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Background and Objective: The use of herbal products globally is substantial, but varying definitions and regulatory frameworks have led to differences in their status as medicinal products and in approaches to monitoring their safety. This article explores the current landscape of herbal pharmacovigilance, drawing insights from interviews with global experts in the field, and offers recommendations for best practices to enhance the safety and benefit-to-harm balance of herbal products., Methods: This study comprised semi-structured interviews with members of the International Society of Pharmacovigilance-Herbal and Traditional Medicines Special Interest Group and the Nutrivigilance Information Exchange Network, recruited using purposive sampling. Data were stored and coded using NVIVO ® and analysed thematically using a qualitative inductive approach., Results: Sixteen participants from 11 countries were interviewed, revealing diverse regulatory approaches and challenges in herbal pharmacovigilance. Key themes included legal status, awareness, identification and coding of herbal products, pre-/post-marketing product control, reporting of adverse drug reactions, causality assessment and signals of herbal products. This study yielded five general recommendations to further improve herbal pharmacovigilance worldwide., Conclusions: This study offers an overview of the global landscape of herbal pharmacovigilance, highlighting challenges in monitoring herbal products and presenting universal recommendations. These recommendations encompass increasing awareness, enhancing education and improving legislative frameworks. Given the growing use of herbal products, the implementation of strong pharmacovigilance practices is crucial to ensure consumer safety., Competing Interests: Declarations. Funding: This study received no additional funding. Conflicts of interest/competing interests: The authors have no conflicts of interest that are directly relevant to the content of this article. Some of the authors were also interviewees. Statements about opinions are those of the interviewees alone, and not necessarily reflecting their institution. Disclaimer: The views expressed in this paper are those of the authors and not do not necessarily reflect those of the authors’ institutions or their stakeholders. Guaranteeing the accuracy and the validity of the data is a sole responsibility of the research team. Ethics approval: If a study in the Netherlands is subject to the Medical Research Involving Human Subjects Act (WMO), it must undergo a review by an accredited Medical Research Ethics Committee or the Central Committee on Research Involving Human Subjects (CCMO). This study does not fall under the WMO. Consent to participate: Participants in the study were informed in writing of the study purposes, including publication of the results, and provided a statement of informed consent prior to participating in the study. Consent for publication: All participants were provided with the finalised version of the results. Feedback of the participants on the results was incorporated. Availability of data and material: The data for this article (transcribed interviews and NVIVO coding) are not publicly available because of the Lareb data protection policy. Requests to access the datasets should be directed to the corresponding author and will be granted upon reasonable request. Code availability: The NVIVO coding for the data used in this article is not publicly available because of the Lareb data protection policy. Requests to access the datasets should be directed to the corresponding author and will be granted upon reasonable request. Authors’ contributions: The original study protocol was designed by FvH, SHPW, SvdK and HJW. The study protocol was reviewed by SS. Interviews were held by SHPW. Data analysis was performed by SHPW, FvH and CE. The first draft of the manuscript was written by CE. All authors contributed to manuscript drafting and revision. All authors approved the final version to be published., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background & Aims: Alpha-lipoic acid (ALA)-containing dietary supplements are widely used in clinical practice, although their safety assessment is under-investigated. We characterize the safety profile of ALA-containing products by analysing spontaneous reports of suspected adverse reactions (ARs)., Methods: Suspected ARs to ALA-containing products were extracted from the Italian Phytovigilance System (IPS), and scrutinized in terms of seriousness and causality (through WHO UMC system), with a specific focus on important (IMEs) and designated medical events (DMEs). To characterize the reporting profile from an international perspective, the WHO-VigiBase was also queried., Results: From March 2002 to February 2020, out of 2147 total reports, 116 reports concerning 212 ARs to ALA-containing products were collected. Women were involved in 68.1% of cases. Skin (44.9%) and gastrointestinal disorders (10.8%) were the most frequently represented ARs. Causality assessment resulted as definite (15), probable (35), possible (24), unlikely (5), and unclassifiable (37). In 70% of cases, events occurred within 30 days of ALA use. Forty-five reports were serious (38.8%), being insulin autoimmune syndrome the most frequently reported (N = 10). IMEs were recorded in 20 cases, including four DMEs (3 angioedema and one anaphylactic shock). Similar distribution emerged from the 5641 reports in the WHO-VigiBase., Conclusions: The remarkable reporting of unpredictable skin, immune and hepatic ARs, coupled with seriousness, strong causality and early onset, calls for a) careful risk-benefit assessment of ALA-containing products by regulators; b) awareness and monitoring by clinicians and c) continuous vigilance of their safety profile through valuable spontaneous reporting systems such as IPS., Competing Interests: Conflict of interest MG, EP, ICA, FDP, ER: none., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

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.

Purpose: The aim of this study was to describe suspected adverse reactions (ARs) associated with herbal products used for weight control in Italy., Methods: Spontaneous reports of suspected ARs associated with herbal products used for weight control were collected by the Italian National Institute of Health (April 2002 to June 2010), and the causality assessment was performed., Results: Forty-six of the suspected ARs were associated with herbal products used for weight control. Women were involved in 85% of the reports. The reactions affected mainly the cardiovascular system, the skin, the digestive system, the central nervous system, and the liver. A large proportion of ARs were serious. In more than half of the suspected ARs, the use of other therapies (herbs and/or drugs) was reported, while concomitant conditions were present in 22% of the reports., Conclusions: The use of herbal dietary supplements for weight loss is associated with several ARs. Considering the risk/benefit ratio, consumers should pay attention when using these products.

Purpose: Natural health products are promoted to the public as equally or more effective and less toxic than conventional drugs. However, some 'natural' medicines, and in particular some herbal medicines, are known to have adverse effects. The Italian Pharmacovigilance System, in charge of the Italian Medicines Agency, collects spontaneous reports only for registered drugs. The awareness of the need of surveillance of the safety of natural health products has stimulated the implementation of a suspected adverse reaction reporting system in Italy. The system has been set up by the Italian National Institute of Health., Methods: An ad hoc reporting form can be downloaded from different institutional web sites. Voluntary reports of suspected adverse reactions are sent to the National Institute of Health and are evaluated by a multidisciplinary group of experts., Results: From April 2002 to March 2007, 233 spontaneous reports of suspected adverse reactions to natural health products were collected. A large proportion of suspected adverse reactions were serious: hospitalization was reported in 35% of forms; 6% reported life threatening clinical events and two fatal events were notified. About 50% of suspected adverse reactions were related to gastrointestinal, skin, psychiatric and nervous system disorders. Mainly herbal products (66%) were involved. Twenty-one cases of hepatitis of various seriousness were reported. Twenty-one reports were associated with 27 homeopathic preparations, mostly preparations containing mixtures of substances. Fourteen reports regarded suspected reactions to products containing propolis., Conclusion: Safety and efficacy of 'natural' medicines have not been thoroughly investigated. It is important to improve communication with the public on safety issues. Encouraging spontaneous reporting can contribute to improve awareness among health personnel and patients about the benefit-harm profile of these remedies.

Use of herbal medicine is increasing in Italy. Herbal preparations are generally used as self-medication, often in the wrong belief that "natural" can be equated with "harmless". Whereas use of these products has been associated with serious adverse events, due to the quality of the raw materials used, to interactions with synthetic drugs or to their use in particular conditions, such as pregnancy or lactation. To monitor herbal preparation use in the population is necessary in order to point out possible adverse reactions. This was the objective of this pilot study, together with the urgency to inform health personnel and patients on the correct use of these products. After this experience we strongly believe that a system to assess the safety of herbal preparations is needed.