This Is MS Multiple Sclerosis Community: Knowledge & Support

Some recent discussion on the forums on the subject of nattokinase prompted me to check what PubMed might have listed on the topic. There were 55 papers listed on nattokinase, the following three seemed like they might be relevant to our CCSVI discussion. The last paper discusses a preventive effect on restenosis after angioplasty in arteries and the full paper is available for free, but it's in Chinese! If someone can read Chinese, Algis perhaps, then they might be interested in taking a look at the full paper.

NHE


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.

We have previously demonstrated that natto-extracts containing nattokinase (NK) inactivates plasminogen activator inhibitor type 1 and then potentiates fibrinolytic activity. In the present study, we investigated the effects of dietary supplementation with natto-extracts on neointima formation and on thrombolysis at the site of endothelial injury. Endothelial damage in the rat femoral artery was induced by intravenous injection of rose bengal followed by focal irradiation by transluminal green light. Dietary natto-extracts supplementation containing NK of 50 or 100 CU/body was started 3 weeks before endothelial injury and then continued for another 3 weeks. Intimal thickening in animals given supplementation was significantly (P<0.01) suppressed compared with controls and the intima/media ratio in animals with 50 and 100 CU/body NK and control group was 0.09 +/- 0.03, 0.09 +/- 0.06 and 0.16 +/- 0.12, respectively. Although femoral arteries were reopened both in control animals and those treated with NK within 8 hours after endothelial injury, mural thrombi were histologically observed at the site of endothelial injury. In the control group, the center of vessel lumen was reopened and mural thrombi were attached on the surface of vessel walls. In contrast, in NK-treated groups, thrombi near the vessel wall showed lysis and most of them detached from the surface of vessel walls. In conclusion, dietary natto-extracts supplementation suppressed intimal thickening produced by endothelial injury in rat femoral artery. These effects may partially be attributable to NK, which showed enhanced thrombolysis near the vessel wall.

Dietary supplementation with fermented soybeans suppresses intimal thickening.
Nutrition. 2003 Mar;19(3):261-4.

Although soy foods have been consumed for more than 1000 y, it is only in the past 20 y that they have made inroads into Western diets. We investigated the effect of dietary supplementation with natto extracts produced from fermented soybeans on intimal thickening of arteries after vessel endothelial denudation. Natto extracts include nattokinase, a potent fibrinolytic enzyme having four times greater fibrinolytic activity than plasmin. Intimal thickening was induced in the femoral arteries by intravenous infusion of rose bengal followed by focal irradiation with a transluminal green light. Dietary natto extract supplementation was started 3 wk before endothelial injury and continued for another 3 wk after. In ex vivo studies, euglobulin clot lysis times were measured 3 wk after the initial supplementation. Neointima formation and thickening were also initiated successfully. The intima media ratio 3 wk after endothelial injury was 0.15 +/- 0.03 in the control group. Dietary natto extract supplementation suppressed intimal thickening (0.06 +/- 0.01; P < 0.05) compared with the control group. Natto extracts shortened euglobulin clot lysis time, suggesting that their thrombolytic activities were enhanced. These findings suggest that natto extracts, because of their thrombolytic activity, suppress intimal thickening after vascular injury as a result of the inhibition of mural thrombi formation.

Effect of nattokinase on restenosis after percutaneous transluminal angioplasty of the abdominal artery in rabbits
Nan Fang Yi Ke Da Xue Xue Bao. 2008 Aug;28(9):1538-41.

OBJECTIVE: To investigate the effect of nattokinase on intimal hyperplasia in rabbit abdominal artery after balloon injury and explore a novel strategy for the preventing restenosis after percutaneous transluminal angioplasty.

METHODS: Fifty-six New Zealand rabbits were randomly divided into 7 groups, namely the solvent control group, model group, natto extract lavage group, refined nattokinse lavage group, intravenous refined nattokinse injection group, clopidogrel group and clopidogrel-aspirin group. Balloon injury was induced by inserting the catheter through the femoral artery into the thoracic aorta of the rabbits. The platelet counts were notad and platelet aggregation was observed, and the abdominal artery was taken for pathological analysis. The expressions of MMP-2 and -9 in the abdominal artery were detected immunohistochemically.

RESULTS: There was no significant difference in the platelet counts, platelet aggregation rate or MMP-2 and -9 expression between the model group and the nattokinse-treated groups (P>0.05). The stenosis index in each nattokinse-treated group was significantly greater and the neointimal proliferation index smaller than that of the model group (P<0.01 or 0.05).

CONCLUSION: Nattokinse can inhibit restenosis of rabbit abdominal artery after percutaneous transluminal angioplasty, which is independent of its actions on the platelet or MMP-2 and -9 expressions.

Although the following paper is a case report with an n=1, it does suggest that there should be some caution in using nattokinase as a supplement.

Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds.
Intern Med. 2008;47(5):467-9. Epub 2008 Mar 3.

Nattokinase is used as a health-promoting medicine for preventing thrombosis due to its fibrinolytic activity. Cerebral microbleed is remnant of blood extravasations from the damaged vessels related to cerebral microangiopathies. We report a patient, having used aspirin for secondary stroke prevention, who had an acute cerebellar hemorrhage after taking nattokinase 400 mg daily for 7 consecutive days. In addition to the hemorrhagic lesion, multiple microbleeds were demonstrated on brain MR images. We suggest that nattokinase may increase risk of intracerebral hemorrhage in patients who have bleeding-prone cerebral microangiopathy and are receiving other antithrombotic agent at the same time.

NHE

Does this suggest that it is safe to take if you are NOT on any other anticoagulant or not suffering from cerebral microangiopathy? I would be very interested in trying this myself......

I'm not able to answer your question. However, there have been a couple of studies using oral administration of nattokinase which did not report any adverse events. One might interpret this in a positive light. However, considering that this "supplement" may have strong effects on blood clotting, it might be best to discuss any proposed treatment with a doctor familiar with the various parameters involved. I could imagine a scenario where treatment with nattokinase is closely monitored with blood tests such as INR among others.

NHE


Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.
Nutr Res. 2009 Mar;29(3):190-6.

Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of 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. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. 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 CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

Effects of nattokinase on blood pressure: a randomized, controlled trial.
Hypertens Res. 2008 Aug;31(8):1583-8.

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. In a randomized, double-blind, placebo-controlled trial, 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. Seventy-three subjects completed the protocol. Compared with the control group, the net changes in SBP and diastolic blood pressure (DBP) were -5.55 mmHg (95% confidence interval [CI], -10.5 to -0.57 mmHg; p<0.05) and -2.84 mmHg (CI, -5.33 to -0.33 mmHg; p<0.05), 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 (p<0.05). 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.

Given my current interest in hypercoagulability, I'm interested to know if CCSVI might be aided thru the use of an anticoagulant like Natto.

Thx, PN

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