Finding the bad actor: Challenges in identifying toxic constituents in botanical dietary supplements

Authors: ROBERTS, GEORGIA - National Institutes Of Health (NIH); Gardner, Dale; FOSTER, PAUL - National Institutes Of Health (NIH); HOWARD, PAUL - Food And Drug Administration(FDA); LUI, EDMUND - Western University; WALKER, LARRY - University Of Mississippi; VAN BREEMEN, RICHARD - Oregon State University; AUERBACH, SCOTT - National Institutes Of Health (NIH); RIDER, CYNTHIA - National Institutes Of Health (NIH)

Submitted to: Food and Chemical Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/17/2018
Publication Date: 2/5/2019
Citation: Roberts, G.K., Gardner, D.R., Foster, P.M., Howard, P.C., Lui, E., Walker, L., Van Breemen, R.B., Auerbach, S.S., Rider, C. 2019. Finding the bad actor: Challenges in identifying toxic constituents in botanical dietary supplements. Food and Chemical Toxicology. 124:431–438. https://doi.org/10.1016/j.fct.2018.12.026.
DOI: https://doi.org/10.1016/j.fct.2018.12.026

Interpretive Summary: Plant based dietary supplements have widespread use worldwide and in general are unregulated. Reports of negative side effects are of concern for human health impacts following consumption of some of these products. The composition of many supplements is complex and variable and the testing of the vast number of available products would almost impossible task given the time and resources required for comprehensive toxicological testing. More efficient methods are needed to assess the safety of products. Identification of toxicologically-active constituents, “finding the bad actor” is often needed. Methods to the find the “bad” components usually involve bioassay-guided fractionation (BGF). Here, we explore BGF, some of the limitations and the potential advances in emerging technologies that may help in the identification of the toxic components. Identification of the bad actors will allow better monitoring of market products, as well as surveying human exposure and thus ensuring the safety of botanical dietary supplements.

Technical Abstract: Botanical-derived dietary supplements have widespread use in the general population. The complex and variable nature of botanical ingredients and reports of adverse responses have led to concern for negative human health impacts following consumption of these products. Toxicity testing of the vast number of available products, formulations, and combinations is not feasible due to the time and resource intensive nature of comprehensive testing. Methods are needed to assess the safety of a large number of products via more efficient frameworks. Identification of toxicologically-active constituents is one approach being used, with many advantages toward product regulation. Bioassay-guided fractionation (BGF) is the leading approach used to identify biologicallyactive constituents. Most BGF studies with botanicals focus on identifying pharmacologically-active constituents for drug discovery or botanical efficacy research. Here, we explore BGF in a toxicological context, drawing from both efficacy and poisonous plant research. Limitations of BGF, including loss of mixture activity and bias toward abundant constituents, and recent advancements in the field (e.g., biochemometrics) are discussed from a toxicological perspective. Identification of active constituents will allow better monitoring of market products for known toxicologically-active constituents, as well as surveying human exposure, two important steps to ensuring the safety of botanical dietary supplements.