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Japanese health product "nattokinase" anti-thrombosis? Please, if you want to fool the countrymen, you have to get the name right first

author:Scientific tornado

Recently, one of my little sisters told me that relatives at home often asked her to bring home a health supplement called nattokinase. Relatives are convinced that this thing from Japan can fight blood clots. After she went to the drugstore to take a look, she found that this "nattokinase" was not cheap. A bottle basically costs about 5,000 yen, about 300 yuan. So, she wanted to ask me if this product was reliable.

The name "nattokinase" really aroused my curiosity to a large extent. After all, I have been dealing with protein for many years. And natto is also widely considered to be a food that is beneficial to health. After a series of investigations, I found that whether it is natto or nattokinase, the truth of them may be very different from what you have seen and heard.

When it comes to natto, a traditional Japanese food, many people's first impression of it is smelly and sticky. Some people are very receptive to this taste. In the eyes of Westerners, this smell is like a piece of cheese that has been steamed away for years. But people who like it are very fond of it, especially in the eyes of the Japanese, natto is basically synonymous with health. In response, Japan's largest telecommunications company, Nippon Telecom Telephone NTT, conducted a questionnaire survey of 3,827 users in March 2009. Among them, 70.2% of users replied that they "like the taste of natto"; 15.1% of users responded that "I don't like it, but for my health, I will stick to it." Only 14.7 percent of users said they "don't like it and won't eat it." ”[1]

Japanese health product "nattokinase" anti-thrombosis? Please, if you want to fool the countrymen, you have to get the name right first

Figure 1: Natto, a traditional Japanese food

If you want to try to understand the origin of natto. Then online, you can retrieve a wide variety of versions. The protagonists of the story are both mythological and historical. However, this is also a basic skill of hyping health care products. Not linked to a long history, national feelings or whatever. I'm embarrassed to sell it.

However, if you search carefully on the Internet, in addition to historical, cultural and other factors, you can indeed search for various health benefits of natto. I think everyone will inevitably wonder, how to judge this situation?

I also understand that people have such doubts. According to our online search habits, the most frequently viewed is often Baidu Encyclopedia[2] or Wikipedia.[3] For the topic of "natto", not only these two encyclopedias, but also a large number of websites are reporting on the health effects of natto at great length, defining natto as a healthy food. There is even a statement that "Japanese people live long because they eat natto." According to their description, the health effect of natto is similar to that of some masters as the "medicine for all diseases".

Since natto is a traditional food of the Japanese, let's take a look at how the Japanese government views natto.

First of all, I found an article on the official website of the Ministry of Agriculture, Forestry and Fisheries of Japan called "Q&A on Soybeans and Soybean Isoflavones" [4]. Japan's Ministry of Agriculture, Forestry and Fisheries is equivalent to China's Ministry of Agriculture. In the article, the Ministry of Agriculture, Forestry and Fisheries said that the structure of soy isoflavones is very similar to that of female estrogen, and excessive intake may have a certain impact on the human body. When eating foods that contain soy isoflavones, you need to pay attention to the following:

For foods containing soy isoflavones, such as "traditional soy foods" such as tofu, natto, boiled beans and miso, please be careful to eat them in a balanced manner with other foods. In addition, please be aware of excessive intake of isoflavones as a health supplement.

The recommended intake of soybean isoflavones in the Ministry of Agriculture, Forestry and Fisheries is approximately 70-75 mg. In addition, according to data published by Japan's Ministry of Health, Labor and Welfare [5], the average content of isoflavones per 100 g of natto is 73.5 mg. The Ministry of Health, Labor and Welfare is the main department responsible for health care and social security. From the perspective of its responsibilities, it is similar to a combination of the Ministry of Human Resources and Social Security and the Ministry of Health in our country. The data given also has a certain degree of authority. According to this data from the Ministry of Health, Labor and Welfare, eating 100 g of natto every day, the intake of isoflavones is basically capped. The weight of 100g of natto is less than two eggs.

However, the Ministry of Agriculture, Forestry and Fisheries and the Ministry of Health, Labor and Welfare also said that soy products are rich in nutritional value, and do not eat it completely because of concerns about isoflavones exceeding the standard. But it also means that natto isn't as much as the merrier is online.

Having said natto, let's talk about nattokinase. When preparing natto from soybeans, people add a bacterium called natto. The bacteria play a role in fermentation during natto preparation, while also producing a protein that is secreted outside the body.

Japanese health product "nattokinase" anti-thrombosis? Please, if you want to fool the countrymen, you have to get the name right first

Figure 2: Natto mushrooms, 30g only 60 yuan

In the 1980s, Japanese doctors noticed this protein. He found that this protein has a hydrolytic effect on blood clots in vitro [6]. So the doctor believed that this protein was a hydrolases. If a protein is an enzyme, its English name will often end with "-ase". And this protein that hydrolyzes blood clots is produced by Natto bacteria. The Japanese pronunciation of nattomycetes is "nattokin". He then added the ase directly after nattokin, and the protein was named "nattokinase" by Dr. Sumi.

Japanese health product "nattokinase" anti-thrombosis? Please, if you want to fool the countrymen, you have to get the name right first

Figure 3: Japanese health products with "nattokinase" as the selling point

At this time, Dr. Sumi did not know that his hasty naming this time would cause a huge misunderstanding. And this misunderstanding has continued to this day.

In the field of biochemistry, you open a textbook, even if it is a popular science book. There will definitely be mention of a protein that plays an important role in human metabolism - "kinase". The role of kinase, as the name suggests, is the meaning of "activating something". And "something" here often refers to some functional protein downstream. Therefore, kinases have the effect of stimulating the activity of other proteins. They change the target protein from an inactive state to an active state by phosphorylating the target protein.

Coincidentally, all protein kinases end with the English word "kinase." This makes many people see "nattokinase" and mistake it for a kinase. According to the function of "nattokinase", it should be translated as natto bacteria hydrolases to be correct. However, because of everyone's habits, I will still call it "nattokinase" in the next show, but it is all in quotation marks.

The wrong translation does not prevent "nattokinase" from becoming a member of universal health products. "Nattokinase" is still active in major health product websites and drugstores in China and Japan.

So is the function of "nattokinase" really so special?

As anyone who has listened to my previous shows knows, the function of a protein is determined by its structure. The structure of "nattokinase" was unraveled in 2012 by Dr. Yasuhito Yanagisawa of Chiba University of Science in Japan. The protein structure PDB database defines it as a "hydrolases" based on its function. And "nattokinase" also got an EC number, called "EC3.4.21.62".

In order to explain this number, I must say a little bit about the International Enzymology Commission and the nomenclature offered by this Committee.

The International Enzymology Commission was established in 1955 and also proposed how enzymes can be functionally divided and named. Since its development in 1955, a complete enzyme naming system has been formed and revised 6 times.

Currently, all proteases can be divided into 7 broad categories, numbered from EC1 to EC7. They include "oxidortase, transferase, hydrolases, lyases, isomerases, ligases, and transposases, respectively." "Nattokinase" belongs to hydrolases, so it belongs to the EC3 category. The following string of numbers further distinguishes the activity of "nattokinase".

Here, I would like to emphasize one point: because ec numbers are divided according to function, enzymes with different names can have the same EC number, which also means that the functions of these enzymes are the same.

So to answer the question is "is the activity of "nattokinase" special? For this question, let's first look at how many otherwise named enzymes have the same EC number as them.

According to the Kyoto Encyclopedia of Genes and Genomes (KEGG),[9] nattokinase is a serine hydrolases. It has a wide range of hydrolyzed various protein peptide bonds, making it into small molecule proteins, especially for uncharged amino acid residues with high hydrolysis effect. You may not understand this sentence, but it doesn't matter, the next information I hope you can remember.

There are up to 41 protein enzymes with the same function as "nattokinase", including bacillus subtilis proteases with a sequence similarity of up to 99.5%. This fully proves that "nattokinase" is not a very special enzyme. Its ability to hydrolyze blood clots in vitro has been successfully achieved by at least 41 individual enzymes on the market. After all, blood clots are made up of platelets and fibrin aggregations in the blood. It is also reasonable to be hydrolyzed by proteases in vitro.

Japanese health product "nattokinase" anti-thrombosis? Please, if you want to fool the countrymen, you have to get the name right first

Figure 4: By functional classification, "nattokinase" and 41 other enzymes are hydrolases

At this time, some people may say that compared to the other 41 proteins, "nattokinase" is extracted from natto, a specific food. Its peculiarity lies in the fact that it is unique to natto.

So is this really the case?

According to the Records of the World Intellectual Property Organization (WIPO),[10] there are currently 1,085 patents related to "nattokinase". Of these, 436 patents are from China. The country where "nattokinase" was found, Japan, has only 46 pieces.

Japanese health product "nattokinase" anti-thrombosis? Please, if you want to fool the countrymen, you have to get the name right first

Figure 5: Patent related to "nattokinase"

The most patented "nattokinase" is a biotechnology company from Hangzhou. There are currently more than 40 patents. Roughly browsing the title of the patent document, we can see that the company mainly uses natto bacteria to prepare various foods rich in "nattokinase". For example, they used natto bacteria to ferment grapefruit and prepared a new grapefruit juice rich in "nattokinase". Using the same method, they prepared watermelon juice, grape juice, black rice juice, strawberry juice, sugarcane juice, pea milk, cucumber juice and so on, which are rich in "nattokinase". Basically, as long as natto bacteria are added to the place where they can grow, a large amount of "nattokinase" will be generated. The production of "nattokinase" does not even require natto, it is just an exocrine protein of natto bacteria.

At this point, some people will certainly insist. "Nattokinase" is not special, it does not matter, as long as there is an anti-thrombotic effect it is useful.

For this type of view, I had to pour cold water on it. Hydrolysis in vitro and antithrombosis in vivo are two concepts. And the oral "nattokinase" practice is not reliable in itself. Because there are a large number of digestive enzymes in the human digestive system, before the "nattokinase" is absorbed by the small intestine, it has been degraded into small molecules by the body's digestive enzymes.

For example, everyone has heard that "insulin cannot be taken orally". If insulin is taken orally, it is broken down into amino acids by various digestive enzymes (such as pepsin, trypsin, and panthering). Therefore, if diabetics want to lower blood sugar through insulin, they can only rely on subcutaneous injection.

The same is true of "nattokinase", if taken orally, when he reaches the small intestine, he has long been hydrolyzed into small molecule amino acids. Therefore, if you really want to rely on "nattokinase" to hydrolyze blood clots in the body, then injection may be more reliable than oral administration.

As for spending money to buy "nattokinase" to eat, that is, spending money to buy some placebo effect. In short, it is not bad to eat stomach, and at most add a little amino acid. In the face of more than 300 bottles of nattokinase on the market now, it is not expensive to say that it is expensive, and it is not cheap to say that it is cheap. So it's not a IQ tax to say it's. After all, many people can still afford to spend 300 yuan a month.

There is a saying that goes, "It is difficult to buy a grandfather who is happy when you have money." People who have developed a mental dependence on "nattokinase" spend 300 yuan a month as a "small snack" and eat happily. Well, this is not impossible.

After trying it for a while, we also seriously thought about the positioning of the show. Today, I plan to briefly introduce our science tornado program to give our program a clear positioning. First of all, we have a main "Science Those Things" program, and the current topic is vitamin those things. The show will be relatively long, estimated to be 20-30 minutes. The second is the two programs of "Life Talk" and "Science and Technology Hot Review", which are estimated to be 10-15 minutes long. The topic is random, it may be a whim, or it may be some problem of the audience. If you think we're doing a pretty good job. Feel free to share it.

[1]https://web.archive.org/web/20121121050051/http://www.research.nttnavi.co.jp/304z/903natto01.html

[2] https://baike.baidu.com/item/%E7%BA%B3%E8%B1%86/2694?fr=aladdin

[3] https://ja.wikipedia.org/wiki/%E7%B4%8D%E8%B1%86

[4] https://www.maff.go.jp/j/syouan/nouan/kome/k_daizu_qa/

[5] https://www.mhlw.go.jp/houdou/2006/02/h0202-1a.html#q08

[6] https://www.jstage.jst.go.jp/article/jbrewsocjapan1988/88/6/88_6_482/_pdf/-char/en

[7] https://pubmed.ncbi.nlm.nih.gov/21139221/

[8] http://www.cis.ac.jp/~kyoin_info/PP/yyanagisawa.html

[9] https://www.genome.jp/dbget-bin/www_bget?EC:3.4.21.62

[10] https://patentscope2.wipo.int/search/en/result.jsf?_vid=JP1-KJ45XA-58650

Contributed by: Lu Peng

Proofreading: Little Night

Japanese health product "nattokinase" anti-thrombosis? Please, if you want to fool the countrymen, you have to get the name right first

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