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Red yeast rice

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Wet rice cultivated with the mold species Monascus purpureus turns red; the rice when dried is called red yeast rice.

Red yeast rice (simplified Chinese: 红曲米; traditional Chinese: 紅麴米; pinyin: hóng qū mǐ; Jyutping: Hung4 Kuk1 Mai5; Pe̍h-ōe-jī: âng-khak-bí; lit. 'red yeast rice'), red rice koji (べにこうじ (benikōji), lit. 'red koji'), red fermented rice, red kojic rice, red koji rice, anka, or angkak, is a bright reddish purple fermented rice, which acquires its color from being cultivated with the mold Monascus purpureus. Red yeast rice is what is referred to as a "koji" in Japanese, meaning "grain or bean overgrown with a mold culture", a food preparation tradition going back to ca. 300 BC.[1] In both the scientific and popular literature in English that draws principally on Japanese traditional use, red yeast rice is most often referred to as "red rice koji." English language articles favoring Chinese literature sources prefer the translation "red yeast rice."

In addition to its culinary use, red yeast rice is also used in Chinese herbology and Traditional Chinese medicine, possibly during the Tang dynasty around AD 800. Red yeast rice is described in the Chinese pharmacopoeia Ben Cao Gang Mu by Li Shizhen.[2][3]

A modern-era use as a dietary supplement developed in the late 1970s after researchers were isolating lovastatin from Aspergillus and monacolins from Monascus, the latter being the same fungus used to make red yeast rice. Chemical analysis soon showed that lovastatin and monacolin K were identical. Lovastatin became the patented prescription drug Mevacor.[4] Red yeast rice went on to become a non-prescription dietary supplement in the United States and other countries. In 1998, the U.S. Food and Drug Administration (FDA) initiated action to ban a dietary supplement containing red yeast rice extract, stating that red yeast rice products containing monacolin K are identical to a prescription drug, and thus subject to regulation as a drug.[5]

Production

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Red yeast rice is produced by cultivating the mold species Monascus purpureus on rice for 3–6 days at room temperature. The rice grains turn bright red at the core and reddish purple on the outside.[6] The fully cultured rice is then either sold as the dried grain, or cooked and pasteurized to be sold as a wet paste, or dried and pulverized to be sold as a fine powder. China is the world's largest producer of red yeast rice, but European companies have entered the market.[7]

Uses

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Culinary

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Fujian red wine chicken with misua noodles

Red yeast rice is used to color a wide variety of food products, including fermented tofu, red rice vinegar, char siu, Peking duck, and Chinese pastries that require red food coloring.

In China, documentation dates back to at least the first century AD.[2] It is also traditionally used in the production of several types of Chinese huangjiu (Shaoxing jiu), and Japanese sake (akaisake), imparting a reddish color to these wines.[8] It was called a "koji" in Japanese, meaning "grain or bean overgrown with a mold culture".[1]

The lees left over from wine production, known as hóngzāo (红糟), can be used as flavoring, imparting a subtle but pleasant taste to food. The lees are particularly commonly used in Fujian cuisine, where they are used for dishes like Fujian red wine chicken, a celebratory dish associated with birthdays and Chinese New Year.[9][3]

Red yeast rice (angkak in Filipino) is also used widely in the Philippines to traditionally color and preserve certain dishes like fermented shrimp (bagoong alamang), burong isda (fermented rice and fish), and balao-balao (fermented rice and shrimp).[10][11][12]

Traditional Chinese medicine

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In addition to its culinary use, red yeast rice is also used in Chinese herbology and traditional Chinese medicine. Medicinal use of red yeast rice is described in the Chinese pharmacopoeia Ben Cao Gang Mu compiled by Li Shizhen ca. 1590.[3][13] Recommendations were to take it internally to invigorate the body, aid in digestion, and revitalize the blood.[2][13] One reference provided the Li Shizgen health claims as a quotation "...the effect of promoting the circulation of blood and releasing stasis, invigorating the spleen, and eliminating [in]digestion."[3]

Red yeast rice and statin drugs

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In the late 1970s, researchers in the United States and Japan were isolating lovastatin from Aspergillus and monacolins from Monascus, the latter being the same fungus used to make red yeast rice (RYR) when cultured under carefully controlled conditions. Chemical analysis soon showed that lovastatin and monacolin K are identical chemical compounds. The two isolations, documentations, and patent applications occurred months apart.[14] Lovastatin became the patented, prescription drug Mevacor.[4] Red yeast rice went on to become a non-prescription dietary supplement in the United States and other countries.

Lovastatin and other prescription statin drugs inhibit cholesterol synthesis by blocking action of the enzyme HMG-CoA reductase. As a consequence, circulating total cholesterol and LDL-cholesterol are lowered by 24–49% depending on the statin and dose.[15] Different strains of Monascus fungus will produce different amounts of monacolins. The 'Went' strain of Monascus purpureus (purpureus=dark red in Latin), when properly fermented and processed, will yield a dried red yeast rice powder that is approximately 0.4% monacolins, of which roughly half will be monacolin K (chemically identical to lovastatin).

U.S. regulatory restrictions

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The US Food and Drug Administration (FDA) position is that red yeast rice products that contain monacolin K are identical to a prescription drug and, thus, subject to regulation as a drug. In 1998, the FDA initiated action to ban a product (Cholestin) containing red yeast rice extract. The U.S. District Court in Utah ruled in favor of allowing the product to be sold without restriction. This decision was reversed on appeal to the U.S. Court of Appeals in 2001.[5] In 2007, the FDA sent warning letters to two dietary supplement companies. One was making a monacolin content claim about its RYR product and the other was not, but the FDA noted that both products contained monacolins. Both products were withdrawn.[16] In a press release the FDA "...is warning consumers to not buy or eat red yeast rice products... may contain an unauthorized drug that could be harmful to health." The rationale for "harmful to health" was that consumers might not understand that the dangers of monacolin-containing red yeast rice are the same as those of prescription statin drugs.[16]

A products analysis report from 2010 tested 12 products commercially available in the U.S. and reported that per 600 mg capsule, total monacolins content ranged from 0.31 to 11.15 mg.[17] A 2017 study tested 28 brands of red yeast rice supplements purchased from U.S. retailers, stating "the quantity of monacolin K varied from none to prescription strength".[18] Many of these avoid FDA regulation by not having any appreciable monacolin content. Their labels and websites say no more than "fermented according to traditional Asian methods" or "similar to that used in culinary applications". The labeling on these products often says nothing about cholesterol lowering. If products do not contain lovastatin, do not claim to contain lovastatin, and do not make a claim to lower cholesterol, they are not subject to FDA action. Two reviews confirm that the monacolin content of red yeast rice dietary supplements can vary over a wide range, with some containing negligible monacolins.[19][20]

Clinical evidence

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The amount typically used in clinical trials is 1200–2400 mg/day of red yeast rice containing approximately 10 mg total monacolins, of which half are monacolin K. A meta-analysis reported LDL-cholesterol lowered by 1.02 mmol/L (39.4 mg/dL) compared to placebo. The incidence of reported adverse effects ranged from 0% to 5% and was not different from controls.[21] A second meta-analysis incorporating more recent clinical trials also reported significant lowering of total cholesterol and LDL-cholesterol.[22]

Within the first review,[21] the largest and longest duration trial was conducted in China. Close to 5,000 post-heart attack patients were enrolled for an average of 4.5 years to receive either a placebo or a RYR product named Xuezhikang (血脂康). The test product was an ethanol extract of red yeast rice, with a monacolin K content of 11.6 mg/day. Key results: in the treated group, risk of subsequent heart attacks was reduced by 45%, cardio deaths by 31%, and all-cause deaths by 33%.[23] These heart attack and cardiovascular death outcomes appear to be better than what has been reported for prescription statin drugs. A 2008 review pointed out that the cardioprotective effects of statins in Japanese populations occur at lower doses than are needed in Western populations, and theorized that the low amount of monacolins found in the Xuezhikang product might have been more effectively athero-protective than expected in the Chinese population for the same reason.[24]

Safety

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The safety of red yeast rice (RYR) products has not been established. Some supplements have been found to contain high levels of citrinin, which can be toxic to the liver, kidneys, and cellular DNA.[17][25] Commercial products also have highly variable amounts of monacolins[17] and rarely declare this content on the label, making risk assessment difficult. Ingredient suppliers have been suspected of "spiking" red yeast rice preparations with purified lovastatin.[3] One published analysis reported several commercial products as being almost entirely monacolin K—which would occur if the drug lovastatin was illegally added—rather than the expected composition of many monacolin compounds.[19]

There are reports in the literature of muscle myopathy and liver damage resulting from red yeast rice usage.[26][27] From a review: "The potential safety signals of myopathies and liver injury raise the hypothesis that the safety profile of RYR is similar to that of statins. Continuous monitoring of dietary supplements should be promoted to finally characterize their risk profile, thus supporting regulatory bodies for appropriate actions."[28] The European Food Safety Authority (EFSA) Panel on Food Additives and Nutrient Sources added to Food concluded that when red yeast rice preparations contained monacolins, the Panel was unable to identify an intake that it could consider as safe. The reason given was case study reports of severe adverse reactions to products containing monacolins at amounts as low as 3 mg/day.[29] Red yeast rice is not recommended during pregnancy or breast-feeding.[30]

In March 2024, the Japanese Ministry of Health ordered stores to remove three RYR dietary supplements (Benikoji ColesteHelp, NaishiHelp Plus Cholesterol and Natto-kinase Sarasara Tsubu) produced by Kobayashi Pharmaceutical after reports of thousands made ill.[31] Over a hundred people between the ages of 40 to 80 were hospitalized, and five had died as of 29 March, with four of them from kidney problems. There have been more than twelve thousand cases of health problems reported by users. The company said it uses a strain that does not produce citrinin.[31] It has found puberulic acid in the recalled products and is looking into whether the substance might be linked to the fatalities.[25] The suspect batch was manufactured in 2023.[31] Some analysts have placed the blame on industry deregulation, intended to boost economic growth by facilitating the approval of health products. Benikoji products such as miso paste, crackers, food coloring, and a vinegar dressing made by other companies were also recalled.[32] Kobayashi Pharmaceutical officially discontinued production of beni koji products on 8 August 2024.[33]

See also

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References

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  1. ^ a b Shurtleff W, Aoyagi A (2012). History of Koji – Grains and/or Beans Overgrown with a Mold Culture (300 BCE to 2012). Lafayette, California: Soyinfo Center.
  2. ^ a b c Erdogrul O, Azirak S. (2004). "Review of the studies on the red yeast rice (Monascus purpureus)". Turkish Electronic J Biotech. 2: 37–49.
  3. ^ a b c d e Song J, Luo J, Ma Z, Sun Q, Wu C, Li X (2019). "Quality and Authenticity Control of Functional Red Yeast Rice-A Review". Molecules. 24 (10): 1944. doi:10.3390/molecules24101944. PMC 6572552. PMID 31137594.
  4. ^ a b Duggan M, Hartman GD (15 August 1989). "Novel HMG-CoA reductase inhibitors". US Patent and Trademark Office. Archived from the original on 14 January 2019. Retrieved 13 January 2019.
  5. ^ a b "Pharmanex Inc. v. Shalala, United States District Court, D. Utah, Central Division Mar 1, 2001 Case No. 2:97CV262K". Casetext. Retrieved 21 June 2019.
  6. ^ Patakova P (2013). "Monascus secondary metabolites: production and biological activity". J. Ind. Microbiol. Biotechnol. 40 (2): 169–181. doi:10.1007/s10295-012-1216-8. PMID 23179468. S2CID 17175319.
  7. ^ Starling S (2012). "Gee-Lawson-enters-China-dominated-red-yeast-rice-supply". NutraIngredients. Retrieved 19 December 2018.
  8. ^ Gauntner J (2001). "Gauntner's Japan Times Stories". The Japan Times. Retrieved 28 December 2018.
  9. ^ "Foochow Red Wine Chicken Recipe". Archived from the original on 2021-07-16. Retrieved 2021-07-16.
  10. ^ Visessanguan W, Chaikaew S (2014). "Shellfish Products". In Sarkar PK, Nout MR (eds.). Handbook of Indigenous Foods Involving Alkaline Fermentation. CRC Press. pp. 212–213. ISBN 978-1-4665-6530-2.
  11. ^ Redhead J (1990). Utilization of Tropical Foods: Animal products. FAO Food and Nutrition Paper. Food & Agriculture Organization of the United Nations. p. 35. ISBN 978-92-5-102878-0.
  12. ^ Sanchez PC (2008). "Lactic-Acid-Fermented Fish and Fishery Products". Philippine Fermented Foods: Principles and Technology. University of the Philippines Press. p. 264. ISBN 978-971-542-554-4.
  13. ^ a b Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VL (1999). "Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement". Am J Clin Nutr. 69 (2): 231–236. doi:10.1093/ajcn/69.2.231. PMID 9989685.
  14. ^ Endo A (2004). "The origin of the statins. 2004". Atheroscler Suppl. 5 (3): 125–130. doi:10.1016/j.atherosclerosissup.2004.08.033. PMID 15531285.
  15. ^ Edwards JE, Moore RA (2003). "Statins in hypercholesterolaemia: a dose-specific meta-analysis of lipid changes in randomised, double blind trials". BMC Fam Pract. 4: 18. doi:10.1186/1471-2296-4-18. PMC 317299. PMID 14969594.
  16. ^ a b FDA (August 9, 2007). "FDA Warns Consumers to Avoid Red Yeast Rice Products Promoted on Internet as Treatments for High Cholesterol". Food and Drug Administration. Archived from the original on January 11, 2017.
  17. ^ a b c Gordon RY, Cooperman T, Obermeyer W, Becker DJ (2010). "Marked Variability of Monacolin Levels in Commercial Red Yeast Rice Products: Buyer Beware!". Archives of Internal Medicine. 170 (19): 1722–1727. doi:10.1001/archinternmed.2010.382. PMID 20975018.
  18. ^ Cohen PA, Avula B, Khan IA (2017). "Variability in strength of red yeast rice supplements purchased from mainstream retailers". Eur J Prev Cardiol. 24 (13): 1431–1434. doi:10.1177/2047487317715714. PMID 28641460. S2CID 22095749.
  19. ^ a b Li YG, Zhang F, Wang ZT, Hu ZB (2004). "Identification and chemical profiling of monacolins in red yeast rice using high-performance liquid chromatography with photodiode array detector and mass spectrometry". J Pharm Biomed Anal. 35 (5): 1101–1112. doi:10.1016/j.jpba.2004.04.004. PMID 15336357.
  20. ^ Heber D, Lembertas A, Lu QY, Bowerman S, Go VL (2001). "An analysis of nine proprietary Chinese red yeast rice dietary supplements: implications of variability in chemical profile and contents". J Altern Complement Med. 7 (2): 133–139. doi:10.1089/107555301750164181. PMID 11327519.
  21. ^ a b Gerards MC, Terlou RJ, Yu H, Koks CH, Gerdes VE (2015). "Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain – a systematic review and meta-analysis". Atherosclerosis. 240 (2): 415–423. doi:10.1016/j.atherosclerosis.2015.04.004. PMID 25897793.
  22. ^ Peng D, Fong A, Pelt AV (2017). "Original Research: The Effects of Red Yeast Rice Supplementation on Cholesterol Levels in Adults". Am J Nurs. 117 (8): 46–54. doi:10.1097/01.NAJ.0000521973.38717.2e. PMID 28749884. S2CID 881259.
  23. ^ Lu ZL, Collaborative Group for China Coronary Secondary Prevention Using Xuezhikang (2005). "[China coronary secondary prevention study (CCSPS)]". Zhonghua Xin Xue Guan Bing Za Zhi (in Chinese). 33 (2): 109–115. PMID 15924803.
  24. ^ Ong HT, Cheah JS (2008). "Statin alternatives or just placebo: an objective review of omega-3, red yeast rice, and garlic in cardiovascular therapeutics". Chin. Med. J. 121 (16): 1588–1594. doi:10.1097/00029330-200808020-00017. PMID 18982874.
  25. ^ a b "What consumers should know about health supplement linked to 5 deaths". Yahoo Finance. 2024-04-01. Retrieved 2024-04-02.
  26. ^ Philibert C, Bres V, Jean-Pastor MJ, Guy C, Lebrun-Vignes B, Robin P, Pinzani V, Hillaire-Buys D (2016). "[Red yeast-rice-induced muscular injuries: Analysis of French pharmacovigilance database and literature review]". Thérapie (in French). 78 (5S): S31–S40. doi:10.2515/therapie/2015053. PMID 28277227.
  27. ^ Becker DJ, Gordon RY, Halbert SC, French B, Morris PB, Rader DJ (2009). "Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial". Ann. Intern. Med. 150 (12): 830–839. doi:10.7326/0003-4819-150-12-200906160-00006. PMID 19528562. S2CID 46513590.
  28. ^ Mazzanti G, Moro PA, Raschi E, Da Cas R, Menniti-Ippolito F (2017). "Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system". Br J Clin Pharmacol. 83 (4): 894–908. doi:10.1111/bcp.13171. PMC 5346868. PMID 28093797.
  29. ^ Younes M, Aggett P, Aguilar F, et al. (2018). "Scientific opinion on the safety of monacolins in red yeast rice". EFSA Journal. 16 (8): 5368. doi:10.2903/j.efsa.2018.5368. PMC 7009499. PMID 32626016.
  30. ^ "Red Yeast Rice". NIH: National Center for Complementary and Integrative Health. 2013. Retrieved 28 December 2018.
  31. ^ a b c Semans H, Lau C (29 March 2024). "Japan recalls 'red rice' health products over suspected link to five deaths". CNN. Retrieved 29 March 2024.
  32. ^ "5 dead and over 100 hospitalized from recalled Japanese health supplements". AP News. 2024-03-29. Retrieved 2024-04-14.
  33. ^ Inoue Y (8 August 2024). "Kobayashi Pharma to withdraw from beni kōji product segment". Japan Times. Retrieved 8 August 2024.
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