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The European Food Safety Authority (EFSA) assessed the use of RYR and, while pointing out several uncertainties regarding the available data, raised a warning related to the safety of RYR when used as a food supplement at a dose of monacolin as low as 3 mg\/day. In their decision in June 2023, EFSA approved the use of monacolins from RYR at doses less than 3 mg\/day. We therefore decided to interrogate the different adverse event reporting systems (FAERS and CAERS) and analyse the characteristics of the cases reported to be associated with RYR supplements, and we reviewed the most recent meta-analyses with a focus on the occurrence of muscle symptoms and liver dysfunction. In terms of all musculoskeletal disorders from September 2013 (when the first case related to RYR consumption was recorded) to 30 September 2023, 363,879 cases were reported in the FAERS, with the number of cases related to RYR consumption being very small and accounting for 0.008% of cases. In the same time frame, 27,032 cases of hepatobiliary disorders were reported, and the cases attributable to RYR ingestion accounted for 0.01% of all cases. A low rate of muscle symptoms and liver dysfunction attributed to RYR ingestion was also observed in the CAERS database, where only 34 cases of adverse muscle events and 10 cases of adverse liver events reported RYR as the suspect product, while 19 cases of both muscle events and 10 cases of adverse liver events reported it as a concomitant product. This profile mirrors that of meta-analyses of randomised clinical trials of RYR, in which RYR use was not associated with either liver dysfunction or muscular adverse symptoms.<\/jats:p>","DOI":"10.3390\/nu16030444","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T09:42:32Z","timestamp":1706866952000},"page":"444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Impact of Red Yeast Rice Extract Use on the Occurrence of Muscle Symptoms and Liver Dysfunction: An Update from the Adverse Event Reporting Systems and Available Meta-Analyses"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6081-1257","authenticated-orcid":false,"given":"Giuseppe Danilo","family":"Norata","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"},{"name":"Center for the Study of Atherosclerosis, Bassini Hospital, 20092 Cinisello Balsamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-6874","authenticated-orcid":false,"given":"Maciej","family":"Banach","sequence":"additional","affiliation":[{"name":"Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), 90-419 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.jacc.2020.11.056","article-title":"Red Yeast Rice for Hypercholesterolemia: JACC Focus Seminar","volume":"77","author":"Cicero","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105719","DOI":"10.1016\/j.fitote.2023.105719","article-title":"Alternative lipid lowering strategies: State-of-the-art review of red yeast rice","volume":"172","author":"Buzzelli","year":"2024","journal-title":"Fitoterapia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.jfutfo.2023.03.003","article-title":"The current trend and challenges of developing red yeast rice-based food supplements for hypercholesterolemia","volume":"3","author":"Chen","year":"2023","journal-title":"J. Future Foods"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/17512433.2023.2138342","article-title":"Impact of red yeast rice supplementation on lipid profile: A systematic review and meta-analysis of randomized-controlled trials","volume":"16","author":"Rahmani","year":"2023","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_5","unstructured":"(2023, November 03). FDA Warns Consumers to Avoid Red Yeast Rice Products Promoted on Internet as Treatments for High Cholesterol, Available online: https:\/\/www.in.gov\/health\/food-protection\/recalls-and-advisories\/2007-advisories\/red-yeast-rice-products\/."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Younes, M., Aggett, P., Aguilar, F., Crebelli, R., Dusemund, B., Filipic, M., Frutos, M.J., Galtier, P., and Gott, D. (2018). Scientific opinion on the safety of monacolins in red yeast rice. EFSA J., 16, e05368.","DOI":"10.2903\/j.efsa.2018.5368"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.pcad.2022.11.010","article-title":"Statin associated muscle symptoms: An update and review","volume":"75","author":"Dicken","year":"2022","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"543","DOI":"10.14218\/JCTH.2021.00271","article-title":"Statin-induced Liver Injury Patterns: A Clinical Review","volume":"10","author":"Averbukh","year":"2022","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101164","DOI":"10.1016\/j.eujim.2020.101164","article-title":"Drug Induced Liver Injury (DILI) due to variability in monacolin K content in Red Yeast Rice (RYR): An expert opinion","volume":"37","author":"Cicero","year":"2020","journal-title":"Eur. J. Integr. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S0140-6736(22)01643-9","article-title":"Statin intolerance: Time to stop letting it get in the way of treating patients","volume":"400","author":"Banach","year":"2022","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"127043","DOI":"10.1155\/2012\/127043","article-title":"Interaction between Red Yeast Rice and CYP450 Enzymes\/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin","volume":"2012","author":"Chen","year":"2012","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"792529","DOI":"10.3389\/fnut.2021.792529","article-title":"Risk Assessment of RYR Food Supplements: Perception vs. Reality","volume":"8","author":"Righetti","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_13","unstructured":"(2023, November 03). COMMISSION REGULATION (EU) 2022\/860 of 1 June 2022 amending Annex III to Regulation (EC) No 1925\/2006 of the European Parliament and of the Council as regards monacolins from red yeast rice. Available online: https:\/\/eur-lex.europa.eu\/eli\/reg\/2022\/860\/oj."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s11883-023-01157-4","article-title":"Rhabdomyolysis or Severe Acute Hepatitis Associated with the Use of Red Yeast Rice Extracts: An Update from the Adverse Event Reporting Systems","volume":"25","author":"Banach","year":"2023","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, Y., Jiang, L., Jia, Z., Xin, W., Yang, S., Yang, Q., and Wang, L. (2014). A meta-analysis of red yeast rice: An effective and relatively safe alternative approach for dyslipidemia. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098611"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.atherosclerosis.2015.04.004","article-title":"Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain-a systematic review and meta-analysis","volume":"240","author":"Gerards","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1097\/01.NAJ.0000521973.38717.2e","article-title":"Original Research: The Effects of Red Yeast Rice Supplementation on Cholesterol Levels in Adults","volume":"117","author":"Peng","year":"2017","journal-title":"Am. J. 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Pharmacol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/3\/444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:53:34Z","timestamp":1760104414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/3\/444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,2]]},"references-count":19,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["nu16030444"],"URL":"https:\/\/doi.org\/10.3390\/nu16030444","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,2]]}}}