Suspected adverse reactions to performance enhancing dietary supplements: Spontaneous reports from the Italian phytovigilance system

Abstract

Herbal tonic and adaptogens are often used to improve overall well-being. However, few clinical evidence supports their use and their safety is not known before marketing. In this context, the aim of our study was to analyze the spontaneous reports of suspected adverse reactions (ARs) to performance enhancing herbal dietary supplements collected by the Italian Phytovigilance System. Between March 2002 and September 2020, 110 spontaneous reports were collected, 58 of which related to products containing botanicals, alone or in association. Twenty-three serious reactions were reported, 21 of which required hospitalization, one was life-threatening and another caused disability. Dermatological and cardiovascular reactions were the most frequent. Hepatic ARs were the most serious (9 out of 10). A positive dechallenge was indicated in 69% of cases, while a positive rechallenge occurred in 15%. Concomitant use of other products was present in 18 reports (31%), while predisposing conditions were indicated in 17 (29%). Present data highlight safety concerns on herbal dietary supplements used as cognitive and physical performance enhancers, mainly due to their quality and use without expert supervision. Considering that postmarketing surveillance is not required for these products, spontaneous reports represent the only tool to point out risks related to food supplements.

Unauthorized ingredients in “nootropic” dietary supplements: A review of the history, pharmacology, prevalence, international regulations, and potential as doping agents

“…Examples of adverse events associated with a combination of nootropic ingredients are provided by the Italian Phytovigilance System. A significant percentage of reported adverse events were related to the use of multi‐ingredient DS including Griffonia simplicifolia (5‐HTP), N‐acetylcysteine combined with Withania somnifera , or blend of rutaecarpine, caffeine, and Vinca minor 175 …”

“…(5-HTP), N-acetylcysteine combined with Withania somnifera, or blend of rutaecarpine, caffeine, and Vinca minor. 175 Certain adverse events may be related to the risk of interactions of the aforementioned ingredients with prescription drugs or conventional foods (coffee and tea) and interactions between other ingredients in functional food (such as energy drinks) and DS. Table 3 lists several confirmed issues in the RASFF that involve mixtures of ingredients.…”

Interaction of Garcinia cambogia (Gaertn.) Desr. and Drugs as a Possible Mechanism of Liver Injury: The Case of Montelukast

“…The reports 1 (ID 275), 3 (ID 1080), 4 (ID 1382), 5 (ID 1389), and 6 (ID 1415) were previously published by Actis et al [ 35 ] and Crescioli et al [ 22 ] but are included in the present manuscript to give a complete picture of the Italian cases. Overall, a small number of cases was highlighted; however, it is important to outline that one of the major limitation of spontaneous reports is the underreporting due to the underestimation of the potential risk associated with natural products’ consumption [ 36 ]. In spite of this, several other cases have been described in the literature.…”

“…In the present study, we performed an in-depth analysis of ARs related to Garcinia cambogia -containing products collected at the IPS from March 2002 to March 2022. All available information on the reports was retrieved and the demographic, clinical, and pharmacological information was collected and analyzed, according to previously published papers [ 36 ]. The causality assessment between the product use and AR occurrence (categorized as certain/definite, probable/likely, possible, unlikely, or unassessable/unclassifiable) was evaluated by a multidisciplinary group according to the standardized case causality assessment criteria of the WHO system.…”

Editorial: Natural Products and Hepatic Health: Light and Shadows

“…The complex picture described above is, at least in part, the cause of the contrasting evidence about the relationship between natural products and hepatic health. Indeed, while some preclinical and clinical studies underpin a potential interest in botanicals to manage liver diseases (Wang et al, 2020), others highlight safety concerns associated with their use (Ippoliti et al, 2021). In line with this evidence, the articles collected within the Research Topic "Natural Products and Hepatic Health: Light and Shadows" can contribute to the advancement of our knowledge about the impact of botanicals on hepatic health.…”