ADVERSE REACTIONS TO HERBAL EXTRACTS USED FOR OVERWEIGHT AND OBESITY

BACKGROUND: The prevalence of overweight and obesity is increasing worldwide. Lifestyle change is a critical aspect in addressing the problem; nevertheless, sometimes a pharmacotherapeutic approach is also needed. In Italy, orlistat, liraglutide, bupropion/naltrexone are approved for the treatment of obesity and overweight, but the adverse effects limit their use. An alternative strategy is represented by the use of dietary supplements and galenic preparations based on herbal extracts. These products have no approved therapeutic effects, but they are perceived as safe due to their natural origin. With the increase of natural products popularity, also reports of adverse events associated with them became more frequent. Therefore, monitoring their safety is an urgent need. METHODS: A comprehensive search was made using PubMed and SCOPUS electronic databases and selecting English as preferred language, although neither language limitations nor filters were applied. For more specific requirements, Google Scholar was considered too. The following searching keywords and their combinations through the Boolean logical operators were used: “overweight”, “obesity”, “phytochemicals”, “nutraceuticals”, “medicinal plants”, “herbal extracts”, “botanicals”, “weight loss”, “weight control”, “adverse effects”, “side effects”, “adverse reaction”, and “safety”. RESULTS: Several herbal preparations used for weight control have been associated with adverse reactions (ARs). Particularly, cardiovascular ARs have been reported for Citrus aurantium, owing to its active substance synephrine, although concomitant use of other compounds (e.g., caffeine) could contribute. Based on this evidence, the Ministry of Health has established that synephrine is not allowed in food supplements and in magistral galenic preparations. Conversely, C. aurantium extract is allowed in both of them, but in food supplements the daily intake of synephrine cannot be higher than 30 mg. Green tea (Camellia sinensis) has been associated with hepatic ARs. Most reports of hepatotoxicity were related to products containing extracts enriched in catechins. These compounds are believed the culprit for the liver injury, but recently association with HLA-B*35:01 polymorphism has been showed. Liver damage, sometimes requiring transplantation, has been also reported for Garcinia cambogia. Although some green tea-based products have been recalled, G. cambogia has never been banned; indeed, often products involved in the ARs contained other components, so making difficult to establish a causal relationship. Recently, turmeric (Curcuma longa) supplements used for slimming purposes have been involved in liver injury. In many products, turmeric was present in particular formulations (inclusion in liposomes and/or nanoparticles, combination with piperine) able to increase the curcumin bioavailability. Furthermore, in some cases, products contained enriched extracts (C. longa dry extract with 95%). Such preparations resemble a pure substance rather than a traditional preparation, so their safety is completely unknown. CONCLUSIONS: Serious ARs have been reported from the use of herbal weight loss preparations, although to establish a causal relationship is often difficult. Considering the poor clinical evidence supporting their use, the safety concerns become more relevant. In this context, since 2017, as established in a Decree issued by the Ministry of Health (DM 31/03/2017), the Italian National Institute of Health has the task to monitor the use and safety of magistral prescriptions for weight control (often containing herbals) in order to point out potential risks associated with their consumption.