The botanical dietary supplement that you’re taking may be natural, but is it safe?

It was 2006 when Mary Paine, a professor at the WSU College of Pharmacy and Pharmaceutical Sciences, first published her clinical research study on the interaction between grapefruit juice and felodipine, a medication used to treat high blood pressure. Her work builds on the foundation laid by David Bailey from the University of Western Ontario, who discovered the “grapefruit juice effect” approximately 30 years ago. Through years of research, multiple investigators, including Paine and her post-doc mentor Paul Watkins, both while at the University of North Carolina at Chapel Hill, determined the mechanism of the grapefruit juice-felodipine interaction.

Specifically, constituents in the juice, furanocoumarins, were identified as major inhibitors of the metabolism (breakdown) of felodipine in the intestine. By inhibiting its metabolism, felodipine levels increase, which can lead to any number of symptoms including low blood pressure, rapid heartbeat, and/or dizziness. The research was a groundbreaking moment for her and highlighted the deficient guidelines in evaluating commonly used natural products and their interactions with everyday medications.

“Natural products, including grapefruit juice and the dietary supplement St. John’s wort, have this common perception that because they’re natural, that means they’re safe,” said Paine. “However, if you’re taking natural products with your medication(s), how do you know that these products don’t have interactions with your medications? Just because they’re natural doesn’t necessarily mean they’re safe.”

More needs to be done to study natural products and their interactions with drugs, according to Paine, who directs the Center of Excellence for Natural Product Drug Interaction Research (NaPDI Center). She and her team of researchers from various institutions across the nation just renewed their competitive U54 grant in September, awarded by the National Institutes of Health, specifically the National Center for Complementary and Integrative Health and in part by the Office of Dietary Supplements. This prestigious and nearly $11 million grant will allow Paine and her team to continue their groundbreaking work for the next five years on these relatively under-studied precipitants of drug interactions. This is the largest grant ever awarded to a researcher at the WSU College of Pharmacy and Pharmaceutical Sciences.

“CPPS faculty brought in over $10 million in FY20 that ended on June 30, 2020.  This milestone is highly significant and should allow us to move up in the national rankings of pharmacy schools. Dr. Paine’s $10.9 million award ensures that FY21 will keep us moving up in those rankings and I could not be more proud of her, her research team, and her collaborators in the college,” said Dean of the WSU College of Pharmacy and Pharmaceutical Sciences Mark Leid. “They have done a fantastic job.”

For Paine, this work is more than just a milestone; it’s a personal mission to ensure the safety of natural products and represent the interests of taxpayers, who are the ultimate funders of the research.

“I don’t want to be perceived as anti-natural product,” said Paine. “As a pharmacist, researcher, and educator, I want to make sure people are taking these products with their drugs in a safe manner, robust guidelines are developed to study natural product-drug interactions optimally, and that definitive information is disseminated to students in the health care professions. Meeting these goals will ensure we are being financially and scientifically responsible to the taxpayers.”

Current regulatory guidance to evaluate drug-drug interactions are not sufficient for natural product-drug interactions. One of the main hurdles in studying natural products as precipitants of drug interactions is the large variation in product composition, as well as concerns about contamination of the product, whether intentional or unintentional. “With drugs, we know everything about them. With natural products, we don’t always know every ingredient in them. Because they’re not regulated like drugs, manufacturers need not put them through the ringer for efficacy and safety like regular drugs,” said Paine. “Relative to drug-drug interactions, we are in an embryonic stage when it comes to understanding natural product-drug interactions.”

Paine and her team will select and prioritize 3-5 natural products to study based on their innovative approach that considers, amongst other sources, chemical structural alerts, clinical case reports, regulatory alerts, scientific meeting reports, and top-selling natural product reports. The data generated by the NaPDI Center will be deposited into an established database that serves a diverse group of researchers interested in assessing natural product-drug interactions. Researchers will be able to access scientific results, raw data, and recommended approaches to assess the clinical relevance of how a natural product may impact the disposition of drugs throughout the body.

The published recommended approaches are significant for an industry that continues to grow exponentially. According to Grand View market research, the global supplements market size is estimated at $123 billion.