Skip to main content

Advertisement

SpringerLink
Log in

Suspected adverse reactions associated with herbal products used for weight loss: spontaneous reports from the Italian Phytovigilance System

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Overweight and obesity represent worldwide a rising health problem. In this context, dietary supplements and herbal preparations are often used as self-medication for weight loss. The aim of this study was to describe the safety profile of dietary supplements for weight control by analyzing spontaneous reports of suspected adverse reactions (ARs) received by the Italian Phytovigilance System, from July 2010 to October 2017.

Methods

The suspected ARs were collected using an ad hoc reporting form, registered in a database at the National Institute of Health and evaluated by a multidisciplinary group of experts. The causality assessment was performed using the WHO-UMC system or the CIOMS/RUCAM score. In case of serious adverse reactions, a feedback is provided to the reporter by e-mail.

Results

Sixty-six spontaneous reports were collected. ARs involved cardiovascular system (26%), liver (14%), central nervous system (12%), skin (9%), gastrointestinal system (17%), thyroid (8%), kidney (4%), and other organs/systems (10%). In 64% of cases, the reaction was serious. Dechallenge was positive in 46 cases; three cases of positive rechallenge were reported. After the causality assessment, the association between the product intake and the adverse reaction was judged as possible in the majority of the cases (n = 43; 65%).

Conclusions

The data collected confirmed the existence of safety concerns on herbal dietary supplements used for body weight control, mainly related to quality of products and their use as self-medication. In this scenario, spontaneous reports represent the only tools available to monitor safety of these products.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. World Health Organization (WHO) (2017) Overweight and obesity. http://www.who.int/gho/ncd/risk_factors/overweight/en/ Accessed 17 Oct 2018

  2. World Health Organization (WHO) (2018) Overweight and obesity. http://www.who.int/mediacentre/factsheets/fs311/en/ Accessed 17 Oct 2018

  3. Cheung BM, Cheung TT, Samaranayake NR (2013) Safety of antiobesity drugs. Ther Adv Drug Saf 4(4):171–181

    Article  Google Scholar 

  4. Gadde KM, Apolzan JW, Berthoud HR (2018) Pharmacotherapy for patients with obesity. Clin Chem 64(1):118–129

    Article  CAS  Google Scholar 

  5. Velazquez A, Apovian CM (2018) Updates on obesity pharmacotherapy. Ann N Y Acad Sci 411(1):106–119

    Article  Google Scholar 

  6. Consumer Goods & FMCG; Food & Nutrition. Sales volume of dietary supplements in Italy between 2008 and March 2017 (in million packs). Statista 2018. https://www.statista.com/statistics/783675/sales-volume-of-dietary-supplements-in-italy/. Accessed 26 Nov 2018

  7. Menniti-Ippolito F, Mazzanti G, Santuccio C, Moro PA, Calapai G, Firenzuoli F, Valeri A, Raschetti R (2008) Surveillance of suspected adverse reactions to natural health products in Italy. Pharmacoepidemiol Drug Saf 7(6):626–635

    Article  Google Scholar 

  8. Lee SW, Lai NM, Chaiyakunapruk N, Chong DW (2017) Adverse effects of herbal or dietary supplements in G6PD deficiency: a systematic review. Br J Clin Pharmacol 83(1):172–179

    Article  CAS  Google Scholar 

  9. Navarro VJ, Khan I, Björnsson E, Seeff LB, Serrano J, Hoofnagle JH (2017) Liver injury from herbal and dietary supplements. Hepatology 65(1):363–373

    Article  CAS  Google Scholar 

  10. Mazzanti G, Moro PA, Raschi E, Da Cas R, Menniti-Ippolito F (2017) Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system. Br J Clin Pharmacol 83(4):894–908

    Article  CAS  Google Scholar 

  11. Timbo BB, Chirtel SJ, Ihrie J, Oladipo T, Velez-Suarez L, Brewer V, Mozersky R (2017) A review of dietary supplement adverse event report data from the FDA Center for food safety and applied nutrition adverse event reporting system (CAERS), 2004-2013. Ann Pharmacother 52(5):431–438

    Article  Google Scholar 

  12. Geller AI, Shehab N, Weidle NJ, Lovegrove MC, Wolpert BJ, Timbo BB, Mozersky RP, Budnitz DS (2015) Emergency department visits related to dietary supplements. N Engl J Med 373(16):1531–1540

    Article  CAS  Google Scholar 

  13. Vitalone A, Menniti-Ippolito F, Moro PA, Firenzuoli F, Raschetti R, Mazzanti G (2011) Suspected adverse reactions associated with herbal products used for weight loss: a case series reported to the Italian National Institute of health. Eur J Clin Pharmacol 67(3):215–224

    Article  Google Scholar 

  14. Brown EG, Wood L, Wood S (1999) The medical dictionary for regulatory activities (MedDRA). Drug Saf 20(2):109–117

    Article  CAS  Google Scholar 

  15. World Health Organization (2004) WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems. http://www.appswhoint/medicinedocs/documents/s7148e/s7148epdf Accessed 24 Oct 2018

  16. The Uppsala Monitoring Center. The use of the WHO-UMC system for standardised case causality assessment. http://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf. Accessed 26 Nov 2018

  17. Danan G, Benichou C (1993) Causality assessment of adverse reactions to drugs-I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 46:1323–1330

    Article  CAS  Google Scholar 

  18. Choudhary NS, Kotecha H, Saraf N, Gautam D, Saigal S (2014) Terbinafine induced liver injury: a case report. J Clin Exp Hepatol 4(3):264–265

    Article  Google Scholar 

  19. Rodman JS, Deutsch DJ, Gutman SI (1976) Methyldopa hepatitis. A report of six cases and review of the literature. Am J Med 60(7):941–948

    Article  CAS  Google Scholar 

  20. Actis GC, Bugianesi E, Ottobrelli A, Rizzetto M (2007) Fatal liver failure following food supplements during chronic treatment with montelukast. Dig Liver Dis 39(10):953–955

    Article  CAS  Google Scholar 

  21. Kothadia JP, Kaminski M, Samant H, Olivera-Martinez M (2018) Hepatotoxicity associated with use of the weight loss supplement Garcinia Cambogia: a case report and review of the literature. Case Reports Hepatol 2018:6483605

    Article  Google Scholar 

  22. Crescioli G, Lombardi N, Bettiol A, Marconi E, Risaliti F, Bertoni M, Menniti-Ippolito F, Maggini V, Gallo E, Firenzuoli F, Vannacci A (2018) Acute liver injury following Garcinia cambogia weight-loss supplementation: case series and literature review. Intern Emerg Med 13(6):857–872

    Article  Google Scholar 

  23. Zheng EX, Rossi S, Fontana RJ, Vuppalanchi R, Hoofnagle JH, Khan I, Navarro VJ (2016) Risk of liver injury associated with green tea extract in SLIMQUICK(®) weight loss products: results from the DILIN prospective study. Drug Saf 39(8):749–754

    Article  CAS  Google Scholar 

  24. Mazzanti G, Menniti-Ippolito F, Moro PA, Cassetti F, Raschetti R, Santuccio C, Mastrangelo S (2009) Hepatotoxicity from green tea: a review of the literature and two unpublished cases. Eur J Clin Pharmacol 65(4):331–341

    Article  Google Scholar 

  25. Mazzanti G, Di Sotto A, Vitalone A (2015) Hepatotoxicity of green tea: an update. Arch Toxicol 89(8):1175–1191

    Article  CAS  Google Scholar 

  26. Food and Drug Administration (2018) DMAA in Products Marketed as Dietary Supplements 2018. https://www.fda.gov/Food/DietarySupplements/ProductsIngredients/ucm346576.htm#warning_letters. Accessed 24 Oct 2018

  27. Campana C, Griffin PL, Simon EL (2014) Caffeine overdose resulting in severe rhabdomyolysis and acute renal failure. Am J Emerg Med 32(1):111.e3–111.e4

    Article  Google Scholar 

  28. Sung DJ, Choi EJ, Kim S, Kim J (2018) Rhabdomyolysis from resistance exercise and caffeine intake. Iran J Public Health 47(1):138–139

    PubMed  PubMed Central  Google Scholar 

  29. Takeuchi Y, Miyamoto T, Kakizawa T, Shigematsu S, Hashizume K (2007) Insulin autoimmune syndrome possibly caused by alpha lipoic acid. Intern Med 46(5):237–239

    Article  Google Scholar 

  30. Furukawa N, Miyamura N, Nishida K, Motoshima H, Taketa K, Araki E (2007) Possible relevance of alpha lipoic acid contained in a health supplement in a case of insulin autoimmune syndrome. Diabetes Res Clin Pract 75(3):366–367

    Article  Google Scholar 

  31. Gullo D, Evans JL, Sortino G, Goldfine ID, Vigneri R (2014) Insulin autoimmune syndrome (Hirata disease) in European Caucasians taking α-lipoic acid. Clin Endocrinol 81(2):204–209

    Article  CAS  Google Scholar 

  32. Michalopoulou Alevras T, Guerrero Gual M, Villabona Artero C, Pérez-Maraver M (2015) Autoimmune hypoglycemia syndrome associated with α lipoic acid consumption. Med Clin 144(2):93–94

    Article  Google Scholar 

  33. Farrington R, Musgrave IF, Byard RW (2019) Evidence for the efficacy and safety of herbal weight loss preparations. J Integr Med 17(2):87–92

    Article  Google Scholar 

  34. Rebbeck TR, Troxel AB, Norman S, Bunin GR, De Michele A, Baumgarten M, Berlin M, Schinnar R, Strom BL (2007) A retrospective case-control study of the use of hormone-related supplements and association with breast cancer. Int J Cancer 120(7):1523–1528

    Article  CAS  Google Scholar 

  35. Zhao LG, Li HL, Sun JW, Yang Y, Ma X, Shu XO, Zheng W, Xiang YB (2017) Green tea consumption and cause-specific mortality: results from two prospective cohort studies in China. J Epidemiol 27(1):36–41

    Article  Google Scholar 

Download references

Funding

No sources of funding were used to conduct the study described in the manuscript, or to assist with the preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology ‘Vittorio Erspamer’, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Gabriela Mazzanti & Annabella Vitalone

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

    Roberto Da Cas & Francesca Menniti-Ippolito

Authors
  1. Gabriela Mazzanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annabella Vitalone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberto Da Cas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francesca Menniti-Ippolito
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All co-authors agreed to be accountable for all aspects of the work and have participated substantially in the work to take public responsibility for appropriate portions of the content. The contribution of each author is stated below. Mazzanti has performed the research, analyzed data, and wrote the paper. Vitalone has analyzed data and wrote the paper. Da Cas has performed the research and analyzed data. Menniti has performed the research, analyzed data, and wrote the paper.

Corresponding author

Correspondence to Annabella Vitalone.

Ethics declarations

“This article does not contain any studies with human participants or animals performed by any of the authors.”

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mazzanti, G., Vitalone, A., Da Cas, R. et al. Suspected adverse reactions associated with herbal products used for weight loss: spontaneous reports from the Italian Phytovigilance System. Eur J Clin Pharmacol 75, 1599–1615 (2019). https://doi.org/10.1007/s00228-019-02746-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-019-02746-6

Keywords

Search

Navigation