Study: Goldenseal Use May Compromise Glucose Control in Diabetics

A recent study published in Clinical Pharmacology & Therapeutics found that diabetic patients taking the natural product goldenseal while taking the prescription drug metformin may be unwittingly sabotaging their efforts to maintain healthy blood glucose levels.

Metformin was included in a cocktail of selected drugs given to participants in a clinical study led by scientists at Washington State University’s College of Pharmacy and Pharmaceutical Sciences. The objective of the study was to determine the impact of goldenseal on specific drug transporters, proteins that facilitate absorption or expulsion of drug molecules in different tissues, such as the intestine, liver, and kidney.

“After 6 days of taking goldenseal, participants had about 25% less metformin in their bodies, a statistically significant change that could potentially impact glucose control in patients with type 2 diabetes,” said the study’s first author James Nguyen, PhD candidate in pharmaceutical sciences and recent Doctor of Pharmacy graduate, in a press release.

Nguyen added that the finding serves as a caution to health care providers and patients that OTC natural product use can lead to unwanted drug interactions, which may lead to negative health outcomes.

Unstable glucose levels increase patients’ risk of serious health complications, such as heart disease, kidney disease, and infections. Nguyen noted that there are reports that diabetic patients are increasingly using goldenseal and berberine—a substance found in goldenseal—to self-treat their condition, likely based on claims that berberine helps lower glucose levels.

Goldenseal is often combined with echinacea, a top-selling botanical product, in herbal remedies used to self-treat the common cold and other respiratory tract infections. It is also commonly used to self-treat digestive issues, such as diarrhea and constipation, as well as rashes and other skin problems.

The research team partnered with a contract research organization to conduct test tube experiments to determine whether a goldenseal extract inhibited any of 15 different transporters. Data from those experiments were incorporated into the models to predict whether goldenseal interacts with any of the drugs included in a drug cocktail slated to be used in the subsequent clinical study, according to the study authors.

The cocktail included low doses of 3 different drugs known to be transported by various transporters: furosemide, rosuvastatin, and metformin. Midazolam was included in the cocktail as a positive control, or a drug known to interact with goldenseal. Goldenseal inhibits the metabolic enzyme that breaks down midazolam, leading to increased midazolam in the body.

The researchers conducted a clinical study with 16 healthy participants to see whether their predictions held up, with participants given just the drug cocktail during the baseline phase. In the exposure phase, participants took goldenseal 3 times daily for 5 days before being given the drug cocktail and another dose of goldenseal on day 6, followed by 2 more doses later that day.

Blood and urine samples were collected at regular intervals after participants took the drug cocktail and analyzed by the researchers to compare how each drug moved through the body with or without exposure to goldenseal, according to the study authors.

The researchers expected to find an interaction between goldenseal and rosuvastatin in the clinical study, but it did not materialize. The clinical data showed that taking goldenseal along with metformin decreased metformin blood concentrations, which the model predictions did not reveal.

These findings will help the researchers refine these models to increase prediction accuracy of future natural product-drug interaction studies, according to the study authors. Nguyen plans to conduct studies to determine the mechanism by which goldenseal alters metformin absorption.

Based on the data, he said that this appears to happen in the intestine and may be driven by the transporter OCT1. Further, the research could lead to the discovery of other natural product-drug interactions involving goldenseal and drugs transported by OCT1.

REFERENCE

Goldenseal use may compromise diabetics’ glucose control. Washington State University. https://news.wsu.edu/2021/02/08/use-goldenseal-may-compromise-glucose-control-diabetics-metformin/. Published February 8, 2021. Accessed February 10, 2021.