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Nattokinase
Potent Fibrinolytic Enzyme Extract of Traditional Japanese Food
Landmark Development for Cardiovascular Health
What Is Nattokinase?
Nattokinase is a potent
fibrinolytic enzyme extracted and highly purified from a traditional Japanese
food called Natto. Natto is a fermented cheese-like food that has been
used in Japan for over 1000 years for its popular taste and as a folk remedy
for heart and vascular diseases. Natto is produced by a fermentation process
by adding Bacillus natto, a benefical bacteria, to boiled soybeans. The
resulting nattokinase enzyme, is produced when Bacillus natto acts on the
soybeans. While other soy foods contain enzymes, it is only the natto preparation
that contains the specific nattokinase enzyme.
The Discovery of Nattokinase
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." 1,7
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." 1,7
The Prolonged Action of Nattokinase
Nattokinase produces a prolonged
action (unlike antithrombin drugs that wear off shortly after IV treatment
is discontinued) in two ways: it prevents coagulation of blood and it dissolves
existing thrombus. Both the efficacy and the prolonged action of NK can
be determined by measuring levels of EFA (euglobulin fibrinolytic activity)
and FDP (fibrin degradation products), which both become elevated as fibrin
is being dissolved. By measuring EFA & FDP levels, activity of NK has
been determined to last from 8 to 12 hours. An additional parameter for
confirming the action of NK following oral administration is a rise in
blood levels of TPA antigen (tissue plasminogen activator), which indicates
a release of TPA from the endothelial cells and/or the liver.6,7
The Mechanism Behind Thrombus
Blood clots (or thrombi)
form when strands of protein called fibrin accumulate in a blood vessel.
In the heart, blood clots cause blockage of blood flow to muscle tissue.
If blood flow is blocked, the oxygen supply to that tissue is cut off and
it eventually dies. This can result in angina and heart attacks. Clots
in chambers of the heart can mobilize to the brain. In the brain, blood
clots also block blood and oxygen from reaching necessary areas, which
can result in senility and/or stroke.1
Thrombolytic enzymes are
normally generated in the endothelial cells of the blood vessels. As the
body ages, production of these enzymes begins to decline, making blood
more prone to coagulation. This mechanism can lead to cardiac or cerebral
infarction, as well as other conditions. Since endothelial cells exist
throughout the body, such as in the arteries, veins and lymphatic system,
poor production of thrombolytic enzymes can lead to the development of
thrombotic conditions virtually anywhere in the body.7
It has recently been revealed
that thrombotic clogging of the cerebral blood vessels may be a cause of
dementia. It has been estimated that sixty percent of senile dementia patients
in Japan is caused by thrombus. Thrombotic diseases typically include cerebral
hemorrhage, cerebral infarction, cardiac infarction and angina pectoris,
and also include diseases caused by blood vessels with lowered flexibility,
including senile dementia and diabetes (caused by pancreatic dysfunction).
Hemorrhoids are considered a local thrombotic condition. If chronic diseases
of the capillaries are also considered, then the number of thrombus related
conditions may be much higher. Cardiac infarction patients may have an
inherent imbalance in that their thrombolytic enzymes are weaker than their
coagulant enzymes. Nattokinase holds great promise to support patients
with such inherent weaknesses in a convenient and consistent manner, without
side effects.1,6,7 Nattokinase is capable of directly and potently decomposing
fibrin as well as activating pro-urokinase (endogenous).
Research In The United States
Dr. Martin Milner of the
Center for Natural Medicine in Portland, Oregon and Dr. Kouhei Makise of
the Imadeqawa Makise Clinica in Kyoto, Japan were able to launch a joint
research project on nattokinase and write an extensive paper on their findings.
"In all my years of research as a professor of cardiovascular and pulmonary
medicine, natto and nattokinase represents the most exciting new development
in the prevention and treatment of cardiovascular related diseases," Dr.
Milner said. "We have finally found a potent natural agent that can thin
and dissolve clots effectively, with relative safety and without side effects."
1
Animal & Human Studies
Nattokinase has been the
subject of 17 studies, including two small human trials. Dr. Sumi and his
colleagues induced blood clots in male dogs, then orally administered either
four capsules of nattokinase (250 mg per capsule) or four placebo capsules
to each dog. Angiograms (X-rays of blood vessels) revealed that the dogs
who received nattokinase regained normal blood circulation (free of the
clot) within five hours of treatment. Blood clots in the dogs who received
only placebo showed no sign of dissolving in the 18 hours following treatment.1,3
Researchers from Biotechnology
Research Laboratories and JCR Pharmaceuticals Co. of Kobe, Japan, tested
nattokinase's ability to dissolve a thrombus in the carotid arteries of
rats. Animals treated with nattokinase regained 62 percent of blood flow,
whereas those treated with plasmin regained just 15.8 percent of blood
flow.1
Researchers from JCR Pharmaceuticals,
Oklahoma State University, and Miyazaki Medical College tested nattokinase
on 12 healthy Japanese volunteers (6 men and 6 women, between the ages
of 21 and 55). They gave the volunteers 200 grams of natto (the food) before
breakfast, then tracked fibrinolytic activity through a series of blood
plasma tests. The tests indicated that the natto generated a heightened
ability to dissolve blood clots: On average, the volunteers' ELT (a measure
of how long it takes to dissolve a blood clot) dropped by 48 percent within
two hours of treatment, and volunteers retained an enhanced ability to
dissolve blood clots for 2 to 8 hours. As a control, researchers later
fed the same amount of boiled soybeans to the same volunteers and tracked
their fibrinolytic activity. The tests showed no significant change.1,3,6
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.1,2
Animal Study
After a single intraperitoneal
administration of 400-450 grams of the test extract (equivalent to 25 mg
of natto food) into male Wister rats, systolic blood pressure (SBP) significantly
decreased from 166 + mmHg to 145 + 24 mmHg in just two hours (p<0.05),
and decreased further to 144 + 27 mmHg in 3 hours (p<0.05). On average,
this data represents a 12.7 percent drop in SBP within two hours.1,2
Human Study
The same natto extract was
then tested on human volunteers with high blood pressure. Blood pressure
levels were measured after 30 grams of lyophilized extract (equivalent
to 200 grams of natto food) was administered orally for 4 consecutive days.
In 4 out of 5 volunteers, the systolic blood pressure (SBP) decreased on
average from 173.8 + 20.5 mmHg to 154.8 + 12.6 mmHg. Diastolic blood pressure
(DBP) decreased on average from 101.0 + 11.4 mmHg to 91.2 + 6.6 mmHg. On
average, this data represents a 10.9 percent drop in SBP and a 9.7 percent
drop in DBP.1,2,6
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.
Glossary of Terms:
Cardiac Infarction: Heart
attack.
Cerebral Infarction: Stroke.
Fibrin: A whitish, filamentous
protein formed by the action of thrombin on fibrinogen and makes up part
of coagulum or blood clots.
Fibrinolytic: Pertaining
to or causing the breaking up of blood clots.
Infarction: Cardiac or cerebral
tissue death due to failure of blood supply to the area usually caused
by a blood clot.
Plasmin: An endogenously
produced fibrinolytic enzyme.
Plasminogen: A precursor
to plasmin. A protein found in many tissues and body fluids.
Thrombus: A blood clot that
obstructs a blood vessel or a cavity of the heart.
Thrombolytic: Pertaining
to or causing the breaking up of a thrombus.
TPA: Tissue plasminogen
activator.
t-PAs: The most commonly
used thrombolytic drugs including activase, urokinase, and streptokinase.
Urokinase: An endogenously
produced thrombolytic enzyme & also a commonly used thrombolytic drug
given intravenously to cardiac and cerbral infarction patients.
References:
1. Prevent Heart Attack
and Stroke with Potent Enzyme that Dissolves Deadly Blood Clots in Hours.
Health Sciences Institute, March 2002.
2. Maruyama M, Sumi H. Effect
of Natto Diet on Blood Pressure. JTTAS, 1995.