Comments on the red yeast incident in Japan

 Tiejun Tang

Recently, there are many people in Japan have been hospitalized or even died due to kidney disease after taking health products containing red yeast rice which produced by Kobayashi Pharmaceutical Company. As of the evening of the 28^th March 2024, there were 5 people died and 114 were hospitalized because of the products. It aroused a great attention in Japan and also, many people were alarmed by the incidents, as well as the safety of how to consume the health care products appropriately.

Red yeast rice have been consuming as food and medicine in China for nearly 700 years. In one of the classic books regarding the food and nutrition - "Yin Shan Zheng Yao", which was published in 1330, was stated that this product had the effects of strengthening the spleen, replenishing qi, and warming the stomach at the time.  Li Shizhen, a famous Chinese herbalist in the Ming Dynasty, the author of "Compendium of Materia Medica" also mentioned that red yeast rice had the same beneficial effects.

In 1979, a Japanese scholar Akira Endo isolated Monacolin K from red yeast rice. In 1985, an American scientists Goldstein and Brown further proposed the mechanism of action of Monacolin K in inhibiting cholesterol synthesis, and thus obtained Nobel Prize, therefore, Monacolin K is regards as the first inventor of statins.

Lowering cholesterol is one of the advantages of taking Statin, but for long-term, it shows some side effects.^[1] According to the results of many pharmacological studies and randomized controlled clinical trials showed that red yeast rice has lipid-lowering effects similar to those of statins^[2-4],  as a natural statin drug, it is relatively safer and is widely used in the treatment of hyperlipidemia in China and Japan.

In traditional Chinese medicine, red yeast often combine with Shanzha (Hawthorn) and  Zexie (Alismatis Rhizoma) and other ingredients that have the similar effect of lowering blood lipids compared with Statin. They are not only lower cholesterol but also reduce triglycerides and balance lipoprotein metabolism.  A research report showed that Chinese herbal medicine, Shanzha have better function in reducing low-density lipoprotein cholesterol (LDL-C) compare to Simvastatin. ^[5] A molecular biology and network pharmacology study showed that Zexie decoction can decrease total cholesterol (TC), Triglycerides (TG) and LDL-c levels in blood of WD-induced hyperlipidemia mouse model, and improved insulin resistance in vivo.^[6]

Why was these incidents happened in Japan?  As Red Yeast Rice has always been considered as a safe and healthy food product.  The current investigation believes that it was due to an error in the process of fermentation during the production, the harmpful substances were in the same batch of the production which caused the people got poisoned accidentially.  The specific investigation results are yet to be determined. The further announcements are to be expecting until further investigations.

Such incident was traumatised, and people would become panicked and worried, however, this incident reminds all pharmaceutical companies that GMP standards and the quality control should be strictly followed.  Moreover, the advantages of using Red Yeast Rice for the treatment of hyperlipidemia as a natural medicine is still valuable.

Reference: 

1.      Natalie C Ward.  Statin Toxicity Circ Res. 2019 Jan 18;124(2):328-350.

2.      Cicero AFG  Red Yeast Rice for Hypercholesterolemia. Methodist Debakey Cardiovasc J. 2019 Jul-Sep;15(3):192-199.

3.      Takuya Minamizuka . Low dose red yeast rice with monacolin K lowers LDL cholesterol and blood pressure in Japanese with mild dyslipidemia: A multicenter, randomized trial. Asia Pac J Clin Nutr. 2021 Sep;30(3):424-435.

4.      Peng D, Original Research: The Effects of Red Yeast Rice Supplementation on Cholesterol Levels in Adults..Am J Nurs. 2017 Aug;117(8):46-54.

5.      Hong Xu. A study of the comparative effects of hawthorn fruit compound and simvastatin on lowering blood lipid levels. Am J Chin Med . 2009;37(5):903-8.

6.      Zhishen Xie. Zexie Tang targeting FKBP38/mTOR/SREBPs pathway improves hyperlipidemia J Ethnopharmacol. 2022 May 23:290:115101