The fibrin-degrading enzyme nattokinase, derived from natto, can have many positive effects on the cardiovascular system.
Nattokinase is a fibrinolytic (i.e., fibrin-degrading) enzyme produced during the fermentation process that creates the Japanese food natto, involving boiled soybeans fermented with the bacteria Bacillus natto.1,2 Nattokinase has fibrinolytic activity that is four-times more potent than plasmin, a blood enzyme that degrades many blood plasma proteins, most notably fibrin clots.3 Nattokinase works by inactivating plasminogen activator inhibitor 1 (PAI-1).4,5 PAI-1 would otherwise inactivate plasminogen and hence fibrinolysis (the breakdown of fibrin clots). Its average activity is about 40 CU (plasmin units) per gram.
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 (CVDs). 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 to break down blood clots.6
The development of edema, and both 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 trial, high-risk subjects on long-haul flights were supplemented with a combination product containing nattokinase plus Pycnogenol� French maritime pine bark extract.8 Two capsules were taken two hours before the flight and again six hours later. The nattokinase combination product reduced thrombotic events and controlled edema in the subjects.
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.9 Nattokinase�s thrombolytic properties were found to be stronger than plasmin or elastase.10 Likewise, other animal research has demonstrated the fibrinolytic effect of nattokinase.11
In vitro and in vivo studies have consistently demonstrated the potent fibrinolytic effect of nattokinase. Additional in vitro research 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 animal trials.12 This additional research data suggests value for nattokinase as a therapeutic blood-thinning agent.
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 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, researchers explored the amyloid-degrading ability of nattokinase.13 Results demonstrated 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, �the amyloid-degrading ability of nattokinase suggests that it may be useful in the treatment of amyloid-related diseases."
Nattokinase may also prove helpful in the area of hypertension. In one 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 eight weeks.14 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 intervention. The corresponding net change in renin activity was -1.17 ng/mL/h for the nattokinase group, compared with the control group.
Another area of research interest is in arterial health. 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.(15) 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.(16,17)
Doctor Hiroyuki Sumi had long researched thrombolytic enzymes searching for a natural agent that could successfully dissolve thrombus associated with cardiac and cerebral infarction (blood clots associated with heart attacks and stroke). Sumi discovered nattokinase in 1980 while working as a researcher and majoring in physiological chemistry at Chicago University Medical School. After testing over 173 natural foods as potential thrombolytic agents, Sumi found what he was looking for when Natto was dropped onto artificial thrombus (fibrin) in a Petri dish and allowed it to stand at 37 C (approximately body temperature). The thrombus around the natto dissolved gradually and had completely dissolved within 18 hours. Sumi named the newly discovered enzyme "nattokinase", which means "enzyme in natto". Sumi commented that nattokinase showed "a potency matched by no other enzyme."
Potent Thrombolytic Activity
The human body produces several types of enzymes for making thrombus, but only one main enzyme for breaking it down and dissolving it - plasmin. The properties of nattokinase closely resemble plasmin. According to Dr. Martin Milner, from the Center for Natural Medicine in Portland, Oregon, what makes nattokinase a particularly potent treatment, is that it enhances the body's natural ability to fight blood clots in several different ways; Because it so closely resembles plasmin, it dissolves fibrin directly. In addition, it also enhances the body's production of both plasmin and other clot-dissolving agents, including urokinase (endogenous). "In some ways, Milner says, nattokinase is actually superior to conventional clot-dissolving drugs. T-PAs (tissue plasminogen activators) like urokinase (the drug), are only effective when taken intravenously and often fail simply because a stroke or heart attack victim's arteries have hardened beyond the point where they can be treated by any other clot-dissolving agent. Nattokinase, however, can help prevent that hardening with an oral dose of as little as 100 mg a day."
The Benefits of Nattokinase on Blood Pressure
Traditionaly in Japan, Natto has been consumed not only for cardiovascular support, but also to lower blood pressure. In recent years, this traditional belief has been confirmed by several clinical trials. In 1995, researchers from Miyazaki Medical College and Kurashiki University of Science and Arts in Japan studied the effects of nattokinase on blood pressure in both animal and human subjects (see below). In addition, the researchers confirmed the presence of inhibitors of angiotensin converting enzyme (ACE), which converts angiotensin I to its active form angiotensin II within the test extract, which consisted of 80% ethanol extract of lyophilized viscous materials of natto. ACE causes blood vessels to narrow and blood pressure to rise - by inhibiting ACE, nattokinase has a lowering effect on blood pressure.
Conclusion
The traditional Japanese food Natto has been used safely for over 1000 years. The potent fibrinolytic enzyme nattokinase appears to be safe based upon the long-term traditional use of this food. Nattokinase has many benefits including convenience of oral administration, confirmed efficacy, prolonged effects, cost effectiveness, and can be used preventatively. It is a naturally occurring, food based dietary supplement that has demonstrated stability in the gastrointestinal tract, as well as to changes in pH and temperature.
Nattokinase side effects, safety and risks and danger
No significant nattokinase side effects have yet been reported in the medical literature when used without other anticoagulants. However, this does not mean that nattokinase is side effect free, it just means that we don't have enough human trials to know all the benefits and risks with nattokinase enzyme treatment. One action of this natural substance is as a blood thinner, hence those on Coumadin, aspirin, or other anticoagulants need to be careful and discuss with their doctor the use of a nattokinase supplement. Using nattokinase with warfarin or aspirin could enhance bleeding risk.
Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds.
Intern Med. 2008. Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University, Kaohsiung, Taiwan.
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 agents at the same time.
Do you know what the best way to take natto with serrapeptase?
right now I am taking 1x natto in the morning with 2x serrapeptase, then 2x serrapeptase by itself at night. Is it fine to take it with serra in the morning 1 hour away from food?
Is 1x 2,000FU (Dr. Best) per day enough to help cholesterol and cardio? I do not have high cholesterol by any means but a little higher than average.
I take nattokinase and serrapeptase at the same time on an empty stomach. I like Doctor's Best too. Although it does have the vitamin K removed from the natto. I wonder about this and may try another brand, if I can't find out why.
I take one of each first thing in the morning and again a couple hours after supper.
So my husband went to see the doc last week.. his first visit with this guy, a VA doc, and they want him to take a baby aspirin a day.. of course this is to prevent blood clots... their form of prevenatative medicine.
He has no history of clots, age 63, but is a smoker who takes 4 grams of vitamin c a day, as well as D3, a B100 complex, iodine, selenium, resveratrol or pycogneol depending on what we have.
I need to know just how much natto for him to take to prevent in such a case. Any idea?
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Nattokinase, however, can help prevent that hardening with an oral dose of as little as 100 mg a day.
If someone told me to take daily aspirin, I would instead take the 100mg natto. I don't know how to translate that to FU. I'm currently taking 2000FU of Doctor's Best. This one says that it delivers 2000FU in 100mg if that helps. https://www.iherb.com/Jarrow-Formulas...aps/16802?at=0
Sorry. I've no experience with clotting. But beware of other medications that thin the blood while taking natto. I take serrapeptase at the same time and have no bleeding problem.
I don't know why doctors like this don't do more to access studies from other countries, in this case Germany and Japan, but there is plenty in plain English to support Natto.
How could he possibly say that it is not absorbed orally? Makes me think he chose not to really look into it at all
His premise is:
" It is an utterly ridiculous notion that anyone should take oral thrombolytic agents to �prevent blood clots�."
Dealing with clots is very risky without professional assistance. It can be severe. I understand that. Natto is a Japanese breakfast food. I assume they have no blood clots to begin with. It's got to be better than warfarin. I would not deal with clots without thorough professional support. Just common sense.
I'm not familiar with Dr. Timothy Kelly, but I like the way he thinks. Good ole Japan. Great role models for many health problems.
I take enzymes only as systemic. Meaning only on an empty stomach so it helps cleanse the blood and other things. Now that I'm using nattokinase and serrapeptase I don't do that so much. However, they are enzymes too, so I guess I still take enzymes systemically.
I take Drs Best, 2000FU. The bottle says take 1-2 per day. I take one in the morning and one in the evening along with serrapeptase at the same time. I monitor the color of my stool. If it is darker than normal, I cut back to one per day of the natto for a couple of days. So I guess it is up to the individual and what else you may be taking that may thin the blood, like omega 3.
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