasma concentrations of plasminogen activator inhibitor (PAI)-1.5
This impaired ability to break down fibrinogen has been linked to diabetic retinopathy. Hypercoagulation has been detected in the eyes of diabetic subjects along with higher fibrinogen activity.6 A state of hypercoagulation and fibrinolytic dysfunction also may contribute to disturbed skin microcirculation and impaired ulcer healing in diabetics.7
The high mortality rate in type 2 diabetes is associated with the increased cardiovascular disease risk seen in these patients. One group of researchers suggested that addressing hypercoagulation issues in type 2 diabetic subjects along with high blood pressure and lipid abnormalities may be a more powerful approach to reducing cardiovascular disease risk than addressing high blood sugar levels alone.17
Nattokinase: A Natural Anti-Coagulant
Nattokinase is an enzyme derived from fermented soy that inhibits fibrin and has fibrinolytic activity. Studies have shown that nattokinase is four times more powerful at dissolving blood clots than plasmin, the human body’s natural defense against clotting activity in the arteries.18-19 Nattokinase is the safest and most potent natural anti-clotting agent known.19-20
Nattokinase shows promise in supporting the health of people with thrombosis,21-22 venous stasis,22embolism formation,23 and the devastating blood clotting that arises from cardiovascular disease.24
Nattokinase’s blood clot dissolving ability is well supported by both animal and human studies. In one study, a control and a nattokinase-fed group of rodents were used to test the formation of blood clots near the site of artery damage. In the nattokinase-fed group, the great majority of the blood clots around the site of arterial injury detached from the surface of the vessel and dissolved.25
In a human study, researchers tested nattokinase on passengers undergoing a long plane flight, who are often at increased risk of deep vein thrombosis (artery blood clots) in the legs. The trial involved 204 passengers on 7- to 8-hour flights. The researchers measured edema (swelling of the legs) and superficial and deep vein thrombosis in persons considered at high risk for developing these conditions.26 An exercise program was used in both the control and the nattokinase-supplemented group.
In the group not given nattokinase, 5.4 percent developed deep vein thrombosis and 7.6 percent developed superficial thromboses. Twelve percent experienced swelling of the legs. In the nattokinase group, no deep vein thromboses developed. The control group had a total of 18 thrombotic events (19.6 percent) compared to only 7 percent (all superficial thromboses) in the nattokinase group. All “events were asymptomatic,” not leading to further complications.26 Furthermore, leg swelling increased 12 percent in the untreated group and was reduced 15 percent in the nattokinase group. The authors concluded that nattokinase was “effective in reducing thrombotic events and in controlling edema in high risk subjects in long flights.”26
Blood Pressure Support
Nattokinase’s effects on the blood vessels also helps maintain healthy blood pressure levels as shown in a trial involving 86 participants previously diagnosed with pre-hypertension or stage I hypertension. These previously untreated people had systolic blood pressure between 130 to 159 mm./Hg.27 The active treatment group was given 2,000 FU (fibrinolytic units) of nattokinase per capsule, versus a placebo in the control group. After eight weeks, systolic blood pressure dropped -5.5 mmHg and diastolic blood pressure declined -2.84 mmHg in the nattokinase group. The study authors concluded, “These findings suggest that increased intake of nattokinase may play an important role in preventing and treating hypertension.”27
Furthermore, nattokinase stopped artery (intimal) thickening in 2 animal studies where it was administered orally. Artery intimal thickening causes blood pressure to rise because of a loss of flexibility of the artery.19, 25
Nattokinase and Cognitive Health
Amyloid deposits are particles of oxidized protein that build up inside all non-dividing, or post mitotic cells, such as the brain, heart and other key cells.28-29 Amyloid buildup slowly shuts down the ability of the cell to function properly and acts as an irritant, increasing free radical generation. Brain cells are especially vulnerable to amyloid buildup during disease processes.28 Amyloid proteins occur in much greater abundance in Alzheimer’s disease and maturity onset diabetes than in the normal aging cells.28-29
Over the past 40 years, only a few compounds have been reported to dissolve amyloid protein. In 2009, however, researchers discovered that nattokinase could cleave amyloid and enhance amyloid clearance.20The researchers discovered that nattokinase, but not trypsin or plasmin, has the ability to degrade amyloid.20
Other Clinical Uses
Health care practitioners find that nattokinase is helpful in supporting the health of individuals with a number of other disorders. Clinicians, for example, have noted that nattokinase is useful in Lyme disease patients possibly because Borrelia burgdorferi, the organism responsible for Lyme disease, uses a critical receptor involved in blood clot formation and impaired circulation (hemostasis) to infect blood platelets.30
Clinicians also have used nattokinase in patients with dysmenorrhea (painful menstruation).
Conclusion
Hypercoagulation is linked to heart disease, strokes, hypertension, pulmonary embolism, venous insufficiency, inflammatory bowel disease, fibromyalgia, chronic fatigue syndrome, diabetes and migraines. Nattokinase has impressive blood clot dissolving or thrombolytic activity matched by no other enzyme. Consequently, nattokinase is an ideal natural approach to stop excessive coagulation, improve heart health, and reduce factors involved in a host of disorders.
References
1. Shen J, Ran ZH, Zhang Y, Cai Q, Yin HM, Zhou XT, Xiao SD. Biomarkers of altered coagulation and fibrinolysis as measures of disease activity in active inflammatory bowel disease: A gender-stratified, cohort analysis. Thromb Res. 2009;123(4):604-11.
2. Yoshida H, Granger DN. Inflammatory bowel disease: A paradigm for the link between coagulation and inflammation. Inflamm Bowel Dis. 2009 Feb 27. Published Online Ahead of Print.
3. Hanington E. Migraine: the platelet hypothesis after 10 years. Biomed Pharmacother. 1989;43(10):719-26.
4. Berg D, Berg LH, Couvaras J, Harrison H. Chronic fatigue syndrome and/or fibromyalgia as a variation of antiphospholipid antibody syndrome: an explanatory model and approach to laboratory diagnosis. Blood Coagul Fibrinolysis. 1999 Oct;10(7):435-8.
5. Aso Y, Matsumoto S, Fujiwara Y, Tayama K, Inukai T, Takemura Y. Impaired fibrinolytic compensation for hypercoagulability in obese patients with type 2 diabetes: association with increased plasminogen activator inhibitor-1. Metabolism. 2002 Apr;51(4):471-6.
6. Evgrafov VIu, Markova OA, Grishin VL, Efimov VS. [Changes in general hemostasis in patients with diabetic retinopathy] [Article in Russian] Vestn Oftalmol. 2004 May-Jun;120(3):29-31.
7. Kalani M, Silveira A, Blombäck M, Apelqvist J, Eliasson B, Eriksson JW, Fagrell B, Torffvit O, Hamsten A, Jörneskog G. Beneficial effects of dalteparin on haemostatic function and local tissue oxygenation in patients with diabetes, severe vascular disease and foot ulcers. Thromb Res. 2007;120(5):653-61.
8. Blomgren L, Johansson G, Siegbahn A, Bergqvist D. Coagulation and fibrinolysis in chronic venous insufficiency. Vasa. 2001 Jul;30(3):184-7.
9. Decousus H, Epinat M, Guillot K, Quenet S, Boissier C, Tardy B. Superficial vein thrombosis: risk factors, diagnosis, and treatment. Curr Opin Pulm Med. 2003 Sep;9(5):393-7.
10. Denis J, Garrigues JM, Trochet JP, Gerentes I, Taccoen A. [Rheological parameters in hemorrhoid pathology] [Article in French]. Ann Gastroenterol Hepatol (Paris). 1994 Sep;30(4):181-4.
11. Hsu RL, Lee KT, Wang JH, Lee LY, Chen, RP. Amyloid-degrading ability of nattokinase from Bacillus subtilis natto. J Agric Food Chem. 2009 Jan 28; 57 (2):503-8.
12. Hannan KL, Berg DE, Baumzweiger W, Harrison HH, Berg LH, Ramirez R, Nichols D. Activation of the coagulation system in Gulf War Illness: a potential pathophysiologic link with chronic fatigue syndrome. A laboratory approach to diagnosis. Blood Coagul Fibrinolysis. 2000 Oct;11(7):673-8.
13. Wirtz PH, Redwine LS, Baertschi C, Spillmann M, Ehlert U, von Känel R. Coagulation activity before and after acute psychosocial stress increases with age. Psychosom Med. 2008 May;70(4):476-81.
14. Stedman’s Medical Dictionary, 21st edition, The Williams and Wilkens Company, Baltimore, 1966.
15. Papa A, Scaldaferri F, Danese S, Guglielmo S, Roberto I, Bonizzi M, Mocci G, Felice C, Ricci C, Andrisani G, Fedeli G, Gasbarrini G, Gasbarrini A. Vascular involvement in inflammatory bowel disease: pathogenesis and clinical aspects. Dig Dis. 2008;26(2):149-55.
16. Gaj F, Trecca A, Suppa M, Sposato M, Coppola A, De Paola G, Aguglia F. [Hemorrhoidal thrombosis. A clinical and therapeutical study on 22 consecutive patients] [Article in Italian] Chir Ital. 2006 Mar-Apr;58(2):219-23.
17. Simon K, Dobó E, Nádasy T, Retih I, Rácz I. [What is the most effective approach to the reduction of cardiovascular risk in type-2 diabetes mellitus?] [Article in Hungarian]. Orv Hetil. 2006 Aug 6;147(31):1443-6.
18. Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet. Experientia. 1987 Oct 15; 43(10): 1110-1.
19. Suzuki Y, Kondo K, Matsumoto Y, Zhao BQ, Otsuguro K, 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 Jul 25; 73(10):1289-98.
20. Hsu RL, Lee KT, Wang JH, Lee LY, Chen RP. Amyloid-degrading ability of nattokinase from Bacillus subtilis natto. J Agric Food Chem. 2009 Jan 28; 57(2):503-8.
21. Tai MW, Sweet BV. Nattokinase for prevention of thrombosis. Am J Health Syst Pharm. 2006 Jun 15; 63 (12); 1121-3.
22. Cesarone MR, Belcaro G, Nickolaides AN, Ricci A, Geroulaklos G., et al. Angiogiology. 2003 Sep-Oct; 54(5); 531-9.
23. Evgrafov VIu, Markova OA, Grishin VL, Efimov VS. [Changes in general hemostasis in patients with diabetic retinopathy] [Article in Russian] Vestn Oftalmol. 2004 May-Jun;120(3):29-31.
24. Pais E, Alexy T, Holsworth RE Jr, Meismelman 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.
25. Suzuki Y, Kondo K, Ichise H, Tsukamato Y, Urano T, Umemura K. Dietary supplementation with fermented soybeans suppresses intimal thickening. Nutrition. 2003 Mar: 19(3): 261-4.
26. Cesarone MR, Belcaro G, Nickolaides AN, Ricci A, Geroulakos G, Ippolito E, Brandoloni R. Prevention of venous thrombosis in long haul flights: the LONFLIT-FLITE randomized, controlled trial. Angiology. 2003 Sep-Oct; 54(5):531-9.
27. Kim JY, Gum SN, Paik JK, Lim HH, Kim KC, Ogasawara K., et al. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens Res. 2008 Aug; 31(8):1583-8.
28. Reddy PH. Mitochondrial dysfunction in aging and Alzheimer’s disease: strategies to protect neurons. Antioxid Redox Signal. 2007 Oct; 9 (10): 1647-58.
29. Pepys MB. Pathogenesis, diagnosis and treatment of systemic amyloidosis. Philos Trans R Soc Lond B Biol Sci. 2001 Feb 28; 356 (1406): 203-10.
30. Coburn J, Leong JM, Erban JK. Integrin alpha IIb beta 3 mediates binding of the Lyme disease agent Borrelia burgdorferi to human platelets. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7059-63.
© 2008 Complementary Prescriptions 4610 Arrowhead Drive, Carson City, NV 89706
Used With Permission
