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Current Nutraceuticals


ISSN (Print): 2665-9786
ISSN (Online): 2665-9794

Systematic Review Article

Adverse Effects of Natural Products: A Brief Pre-Systematic Review

Author(s): Carla Pires and Ana S. Fernandes*

Volume 2, Issue 1, 2021

Published on: 02 July, 2020

Page: [14 - 20] Pages: 7

DOI: 10.2174/2665978601999200702163914


Background: Natural products are commonly used for treating health problems. These products may be associated with adverse events, which are defined as "noxious and unintended response to a medicinal product" by the European Medicine Agency.

Objectives: To identify studies describing at least one adverse event (or with potential to promote an adverse event) related to the use of natural products, as well as to describe the involved product(s) and adverse event(s).

Methods: A pre-systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Keywords: "natural product(s)" and ["adverse drug reaction(s)" or "adverse effect(s)"]. Screened databases: PubMed, SciELO, DOAJ and Google Scholar. Inclusion criteria: Papers describing at least one adverse event associated with the use of natural products and published between 2017 and 2019. Exclusion criteria: Repeated studies, reviews and papers written in other languages than English, Portuguese, French or Spanish.

Results: 104 studies were identified (20 PubMed; 0 SciELO; 2 DOAJ; 82 Google Scholar), but only 10 were selected (4 PubMed and 6 Google Scholar): 1 in-vitro study; 2 non-clinical studies, 1 study reporting in-vitro and clinical data and 5 case reports. Globally, 997 reports of adverse drug reactions with natural products were identified, mainly non-severe cases.

Conclusion: Since a limited number of studies was found, we conclude that adverse events due to natural products may be underreported or natural products may have a good safety profile. This review contributes to assuring the safety of natural products consumers by evaluating the knowledge/information on the potential adverse events and interactions of these products.

Keywords: Natural products, bioactive compounds, adverse drug reaction, adverse effect, patients' safety.

Graphical Abstract
Calixto, J.B. The role of natural products in modern drug discovery. An. Acad. Bras. Cienc., 2019, 91(Suppl. 3)e20190105
[] [PMID: 31166478]
Strohl, W.R.; Strohl, W.R. The role of natural products in a modern drug discovery program. Drug Discov. Today, 2000, 5(2), 39-41.
[] [PMID: 10652450]
Dias, D.A.; Urban, S.; Roessner, U. A historical overview of natural products in drug discovery. Metabolites, 2012, 2(2), 303-336.
[] [PMID: 24957513]
European Commission. Nutrition beyond the trends: Science for Environment Policy THEMATIC ISSUE: Biodiversity, agriculture and health, 2013. Available at:. on January 11, 2020).
Andrews, L.; Ralston, S.; Blomme, E.; Barnhart, K. A snapshot of biologic drug development: Challenges and opportunities. Hum. Exp. Toxicol., 2015, 34(12), 1279-1285.
[] [PMID: 26614816]
Yeh, B.J.; Lim, W.A. Synthetic biology: Lessons from the history of synthetic organic chemistry. Nat. Chem. Biol., 2007, 3(9), 521-525.
[] [PMID: 17710092]
European Medicine Agency. Guideline on good pharmacovigilance practices (GVP). Annex I: Definitions, Rev4, 2017. Available at. (Accessed on January 11, 2020).
European Medicine Agency. 2018 Annual Report on EudraVigilance for the European Parliament, the Council and the Commission, 2019. Available at:, on January 11, 2020).
Geller, A.I.; Shehab, N.; Weidle, N.J.; Lovegrove, M.C.; Wolpert, B.J.; Timbo, B.B.; Mozersky, R.P.; Budnitz, D.S. Emergency Department Visits for Adverse Events Related to Dietary Supplements. N. Engl. J. Med., 2015, 373(16), 1531-1540.
[] [PMID: 26465986]
Huang, Y.L.; Moon, J.; Segal, J.B. A comparison of active adverse event surveillance systems worldwide. Drug Saf., 2014, 37(8), 581-596.
[] [PMID: 25022829]
Elshafie, S.; Zaghloul, I.; Roberti, A.M. Pharmacovigilance in developing countries (part I): Importance and challenges. Int. J. Clin. Pharm., 2018, 40(4), 758-763.
[] [PMID: 29248988]
World Health Organization Members of the WHO Programme for International Drug Monitoring, 2020.Available at:. on January 11, 2020).
Tewari, D.; Rawat, P.; Singh, P.K. Adverse drug reactions of anticancer drugs derived from natural sources. Food Chem. Toxicol., 2019, 123, 522-535.
[] [PMID: 30471312]
PRISMA. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 2020. Available at:, on January 12, 2020).
PubMed. US National Library of Medicine National Institutes of Health, , 2020.
ciELO. Scientific Electronic Library Online, 2020.Available at:. (Accessed on January 12, 2020).
DOAJ Directory of Open Access Journals Online, 2020.
Khabsa, M.; Giles, C.L. The number of scholarly documents on the public web. PLoS One, 2014, 9(5)e93949
[] [PMID: 24817403]
CDSR. Cochrane Database of Systematic Reviews, 2020. Available at: , on January 19, 2020).
Picking, D.; Chambers, B.; Barker, J.; Shah, I.; Porter, R.; Naughton, D.P.; Delgoda, R. Inhibition of cytochrome P450 activities by extracts of hyptis verticillata Jacq.: Assessment for potential HERB-drug interactions. Molecules, 2018, 23(2), 430.
[] [PMID: 29462868]
Savage, R.L.; Hill, G.R.; Barnes, J.; Kenyon, S.H.; Tatley, M.V. Suspected hepatotoxicity with a supercritical carbon dioxide extract of Artemisia annua in grapeseed oil used in New Zealand. Front. Pharmacol., 2019, 10, 1448.
[] [PMID: 31920644]
Avonto, C.; Rua, D.; Lasonkar, P.B.; Chittiboyina, A.G.; Khan, I.A. Identification of a compound isolated from German chamomile (Matricaria chamomilla) with dermal sensitization potential. Toxicol. Appl. Pharmacol., 2017, 318, 16-22..
[] [PMID: 28109818]
Abdalla, Y.O.A.; Nyamathulla, S.; Shamsuddin, N.; Arshad, N.M.; Mun, K.S.; Awang, K.; Nagoor, N.H. Acute and 28-day sub-acute intravenous toxicity studies of 1′-S-1′-acetoxychavicol acetate in rats. Toxicol. Appl. Pharmacol., 2018, 356, 204-213.
[] [PMID: 30138658]
Minciullo, P.L.; Calapai, G.; Miroddi, M.; Mannucci, C.; Chinou, I.; Gangemi, S.; Schmidt, R.J. Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - part 4: Solidago virgaurea-Vitis vinifera. Contact Dermat., 2017, 77(2), 67-87.
[] [PMID: 28543097]
Gari, M.; Majhee, L.; Kumari, K. Herbal drug-induced adverse drug reaction: a case report.Asian J. Pharm. Clin. Res., 2018, 11(2), 9-11.,
Mertz, P.; Lebrun-Vignes, B.; Salem, J.E.; Arnaud, L. Characterizing drug-induced capillary leak syndromes using the World Health Organization VigiBase. J. Allergy Clin. Immunol., 2019, 143(1), 433-436.
[] [PMID: 30244023]
Xu, Y.; Patel, D.N.; Ng, S.P.; Tan, S.H.; Toh, D.; Poh, J.; Lim, A.T.; Chan, C.L.; Low, M.Y.; Koh, H.L. Retrospective study of reported adverse events due to complementary health products in singapore from 2010 to 2016. Front. Med. (Lausanne), 2018, 5, 167.
[] [PMID: 29946545]
Paudyal, B.; Thapa, A.; Sigdel, K.R.; Adhikari, S.; Basnyat, B. Adverse events with ayurvedic medicines- possible adulteration and some inherent toxicities. Wellcome Open Res., 2019, 4, 23.
[] [PMID: 31641694]
Chang, S.H.; Song, Y.K.; Nah, S.S. The clinical efficacy and safety of gumiganghwal-tang in knee osteoarthritis: A phase II randomized double blind placebo controlled study. Evid. Based Complement. Alternat. Med., 2018.20183165125
[] [PMID: 30538759]
Lia, J.; Olleyea, O.E.; Yu, X. High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care.Acta Pharmaceutica Sinica B, 2019, 9(5), 1035-1049.,
Awortwe, C.; Makiwane, M.; Reuter, H.; Muller, C.; Louw, J.; Rosenkranz, B. Critical evaluation of causality assessment of herb-drug interactions in patients. Br. J. Clin. Pharmacol., 2018, 84(4), 679-693.
[] [PMID: 29363155]
Costa, J.G.; Vidovic, B.; Saraiva, N.; do Céu Costa, M.; Del Favero, G.; Marko, D.; Oliveira, N.G.; Fernandes, A.S. Contaminants: A dark side of food supplements? Free Radic. Res., 2019, 53(Suppl. 1), 1113-1135.
[] [PMID: 31500469 ]

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