Wednesday, August 16, 2017

Are We Hollow?

We are used to thinking of our human bodies as solid, and that everything that lies beneath our skin belongs to an inside world. It would be more correct to say that we are hollow. The design of the human body is much more interesting, and artistic than you may or dare think.

Running through the middle of the body is a log tunnel, the digestive tract. The space inside this tunnel (the lumen, from the Latin for light or opening inside a tubular structure), bordered by the inner layers of the mucosa, carries substances that don't belong to you. This strange exterior world flows inside you, transporting foods, liquids, substances, chemicals, and bacteria ー everything that you have swallowed and consumed. The digestive tract controls the passage of all these foreign substances, as they pass through your body from the mouth to the anus during digestion. En route, the foods you eat are assimilated and become the building blocks that make up your body, they become you. 

The digestive mucosa is the human body's customs service: a "high-intelligence service of the state." You depend on its work for your health and your life. The digestion and absorption of nutrients that it undertakes are vital functions, as essential as breathing and the beating of the heart. A bad digestion should be given equal importance to poor respiration or a cadiac condition.

Looked at in a certain way, you really are hollow. Your essence and continuity to interrupted by the lumen of this tube that runs through you carrying foreign substances; this tube is in charge of the vital functions of defence, strength, nutrition, energy, growth, construction of new tissues, and detoxification. 

Tuesday, August 15, 2017

Drinking Water and Health

Historical Note
As noted by Baker (1949), the quest for pure 
water began in prehistoric times. Recorded 
knowledge of water treatment is found in 
Sanskrit medical lore and in Egyptian 
inscriptions. Pictures of apparatus to clarify 
liquids (both water and wine) have been 
found on Egyptian walls dating back to the 
fifteenth century B.C. Boiling of water, the use of 
wick siphons, filtration through porous vessels, 
and even filtration with sand and gravel, as 
means to purify water, are methods that have been 
prescribed for thousands of years. In his writings 
on public hygiene, Hippocrates (460-354 B.C.) 
directed attention principally to the importance of 
water in the maintenance of health, but he also 
prescribed that rain water should be boiled and 
strained. The cloth bag that he recommended for 
straining became known in later times as 
"Hippocrates' sleeve."

Public water supplies, already developed in 
ancient times, assumed added importance with 
the progressive increase in urbanization. But 
though they were clearly beneficial in 
distributing water of uniform quality, large 
numbers of people ran the risk of suffering 
adverse effects when the water was unsafe to 
drink.

The first clear proof that public water supplies 
could be a source of infection for humans was 
based on careful epidemiological studies of 
cholera in the city of London by Dr. John Snow in 
1854 (Snow, 1855). Although Snow's study of the
contaminated Broad Street pump is the most 
famous, his definitive work concerned the spread 
of cholera through water supplied by the 
Southwark and Vauxhall Company and the 
Lambeth Company. The former obtained its water 
from the Thames at Battersea, in the middle of 
London in an area almost certainly polluted with 
sewage, whereas the Lambeth Company obtained
its water considerably upstream on the Thames, 
above the major sources of pollution. In one 
particular area served by these two companies, 
containing about 300,000 residents, the pipes of 
both companies were laid in the streets, and 
houses were connected to one or the other 
sources of supply. Snow's examination of the 
statistics of cholera deaths gave striking results. 
Those houses served by the Lambeth Company 
had a low incidence of cholera, lower than the 
average for the population of London as a whole, 
whereas those served by the Southwark and 
Vauxhall Company had a very high incidence. 
As the socioeconomic conditions, climate, soil, 
and all other factors were identical for the populations served by the two companies, Snow
concluded that the water supply was transmitting the cholera agent. Snow's study, a classic in the field of epidemiology, is even more impressive when it is realized that at the time he was working, the germ theory of disease had not yet been established. 

  During the seventeenth to the early nineteenth 
centuries, a number of improvements in water 
supply were made, most of them related to 
improvements in filtration to remove the turbidity 
of waters. During this same period, the germ 
theory of disease became firmly established as a 
result of research by Louis Pasteur, Robert Koch, 
and others, and in 1884 Koch isolated the causal 
agent of cholera, Vibrio cholera. 

Importance of Water Filtration

In 1892, a study of cholera by Koch in the German 
cities of Hamburg and Altona provided some of 
the best evidence of the importance of water 
filtration for protection against this disease 
(Koch, 1894). The cities of Hamburg and Altona 
both received their drinking water from the Elbe 
River, but Altona used filtration, since its water 
was taken from the Elbe below the city of Hamburg and
hence was more grossly contaminated. Hamburg and Altona are contiguous
cities, and in some places the border between the two follows a contorted course.
Koch traced the incidence of cholera in the 1892 epidemic through these two
cities, with special attention directed to the contiguous areas. In such areas it was
assumed that climate, soil, and other factors would be identical, the principal
variable being the source of water. The results of this study were dear-cut:
Altona, even with an inferior water source, had a markedly lower incidence of
cholera than Hamburg. Since by this time it was well established that cholera was
caused by intestinal bacteria excreted in large numbers in the feces, it was concluded that the role of filtration was to remove the contaminating bacteria from the water. 

In the United States, cholera was not a problem 
after the mid-nineteenth century; the waterborne 
disease of particular concern was typhoid fever. 
In England, William Budd had shown by the 
mid-nineteenth century that typhoid fever was a 
contagious disease, and the causal agent was 
isolated and identified by Eberth in 1880 and 
Gaffky in 1884 (Wilson and Miles, 1957). 
Although the causal agent, now called 
Salmonella typhi, is transmitted in a variety of 
ways, one of the most significant is by drinking 
water. 

Experiments on water filtration were carried out 
in the United States during the late 1880's and 
early 1890's, notably by the Massachusetts State 
Board of Health experiment station established 
in 1887 at the city of Lawrence. At this station 
the treatment of water as well as sewage was 
considered by an interdisciplinary group that 
included engineers, chemists, and biologists. A 
leader in this work was W. T. Sedgwick, a 
professor at the Massachusetts Institute of 
Technology (MIT), and MIT's influence on 
water-supply research remained strong 
throughout the first quarter of the twentieth 
century. Much of the history of this work has 
been reviewed by Whipple (1921) and in the 
two editions of Hazen's book (1907, 1914); the 
technical aspects are discussed and clearly 
illustrated by Johnson (1913). One important 
technological advance that made water filtration adaptable even to rather turbid sources of water was the use of chemical-coagulation filtration processes, patented about 1884 by the brothers J. W. and I. S. Hyatt. 

While the Lawerence experiments were going on, an epidemic of typhoid swept through the city, hitting especially hard at those parts that were using the Merrimac River as its water supply. As a result, the city of Lawrence built a sand filter, and its use led a marked reduction in the typhoid fever incidence. As reported by Hazen (1907), the death rate from typhoid fever in Lawrence dropped 79% when the 5-yr periods before and after the introduction of the filter were compared. Of additional interest was a reduction in the general death rate (all causes) of 10%, from 22.4 to 19.9 per 1,000 living. 

Another major series of filtration experiments were made in 1895-1897 at Louisville, Ky., where the source of water was the muddy and polluted Ohio River. These experiments were successful, and from an engineering point of view were of importance because they showed that it was possible to treat source waters of a rather poor quality (the Merrimac River at Lawrence may have been polluted, but at least it was a clear water, making filtration rather easier.) The success of the Louisville experiments and the other studies led to rapid establishment of filters as a means of water purification; by 1907 Hazen could list 33 cities in the United States, some of comparatively large size, which were using mechanical filters, and 13 cities that were using slow sand filters. As discussed by Hazen, filtration led to an elimination of turbidity and color from the water, and to a removal of about 99% of the bacteria present. At that time these conditions were considered as a standard by which the quality of a treated water should be judged. As Hazen states: "There is no final reason for such standards. They have been adopted by consent because they represent a purification that is reasonably satisfactory and that can be reached at a cost which is not burdensome to those who have to pay for it . . .. There is no evidence that the germs (characteristic of sewage pollution) so left in the water are in any way injurious. Certainly if injurious influence is exercised it is too small to be determined or measured by any methods now at our disposal." This last statement is of considerable importance when considered in the light of the important advance in water purification practice yet to come, chlorination. 

An excellent overview of the relationship between water quality and typhoid fever incidence was published at about this time by Fuertes (1897). He gathered typhoid fever statistics for a large number of cities in North America and Europe and grouped the data by type of source water and water treatment. 

Chlorination, The Most Significant Advance in Water Treatment

Although a reading of Hazen's 1907 book might lead one to conclude that excellent water quality had been well established by filtration, the most important technological advance in water treatment was yet to come. The introduction of chlorination after 1908 provided a cheap, reproducible method of ensuring the bacteriological quality of water. Chlorination has come down to us today as one of the major factors ensuring safety of our drinking water. 

Calcium hypochlorite was manufactured industrially for use as a bleaching powder and was used in paper mills and textile industries. It was a cheap chemical, and hence readily adaptable to use on the large scale necessary for drinking water. The first practical demonstration in the United States of its use in water supply was at the filter plant of the Chicago Stock Yards, where it was introduced by Johnson in the fall of 1908 (Johnson, 1913). 

The use of chlorination in an urban water supply was introduced in Jersey City, N.J., in the latter part of 1908. The circumstances surrounding the Jersey City case are of some interest from a historical point of view and will be briefly reviewed. Jersey City received its water from a private company that used a large reservoir at Boonton, an impoundment of the Rockaway River. The water was supplied to the city unfiltered, although some settling took place in the reservoir. Several years before 1908 the city raised the contention that the water being supplied was not at all times pure and wholesome for drinking, as was required by the terms of its contract with the private company. At certain times of the year, the water in the reservoir became polluted as a result of sewage influx from communities on the river above the reservoir. Rather than undergo the expense of a filtration plant, or attempt to control the sewage influx from the various communities, the private company chose to introduce a chlorination system. The results were dramatic. A marked drop in total bacterial count was obtained, and at a cost far lower than any other procedure. After many months of operation, further testimony before the court was held, to determine whether the company was meeting its contract, and the court decided that the evidence was favorable to the company. As stated by the court examiner: ''I do therefore find and report that this device [chlorination] is capable of rendering the water delivered to Jersey City pure and wholesome for the purposes for which it is intended and is effective in removing from the water those dangerous germs which were deemed by the decree to possibly exist therein at certain times.'' 

The dramatic effect that chlorination had on water-supply problems is well illustrated by comparing the first and second editions of Hazen's book (1907 and 1914). In the first edition, barely any mention of disinfection is made (merely a remark about ozone being too expensive), but in the second edition Hazen waxes enthusiastic about the advantages of chlorination. As he says, chlorination could be used "at a cost so low that it could be used in any public waterworks plant where it was required or advantageous . . .. When the advantages to be obtained by this simple and inexpensive treatment became realized, as a result of the publicity given by the Jersey City experience, the use of the process extended with unprecedented rapidity, until at the present (1914) the greater part of the water supplied in cities in the United States is treated in this way or by some substitute and equivalent method." 

Interestingly from the point of view of the present report, the introduction of chlorination also changed markedly the established ideas about water-quality standards: "The use of methods of disinfection has changed these standards radically. By their use it has been found possible to remove most of the remaining bacteria so that the water supplied can be as easily and certainly held within onetenth of one percent of those in the raw water, as it formerly could be held within one percent . . . . Even today the limit has not been reached. It may be admitted that the time will come when a still higher degree of bacterial efficiency will be required. Present conditions do not seem to demand it, but we must expect that in some time in the future conditions will arise which will make it necessary. When additional purification is required it can be furnished." (Hazen, 1914). 

The importance of Hazen's book is that Hazen was a major consulting engineer for a wide variety of water works, and was very influential in recommending treatment methods. Chlorination was introduced at about the time that adequate methods of bacteriological examination of water had developed, permitting an objective evaluation of the efficiency of treatment. This evaluation was not based on the incidence of typhoid fever directly, but was based on an indirect evaluation using bacterial or coliform counts. 

Soon after chlorination was introduced, it was possible to obtain firm epidemiological evidence that cities chlorinating water had lowered incidences of typhoid fever (G. C. Whipple, 1921). Filtration was introduced in 1906 and chlorination in 1908, and both led to marked reductions in the incidence of typhoid fever. Another dramatic example derives from observations at Wheeling, W.Va., in 1917-1918 (Gainey and Lord, 1952). The incidence of typhoid fever in Wheeling was 155-200 per 100,000 during these years. Chlorination was introduced in the latter part of 1918, with the result that during the first 3 months of 1919 only seven cases were recorded. For 3 weeks during April 1919 chlorination was discontinued, with the result that the number of cases increased to 21, or a 300% increase. Chlorination was continued thereafter, and only 11 cases were recorded for the last 6 months of the year. Other examples of this sort could be cited (Gainey and Lord, 1952). 

Summary 

We thus see that by the beginning of World War I the essential features of water purification techniques were known, and their worth had been well established. Since that time there have been many refinements made at an engineering level, but no changes in the basic concepts. It is clear that the prime motivation for the development and introduction of purification methods has been to protect the public health, with special concern for controlling the spread of typhoid fever. An ancillary consideration has been esthetics, showing concern for the appearance, taste, and odor of the water. 

One point worth emphasizing is that the availability of adequate treatment methods has influenced the standards for drinking water. This point was implied in the books by Hazen (1907 and 1914), but is most clearly seen in the preamble to the 1925 Federal Standards, which superseded the brief 1914 Standards (see Standard Methods, 7th edition, 1933, p. 136, for the complete 1925 Standards). The following quote is relevant: 

The first step toward the establishment of standards which will insure the safety of water supplies conforming to them is to agree upon some criterion of safety. This is necessary because "safety" in water supplies, as they are actually produced, is relative and quantitative, not absolute. Thus, to state that a water supply is 'safe' does not necessarily signify that absolutely no risk is ever incurred in drinking it. What is usually meant, and all that can be asserted from any evidence at hand, is that the danger, if any, is so small that it cannot be discovered by available means of observation. Nevertheless, while it is impossible to demonstrate the absolute safety of a water supply, it is well established that the water supplies of many of our large cities are safe in the sense stated above, since the large populations using them continuously have, in recent years, suffered only a minimal incidence of typhoid fever and other potentially waterborne infections. Whether or not these water supplies have had any part whatsoever in the conveyance of such infections during the period referred to is a question that cannot be answered with full certainty; but the total incidence of the diseases has been so low that even though the water supplies be charged with responsibility for the maximum Share Which may reasonably be suggested, the risk of infection through them is still very small compared to the ordinary hazards of everyday life. 

At present other considerations make it necessary [for us] to be less confident than was the 1925 Committee on Standards. Typhoid fever and cholera are dramatic diseases whose causal agents are transmitted by the water route. Typhoid fever statistics have provided some of the best evidence of the efficacy of treatment systems, but it should be kept in mind that other diseases, not so easily diagnosed, might also be kept under control at the same time. The so-called Mills-Reincke theorem held that, for every death from waterborne typhoid, there were several deaths from other diseases for which the causal agents were transmitted by water (Shipple, 1921). At present, the incidence of typhoid fever in the United States is so low that no useful information on the effectiveness of recent changes in water-purification practices can be obtained from an examination of the statistics. During the years 1946-1970, there were 53 outbreaks of waterborne infectious disease due to typhoid, but there were 297 outbreaks due to other bacterial or vital agents, including 178 outbreaks of gastroenteritis of undetermined etiology (Craun and McCabe, 1973). Of the outbreaks, 71 percent resulted from contamination of private water systems, but most of the illness (83%) was associated with community water systems. During the period 1946-1960 there were 70 outbreaks of waterborne disease in communities served by public utilities (Weibel et al., 1964), of which only 6 were typhoid fever. When data during this period for the number of outbreaks are examined, the incidence of typhoid is even lower—103 cases out of a total of 19,928 (for a percentage of 0.5%). Even considering that typhoid is more likely to be fatal than infectious hepatitis or gastroenteritis of unknown etiology, the Mills-Reincke theorem does seem to have considerable merit. Thus, the rationale that has been used in devising standards for microbiological contaminants (see quotation above from the 1925 Standards) does not necessarily hold up on careful examination. The coliform standards may have ensured freedom from typhoid fever, but we do not have the same assuredness that they have guaranteed freedom from other infections. Even granted that most of the outbreaks reported have occurred because of breakdowns in the proper functioning of water systems, the results show that intestinal infections other than typhoid are common and, because of their often ill-defined nature, may be improperly diagnosed. Finally, only "outbreaks" find their way into public health statistics, whereas sporadic, random cases of gastroenteritis generally go unreported. The epidemiological significance of the present microbiological standards warrants continuing investigation to bring about further refinements in meeting the goal of maximum protection of public health.


Monday, August 14, 2017

Virtues of the Human Digestive System

Welcome to the world of digestion! 
Now is the good moment to decipher the demands of your gut and to create a friendly relationship with your second brain - digestion system.

  Here you can discover the physiological, emotional, and intellectual potential that we have in our human digestive  systems, and to teach you to listen, to learn from, and to work with your gut. When you do this, it will bring purely digestive benefits and also lead to physical, psychological, and emotional well-being. Through this trip , there will be various stops at particular points of interest.

  The average adult's digestive tract has a total length of 8 to 12 meters (25 to 40 feet). It is long (about the height of two-storey building) and also wide. The total area of your intestines spread out flat in two dimensions would cover 300 square meters (3000 sq.ft.) That means you are carrying the equivalent  area of a tennis court hidden in your gut! 

Image result for tennis court hidden in your gut!

Image result for tennis court hidden in your gut!

Over a lifetime, approximately 7- tons of food and 100 tons of liquid pass through your digestive system. Your gut is able to process, analyze, absorb, and eliminate this industrial quantity without breakdown or the need for replacement parts ― if, that is, it is treated well. That is a big if , as we so often mistreat our own , one and only, digestive systems, even though they are alerting us to alterations in their normal functioning by sending us signal and warnings that they are in urgent need of "service."

  The human digestive system has a spectacular design. 
Image result for human digestive system has a spectacular design

Image result for human digestive system has a spectacular design

Image result for human digestive system has a spectacular design

Image result for human digestive system has a spectacular design

One example: the inner lining of the small intestine is "folded" into thousands of villi and on the surface of these are thousands of microvilli (smaller folds). 

Image result for human digestive system has a spectacular design

Image result for microvilli structure

Under a microscope, the lining of the small intestine looks like a dense brush or a piece of velvet fabric. These anatomical intricacies enable the mucosa to completely absorb all the vital nutrients in our food and exert inmmunological control ― 70 percent of the total immune defences of the body are found in the belly. 

Image result for intestinal mucosa

Saturday, August 12, 2017

NATTOKINASE

Other Names: BSP, Extrait de Natto, Fermented Soybeans, Haricots de Soja Fermentés, Natto de Soja, Natto Extract, Nattokinasa, NK, Soy Natto, Subtilisin NAT.

NATTOKINASE OVERVIEW INFORMATION
Nattokinase is an enzyme (a protein that speeds up biochemical reactions) that is extracted from a popular Japanese food called natto. Natto is boiled soybeans that have been fermented with a bacterium called Bacillus natto.

Natto has been used as a folk remedy for diseases of the heart and circulatory system (cardiovascular disease) for hundreds of years. Nattokinase, the chemical in natto that is probably responsible for its effects, was discovered by a University of Chicago researcher, Dr. Hiroyuki Sumi.

You won’t find nattokinase in soy foods other than natto, since nattokinase is produced through the specific fermentation process used to make natto.

Nattokinase is used for cardiovascular diseases including heart disease, high blood pressure, stroke, chest pain (angina), deep vein thrombosis (DVT), “hardening of the arteries” (atherosclerosis), hemorrhoids, varicose veins, poor circulation, and peripheral artery disease (PAD).

It is also used for pain, fibromyalgia, chronic fatigue syndrome, endometriosis, uterine fibroids, muscle spasms, infertility, cancer, and a vitamin-deficiency disease called beriberi.

How does it work?
Nattokinase decreases the ability of blood to clot. This "thins the blood" and might protect against conditions caused by blood clots such as stroke, heart attack, and others.

NATTOKINASE USES & EFFECTIVENESS 

Possibly Effective for:
High blood pressure. Research suggests that taking nattokinase (NSK II, Japan Bio Sciences Laboratories Company Ltd., Japan) daily for 8 weeks can reduce blood pressure in people with high blood pressure.

Insufficient Evidence for:
Deep vein thrombosis (DVT). There is some evidence that taking a specific combination product (Flite Tabs) might decrease the chance of getting a blood clot in the legs during long plane flights. This product combines a blend of 150 mg of nattokinase plus pycnogenol. Two capsules are taken 2 hours before the flight and then again 6 hours later.
Heart disease.
Stroke.
Angina.
“Hardening of the ateries” (atherosclerosis).
Hemorrhoids.
Poor circulation.
Varicose veins.
Peripheral artery disease (PAD).
Pain.
Fibromyalgia.
Chronic fatigue syndrome.
Endometriosis.
Uterine fibroids.
Muscle spasms.
Infertility.
Cancer.
Beriberi.
Other conditions.

More evidence is needed to rate the effectiveness of nattokinase for these uses.

NATTOKINASE SIDE EFFECTS & SAFETY
Nattokinase is LIKELY SAFE when taken by mouth in amounts commonly found in foods. Nattokinase is a natural component of the soy food natto. It has been routinely consumed in Japanese cultures for hundreds of years.

Nattokinase is POSSIBLY SAFE when taken by mouth as medicine. Taking two doses of a specific product containing nattokinase (Flite Tabs) seems to be safe. However, it is not known if taking more than two doses is safe.

Special Precautions & Warnings:
Pregnancy and breast-feeding: There is not enough reliable information about the safety of taking nattokinase if you are pregnant or breast-feeding. Stay on the safe side and avoid use.

Bleeding disorders: Nattokinase seems to act like a “clot thinner” and might make bleeding disorders worse. Use with caution.


Surgery: Nattokinase might increase the chance of bleeding too much during or after surgery. Stop taking it at least 2 weeks before a scheduled surgery.

NATTOKINASE INTERACTIONS 

Moderate Interaction: Be cautious with this combination
Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs) interacts with NATTOKINASE.

Nattokinase can decrease blood clotting. Taking nattokinase along with medications that also slow clotting might increase the chances of bruising and bleeding.


Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.

NATTOKINASE DOSING

The appropriate dose of nattokinase depends on several factors such as the user's age, health, and several other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for nattokinase. Keep in mind that natural products are not always necessarily safe and dosages can be important. Be sure to follow relevant directions on product labels and consult your pharmacist or physician or other healthcare professional before using.

User Reviews

1. Comment:
Have AFib with episodes maybe 1 in 6 months or longer. I've been taking "Healthy Origins" Nattokinase with Vit K removed 100mg 2x's day. I feel that my circulation has improved and I also have T2 diabetes and worry a lot about it and believe it's amazing. I also don't worry about not taking pradaxa or any other blood thinner ( to prevent strokes and heart attacks) that could be harmful and dangerous, i trust Nattokinase! Healthy Origins brand has the ingredients I want and doesn't what I don't want! 

2. Comment:
Seven years ago I had a heart catherization completed.I was diagnosed with a 50% blockage of the LAD (The widow maker) Three and one half years ago I had a 64 bit CAT Scan of the Heart, this also revealed a 50% blockage of the LAD. The interesting part is that approx. 6 years ago on the recommendation of my son who incidentally has his PharmD I began a regiment of NattoZyme 100mg 2000FU taking 1 capsule twice daily. now seven years later the blockage has not progressed at all. Strange / Coincidental / Fact. I do not know but it worked for me. i am a believer!

3. Comment: 
Why haven't further studies been done to provide more data for determining effectiveness of this supplement?

4. Comment:
Suffered a brain stem stroke 3/2012. After I slowly got off Pradaxa, a prescription anti-coagulant, I thought I needed something other than low dose aspirin, so I tried Nattokinase. No side effects, but I noticed shaving & bleeding cuts took a few seconds longer to coagulate. I switched to a plant base diet, low dose vitamin K2 & magnesium glycinate. No 2nd stroke nor TIAs to report since 3/2012.

5. Comment: 
Nattokinase is not only a folk remedy for stroke but also is currently a beneficial treatment for ischemic stroke esp. TIA.

6. Comment:
Update from my post of 6/2/12. I now have been taking natto for 7 years for my antiphospholipid syndrome and it continues to work very effectively for me, without any side effects nor further stroke/tia. I have had close calls, a few perhaps mini-tia's, but as said previously, compared to having monthly tia's, I can deal with this. As it still is not approved by the FDA (I so wish they would do testing for it), my doctors take it casually. One doctor would not see me, another does accept it. However, I know it helps. One note of caution: Do be very careful with your vitamin K intake because natto will not be absorbed if too much is taken in. All dark, leafy vegetables. I was taking a protein supplement which did not state it contained high amounts of vitamin K and that is when I had a close call. Also, do be sure you are buying high grade natto and with the vitamin K removed. The top grade ones can be bought through the internet vitamin stores, I use NutriCology. (hope that's ok to post here). Good luck!

7. Comment: 
works well as a blood thinner.

8. Comment: 
Nattokinase is a natural supplement that has worked well for me. There has been so much research for Nattokinase especially in Japan. Check out this video for more information. https://www.youtube.com/watch?v=TYp EKGd7iIQ


9. Comment:
Have had consistant atrial fib for over 3 years now and have chosen to take Nattokinase rather than prescription blood thinners, after reading about this alternative. Of course the Docs (cardiologists) dismiss it and not one has even heard of or acknol'd it. In any case, I've taken 2 of the 2,000 unit each early AM (for an empty stomach) since diagnosed and have had no problems. Recent cardiac cath shows NO blockages, clean arteries/veins. Have had none of the typical swelling of ankles, nor other symptoms. Not sure if I'm taking enough to prevent that everpresent threat of stroke from AF, but so far so good. I am Stuart at DrinksScotch@gmail.com

10. Comment:
Decided to use Nattokinase when side effects from Plavix became intolerable. While using it, had no TIAs though I did with Plavix. Stopped the natto' briefly to try to return to Plavix due to Dr's wishes, had visual disturbances and tinnitus immediately. Also all my joint and muscle pain mysteriously goes away on the Nattokinase, some skin tags disappeared, and I just feel better. I take one Doctors' Best 2000 mg every other day just before sleep or in middle of the night to assure no food interferes with its absorbtion. Even if it doesn't replace Plavix, I will take it, as it erradicates my 24/7 knee/body inflamation pain totally. 

11. Comment: 
I have been taking this for help with menstrual cramps. I find it to be effective, but it is hard to make sure to take it on an empty stomach.

12. Comment: 
had a mini stoke prescribed wafferin and asprin I have canceled them and have been taking natto for five years now feel good.

13. Comment:
Condition: Protein-S Deficiency My husband was told he couldn't have the IV antibiotic treatment he needed for his neurological lyme disease because he was so severely deficient in anti-clotting factor, protein-s. Normal range: 60-145, His result: 9! They said they'd retest in a month. I read everything I could find on protein-s and decided to give him nattokinase for it's high vitamin k content. When they retested him a month later, his level had risen from a 9 to a 95, well within normal range and he was able to go on IV antibiotics for his lyme disease, which has given him his life back.

14. Comment: 
Heart has remained in Atrial Fibrillation for 9 years. Took Coumadin following several orthopedic surgeries, but am not willing to take it long term. Have taken Nattokinase for at least 3 years. Recently had a cardiac catheterization and they found no blockages. I attribute that to the nattokinase.

15. Comment: 
Have AF. No blood clots in over 10 years! No side effects.

16. Comment: 
I have atrial fibrillation. Nattokinase is my treatment of choice, as opposed to coumadin or xarelto. NO SIDE EFFECTS.

17. Comment:
I have Peripheral Artery Disease. I got it in my late 40s due to blood coagulation problem. I also had very high cholesterol (over 300+ my entire life). I had difficulty walking by age 50. I put myself on high dose nattokinase and serrapeptase and the symptoms disappeared within 6 weeks. You will know it is working within 1 month. I eat as much cholesterol as I want. I have been on this over 6 years. I am on maintenance dose. Just experiment with dosage over time to get the minimum dose and cost. Please be aware that conventional medicine perpetuates lies about cholesterol. Just take the time to look at the studies. If the arteries are clean enough, you won't have heart disease. Ignore the cholesterol propaganda. They have Nattokinase made from bacteria and fungus, with and without vitamin K. Both work but I prefer the Nattokinase with Vitamin K. Without vitamin K is for people on prescriptions drugs. I take Best Nattokinase and Serrapeptase. I buy from Swanson vitamin because they are cheap. iI'm amazed they don't have Heart disease category for this. Chinese have done thousands of studies on effectiveness of fibrolytic enzymes for heart attack and stroke prevention. 

18. Comment:
I've suffered high blood pressure and high triglyceride levels. I have suffered what it used to a "minor" heart attack in the past due to a blockage of artery in my heart. But since taking nattokinase, I have been able to control my blood pressure without drug prescriptions, and my triglycerides and the good cholesteral level are normal. And all this, without going to extremes in watching my diet.

19. Comment:
I was diagnosed with antiphospholipid syndrome along with low factor VIII levels in December of 2007. I had had numerous tia's previously. Because of the low factor VIII levels I was not a candidate for wayfarin but my hematologist put me on coumadin. After 4 months it was determined the coumadin was also imcompatible; my hematologist literally told me to get my will in order as nothing could be done. I found out about nattokinase and found a pharmaceutical grade brand containing no vitamin K. Have been taking 400 mg. daily, divided, without food, for 4 years now. No bad side effects at all. Cannot take aspirin with it. The good benefits? I have had a few tia's, yes - perhaps 5 total in 4 1/2 years. But when you compare that to the average of perhaps 4 per month was having in the 6 months prior to being diagnosed, this is amazing. It took the doctors that long to diagnose me and I was so fortunate not to have had a major stroke. I also watch my diet, not eating vegetables high in vitamin K. Other than that I feel I owe nattokinase my life. I so wish it would be properly tested and therefore approved.

20. Comment: 
I have MTHFR C667T and my husband has MTHFR A1298C and we miscarried 4 babies on Lovenox. So I tried nattokinase 2 times a day and now have a beautiful princess! I still take it to prevents clots and fibroids.

21. Comment: 
I am using nattokinase and serrapeptase to shrink some large uterine fibroids. So far it is working, I estimate that since my fibroids are large it will take up to 6 months for my belly to flatten. but so far i can feel they are getting smaller.

22. Comment:
I had a six inch clot in my inferior vena cava which blocked 90 percent of the blood flow. My hematologist stated after examining me that he could do nothing and that I was a walking time bomb. I react badly to Coumadin and I had DVT in my right leg which blocked blood flow on all outside veins from ankle to groin so I chose a Nattokinaise that did not contain vitamin "K". The major clot is almost totally dissolved and the blocked veins in my leg have regained much of their blood flow. I have been taking 300 mg. twelve hours apart. I have not experienced the headaches I had with Coumadin nor the elevation in blood pressure in excess of 240 systolic, which happened on several occasions. I was careful not to take anything that might act as a blood thinner and not to consume green vegetables rich in vitamin "K" during my use of Nattokinaise. Now that the clot has been greatly reduced, my doctor placed a "Greenfield" filter in the vena cava, above the blood flow from the right leg; I shall worry less about the remaining clots. I thank GOD for the people that make this type of Nattokinaise as I was concerned that continued use of Coumadin presented a stroke possibility for me. 

23. Comment: 
great energy , sever heart palpitations.

24.  Comment:
Important to take on empty stomach or between meals, otherwise it will become a digestive aide. I am using for diabetic restless legs and results were almost instantaneous.Developed surface clots at ankles so doubled dose on Dr's advice.Working good! Using Dr's Best Nattokinase,( 2000FU caps.)- 2 capsules twice a day. Added bonus is reduction of blood pressure allowing me to cut medicine in half and possibly stoping it soon. My memory is much much improved also.I am 71 and I'm sure the improved circulation is good for the whole body. To me, Nattokinase is like a miracle.

25. Comment:
I was tested positive for the prothrombin gene mutation and MTHFR. I got pregnant twice and miscarried and was told the mutation could be causing it. I was told that I should start heparin and try to get pregnant. I started researching and found nattokinase and thought I would try that before heparin. I started taking 2 a day in January of 2008 and February 2008 got pregnant. Continued taking Nattokinase through my pregnancy without taking heparin. I have since had two healthy girls. My high risk doctor told me on many occasions that I'm taking a chance with my life but I really felt that he just had no knowledge of nattokinase. I am still taking 1 tablet a day now to prevent future clots and I feel great.

26. Comment: 
77 year old woman -Used for atherosclerosis. Told that my carotid and several other arteries were 90+% blocked and was scheduled for arteriogram 2 months later. Started Nattokinase 4 times/day. Vascular surgeon says only 20-25% blocked when arteriogram happened. Amazing.

27. Comment: 
have tried everythng for hypertension and blood press still out of control. took my bp monday 151 over 101. started on natto 100mg once a day, third day bp 121/76 wow! fourth and fifth day 121/82, 126/76. it works! i'm 36 years old and have had high bp for 8 years, wish i would've found out about natto sooner!

Frequently Asked Questions
Answers to frequently asked questions on natto NKCP

Who first isolated the active component of natto?

The main active component of the food natto is an enzyme that was first isolated and identified by Dr. Hiroyuki Sumi in 1980, a researcher at the Japan Ministry of Education. Dr Sumi named this enzyme "nattokinase", commenting at the time that it showed "a potency matched by no other enzyme." NKCP is a high quality proprietary extract of natto that contains a high concentration of nattokinase.

Is NKCP a medicine?

NKCP has no direct effect on blood viscosity. What it actually does is help increase the efficiency of the body's own control mechanism. By doing this, if blood viscosity is too high, the body is able to naturally reduce it. It does not interfere with normal blood coagulation.

Why use NKCP for maintaining optimum blood flow when I can use aspirin which is much cheaper?

Aspirin is an over-the-counter medicine that has a direct effect on blood coagulation. Affecting body physiology directly like that can be problematic. For example, although the there are health benefits from aspirin use (and you must follow your doctor's advice) it should not be forgotten that aspirin is a strong medicine and that, although it is overall a relatively safe medicine considering how much has been taken around the world, long-term use has been linked to pancreatic cancer, gastrointestinal irritation, stomach bleeding, stomach ulcers (caused by bacteria), allergic hypersensitivity in asthmatics, brain haemorrhage and inflammation (Reye's syndrome). NKCP is not a medicine and does not have a medicinal action; what it does is helps the body to control its own blood viscosity. This is why it does not affect blood coagulation and can safely be taken, even long-term, without increasing the risk of haemorrhage. It can also be taken in conjunction with anti-coagulants such as Warfarin, although you are always advised to clear any food supplement with your doctor if you are on medication or have a specific medical condition.

How safe is NKCP to take?

NKCP is an extremely safe natural health supplement with no reported contra-indications or side-effects, even in large amounts over long periods of time. If you are on medication, however, you should always check with your doctor before adding any food supplement to your diet.

If I am taking NKCP to help with circulation during a long haul plane flight, how soon before should I start taking it?

NKCP needs to be taken at least 8 hours before a flight for it to be effective. Ideally, a person should start taking a daily dose a few days before.

Can NKCP help those with high blood pressure?

There are many reasons for high blood pressure and these should be explored with your doctor. That said, Dr. Maeda at Daiwa Pharmaceutical has stated that improved blood flow in peripheral vascular regions could help lower high blood pressure. In fact, in a Japanese NKCP clinical trail on humans, one subject with high blood pressure had it lowered. So it is certainly worth a try but also check with your doctor.

Can NKCP help patients with carotid artery stenosis?

Carotid artery stenosis is a disease causing atherosclerosis in the carotid artery, in which the carotid artery becomes narrower. Progressive hardening of the arteries may result in the clot formation in the artery. These clots sometimes cause stroke or myocardial infarction. We have no clinical data about the effect of NKCP on the patients with carotid arterystenosis. However, NKCP has been shown to be effective in inhibiting thrombus formation (prolongation of APTT and PT) and in promoting thrombolysis in animal experiments. Also, a clinical study reported that NKCP enhanced fibrinolytic activity by reducing the Euglobulin Lysis time (ELT). In addition, several studies reported NKCP improved stiff shoulders and other symptoms by improving the blood flow, and lowered the blood pressure. Based on these studies, we recommend the patient take NKCP, since this product is considered to be beneficial in carotid artery stenosis.

Is NKCP suitable for vegetarians?

NKCP is vegetarian although, because it contains shellac wax as a tablet coating, it is not be suitable for vegans. (Shellac is classified as vegetarian by The Vegetarian Society in the United Kingdom.)

How should NKCP be taken?

It is recommended to take 2 to 4 x 125mg tablets once a day after the evening meal.

Why is this product tested on animals?


It is always regrettable to cause suffering, but it must not be forgotten that it is a legal requirement for new food extracts such as this one to be exhaustively tested, and that includes animals studies. All food supplements components and ingredients on the market today have at one time or another been required to go through this sort of testing, although if such testing was undertaken far enough back in time, or if a new product is merely a recombination of established tested ingredients, then a particular brand can state that it has not been tested on animals. Being an innovative food extract, this testing is highlighted with NKCP.

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nkcp nattokinase

NKCP® Nattokinase
Purified Filtrate of Bacillus Subtilis Natto Culture - the safe blood flow supplement

NATTO is a traditional Japanese food of fermented soybeans that has been eaten for many centuries. It is believed to be a health-giving delicacy and has an "acquired" taste and smell. New scientific research has discovered why natto is so good for health — the Bacillus subtilis natto (the good bacteria that form during the fermentation process) produce functional proteins (including nattokinase) which naturally and safely help the body to maintain optimum blood viscosity. Natto is, therefore, an important food for those wishing to help reduce the risk of thrombosis (blood clots) — a central factor in heart disease and strokes, two of the biggest killers in Western society today, and Deep Vein Thrombosis (DVT), a concern for those taking long haul airplane journeys. This is of particular interest for those wanting a safe, non-drug, Aspirin alternative for healthy blood flow.

The problem with eating natto is fourfold: the taste, smell and texture is unpleasant; it can contain large amounts of Vitamin K2 which interferes with medicines such as warfarin; activity can vary greatly from brand to brand; and this food is not widely available outside Japan. But now Daiwa Pharmaceutical has produced natto NKCP nattokinase — a standardized extract of natto bacillus culture (Bacillopeptidase F) in small odorless tablets with the vitamin K2 largely removed — so now everyone can enjoy the benefits of natto!

Summary
Summary information on natto NKCP.

Description

NKCP Nattokinase is a standardized extract of Bacillus Subtilis Natto Culture, a good bacteria found in the traditional Japanese delicacy called natto — fermented soybeans. The vitamin K2 content is also largely removed so that NKCP is compatible with anticoagulant medications such as Warfarin. NKCP tablets are odourless, easy to swallow, and contain no genetically modified ingredients.

Development

NKCP Nattokinase was developed and is manufactured by Daiwa Pharmaceutical Co. Ltd. in Japan, a small and innovative pharmaceutical company dedicated to producing natural food extracts and supplements for health and well being. Daiwa Pharmaceutical is renowned for being the developer and manufacturer of immune system supplement BioBran MGN-3.

Function

There a a number of enzymes that have been identified by Daiwa Pharmaceutical in NKCP natto extract, including Nattokinase, which have been shown to inactivate an unhealthy enzyme in the blood called plasminogen activator inhibitor (PAI-1), which increases as we get older. By helping to reduce PAI-1, NKCP greatly increases the efficiency of our body's natural control mechanisms for blood viscosity. The breakthrough with NKCP is that it has no medicinal effect — it does not directly act upon blood viscosity and does not directly dissolve blood clots. Rather, NKCP merely increases the efficiency of the body's own blood-control mechanisms. This means that this natural food supplement does not adversely affect blood coagulation — something that can happen using medicinal blood thinners such as aspirin.

Safety

NKCP Nattokinase safety has been confirmed by extensive testing, including independent safety examinations concerning acute toxicity, sub acute toxicity, mutagenicity, antigenicity and overdose. However, as with any food supplement, if you have a specific medical condition or are taking medication (especially relating to thrombosis or blood circulation), you are advised to consult with your doctor before taking NKCP Nattokinase.

Standard Dose


Base on evaluation of effectiveness and overdose tests on human, 250-500mg of NKCP (2-4 tablets) is recommended as the standard dose per day, taken after the evening meal.

Development
Development of Natto NKCP

Background

Heart disease and cerebrovascular disease (strokes) are respectively the first and the third leading causes of all deaths in developed parts of the world, with heart disease accounting for as much as 30% of all deaths and cerebrovascular disease accounting for nearly 10%. And these figures are only the tip of the iceberg in regards to the devastation of these diseases: for every one who actually dies from them, there are several others suffering from their ill effects — a stroke or a heart attack, for example, can leave a person bedridden. More mild symptoms might include neck stiffness, chronic headache, cold hands and feet, breathlessness, chest pains, poor mental function and dizziness.

Any focus on increasing length and quality of life must look, therefore, at methods to maintain a healthy vascular system and blood flow. This is fundamental to good health and was the reason why Daiwa Pharmaceutical Co. Ltd. started research into the health properties of a traditional Japanese food called natto which was supposed to be so beneficial to health and the circulation. What they discovered was that there is a good good bacteria in this traditional fermented food, B. subtilis natto, which contains enzymes that help the body to maintain optimum blood flow and viscosity by breaking down a substance in the blood called PAI-1 that interferes with the body's natural processes. PAI-1 concentrations increase as we get older which is why our blood gets more sticky as we age and why we are increasingly at risk from vascular diseases.

The problem with natto is is that it is a very unpleasant food to eat (it has an "acquired" taste/smell and a slimy texture); it contains high amounts of vitamin K2 which can interfere with anticoagulants such as Warfarin; the active enzyme content of natto can vary enormously from brand to brand (see below) and it is not easy to get hold of in Western countries. Daiwa Pharaceutical Co. Ltd., therefore, decided to extract the active ingredient (in the same way that good bacteria is extracted from yogart), remove the vitmain K2 in the process and to produce a standardized small tablet that would allow people to enjoy the benefits of natto without any of the drawbacks associated with it. They have called this "natto in a tablet" NKCP.

Comparison of good bacteria activity in 89 different natto brands found in Japan showing the variation in peptidase activity. Daiwa Pharmaceutical therefore decided to produced a standardized "natto in a tablet" equivalent.


Daiwa Pharmaceutical Co. Ltd.

Daiwa Pharmaceutical Co. is a new breed of pharmaceutical company focused entirely on the development of natural food solutions. Already renowned for producing what is now the leading serious immune system supplement, BioBran MGN-3, a food extract made entirely from rice bran, Daiwa Pharmaceutical have now developed the highest quality and most active Natto extract (sometimes called nattokinase, although this is just one of its components) — NKCP. What sets Daiwa Pharmaceutical apart from many other developers of innovative foods and food supplements is its dedication to high quality research and production. Daiwa is not afraid to developing natural (and therefore not patentable) products, something which most pharmaceutical companies would be reluctant to do.


Manufacturing Process

NKCP is manufactured by culturing B. subtilis natto -- the good bacteria isolated from the natto food -- in a liquid medium under conditions suitable for the production of the active protein. The cell bodies, insoluble matter and low-molecular weight substances (which include the characterisitic odour molecules) are then removed. The peptide concentration is then standardized and the NKCP is powdered and then pressed into tablets. Below is the manufacturing flow chart for NKCP.
NKCP Manufacturing Flow Chart
   
 
Cultivation of a particular strain of Bacillus subtilis natto culture on a medium of soybean protein, glucose and soluble starch

   
 
Removal of insoluble fraction by continuous centrifugation and filtration by celite

   
 
Removal of ultra-low-molecular weight fraction by ultrafiltration

   
 
Removal of cells by membrane filtration

   
 
Addition of excipients

   
 
Freeze-drying

   
 
Powdering & Tableting



Development

Development of Natto NKCP
  1. Background
    Heart disease and cerebrovascular disease (strokes) are respectively the first and the third leading causes of all deaths in developed parts of the world, with heart disease accounting for as much as 30% of all deaths and cerebrovascular disease accounting for nearly 10%. And these figures are only the tip of the iceberg in regards to the devastation of these diseases: for every one who actually dies from them, there are several others suffering from their ill effects — a stroke or a heart attack, for example, can leave a person bedridden. More mild symptoms might include neck stiffness, chronic headache, cold hands and feet, breathlessness, chest pains, poor mental function and dizziness.

    Any focus on increasing length and quality of life must look, therefore, at methods to maintain a healthy vascular system and blood flow. This is fundamental to good health and was the reason why Daiwa Pharmaceutical Co. Ltd. started research into the health properties of a traditional Japanese food called natto which was supposed to be so beneficial to health and the circulation. What they discovered was that there is a good good bacteria in this traditional fermented food, B. subtilis natto, which contains enzymes that help the body to maintain optimum blood flow and viscosity by breaking down a substance in the blood called PAI-1 that interferes with the body's natural processes. PAI-1 concentrations increase as we get older which is why our blood gets more sticky as we age and why we are increasingly at risk from vascular diseases.

    The problem with natto is is that it is a very unpleasant food to eat (it has an "acquired" taste/smell and a slimy texture); it contains high amounts of vitamin K2 which can interfere with anticoagulants such as Warfarin; the active enzyme content of natto can vary enormously from brand to brand (see below) and it is not easy to get hold of in Western countries. Daiwa Pharaceutical Co. Ltd., therefore, decided to extract the active ingredient (in the same way that good bacteria is extracted from yogart), remove the vitmain K2 in the process and to produce a standardized small tablet that would allow people to enjoy the benefits of natto without any of the drawbacks associated with it. They have called this "natto in a tablet" NKCP.

    Comparison of good bacteria activity in 89 different natto brands found in Japan showing the variation in peptidase activity. Daiwa Pharmaceutical therefore decided to produced a standardized "natto in a tablet" equivalent.

  2. Daiwa Pharmaceutical Co. Ltd.
    Daiwa Pharmaceutical Co. is a new breed of pharmaceutical company focused entirely on the development of natural food solutions. Already renowned for producing what is now the leading serious immune system supplement, BioBran MGN-3, a food extract made entirely from rice bran, Daiwa Pharmaceutical have now developed the highest quality and most active Natto extract (sometimes called nattokinase, although this is just one of its components) — NKCP. What sets Daiwa Pharmaceutical apart from many other developers of innovative foods and food supplements is its dedication to high quality research and production. Daiwa is not afraid to developing natural (and therefore not patentable) products, something which most pharmaceutical companies would be reluctant to do.

  3. Manufacturing Process
    NKCP is manufactured by culturing B. subtilis natto -- the good bacteria isolated from the natto food -- in a liquid medium under conditions suitable for the production of the active protein. The cell bodies, insoluble matter and low-molecular weight substances (which include the characterisitic odour molecules) are then removed. The peptide concentration is then standardized and the NKCP is powdered and then pressed into tablets. Below is the manufacturing flow chart for NKCP.
NKCP Manufacturing Flow Chart
   
 
Cultivation of a particular strain of Bacillus subtilis natto culture on a medium of soybean protein, glucose and soluble starch
 
  
 
Removal of insoluble fraction by continuous centrifugation and filtration by celite
 
  
 
Removal of ultra-low-molecular weight fraction by ultrafiltration
 
  
 
Removal of cells by membrane filtration
 
  
 
Addition of excipients
 
  
 
Freeze-drying
 
  
 
Powdering & Tableting
 

Function

Biological function of Natto NKCP
1. Functional Ingredients
The functional ingredient in the food natto and the NKCP natto extract responsible for reducing the risk of thrombosis is a protein (sometimes called Nattokinase) produced by natto bacillus (B. subtilis natto). This is one of a number of proteins with differing molecular weights contained in natto. Its activity is confirmed through its ability to hydrolyze synthetic substrates for plasmin and fibrin. Improved thrombolytic activity has been demonstrated in a study on dogs given natto or partially purified extract of natto and in a study on humans taking natto.
NKCP has stable peptidase activity and its major active ingredient is a 34,000-45,000-dalton protein produced by the natto bacillus, belonging to the bacillopeptidase F family. The activity is stable at pH 6.0 ~ pH 9.0 under 60ºC and the optimum is pH 9.0. Its activity is measured by determining the ability to hydrolyze synthetic substrate for plasmin (S-2251) and its quantitative determination is carried out by measuring the amount of antigen reacting with the antibody specific for the protein, using ELISA.
Enzymes synthesized and excreted outside the cells by Bacillus subtilis after exponential multiplication.
TypesGeneProperties
Subtilisin (alkaline) proteaseaprMolecular weight by SDS-PAGE: 20 kDa (1), 28 kDa (2) Nattokinase. Its casein decomposing activity and direct fibrinolytic activity have been confirmed. The ability to decompose and inactivate plasminogen activator inhibitor type 1 (PAI-1) has also been reported (2).
Neutral proteasenprMajor exoproteinase as with apr.
Extracellular proteaseeprMolecular weight by SDS-PAGE: 40-34 kDa
Metallo proteasemprMolecular weight by SDS-PAGE: 28 kDa (3)
Bacillopeptidase FbprMolecular weight by SDS-PAGE: 47 kDa (3), 48 kDa (4). Secreted as a 92 kDa protein and converted into 80 kDa and 48 kDa proteins (4). Has high esterase activity as well as proteinase activity (5).
(1) Sumi, et al., Experientia, Vol. 43, 1110-1111, 1987.
(2) The Journal of Biological Chemistry, Vol. 276, pp. 24690-24696, 2001.
     Mol Gen Genet 1990 May; 221 (3): 486-90
(3) Journal of Bacteriology, Vol. 172, pp. 1019-1023, 1990.
(4) The Journal of Biological Chemistry, Vol. 265, pp. 6845-6850, 1990.
(5) Journal of Bacteriology, Vol. 172, pp. 1470-1477, 1990.

2. Mode of Action
NKCP has a thrombolytic effect in vitro and in vivo by ingestion and the effect is milder compared to the plasminogen activator (t-PA). NKCP has been confirmed to decompose and inactivate plasminogen activator inhibitor (PAI-1) in cell culture systems and it also reduces blood viscosity. Ingestion of NKCP reduces the plasminogen activator inhibitor (PAI-1) and helps the plasminogen activator (t-PA) to work efficiently. t-PA activates plasmin and reduces blood fibrin. Thus, NKCP facilitates the activation of fibrinolysis cascade reactions by reducing PAI-1 and helps maintain the balance between coagulation and fibrinolysis. Consequently, NKCP ingestion is unlikely to dissolve fibrin excessively.
Because of decreased PAI-1, NKCP fully activates the fibrinolytic cascade process and helps in maintaining the balance between coagulation and fibrinolysis of the blood. In other words, NKCP ingestion is unlikely to cause unexpected fibrinolysis. NKCP also reduces blood viscosity in vitro and in vivo. Although the association between this action and increased fibrinolytic activity is unknown, reduced blood viscosity is likely to contribute to maintaining sound blood conditions since it prevents stagnant blood flow.
3. Scientific Data on NKCP Functionality
a) Functionality in animals
i) Thrombolytic action of NKCP in rat thrombosis models
A comparative study was conducted by the Material Research Center to evaluate the thrombolytic action of NKCP by the in situ loop method using thrombosis models.
Thrombosis was produced in rats through platelet adhesion and agglutination, induced by injuries in the endothelial cells of the abdominal descending aorta. Six hours after the induction of thrombosis, the activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured as indicators for blood clotting activity.
The APTT values were 33.5 ± 2.4 sec, 52.0 ± 4.5 sec and 63.3 ± 2.9 sec for the control, NKCP 100 mg/kg group and NKCP 250 mg/kg group, respectively, indicating a significant prolongation for NKCP. The PT values were 16.7?0.5 sec, 20.6 ± 0.9 sec and 21.3 ± 1.7 sec for the control, NKCP 100 mg/kg group and NKCP 250 mg/kg group, respectively, indicating a similar result for APTT. Since NKCP showed a significant prolongation of the coagulation time, as indicated above, its possible role in reducing thrombosis was suggested.
ii) In vivo effect of oral NKCP in experimental thrombolysis models
Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University
The thrombolytic activity of NKCP after 14 weeks ingestion of feed containing 0.2% NKCP was evaluated in rat experimental thrombolysis models for arterial thrombosis mainly consisting of platelets using mesenteric microvessels.
The NKCP group showed an obvious increase in endogenous thrombolytic activity in a dose-dependent manner compared to the control group. The activity was equivalent to 0.2 mg/kg of tissue-type plasminogen activator (t-PA).
b) Activity in humans
i) Relation between NKCP ingestion and activity in humans
Daiwa Pharmaceutical Report
The effectiveness and safety of NKCP in a dose range between 1 and 8 tablets daily (125-1,000 mg on the NKCP basis) was evaluated in 40 healthy adults. The subjects ingested NKCP for a period from 1 day to 3 weeks. Various tests were performed to determine the optimum intake recommendations using the euglobulin lysis time (ELT) as the main indicator.
Doses of 2 tablets or more (250 mg in terms of NKCP) daily for a minimum of 4 days showed stable activity.
ii) Effect of the natto bacillus culture filtrate "NKCP" on the coagulative/fibrinolytic system: published as "Fibrinolytic and anti-thrombotic effect of the protein from Bacillus subtilis (natto) by the oral administration" - Japanese Society of Biorheology
The effect on the coagulation/fibrinolysis system of NKCP at a dose of 2 tablets daily (250 mg on NKCP basis) for 2 weeks was evaluated in 28 adults including patients with metabolic disease carrying the risk of thrombosis.
NKCP decreased the ELT by 10.1% without affecting the tissue-type plasminogen activator (t-PA) or the activated partial thromboplastin time (APTT), and this suggests that NKCP enhances fibrinolysis without intermediation by plasmin.
The effect of chronic use of NKCP at the dose of 2 tablets daily (250 mg on the NKCP basis) was evaluated in 23 subjects for 2 months. The ELT showed a significant decrease at 1 and 2 months and t-PA showed a significant increase at 2 months. Improvement in neck stiffness was observed at 1 and 2 months.
Changes in subjective symptoms due to NKCP intake
SymptomConditionsBefore intakeAt 1 monthAt 2 months
HeadacheSevere111
Moderate734
No symptom (including mild neck stiffness)151616
Remarkable improvement-32
Shirley-Williams multiple test-N.S.N.S.
Neck stiffnessSevere511
Moderate10910
No symptom (including mild neck stiffness)8911
Remarkable improvement-41
Shirley-Williams multiple test-P<0 .05="" td="">P<0 .05="" td="">
DizzinessSevere000
Moderate644
No symptom (including mild neck stiffness)171818
Remarkable improvement-11
Shirley-Williams multiple test-N.S.N.S.
Figures represent the numbers of patients
Significant difference by Multiple Range Test: N.S. Not Significant, p<0 .05="" danger="" difference="" of="" rate="" significant="" span="" the="">
Changes in fibrinolysis/coagulation parameters due to NKCP intake (n=23)
ParametersNormal valuesBefore intakeAt 1 monthAt 2 months
ELT(1)6-12 hrs.9.0 ± 1.38.1 ± 1.5**8.0 ± 1.5**
t-PA(2)≤ 10ng/mL5.4 ± 2.65.8 ± 2.86.4 ± 2.2*
FDP(3)≤ 4μg/mL3.0 ± 0.72.0 ± 0.6*3.0 ± 0.7
Figure represents ± Standard deviation. According to the significant difference by Duncan's Multiple Range Test, * shows the significant difference in 5 % of danger rate, and ** shows the significant difference in 1 % of danger rate.
1) Upper limit of measurement (ULM) is 12 hrs.
2) Lower limit of measurement (LLM) is 1.5 ng/mL.
3) LLM is 2 μg/mL.
iii) Anticoagulative/fibrinolytic effect of new natto extract
The 26th meeting of the Japanese Society of Biorheology
Natto culture filtrate without B. subtilis natto cells or vitamin K (hereafter abbreviated as NKCP) was subjected to gel filtration using a carrier such as Toyopearl HW-40F to extract NKCP with a molecular weight of 45 KDa. NKCP was shown to hydrolyze S-2251, a synthetic substrate specific to plasmin at 10 IU/mg/min. A saline solution of NKCP was added to human blood immediately after collection to measure laboratory parameters related to coagulation/fibrinolysis. As a result, NKCP treatment decreased both concentrations of thrombin-antithrombin III compound (TAT) and fibrin monomer (FM), showing that it has an anticoagulant action like heparin. Moreover, the concentration of D-dimmer (D-d) was high and that of fibrinogen (Fbn) was low, showing that it has a fibrinolytic effect like alteplase. Different from alteplase, however, the fibrinolytic effect was accompanied by no increase in the concentration of α2 plasmin inhibitor-plasmin compound (PIC), suggesting the fibrinolytic effect is independent of plasmin. As the concentration of NKCP was higher, the effect became larger.
These results demonstrated that the new extract with a molecular weight of 45 KDa from natto culture fluid has an anticoagulant effect and a plasmin-independent fibrinolytic effect on human blood.
iv) Effect of the dried filtrate of natto bacilli culture "NKCP" on blood fluidity
Journal of the Japanese Society of Hemorhelogy Vol. 5 (1), 2002
NKCP was given orally to 13 healthy adults for a week to measure the euglobulin lysis time (ELT) as the indicator for fibrinolysis activity. Doses of 2-4 tablets (equivalent to 250-500 mg of NKCP) daily increased fibrinolysis activity. One healthy adult volunteer, who took 8 tablets (equivalent to 1,000 mg of NKCP) of NKCP daily continuously after meals, showed a remarkably shortened whole blood passage time as determined with a micro channel array flow analyzer (MC-FAN) on Day 7 or later.



Safety

Safety data on natto NKCP
There are currently no reported safety issues or contraindications with NKCP Nattokinase. Being an extract from a traditional food, this product is very safe to take. We do advise, however, that if you have a specific medical problem or if you are taking prescription medications (especially medication relating to thrombosis or blood circulation), you consult your doctor before taking NKCP nattokinase. Over 14 safety studies have been carried out with NKCP, all of which show absolutely no safety problems or toxicity. Eight of these studies are summarized below:
1.MutagenicityNegative
2.Acute toxicity (rat)LD50 > 5,000 mg/kg
3.Subacute toxicity (rat)Non-toxic-effect dose > 1,325 mg/kg body weight/day male
Non-toxic-effect dose > 1,541 mg/kg body weight/day female
4.Antigenicity (guinea pig)None (subcutaneous, intravenous)
5.Excess intake (rat)Rat models of prolonged coagulation given five times the normal dose through the duodenum showed no bleeding, and NKCP induced no remarkable symptoms in the coagulation system.
6.Prolongation of bleeding time (rat)An oral dose of a maximum 300 mg/kg body weight had no effect on the prolongation of the bleeding time.
7.Long-term intake in humans:Eight healthy adults were given 750 mg of NKCP daily for 6 weeks and no clinical adverse effects were observed.
8.Excess intake in humans23 healthy adults were given 1,250 mg of NKCP daily for 7 days and no clinical adverse effects were observed.

Specification

Spec data on natto NKCP
There are currently no reported safety issues or contraindications with NKCP Nattokinase. Being an extract from a traditional food, this product is very safe to take. We do advise, however, that if you have a specific medical problem or if you are taking prescription medications (especially medication relating to thrombosis or blood circulation), you consult your doctor before taking NKCP nattokinase. Over 14 safety studies have been carried out with NKCP, all of which show absolutely no safety problems or toxicity. Eight of these studies are summarized below:
AppearanceLight yellow powder
OdorNo odor or slight fermented odor
Genetically modified ingredientsnone
Moisture8% or less
Arsenic1ppm or less
Heavy Metal10ppm or less
Aerobic Plate Count3000FU/g or less
Coliform BacteriaNegative
Protein Produced by B. subtilis natto90mg/kg or more
Vitmain K2 ContentNegligible
Function Protein Stabilityph 6.0 - 9.0 / <60 td="">
B. subtilis natto cell contentremoved / none
ActivityNattokinase activity was measured by reference to the plasmin substrate (H-D-Val-Leu-Lys-pNA). The activity of 1g is 10 units.
Standard Dose250-500mg (2-4 tablets) /day
Tablet IngredientsProprietary extract of Natto Bacilli Culture, microcrystalline cellulose (bulking agent), resistant dextrin (bulking agent), sucrose esters of fatty acids (emulsifier), silicon dioxide (anticaking agent), shellac (tablet coating). These excipients are completely and are necessary to make the NKCP into tablets.

Activity

Measuring the activity of Natto NKCP
The effectiveness of Natto Extract products is often difficult to compare because there is no standard test for products that help to optimize blood viscosity. Many companies marketing nattokinase compounds measure the enzymatic activity of their product in Fibrinolytic Units (FU), making the assumption that the effectiveness of these enzyme supplements lies solely in the degree with which they can break up fibrin. This is misleading, however, because:
  1. Fibrinolysis is just one of the in vitro activities of nattokinase. In vivo, it can have differing activities and functions.
  2. Fibrin is an insoluble protein and does not allow formation of uniform suspensions or plates. This makes it unsuitable for a substrate for quantifying enzymatic activity. It should therefore only be used as a substrate for qualitative analysis.
  3. Fibrin suspensions or plates have a network structure, and so it is unclear whether the enzymatic activity is associated with the degradation of the network structure or that of fibrin monomers.
  4. When fibrin is used as the substrate, the reaction proceeds in a logarithmic manner against the enzyme concentration. Thus, a linear standard curve is not obtained, resulting in an accuracy problem.
  5. When fibrin is used as the substrate, reactivity is likely to vary according to the enzymes used. Because there are multiple types of nattokinase, standards for all of these types is necessary. (Current analysis is based on a certain standard product of unknown origin.)
For these reasons, instead of giving the activity of NKCP in FU, Daiwa uses two other methods to determine activity, which results in a much more accurate assessment of their product:
  1. Method for determining peptidase activity
    The sample is incubated at 37°C for 5 minutes with the synthetic chromogenic substrate S-2251 (H-D-valyl-L-leucyl-L-lysine-p-nitroanilide dihydrochloride) as substrate and the PNA, which is freed by hydrolysis, is determined by measuring the absorbance at 405 mm. Peptidase activity (unit/gm) is defined 1 unit when 1nmol of pNA per minute is freed from the substrate of 2mM S-2251 at 37°C by 1gm NKCP.
  2. Method for determining functional ingredients (antigen measurement method)The natto bacillus-produced protein responsible for NKCP's peptidase activity is purified to prepare antibodies specific for rabbits and mice. The amount of antigen reacting with the specific NKCP antibodies is determined using the sandwich ELISA method. The functional ingredients are represented as μg/g or mg/kg.

Stability

Stability data on natto NKCP

1. Storage Stability
The dried filtrate of B. subtilis natto culture (NKCP Nattokinase) was examined for changes in the content of natto bacillus-produced proteins and peptidase activity during storage. No changes in the content and activity were observed after 6 months of storage at 37ºC or 24 months of storage at room temperature.
Changes in peptidase activity of NKCP powder were ±5% or less when stored at 25ºC or 37ºC for 6 months.

2. Heat Stability
A solution of 1g of NKCP powder in 10ml of 50mM tris–hydrochloric acid buffer (containing 100mM of NaCl, pH 9.0) was used in a heat-stability test for peptidase activity. The NKCP solution, treated under different temperatures and times, was examined for the residual rate of peptidase activity of B. subtilis natto produced protein using a synthetic chromatogenic substrate, S-2251. As shown in the figure below, the peptidase in NKCP was stable when heated up to 60ºC.



Research Papers
Determination of the Thrombolytic Activity of Natto Extract Masahiro Msada (Laboratory of Biochemistry, Department of Bioproduction Science, Faculty of Horticulture, Chiba University)
Improvement of Blood Fluidity using NKCP, a Dried Culture Filtrate of Bacillus Subtilis
Tetsuya Hayashi (Daiwa Pharm), Chie Takahashi (Microchannel Array Technology Team), and Yuji Kikuchi (Microchannel Array Techology Team). Journal of Hemorheology Research 5 (1), 2002

Research Listing
Foods Pioneer. 1975. “Historical Record of Natto (in Japanese)”, National Cooperative Union of Natto, Tokyo.
Hashima Laboratory of Nihon Bioresearch Inc. 2001. “Antigenicity Study of NKCP with Guinea Pigs”.
Hayashi T., Takahashi C., and Y. Kikuchi: 2002. “Effect of the dried filtrate of natto bacilli culture "NKCP" on blood fluidity”, Journal of the Japanese Society of Hemorheology, Vol. 5, pp 43-45.
Hitosugi M., Niwa M. and A.Takatsu: 2000. “Rheologic Changes in Venous Blood During Prolonged Sitting.” Thrombosis Research, pp 409-412, 100.
Hitosugi M., Niwa M. and A.Takatsu: 2001. “Changes in Blood Viscosity by Heparin and Argatroban”, Thrombosis Research, pp 371-374, 104.
Hitosugi M., Tanba M., Koike S., Omura K., Yufu T., Iida N., and S. Tokutome. 2003. “Anticoagulant/fibrinolytic effect of new natto extract”, Abstracts of the 26th meeting of the Japanese Society of Biorheology.
Japan Functional Food Research Association. 1999. “Fibrinolytic Activator of Nattokinase (in Japanese)”, ART Co. Ltd., Tokyo.
Kaketani K., Omura K., and H. Maeda: 2003. “Effect of the natto bacillus culture filtrate "NKCP" on the coagulation/fibrinolysis system”, Submitted to Biorheology.
Kudo T., Uchibori Y., Atsumi K., Numao Y., Miura I., Shitara M. and A. Hashimoto:1978. “Wafarin Antagonism by the fermented soybeans Natto in the Anticoagulant therapy”, Journal of Clinical and Experimental Medicine, Vol. 104, pp36-38.
Maeda H., Daiwa Pharmaceutical 2003. "Pregnancy and thrombosis, and its prevention", Medex Journal Vol 46 pp.2-3.
Material Research Center Ltd. 2001. “Evaluation of the thrombolytic activity of NKCP in a rat model of thrombus formation”.
Operation Division, Vivitec Japan, Animal Care Inc. 2000. Study of NKCP on Blood Coagulation Using a Delayed Blood Coagulation Model Duodenal Administration (in situLoop Method)”
Product Safety Labs. 2001. “Acute Oral Toxicity Study in Rats-LD50”
Product Safety Labs. 2001. “Sub-Acute Dietary Toxicity: 90 Day Rodent Study”
Product Safety Labs. 2002. “Thrombolytic Activity and Clotting Potential in Rats”
Sitek Research Laboratories. 2000. “Evaluation of a Test Article in the Salmonella typhimurium/ Escherichia coil Plate Incorporation Mutation Assay in the Presence and Absence of Induced Rat Liver S-9”
Sumi H. 1996. “Invitation to Food Function ~ Functional Food and its Effect (in Japanese)”, pp. 35-45. Sankyo Publication, Tokyo.
Sumi H. 2001. “Nattokinase that is Dramatically Effective against Myocardial Infarction, Cerebral Infarction and Dementia (in Japanese)”, Jitsugyo no Nihon Sha, Ltd. Tokyo.
Sumi H., Hamada H., Nakanishi K. and H.Hiratani: 1990. “Enhancement of the Fibrinolytic Activity in Plasma by Oral Administration of Nattokinase”, Acte Haematol, pp 139-143, 84.
Sumi H., Hamada H., Tsushima H., Mihara H. and H. Muraki: 1987. “A Novel fibrinolytic enzyme(nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet”, Experientia, 43, 1110
Tanimura A. 1998. “Handbook on Physiological Activator in Botanical Resources (in Japanese)”., pp. 579-583. Science Forum, Tokyo.
Yamamoto J. 2001. “Anti-fibrinolytic Effect of Nattokinase (in Japanese)”, Research Report 2001 Kobegakuin University.
Yamamoto J. and T. Yamashita. 2002. “The effect of dietary BNPP (Bacillus Natto Productive Protein) administration on experimental thrombolysis model in vivo” Research Report 2001 Kobegakuin University.
Yamashita T. 2001. “In Vivo Evaluation with He-Ne laser-induced thrombolysis model in rat mesenteric microvessel”, Research Report 2001 Kobegakuin University.

daiwa-pharm.comDaiwa Pharmaceutical Co. Ltd. in Japan is the developer and manufacturer of NKCP.
dhdeurope.comDHD Europe is the European branch of Daiwa Pharmaceutical and their site contains good research information.
jafra.gr.jpGood Japanese site that gives some of the research that has been done with natto nattokinase.