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Center of Excellence for Natural Product Drug Interaction Research

Council Date: June 1, 2018        

Program Officer: D. Craig Hopp, Ph.D.


The National Health Interview Survey continues to show that dietary supplements (DS) are consumed by millions of people for a variety of reasons. Furthermore, about 20 to 30 percent of patients on prescription medication indicate they are also taking DS concomitantly, thus creating the potential for interactions. In the late 1990s, reports emerged regarding severe and life-threatening interactions involving St. John’s wort and grapefruit juice and a variety of pharmaceuticals (Rx). This led to widespread concerns about potential interactions with other DS. Subsequently, numerous reports emerged describing possible interactions between large numbers of DS/Rx pairs. However, the evidence for many of these purported interactions was in preclinical models, case studies, or based on purely hypothetical arguments, leading to questions about their clinical relevance. Nevertheless, multiple public resources continue to warn against the use of DS in combination with various Rx as a precautionary measure. Additionally, some research studies suggest that combining DS with Rx can be beneficial in certain contexts. This has resulted in much confusion on the part of consumers and health care providers.

In 2015, NCCIH funded a Center devoted to research in this area with the charge to “develop a definitive approach to determining the clinical relevance of pharmacokinetic interactions between natural products and medications.” That Center has produced numerous publications seeking to educate the research community about important factors to consider in studying pharmacokinetic interactions involving complex plant products. Publications have also included recommendations for how to design and execute studies to provide maximally informative results. Finally, the group has created a comprehensive data repository that will provide a portal for other interested scientists to directly access their data. While much has been accomplished, there are many remaining unanswered questions. It will require a consistent and prolonged investment to improve the quality of research in this field, fill in the gaps in knowledge for additional DS, as well as elevate the dialogue regarding the true risks associated with concomitant use of DS and Rx.

Purpose of Proposed Initiative

NCCIH seeks to continue building upon the existing body of knowledge emerging from our current funding. The results to date represent a promising beginning, but there is still much work remaining. The evidence for interactions between specific dietary supplements and pharmaceuticals remains extremely variable. High-quality data from controlled human subjects studies is rare, and even then questions remain about the clinical relevance of the findings. Based on current information, fears that concomitant use of DS and Rx would produce widespread severe risks to patients appear to be unfounded. While it is entirely possible that a new supplement could emerge on the market with the potential for severe drug interactions, of greater value currently is the characterization of non-life-threatening interactions which are poorly understood. The clinical consequences of such interactions are unknown in many instances and may have an impact on the course of treatment, outcomes, and quality of life. NCCIH wishes to continue the existing model, which pursues the systematic in vitro and in vivo characterization of potential interactions between DS and Rx. As work continues, the existing repository of carefully controlled experiments and their results will continue to grow thereby increasing in value and utility. This will allow for subsequent rational assessment of the relative risks and/or benefits of selected DS/Rx combinations. It should also provide a more in-depth understanding of the pharmacokinetic and metabolic pathways for a large number of DS.


The successful grantee will be expected to survey the available information on natural product drug interactions, including existing literature, public databases, adverse event reports, etc., to identify and prioritize candidate natural products for further study. They also will have primary responsibility for sourcing the natural products selected, performing necessary quality control, and subsequently executing necessary in vitro and in vivo research. Furthermore, the grantee will be charged with organizing, analyzing, and archiving the results of that work through an open access repository. Lastly, the data and methodology generated should be actively pushed out to the research community to improve future research hypotheses and quality. Objectives for this cycle of the Natural Products Drug Interaction Program include, but are not limited to:

  • High throughput in vitro studies to rapidly characterize the ability of isolated natural products to interfere with the pharmacokinetics of medications via Phase I and Phase II metabolizing enzymes, transporters, etc.
  • Identification of high priority natural products as candidates for more in-depth in vitro evaluation
  • Additional human subjects studies where justified to establish clinical relevance of any potential interactions suggested by in vitro data.
  • Continue to develop and expand the data repository into a national resource for the scientific community.