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| Neprinol AFD |
Nattokinase
Nattokinase is produced during the very fermentation process which creates Natto, involving boiled soybeans fermented with the bacteria Bacillus natto.[2] [3] Nattokinase has fibrinolytic activity that is 4-times more potent than plasmin[4] (a blood enzyme that degrades many blood plasma proteins, most notable, fibrin clots).[5] Nattokinase works by inactivating plasminogen activator inhibitor 1 (PAI-1).[6] [7] PAI-1 would otherwise inactivate plasminogen and hence fibrinolysis (the breakdown of fibrin clots). Its average activity is about 40 CU (plasmin units) /gram.[8] Also, Nattokinase is orally available as a dietary supplement. This has been demonstrated in both human and animal research.[9] [10]
Nattokinase & 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).[11]
In an open-label, self-controlled clinical trial[12], 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 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 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 3 coagulation factors continuously declined during intake:
Fibrinogen | Factor VII | Factor VIII | |
Healthy Group | 9% | 14% | 17% |
Cardiovascular Group | 7% | 13% | 19% |
Dialysis Group | 10% | 7% | 19% |
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 (7-8 hours), particularly in high-risk subjects. In a randomized, controlled trial[13], high-risk subjects on long-haul flights were supplemented with a combination product containing nattokinase plus pycnogenol. Two capsules were taken 2 hours before the flight and then again 6 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.[14] Likewise, other animal research has also demonstrated the fibrinolytic effect of nattokinase.[15] [16]
In-vitro and in-vivo studies have consistently demonstrated the potent fibrinolytic effect of nattokinase. Additional in-vitro research [17] 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 & Hydrolyzing Amyloid Fibrils
More than 20 unrelated proteins can form amyloid fibrils in vivo 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 study [18], 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 & Hypertension
In a randomized, double-blind, placebo-controlled trial[19], 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 8 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 & 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 clotting 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.[20] 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.[21] [22]
Serrapeptase has been shown in in-vivo research to be absorbed from the gastrointestinal tract when taken orally.[23] [24] It has anti-inflammatory, antiedemic, and fibrinolytic effects[25] [26] as well as decreasing pain―apparently by inhibiting the release of bradykinin and other factors from inflamed or damaged tissue.[27] Research has demonstrated serrapeptase anti-inflammatory effects in such conditions as post-operative swelling, pharyngitis, sinusitis, and others. [28] In addition, serrapeptase helps to help break down proteinaceous secretions and therefore facilitate the elimination of excessive secretions.[29] For example, serrapeptase has decreased sputum viscosity and decrease neutrophils in the sputum of patients with chronic airway disease.[30] Also, serrapeptase has antibacterial properties[31], and a synergistic relationship with antiobiotics, helping to disperse them more effectively throughout tissues. [32]
Post-operative swelling/pain/edema
Patients undergoing maxillary antrotomy for empyema who take serrapeptase 10 mg orally three times on the day before surgery, once in evening after surgery, and three times daily for 5 days after surgery seem to have modestly reduced buccal swelling compared to placebo.[33]
Patients undergoing surgical removal of impacted third molars were randomly sorted to receive ibuprofen, paracetamol, betamethasone, serrapeptase or placebo. Serrapeptase did not show significant analgesic and anti-inflammatory action.[34] However, in a similar study of patients undergoing surgical removal of impacted third molars, 5 mg serrapeptase 5mg or placebo was given with 1000 mg paracetamol. There was a significant reduction in the extent of cheek swelling and pain intensity in the serrapeptase group at the 2nd, 3rd and 7th postoperative days.[35]
Preventive edema protection using Serrapeptase after standardized one-stage osteotomy procedures of 4 third molars was verified by means of an opto-electronic measuring instrument. This measuring technique proved to be a sensitive tool for demonstrating the efficacy of this enzyme.
In other research serrapeptase demonstrated statistically significant effectiveness in reducing postoperative edema in patients undergoing the removal of 4 third molars.[36] Sixty-six patients who underwent surgical treatment of the lateral ligament, were treated with elevation of the leg, bed rest (with and without the application of ice) or serrapeptase. In the serrapeptase group, the swelling had decreased by 50% on the third post-operative day, while in the other two control groups no reduction in swelling had occurred at that time. Decreasing pain correlated for the most part with the reduction in swelling. Thus, the patients receiving the test substance more rapidly became pain-free than did the control groups.[37]
Parflex, a single pharmaceutical product combining aceclofenac with paracetamol and serrapeptase, was assessed in management of pain and inflammation in adult patients undergoing ENT, orthopedic or gynecologic surgical procedures. Effectiveness was rated as excellent or good by 54% of patients and by 59% of treating physicians. The conclusion was that parflex is an effective analgesic, anti-inflammatory drug that has a valuable therapeutic option for controlling pain and inflammation after surgical procedures.[38]
Antibacterial treatment
Listeria monocytogenes is a notably invasive bacterium associated with life-threatening food-borne disease in humans. Several surface proteins (biofilms) have been shown to be essential in the adhesion of L. monocytogenes, and in the subsequent invasion of phagocytes. In research, treatment with serrapeptase reduced the ability of L. monocytogenes to form biofilms and to invade host cells in the human gut.[39]
In an animal model, bacterial infections associated with knee surgery were treated with either serrapeptase + antibiotic, antibiotic only, or nothing. At two weeks, Microbiological testing suggested that infection existed in 63.2% of animals in the no-treatment group, 37.5% of animals in the antibiotic-only group, and only 5.6% of animals in the serrapeptase + antibiotic group. Researchers concluded that serrapeptase was effective at eradicating infection caused by biofilm-forming bacteria.[40]
Other research has also demonstrated the effectiveness of serrapeptase at inhibiting biofilm-embedded bacteria in prosthetic device infections. [41]
Cephalosporin antibiotics are widely used to prevent infection in patients undergoing thoracotomy. Augmentation by serrapeptase on tissue permeation of the cephalosporin Cefotiam (CTM) was examined in 35 thoracotomy patients with lung cancer. The subjects were divided into two groups, one receiving a single dose CTM alone, the other receiving a combination of CTM and serrapeptase (30 mg daily) for three days before surgery. The results were the concentration of the drug in pulmonary tissues was 29.1% in the single dose group, and 44.2% in the combination group. The researchers concluded serrapeptase stimulated permeation of the antibiotic into tissues.[42] Similar beneficial effects on the distribution of antibiotics in tissues with serrapeptase were seen in other human[43] and animal[44] research.
Carpal tunnel syndrome
Twenty patients with carpal tunnel syndrome (CTS) were evaluated clinically, and treated with 10 mg serratiopeptidase twice daily for six weeks with an initial short course of nimesulide (a COX-2 inhibitor). The results were that 65% of cases showed significant clinical improvement which was supported by significant improvement in electrophysiological parameters.[45]
Inflammatory venous diseases
Patients with thrombophlebitis were treated with 5 mg tablets, at a dose of 30 mg serrapeptase daily (two 5 mg tabs, three times daily) for 14 days. By the end of treatment spontaneous pain was reduced 63.3% from the baseline mean score. Pain on pressure was reduced 57.6%. Edema was reduced 56.2%; erythema (redness of skin) diminished 58.3%; nighttime cramps were 52.9% less; hemorrhagic suffusion was 41.7% less (from 1.2 to 0.7); cutaneous dystrophy (skin wasting) was reduced by 7.7%. At the end of the treatment with serrapeptase, efficacy was assessed as good or excellent in 65% of the cases.[46]
Breast engorgement
Seventy patients complaining of breast engorgement were treated with serrapeptase or placebo for three days. The results were that serrapeptase was superior to placebo for improvement of breast pain, breast swelling and induration (tissue hardening), with 85.7% of the patients experiencing “moderate to marked” improvement compared to 60.0% in the placebo group. Furthermore, “marked” improvement was found in 22.9% of the serrapeptase group compared to 2.9% of the placebo group.[47]
Bronchitis
Preliminary evidence suggests that patients with chronic bronchitis or bronchiectasis who take serrapeptase 30 mg daily for 4 weeks have significantly reduced frequency of cough and expectoration. These patients who took serrapeptase also seem to have decreased sputum viscosity and lower neutrophil counts in sputum samples.[48] Similar beneficial results were demonstrated in animal research.[49]
Chronic pulmonary disease
Forty patients with chronic pulmonary disease were treated with expectorants to determine the effect on sputum viscoelasticity. Patients were randomly put into the control group or a group which would be given oral treatments with an expectorant for a week after a one week washout period. The groups were as follows: Group I, control; Group II, Bromhexine hydrochloride 24 mg per day; Group III, Ambroxol 90 mg per day; Group IV alpha – Chymotrypsin buccle 100 ch.u. per day; Group V, Serratiopeptidase 30 mg per day. The results were that the sputum viscoelasticity in the serrapeptase and chymotrypsin groups were clearly changed after the treatments, with the magnitude of the sputem relaxation and its main relaxation time were significantly increased. No significant changes were observed in the other groups. These findings suggest that proteolytic enzymes administered orally work on the molecular structure of sputum, and break down their linkages between subunits of the structure.[50]
Laryngitis
Research demonstrated that patients with laryngitis who take serrapeptase 10 mg three times daily have significantly reduced pain, secretions, difficulty swallowing, and body temperature after 3-4 days of treatment.[51]
Pharyngitis
Research demonstrated that patients with pharyngitis who take serrapeptase 10 mg three times daily have significantly reduced pain, secretions, difficulty swallowing, and body temperature after 3-4 days of treatment.[52]
Sinusitis
Serrapeptase was found to improve the flow properties of nasal mucus secretions in adult chronic sinusitis patients.[53] When 30 mg serrapeptase daily was administered to adult patients with chronic sinusitis for 4 weeks, the viscosity of nasal mucus was reduced.[54] Research has shown that patients with sinusitis who take serrapeptase 10 mg three times daily also have significantly reduced pain, nasal secretions, nasal obstruction, and anosmia (lack of sense of smell) after 3-4 days of treatment.[55]
Serrapeptase liposomes
Research indicates that in comparison with pure serrapeptase, incorporation of serrapeptase into liposomes improved permeability, and thus it could be concluded that the liposomal formulation would improve the oral absorption of enzyme.[56]
Other Neprinol Ingredients
In addition to nattokinase, Neprinol also contains serrapeptase, fungal proteases, Amla, papain, bromelain, rutin and coenzyme Q10. A previous research project provided substantial data on serrapeptase. Following is a brief discussion on each of the other ingredients.
Proteases
Fungal proteases (i.e., proteolytic enzymes) are usually derived by fermentation of various strains ofAspergillus. They also exhibit a broad range of activity to sever peptide bonds, and are effective over a wide range of temperature and pH[57]. A number of studies show that fungal enzymes have anti-inflammatory activity as well as fibrinolytic properties, as demonstrated by their ability to hydrolyze fibrin and fibrinogen.[58] [59]
Alma
The leaf of Alma (Emblica officinalis), also known as Indian Gooseberry, has anti-inflammatory activity.[60] [61] In fact, it is used in traditional Asian medicine in the treatment of tissue inflammation.[62] Alma is also used as part of herbal eye drop formulation and has been shown to be useful role in a variety of inflammatory ophthalmic disorders.[63] In addition, a standardized extract of Alma was found to have a long-lasting and broad-spectrum antioxidant activity, protecting tissue from the damaging effects of free radicals, non-radicals and transition metal-induced oxidative stress.[64]
Papain
Papain is a protease or proteolytic enzyme derived from papaya. The therapeutic use of papain as an anti-inflammatory agent is empirically based, but is also supported by scientific studies.[65] [66] Taking papain orally, in combination with other agents, was shown to relieve inflammation and swelling of the throat.[67] [68] [69] Furthermore, papain is one of several enzymes and enzyme combinations which are effective in treating inflammation because they help limit the injury, aid its rectification, and promote new, healthy tissue formation.[70] According to the German Commission E Monographs, experiments have shown that papain also has an edema-reducing effect.[71]
Bromelain
Bromelain is a protease or proteolytic enzyme derived from pineapple. Research indicates that oral supplementation with bromelain can reduce mild, acute (duration of less than 3 months) knee pain, stiffness, and physical function of the knee in otherwise healthy patients.[72] Likewise, oral bromelain taken with trypsin and rutin was shown to reduce discomfort and improve knee function in arthritic patients.[73] In addition, clinical research suggests bromelain might reduce swelling and pain after trauma or surgery[74], but not after oral surgery.[75] Bromelain’s anti-inflammatory activity may result from its altering leukocyte migration and activation.[76]
Rutin
Rutin is a flavonoid with antioxidant [77] [78] and anti-inflammatory[79] [80] properties. Rutin is hydrolyzed in the gastrointestinal tract to release quercetin, which is responsible for many of the actions of rutin.[81] Research shows that quercetin and rutin inhibit inflammation caused by edema and colitis in animals. Specifically, they inhibit the production of nitric oxide, lysosomal enzymes (which cause tissue damage), phospholipase A2 (a precursor in eicosanoid synthesis), and intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1), which facilitate leukocyte activity.[82] In human clinical researchfact, rutin was shown to reduce discomfort and improve knee function in arthritic patients when taken with bromelain and trypsin.[83]
References
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