Japan's Ministry of Health, Labor and Welfare announced on March 26 that the number of hospital admissions has risen to 106 after ingesting a health supplement containing Kobayashi Pharmaceutical's "red yeast rice." As early as March 22, Kobayashi Pharmaceutical's official website showed that the health food "Red Koji Cholesterol Granules" manufactured and sold in Japan received some reports that it may cause kidney disease and other problems after consumption. In the afternoon of the same day, at a press conference held by Kobayashi Pharmaceutical, information provided by the person in charge showed that six people were hospitalized with kidney disease and other diseases at that time. At present, Kobayashi Pharmaceutical has issued an announcement to recall 3 products, including Red Koji Cholesterol Granules, Gastrointestinal + Cholesterol Help, and Nattokinase Dry Granules GOLD, and calls on consumers to immediately stop taking these 3 products1-2.
At Qingming time, there was a custom of eating colored rice, such as red rice, in some parts of the mainland. Therefore, some people are concerned about this custom, that is, can we still eat red rice or foods containing red yeast rice (such as fermented bean curd, soy sauce, alcohol) during the Qingming Festival or on weekdays?
Figure 1 Red rice
What is Red Yeast Rice?
Monascus spp. is a fermentation product of Monascus spp., and the strains can be roughly divided into three types: Monascus ankasp., Monascus pilosusSato, and Monascus purpureusWent. Most of its cultures are purple-red, and in ancient times it was called Danqu, also known as red yeast, and it was mainly made by fermentation with rice and inoculation with monascus fungus.3
In the ancient scientific and technological masterpiece of the mainland, "Heavenly Creations" (Fig. 2), the traditional way of making red yeast rice/red rice is clarified4.
Fig.2 The way of making red yeast rice/red rice in Tiangong Kaiwu
In addition to the mainland, red yeast rice and red yeast rice play an important role in the traditional culture of the whole East Asian region. In some parts of East Asia, such as Japan, the way of brewing and fermentation is significantly different from that of the West. In addition to red rice, the most well-known fermented food of red yeast rice in mainland China is tofu milk (called Okinawa-style fermented tofu in Japan). Since the 50s of the 20th century, red yeast rice has also been widely used in industrial food processing, and it is also added to processed meat products such as crab sticks, hams, and sausages4.
What are the benefits of Red Yeast Rice/Red Rice?
In fact, red yeast rice has been eaten in mainland China for more than 1,000 years and is widely used in traditional Chinese medicine, winemaking, food coloring, etc. Red yeast rice is sweet in taste, warm in nature, and returns to the liver, spleen, stomach, and large intestine meridians, and has the effects of eliminating appetite and stomach, invigorating blood and relieving pain, and strengthening the spleen and stomach. Modern studies have shown that the statins, fatty acids, sterols, pigments and other components contained in it have pharmacological effects such as regulating blood lipids, anti-inflammatory, anti-tumor, and antioxidant3.
In the 70s of the last century, Japanese scholars extracted monacolin from red yeast rice, which is a 3-hydroxy-3-methylglutarylyl COA (HMG-CoA) reductase (a key enzyme that regulates liver cholesterol synthesis) (Figure 3). Red yeast rice significantly reduced LDL cholesterol (LDL-c, Figure 4) in healthy volunteers compared to the placebo group. After more in-depth research by scientists, the first generation of statin-lowering lipids, lovastatin, was finally born in 1987, which was officially approved by the U.S. Food and Drug Administration (FDA)4.
Fig.3 Effect of red yeast rice/red rice on blood lipids
Fig.4 Changes in LDL-c in healthy volunteers
How safe is Red Yeast Rice/Red Rice?
01
Safety for the kidneys
First of all, the safety of red yeast rice/red rice is related to how it is made. The reason for the recall announced by Kobayashi Pharmaceutical is that some red yeast rice raw materials may contain unexpected ingredients 1-2. A review from Germany has shown that red yeast rice/red rice may produce substances that have not been toxically evaluated if they are not produced in accordance with regulations (e.g., abnormal temperatures)5, and some scholars believe that substandard storage (e.g., high temperatures, secondary fermentation, or decomposition of the substance) may also produce substances that are harmful to humans4,6. Some Japanese scholars have found that some red yeast rice may also produce mycotoxins (CIT). However, modern food factories have better monitoring methods for toxins such as CIT, and the occurrence of CIT can be reduced or even avoided through temperature and substrate control6. In addition, numerous studies have shown that consuming only traditional foods containing red rice/red yeast rice, such as fermented bean curd and red rice, does not cause significant effects on the kidneys4. In conclusion, red rice or foods containing red yeast rice that are properly produced, stored and sold do not have a negative impact on public health.
02
Security to other systems
Although, in prospective controlled studies, red rice was not associated with elevated serum enzymes or liver damage, there have been isolated cases suggesting that red rice extract may be associated with liver damage. According to case reports, taking red yeast rice extract may cause elevated serum enzymes in patients treated with conventional lovastatin, a rare cause of liver damage. There are two theories about the specific mechanism: (1) the accumulation of lovastatin by the metabolism of the same hepatic enzyme (CYP3A4) and (2) the formation of lovastatin accumulation and liver injury, and (2) the liver injury due to toxicity or immunogenic metabolites7.
In conclusion, daily consumption of red yeast rice or red yeast rice is safer, but it may be avoided at the same time as lovastatin.
bibliography
1. Sohu News, Xiaolin Pharmaceutical's "Red Koji" product has caused 2 deaths and 106 hospitalizations, and domestic pharmaceutical companies have responded to the safety of relevant raw materials. 2024,3,28. Link：https://www.sohu.com/a/767407991_121219327
2. International Finance News. Well-known pharmaceutical companies urgently recall!Can red yeast rice still be eaten with confidence?Expert response. 2024.3.25. Link：https://m.thepaper.cn/baijiahao_26816871
3. Jiang Yuanqi, Dong Yujie, Zhou Fujun, et al. Research progress on chemical composition, pharmacological effects and clinical application of red yeast rice [J]. Chinese Herbal Medicine, 2021, 52(23): 7379-7388
4. Fukami H, Higa Y, Hisano T, et al. 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.
5. Steffen C. Red Yeast Rice: A Questionable Food Supplement? [Red yeast rice: An unsafe food supplement?]. Federal Health Journal Health Research Health Protection. 2017 Mar; 60(3):292-296.
6. Farawahida AH, Palmer J, Flint S. Monascus spp. and citrinin: Identification, selection of Monascus spp. isolates, occurrence, detection and reduction of citrinin during the fermentation of red fermented rice. Int J Food Microbiol. 2022 Oct 16;379:109829.
7. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Red Yeast Rice. [Updated 2018 Jun 4]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548168/
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