Japan's Kobayashi Pharmaceutical's red yeast rice health products accident is getting bigger and bigger.
After taking the red yeast rice health supplement that claims to "lower cholesterol", many consumers have kidney problems, such as changes in urine color, edema of the limbs, and fatigue.
Five consumers who had taken Kobayashi Pharmaceutical's supplements containing red yeast rice have died, and 106 others have been hospitalized. The China Consumers Association also issued a reminder asking Chinese consumers to immediately stop taking Japan's Kobayashi Pharmaceutical's related products.
小林制药的总裁Akihiro Kobayashi (左一)3月22日在记者会上| KYODO
In the case of food and health products, such accidents are serious enough to "go down in history".
What exactly is the red yeast rice health supplement involved and why did such an accident happen?
What is Red Yeast Rice?
Briefly distinguish a few concepts: red yeast rice, red yeast rice, and red yeast rice health products.
Red yeast rice is a specialty food that originated in China and can be traced back to the Tang Dynasty. It is a red granule obtained by fermentation and culture of monascus mold using rice as raw material. In practical applications, red particles are often further ground into powder.
In ancient times, it was often used as medicine, and the "Compendium of Materia Medica" said that it had a variety of functions, such as "eliminating food and invigorating blood", "strengthening the spleen and stomach", "beating and hurting injuries", "women's blood and gas pain, and postpartum bad blood is inexhaustible" and so on. In traditional cooking, red yeast rice is often used as a pigment, such as tofu milk, roast duck, and some rice wine, rice vinegar, and so on.
Red Yeast Rice Appearance | Papers published by Kobayashi Pharmaceutical, references [8]
"Monascus red" (or often referred to simply as "monascus rice") is manufactured in two ways: one is obtained by extracting, concentrating and refining monascus rice as raw material, and the other is obtained by fermenting, cultivating, concentrating and refining monascus mold with rice or soybean as the main raw material.
The production method of red yeast rice recorded in "Heavenly Creation". The rice inoculated with Monascus is divided into several bamboo trays that are placed on shelves to maintain good air circulation. The environment and air during the incubation period are key factors. The room where the shelves are placed must be spacious, the ceiling must be high, and the temperature must be well controlled. The room must be south-facing, protected from direct sunlight in the afternoon. Rice inoculated with Monascus must be stirred up and down 3 times every 2 hours References[7]
Based on the application history of red yeast rice and red yeast rice, it has obtained the qualification of "food and medicine homology". Therefore, red yeast rice and red yeast rice can be added to food as food ingredients, and can also be used as medicinal materials to make health care products or as medicines.
In food, red yeast rice and monascus red are commonly used as pigments in various types of foods.
Red yeast rice health products are "functional foods" or "health foods" made by using red yeast rice as "functional raw materials" and adding other auxiliary materials.
Does red yeast rice really have health benefits?
Modern science has done some research on the efficacy of red yeast rice mentioned in the Compendium of Materia Medica, but there is no reliable evidence to support those legends.
In the 1970s, Japanese scholars discovered an ingredient from red yeast rice that was effective in lowering cholesterol. This substance was named "monacolin K". Later, it was discovered that "monacolin K" was the active ingredient "lovastatin" of the prescription drug "statin" to lower cholesterol.
In other words, red yeast rice naturally contains cholesterol-lowering pharmaceutical ingredients. Since then, research on the lowering of cholesterol by red yeast rice has attracted great attention. There are a large number of clinical studies in China that have verified its cholesterol-lowering effect, and some studies abroad have obtained similar evidence.
The research paper on the efficacy of red yeast rice released by researchers from Kobayashi Pharmaceutical actually stated at the end that there was "no conflict of interest"| Reference Papers[7]
As a result, many red yeast rice health products at home and abroad that claim to "lower cholesterol" or "protect cardiovascular and cerebrovascular health" have appeared.
The China Food and Drug Administration has also set a standard for red yeast rice as a raw material for health products: "The recommended amount of red yeast rice is tentatively not more than 2g per day. The lovastatin in the product should be derived from red yeast rice, and the recommended daily dose of lovastatin should not exceed 10mg. If the limit is exceeded, sufficient food safety basis should be provided. In the product instructions, 'adolescents, children, pregnant women, and nursing mothers' are added to the unsuitable population, and the precautions are added 'this product should not be used at the same time with statins'. ”
It should be noted that "whether or not it contains lovastatin" and "how much lovastatin it contains" in red yeast rice are closely related to the fermentation process. The content of "red yeast rice" is usually marked in the product promotion, not the content of "lovastatin".
In other words, how much "active ingredient" is contained in the red yeast rice supplements you eat is quite unpredictable.
Are red yeast rice supplements safe?
Taxonomically speaking, Monascus belongs to the genus Aspergillus. In the same genus, there are many useful "relatives", such as soy sauce, sake, and miso, which often use Aspergillus oryzae, and Aspergillus niger is often used to make citric acid, lactase, and lysozyme. But there are also many harmful "relatives", such as Aspergillus fumigatus and Aspergillus flavus, which can also infect people with low immunity, causing aspergillosis.
Monascus mold, which is often used in brewing wine or fermented foods, is considered a relatively safe strain. Theoretically, the monascus produced by fermentation of rice by Monascus mold is safe.
However, the fermentation process is too complex to control other "bacteria" or "by-products".
For example, in 1995, French scholars discovered that two strains of Monascus were capable of producing citrinin (or "citrinin" for short). This toxin is nephrotoxic and can cause teratogenesis and cancer.
Structural formula of some metabolites of Monascus | References[8]
Since then, there have been many efforts by the academic community to control citrindicin in red yeast rice, and countries have set limit standards. For example, Japan's limit is 200 micrograms/kg, the European Union's standard is 100 micrograms/kg, while China's red yeast rice health products are 50 micrograms/kg, and the food additive red is 50 micrograms/kg.
Kobayashi Pharmaceutical recalled a total of 5 products containing red yeast rice, and after the accident of Kobayashi's red yeast rice health products in Japan, it was reported that the citricillin content of that batch of products had been tested and its suspicion was ruled out. Therefore, the current announcement says that "there may be unintended ingredients".
But whether the detection is accurate or not, and what the "unexpected ingredients" are, is still an unsolved mystery.
What do you think about red yeast rice and red yeast rice supplements?
Red yeast rice is a fermented product, and in addition to the "expected ingredients", there may also be uncertain "unexpected ingredients".
As with other products, standardized fermentation operations and subsequent testing can minimize "unintended ingredients that may be toxic and harmful". Therefore, there is generally not much risk in using fermented foods made in the standard.
However, when we extract, concentrate and refine the "target ingredients", we may also extract and concentrate the "unexpected ingredients", and the "potential risks" are magnified.
In other words, a "natural food" is safe, but it does not mean that the "health products" extracted from this "natural food" are safe.
As far as red yeast rice supplements are concerned, the amount of lovastatin contained in them varies from very little to "ineffective", or it may be too high to "produce toxic side effects".
For example, the US FDA believes that statins may cause rhabdomyolysis and may also cause liver and kidney damage, so they should be managed as prescription drugs. Since monacolin K in red yeast rice is the same as the active ingredient of statins, red yeast rice and various extract products need to be managed as medicines. This requirement caused red yeast rice and its products to disappear from the U.S. market for a time. Now, red yeast rice and its products on the U.S. market have reduced the level of monacolin K to almost none, and no longer claim to lower cholesterol.
Secondly, the "functional ingredient" monacolin K in red yeast rice is the same as the "lovastatin" in the drug statin, so for people who need to lower cholesterol or blood lipids, the content of statin is accurate and controllable, and it is unlikely to contain other impurities, which is a better choice than "red yeast rice health products".
Finally, I would like to remind you once again that the supervision method of health care products (or "dietary supplements") in foreign countries, especially in the United States and Japan, is the "filing system". In other words, its safety and effectiveness have not been reviewed and confirmed by the regulatory authorities, but are determined by the merchant's own evaluation. The safety and efficacy of products under this "filing system" are completely different from those of drugs.
After the Red Yeast Rice incident, the Japanese government announced that it would carry out emergency inspections of more than 6,000 functional foods, and it is unclear whether new problems will be found.
For people with chronic diseases, it is still recommended to take regular medication under the guidance of a doctor. Because many health products that claim to be "all-natural" and "have no toxic side effects", there are too many potential risks.
bibliography
[1] Notice on the declaration of health food products with red yeast rice as raw materials: https://www.gov.cn/gzdt/2010-01/11/content_1507641.htm
[2] National food safety standard for the use of food additives GB2760-2014
[3] The European Union revised the maximum limit for citrinin in a food supplement: http://news.foodmate.net/2019/11/540684.html
[4] Study on the contamination level of citric penicillin in domestic red yeast rice products. Health Research, Vol. 34, No. 4, July 2005.
[5] National food safety standard Food additive monascus red GB1886.188-2016
[6] National food safety standard Food additive red yeast rice GB1886.19-2015
[7] Fukami H, Higa Y, Hisano T, Asano K, Hirata T, Nishibe S. A Review of Red Yeast Rice, a Traditional Fermented Food in Japan and East Asia: Its Characteristic Ingredients and Application in the Maintenance and Improvement of Health in Lipid Metabolism and the Circulatory System. Molecules. 2021 Mar 15; 26(6):1619. doi: 10.3390/molecules26061619. PMID: 33803982; PMCID: PMC8001704.
[8] Yuki, Higa & Fukami, Hiroyuki & Ono, Naoaki & Kanaya, Shigehiko. (2022). Research on the fungal toxin citrinin of red yeast rice used in food. JSM Mycotoxins. 72. 10.2520/myco.72-2-1.
[9] Mao, B. F. (2024). Beni kōji: One dead and dozens sick after taking red yeast pill in Japan. BBC News. Retrieved from https://www.bbc.com/news/world-asia-68662585
Planning and production
Source丨Guoke (ID: Guokr42), Popular Science China
Author丨Yun Wuxin, Ph.D. in Food Engineering