Numerous serious complications have led to an increasing use of systemic enzyme therapy as a safe alternative to alleviate symptoms and improve quality of life. Certain proteolytic (protein digesting) enzymes have been identified to have extremely beneficial actions when applied to the inflammation related to this condition. Systemic enzymes, typically taken orally and on an empty stomach, enter directly into the blood stream. Enzymes can then circulate throughout the body, acting upon complexes in the blood as well as in tissues and organs.
Systemic enzymes have successfully demonstrated the ability to reduce signs of inflammation throughout the body. Serrapeptase, an enzyme extracted from silk worms, and nattokinase, an enzyme extracted from the Japanese fermented soybean food Nattō, have been evaluated in numerous studies for their effectiveness in inflammation reduction and show favorable results.
The use of proteolytic enzymes (proteases) for reducing of inflammation associated with type 1 diabetes has been investigated, showing positive results. Proteases have the ability to affect the immune response in different ways; they regulate T-cell (a type of white blood cell) activity by multiple interferences in immune responsiveness, including changing the expression of cell surface molecules and reducing the production of chemical signals called cytokines to a non-inflammatory level.1 In animal models for Type I diabetes protease treatment prevented or delayed the onset of the disease.2
Research indicates that patients with type 2 diabetes have excessive amounts of plasminogen activator inhibitor-1 (PAI-1)3. PAI-1 prevents the conversion of the enzyme precursor plasminogen into plasmin, drastically reducing the body’s innate ability to dissolve fibrin and reduce inflammation. Nattokinase appears to reduce the formation of dangerous clots and inhibit arterial thickening, not only by direct fibrinolysis of clots but also by inhibition of the plasma protein plasminogen activator inhibitor.4
Inflammatory marker reduction has been documented with the supplementation of proteases. One study compared blood laboratory values before and after supplementation of Exclzyme (a blend containing enzymes serrapeptase, bromelain, lipase, amylase and other proteases) in patients with inflammation related to rheumatic disease or trauma. Results showed a significant decrease in erythrocyte sedimentation rate (ESR), a long-term predictor of cardiovascular disease. ESR is a measurement comparable to C-reactive protein (CRP) levels in predicting risk of a cardiac event. However, ESR does not change as rapidly as does CRP, and CRP is not affected by other factors as is ESR .5,6
Bromelain, a proteolytic enzyme extracted from pineapple, has also been found effective in reducing inflammation by blocking cytokines that promote and increase inflammation.7,8 Cytokines play a significant role in the destruction of beta cells in type 1 diabetes.9 Research has also shown that bromelain disrupts the migration of neutrophils (a type of white blood cell) to an inflamed area, where they would otherwise propagate the process. One study measured a 50-85% decrease in the migration of neutrophils after bromelain treatment.10
Diabetes mellitus and hypertension are interrelated diseases that strongly predispose an individual to atherosclerotic cardiovascular disease. In fact, hypertension is about twice as frequent in individuals with diabetes as in those without, according to the American Heart Association.11 Maintaining a healthy blood pressure and improving overall circulation are important components of treating diabetes.
Blood clots (thrombi) form when strands of fibrin accumulate in the circulatory system. These clots can cause blockage of blood flow. If blood flow is blocked, the oxygen supply to that tissue is cut off and it eventually dies. In the heart, this can result in myocardial infarction (heart attack). In the brain, it can result in strokes or mini-strokes. Deep vein thrombosis can result in pulmonary emboli. All these events can be life-threatening. An in vitro study, not only demonstrated the powerful fibrinolytic activity of nattokinase, but also significantly reduced the aggregation of red blood cells and lowered whole blood viscosity. The net results are vascular conditions that are less likely to produce blood clots. The authors suggest that nattokinase possesses very real potential as a therapeutic agent in cardiovascular health.12
Research with nattokinase demonstrates that it may help avoid or reduce the likelihood of deep vein thrombosis, cardiac infarction, pulmonary emboli and stroke. It appears to accomplish this via its fibrinolytic, anti-inflammatory and modulating effect on blood pressure. Studies on hypertension demonstrate an average drop of 10.9% in Systolic Blood Pressure and a 9.7 percent drop in Diastolic Blood Pressure.13,14,15
A study with rat femoral artery investigating the effect of dietary supplementation with natto extracts on the thickening of the inner most membrane (intimal) of arteries was conducted. It was shown that dietary natto extract supplementation suppressed intimal thickening (0.06 +/- 0.01; P < 0.05) compared with the control group. These findings suggest that natto extracts, because of their thrombolytic activity, suppress intimal thickening after vascular injury as a result of the inhibition of thrombi formation.16,17
Managing the amounts of lipids, specifically triglycerides and cholesterol, in the blood is a major goal of those with diabetes. This helps lower the risk of atherosclerosis and related vascular issues.
A study looked at the blood lipid content in rats after 3 weeks of supplementation with the food natto and a basal diet containing 1% cholesterol. Results showed lowered plasma triglyceride and total cholesterol. A reduction in lipid peroxidation (which causes cell damage) in liver and aorta in vivo was also observed. These results show that ingestion of the natto led to inhibition of LDL oxidation, and that natto performs direct antioxidant action in the body. It is suggested that natto might help to prevent arteriosclerosis, as it appears to reduce lipid peroxidation and improve lipid metabolism.18
Diabetic patients are at increased risk for the development of infection and impaired wound healing.19Multiple studies have shown the effectiveness of serrapeptase in helping with proper wound healing.
A prospective study was conducted on the effect of serrapeptase on post-operative swelling and pain of the ankle. In the serrapeptase group, the swelling decreased by 50% on the third post-operative day, while in the control groups (no treatment and treatment with ice) no reduction in swelling occurred. A decrease in pain correlated for the most part with the reduction in swelling. On the basis of these results, serrapeptase would appear to be an effective preparation for the post-operative reduction of swelling, in comparison with the classical conservative measures, for example, the application of ice.20
An unusual clinical trial evaluated the effectiveness of serrapeptase in the elimination of a periprosthetic infection (an infection at the site of an implanted orthopedic device) in an in vivo animal model. Infections of slime-forming bacteria are especially difficult at these sites. Staphylococcus epidermidis was introduced at the prosthetic site in rats. After two weeks, infection persisted in 63.2% of animals in the no-treatment group; 37.5% of animals in an antibiotic-only group; and only 5.6% of animals in the serrapeptase-and-antibiotic group. The authors conclude that serrapeptase was effective at eradicating infection in this experimental animal model and may enhance antibiotic efficacy in the treatment of staphylococcal infections.21
Blood viscosity is an important consideration when assessing blood pressure concerns which arise during disease progression. Studies suggest enzymes such as nattokinase can help reduce red blood cell aggregation and improve flow rates.22 Serrapeptase has demonstrated the ability to cleanse blood by removing excess fibrin from circulation, thus reducing blood stickiness and the threat of blood clot formation. Additionally, toxic substances and remnant food particles can be further degraded in the blood by serrapeptase, and prepared for filtration through the liver and expulsion.23