Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system
Open accessAbstract
AIMS: Red yeast rice (RYR) is contained in dietary supplements for patients with dyslipidemia. RYR supplements contain monacolin K, which is chemically identical to lovastatin, a licensed drug with a well-known risk profile. We aim to describe the safety profile of RYR by analysing spontaneous reports of suspected adverse reactions (ARs). METHODS: Within the Italian Surveillance System of Natural Health Products, suspected ARs were collected and evaluated by a multidisciplinary group of experts to assess causality using the WHO-UMC system or the CIOMS/RUCAM score, for hepatic reactions. The public version of the WHO-Vigibase was also queried. RESULTS: From April 2002 to September 2015, out of 1261 total reports, 52 reports concerning 55 ARs to RYR dietary supplements were collected. ARs consisted in myalgia and/or increase in creatine phosphokinase (19), rhabdomyolysis (1), liver injury (10), gastrointestinal reactions (12), cutaneous reactions (9) and other reactions (4). Women were involved in 70% of cases. In 13 cases, the reaction required hospitalization, and 28 patients were taking other medications. Dechallenge was positive in 40 reactions (73%), rechallenge was positive in 7. Causality resulted as certain (1), probable (31, 56%), possible (18, 34%), unlikely (3) or unassessable (2). Similar distribution emerged from the WHO-Vigibase. CONCLUSIONS: 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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Curcumin may modulate HDL production and HDL functionality biomarkers, including apolipoprotein AI, cholesteryl ester transfer protein, lecithin cholesterol acyl transferase, paraoxonase-1, myeloperoxidase, and lipoprotein-associated phospholipase A2.
“Curcumin may also modulate the production of HDL and biomarkers of HDL functionality, including apolipoprotein AI ([), cholesteryl ester transfer protein (Y), lecithin cholesterol acyl transferase ([), paraoxonase-1 (Y), myeloperoxidase (Y), and lipoprotein-associated phospholipase A2 (Y) (174-177).”
From The Role of Nutraceuticals in Statin Intolerant Patients (2018) · cites this paper as [175]
RYR has a safety profile similar to or better than low-dose statins.
“It has been shown that the safety profile of RYR is similar to that of LDS or even less (175).”
From The Role of Nutraceuticals in Statin Intolerant Patients (2018) · cites this paper as [175]
Cites
Adverse drug reactions: definitions, diagnosis, and management
Edwards, I. R., & Aronson, J. K. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02799-9 · Cited by 2,988 · see citing works
Danan, G., & Benichou, C. (1993) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(93)90101-6 · Cited by 1,481 · see citing works
Southan, C., Sharman, J., Benson, H., Faccenda, E., Pawson, A. J., Alexander, S. P. H., Buneman, O., Davenport, A., McGrath, J., Peters, J., et al. (2015) · Nucleic Acids Res. · doi:10.1093/nar/gkv1037 · Cited by 1,121 · see citing works
Case Definition and Phenotype Standardization in Drug-Induced Liver Injury
Aithal, G. P., Watkins, P. B., Andrade, R. J., Larrey, D. G., Molokhia, M., Takikawa, H., Hunt, C., Wilke, R. A., Avigan, M., Kaplowitz, N., et al. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.58 · Cited by 1,045 · see citing works
The Concise Guide to PHARMACOLOGY 2015/16: Enzymes
Alexander, S. P. H., Fabbro, D., Kelly, E., Marrion, N. V., Peters, J. A., Benson, H. E., Faccenda, E., Pawson, A. J., Sharman, J. L., Southan, C., et al. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13354 · Cited by 604 · see citing works
Benichou, C., Danan, G., & Flahault, A. (1993) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(93)90102-7 · Cited by 571 · see citing works
Emergency Department Visits for Adverse Events Related to Dietary Supplements
Geller, A. I., Shehab, N., Weidle, N. J., Lovegrove, M. C., Wolpert, B. J., Timbo, B. B., Mozersky, R. P., & Budnitz, D. S. (2015) · New England Journal of Medicine · doi:10.1056/nejmsa1504267 · Cited by 502 · see citing works
Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement
Heber, D., Yip, I., Ashley, J. M., Elashoff, D. A., Elashoff, R. M., & Go, V. L. W. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.2.231 · Cited by 499 · see citing works
Constituents of Red Yeast Rice, a Traditional Chinese Food and Medicine
Ma, J., Li, Y., Ye, Q., Li, J., Hua, Y., Ju, D., Zhang, D., Cooper, R., & Chang, M. N. T. (2000) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf000338c · Cited by 447 · see citing works
Hepatotoxicity associated with statins: Reports of idiosyncratic liver injury post-marketing
Bjornsson, E. S., Jacobsen, E. I., & Kalaitzakis, E. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.07.023 · Cited by 320 · see citing works
Naci, H., Brugts, J., & Ades, T. (2013) · Circulation: Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.111.000071 · Cited by 292 · see citing works
Red Yeast Rice for Dyslipidemia in Statin-Intolerant Patients: A Randomized Trial
Becker, D. J., Gordon, R. Y., Halbert, S. C., French, B., Morris, P. B., & Rader, D. J. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-150-12-200906160-00006 · Cited by 275 · see citing works
Barnes, J., Mills, S. Y., Abbot, N. C., Willoughby, M., & Ernst, E. (1998) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.1998.00715.x · Cited by 260 · see citing works
Toxicological Properties of Citrinin
Flajs, D., & Peraica, M. (2009) · Archives of Industrial Hygiene and Toxicology · doi:10.2478/10004-1254-60-2009-1992 · Cited by 220 · see citing works
Anecdotes that provide definitive evidence
Aronson, J. K., & Hauben, M. (2006) · BMJ · doi:10.1136/bmj.39036.666389.94 · Cited by 185 · see citing works
Marked Variability of Monacolin Levels in Commercial Red Yeast Rice Products: Buyer Beware!
Gordon, R. Y., Cooperman, T., Obermeyer, W., & Becker, D. J. (2010) · Archives of Internal Medicine · doi:10.1001/archinternmed.2010.382 · Cited by 184 · cited 1× · see citing works
“, [66] analyzing 12 RYR products, labeled “600 mg/capsule” of active product, found: monacolins 0.”
BackgroundBrown, A. C. (2017) · Food and Chemical Toxicology · doi:10.1016/j.fct.2016.07.024 · Cited by 184 · see citing works
Pharmacovigilance of Herbal Medicines
Barnes, J. (2003) · Drug Safety · doi:10.2165/00002018-200326120-00001 · Cited by 181 · see citing works
Gerards, M. C., Terlou, R. J., Yu, H., Koks, C. H. W., & Gerdes, V. E. A. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.04.004 · Cited by 169 · cited 1× · see citing works
“underestimation of adverse reactions [22].”
Halbert, S. C., French, B., Gordon, R. Y., Farrar, J. T., Schmitz, K., Morris, P. B., Thompson, P. D., Rader, D. J., & Becker, D. J. (2010) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2009.08.672 · Cited by 154 · see citing works
Brown, A. C. (2016) · Food and Chemical Toxicology · doi:10.1016/j.fct.2016.07.001 · Cited by 152 · see citing works
Lorenzo, C. D., Ceschi, A., Kupferschmidt, H., Lüde, S., Nascimento, E. D. S., Santos, A. D., Colombo, F., Frigerio, G., Nørby, K. K., Plumb, J. A., et al. (2014) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12519 · Cited by 142 · see citing works
Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient
Prasad, G. V. R., Wong, T., Meliton, G., & Bhaloo, S. (2002) · Transplantation · doi:10.1097/00007890-200210270-00028 · Cited by 119 · see citing works
Descamps, V., & Ranger‐Rogez, S. (2013) · Joint Bone Spine · doi:10.1016/j.jbspin.2013.05.002 · Cited by 119 · see citing works
New Monascus Metabolite Isolated from Red Yeast Rice (Angkak, Red Koji)
WILD, D., Tóth, G., & Humpf, H. (2002) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf020023s · Cited by 103 · see citing works
Herbal hepatotoxicity: a critical review
Teschke, R., Frenzel, C., Glass, X., et al. (2012) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04395.x · Cited by 94 · see citing works
EFSA Panel on Dietetic Products, N. A. A. (. (2011) · EFSA Journal · doi:10.2903/j.efsa.2011.2304 · Cited by 84 · see citing works
Lipid-Lowering Efficacy of Red Yeast Rice in a Population Intolerant to Statins
Venero, C. V., Venero, J., Wortham, D. C., & Thompson, P. D. (2010) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2009.10.045 · Cited by 83 · see citing works
Surveillance of suspected adverse reactions to natural health products in Italy
Menniti‐Ippolito, F., Mazzanti, G., Santuccio, C., et al. (2008) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1566 · Cited by 81 · see citing works
Self-citationMarques-Vidal, P. M., Pécoud, A. R., Hayoz, D., Paccaud, F. M., Mooser, V., Waeber, G., & Vollenweider, P. (2007) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602932 · Cited by 81 · see citing works
Review of red yeast rice content and current Food and Drug Administration oversight
Childress, L., Gay, A., Zargar, A., & Ito, M. K. (2012) · Journal of clinical lipidology · doi:10.1016/j.jacl.2012.09.003 · Cited by 77 · see citing works
Red Yeast Rice for the Treatment of Dyslipidemia
Burke, F. M. (2015) · Current Atherosclerosis Reports · doi:10.1007/s11883-015-0495-8 · Cited by 73 · see citing works
Perdices, E. V., Medina‐Cáliz, I., Hernando, S., Ortega, A., Martín-Ocaña, F., Navarro, J. M., Peláez, G. I. C., Castiella, A., Hallal, H., Romero‐Gómez, M., et al. (2014) · PubMed · Cited by 71 · see citing works
Avula, B., Cohen, P. A., Wang, Y., Sagi, S., Wei, F., Wang, M., Zweigenbaum, J. A., Ma, S., & Khan, I. A. (2014) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2014.07.039 · Cited by 68 · see citing works
Moriarty, P. M., Roth, E. M., Karns, A., Ye, P., Zhao, S.-P., Liao, Y., Capuzzi, D. M., Bays, H. E., Zhang, F., Liu, S., et al. (2014) · Journal of clinical lipidology · doi:10.1016/j.jacl.2014.09.002 · Cited by 65 · see citing works
Systematic Review of Adverse Effects from Herbal Drugs Reported in Randomized Controlled Trials
Lee, J. Y., Jun, S. A., Hong, S. S., et al. (2016) · Phytotherapy Research · doi:10.1002/ptr.5647 · Cited by 61 · see citing works
Avancini, J., Maragno, L., Santi, C. G., et al. (2015) · Clinical and Experimental Dermatology · doi:10.1111/ced.12682 · Cited by 58 · see citing works
Chinese Red Rice-induced Myopathy
Smith, D. J., & Olive, K. E. (2003) · Southern Medical Journal · doi:10.1097/01.smj.0000100117.79718.dc · Cited by 54 · see citing works
Lapi, F., Gallo, E. R., Bernasconi, S., Vietri, M., Menniti‐Ippolito, F., Raschetti, R., Gori, L., Firenzuoli, F., Mugelli, A., & Vannacci, A. (2008) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2008.03224.x · Cited by 53 · see citing works
Self-citationVENLAFAXINE INGESTION IS ASSOCIATED WITH RHABDOMYOLYSIS IN ADULTS: A CASE SERIES
WILSON, A. D., Howell, C., & Waring, W. S. (2007) · The Journal of Toxicological Sciences · doi:10.2131/jts.32.97 · Cited by 52 · see citing works
Anaphylaxis to proton pump inhibitors
González, P., Soriano-Gomis, V., López, P., et al. (2002) · Allergologia et Immunopathologia · doi:10.1016/s0301-0546(02)79150-7 · Cited by 51 · see citing works
Grieco, A., Miele, L., Pompili, M., Biolato, M., Vecchio, F. M., Grattagliano, I., & Gasbarrini, A. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.02.021 · Cited by 50 · see citing works
Gonnelli, S., Caffarelli, C., Stolakis, K., Cuda, C., Giordano, N. G., & Nuti, R. (2014) · Current Therapeutic Research · doi:10.1016/j.curtheres.2014.07.003 · Cited by 49 · see citing works
Marazzi, G., Pelliccia, F., Campolongo, G., Quattrino, S., Cacciotti, L., Volterrani, M., Gaudio, C., & Rosano, G. (2015) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2015.09.023 · Cited by 48 · see citing works
Symptomatic Myopathy due to Red Yeast Rice
Mueller, P. S. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-145-6-200609190-00021 · Cited by 48 · see citing works
The Role of Red Yeast Rice for the Physician
Gordon, R. Y., & Becker, D. J. (2010) · Current Atherosclerosis Reports · doi:10.1007/s11883-010-0145-0 · Cited by 44 · see citing works
Symptomatic Hepatitis Associated with the Use of Herbal Red Yeast Rice
Roselle, H. A., Ekatan, A., Tzeng, J., Sapienza, M., & Kocher, J. (2008) · Annals of Internal Medicine · doi:10.7326/0003-4819-149-7-200810070-00021 · Cited by 44 · see citing works
Adverse reactions in the skin from anti-hypertensive drugs.
Thestrup‐Pedersen, K. (1987) · PubMed · Cited by 41 · see citing works
Schwab, S., Heier, M., Schneider, A. L. C., Fischer, B., Huth, C., Peters, A., & Thorand, B. (2013) · The journal of nutrition health & aging · doi:10.1007/s12603-013-0418-8 · Cited by 40 · see citing works
Syndrome d’hypersensibilité médicamenteuse induit par l’atorvastatine
Gressier, L., Pruvost‐Balland, C., Dubertret, L., et al. (2008) · Annales de Dermatologie et de Vénéréologie · doi:10.1016/j.annder.2008.07.063 · Cited by 38 · see citing works
Systematic review of red yeast rice compared with simvastatin in dyslipidaemia
Ong, Y. C., & Aziz, Z. (2016) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12374 · Cited by 36 · see citing works
Vercelli, L., Mongini, T., Olivero, N., Rodolico, C., Musumeci, O., & Palmucci, L. (2006) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2006.00668_7.x · Cited by 20 · see citing works
Omeprazole-induced drug reaction with eosinophilia and systemic symptoms (DRESS)
Bourneau‐Martin, D., Leclech, C., Jamet, A., et al. (2014) · European Journal of Dermatology · doi:10.1684/ejd.2014.2343 · Cited by 20 · see citing works
A case report of myopathy from consumption of red yeast rice
Polsani, V. R., Jones, P. H., Ballantyne, C. M., et al. (2008) · Journal of clinical lipidology · doi:10.1016/j.jacl.2007.12.005 · Cited by 18 · see citing works
Adams, A. E., Bobrove, A. M., & Gilliam, A. C. (2010) · Journal of Cutaneous Medicine and Surgery · doi:10.2310/7750.2010.09042 · Cited by 17 · see citing works
[Hepatitis associated with treatment with lovastatin. Presentation of 2 cases].
Bruguera, M., Joya, P., & Rodés, J. (1998) · PubMed · Cited by 12 · see citing works
Low-dose venlafaxine-induced severe rhabdomyolysis: a case report
Huang, S., Yang, H., Lin, Y.-C., et al. (2012) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2012.01.016 · Cited by 9 · see citing works
Adverse drug reaction: rosuvastatin as a cause for ischaemic colitis in a 64-year-old woman
Tan, J., Pretorius, C., Flanagan, P. V., & Pais, A. (2012) · BMJ Case Reports · doi:10.1136/bcr.11.2011.5270 · Cited by 9 · see citing works
Philibert, C., Brès, V., Jean-Pastor, M.-J., Guy, C., Lebrun‐Vignes, B., Robin, P., Pinzani, V., & Hillaire‐Buys, D. (2015) · Therapies · doi:10.2515/therapie/2015053 · Cited by 8 · see citing works
Wiliński, J., & Dąbrowski, M. (2013) · PubMed · Cited by 6 · see citing works
Interferon‐γ (INF‐γ) release test can detect cutaneous adverse effects to statins
Goldberg, I., Isman, G., Shirazi, I., et al. (2009) · International Journal of Dermatology · doi:10.1111/j.1365-4632.2008.03896.x · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cicero, A. F. G., Colletti, A., Bajraktari, G., Descamps, O., Djuric, D. M., Ezhov, M., Fras, Z., Katsiki, N., Langlois, M., Latkovskis, G., et al. (2017) · Archives of Medical Science · doi:10.5114/aoms.2017.69326 · Cited by 281 · see citing works
The Role of Nutraceuticals in Statin Intolerant Patients
Banach, M., Patti, A. M., Giglio, R. V., Cicero, A. F. G., Atanasov, A. G., Bajraktari, G., Bruckert, E., Descamps, O., Djuric, D. M., Ezhov, M., et al. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.04.040 · Cited by 272 · see citing works
Poli, A., Barbagallo, C. M., Cicero, A. F. G., Corsini, A., Manzato, E., Trimarco, B., Bernini, F., Visioli, F., Bianchi, A., Canzone, G., et al. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.05.015 · Cited by 134 · see citing works
Marazzi, G., Campolongo, G., Pelliccia, F., Quattrino, S., Vitale, C., Cacciotti, L., Massaro, R., Volterrani, M., & Rosano, G. (2017) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2017.06.015 · Cited by 36 · see citing works
Food supplements with red yeast rice: more regulations are needed
De Backer, G. G. (2017) · European Journal of Preventive Cardiology · doi:10.1177/2047487317716500 · Cited by 17 · see citing works
- Authors
- Mazzanti, G., Moro, P. A., Raschi, E., Da Cas, R., & Menniti‐Ippolito, F.
- Affiliations
- Sapienza University of Rome (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- University of Bologna (IT)
- Centre for Epidemiology National Institute of Health Viale Regina Elena 299 00161 Rome Italy
- Istituto Superiore di Sanità (IT)
- Corresponding author
- Mazzanti, Gabriela
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2017-01-19
- Volume
- 83
- Issue
- 4
- Pages
- 894-908
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC5346868
- OpenAlex
- W2572825966
- Cited by
- 81
- References
- 61
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 4 · 2022: 12 · 2021: 8 · 2020: 13 · 2019: 11 · 2018: 9 · 2017: 8
- FWCI
- 16.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- National Institutes of Health
- Agenzia Italiana del Farmaco, Ministero della Salute
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- red yeast rice, dietary supplements, lovastatin, adverse drug reactions, rhabdomyolysis, myopathy, liver injury, drug safety, spontaneous reporting, natural health products, dyslipidemia, causality assessment, WHO VigiBase
- MeSH terms
- Adult, Aged, Aged, 80 and over, Biological Products, Female, Hospitalization, Humans, Italy, Male, Middle Aged, Databases, Factual, Adverse Drug Reaction Reporting Systems, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Dietary Supplements
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
