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Adverse Events to Food Supplements Containing Red Yeast Rice: Comparative Analysis of FAERS and CAERS Reporting Systems

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Abstract

Introduction

Food supplements containing red yeast rice (RYR) are proposed as an alternative in statin-intolerant patients, although they actually contain natural statin(s) and their safety in clinical practice is still incompletely characterized. We described and compared adverse events (AEs) associated with RYR products submitted to reporting systems maintained by the Food and Drug Administration (FDA), with a focus on liver and muscular events.

Methods

We extracted RYR-related AEs from the FDA Adverse Event Reporting System (FAERS) [first quarter (Q1)-2004 to Q2-2016], a drug-based archive, and the Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) (Q1-2004 to Q1-2017). Disproportionality via reporting odds ratio (ROR) with 95% confidence interval (CI) calculation and case-by-case inspection were performed, with a focus on muscular and hepatic AEs.

Results

One thousand three hundred AEs were extracted from FAERS (RYR mainly reported as a concomitant agent), whereas only 159 AEs were found in CAERS (RYR recorded mainly as a suspect agent). In FAERS, a large number of reports emerged for “general disorders and administration site conditions,” whereas CAERS received also a high number of reports for “investigations” and “musculoskeletal and connective tissue disorders”. Disproportionality analyses confirmed higher reporting of serious muscular and liver injuries: in FAERS, five cases of hepatic disorders (ROR = 13.71; 95% CI 5.44–34.57); in CAERS, 27 cases of rhabdomyolysis/myopathy (8.44; 5.44–13.10).

Conclusions

Notwithstanding recognized limitations, these findings strengthen the importance of exploring multiple databases in safety assessment of RYR products, which should be monitored by clinicians for muscular and hepatic safety, and call for urgent review by policymakers to harmonize their regulatory status.

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Acknowledgements

E.R. conceived and designed the study, provided guidance with regard to data analysis, and drafted the first version of the manuscript; A.G. and E.F. analyzed the data and provided substantial contributions to data interpretation and discussion; E.P., F.M.I., G.M. and F.D.P. provided substantial contributions to the study design, data interpretation and discussion; all authors critically revised the content and approved the final version of the manuscript.

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Authors and Affiliations

  1. Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Via Irnerio 48, 40126, Bologna, BO, Italy

    Emanuel Raschi, Anna Girardi, Elisabetta Poluzzi, Emanuele Forcesi & Fabrizio De Ponti

  2. National Centre for Drug Research and Evaluation, National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy

    Francesca Menniti-Ippolito

  3. Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Gabriela Mazzanti

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  1. Emanuel Raschi
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Correspondence to Emanuel Raschi.

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Funding

No sources of funding were used to assist in the preparation of this study. Authors at the University of Bologna (E.R., A.G., E.P., E.F., F.D.P.) are supported by Institutional Research Funds (Ricerca Fondamentale Orientata).

Conflicts of Interest

Emanuel Raschi, Anna Girardi, Elisabetta Poluzzi, Emanuele Forcesi, Francesca Menniti-Ippolito, Gabriela Mazzanti and Fabrizio De Ponti declare no potential conflicts of interest relevant to the content of the manuscript.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Disproportionality analysis according to relevant System Organ Classes (SOCs). na: not applicable (number of cases <3). The total count exceeds the number of AEs because a given sign/symptoms (PT of the MedDRA terminology) may be classified in different SOCs (PDF 292 kb)

Supplementary Material 2

Case-by-case analysis of serious reports (SMQs for muscular or liver toxicities) where RYR was recorded as suspect in FAERS (PDF 242 kb)

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Raschi, E., Girardi, A., Poluzzi, E. et al. Adverse Events to Food Supplements Containing Red Yeast Rice: Comparative Analysis of FAERS and CAERS Reporting Systems. Drug Saf 41, 745–752 (2018). https://doi.org/10.1007/s40264-018-0661-3

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