Supplements are everywhere, but research is limited: insights from the NatMed study

If you have ever walked into a health store and stared at the rows of dietary supplements—each promising better health, more energy, or a stronger immune system—you are not alone. In fact, millions of people, including patients with cancer and other chronic diseases, turn to these products to complement their health journey. But as promising as these supplements sound, how do we know their safety when paired with treatments like chemotherapy? That is the question a recent study, published in JCO Oncology Advances, sought to answer by evaluating NatMed, a widely used database for drug-supplement interactions. By focusing on doxorubicin, a common chemotherapy drug, the study assessed whether NatMed provides reliable information about interactions between chemotherapy and dietary supplements.

Patients with cancer often use dietary supplements, hoping to ease treatment side effects, boost recovery, or improve their overall health. While this seems like a harmless addition to their care plan, supplements can sometimes interact with chemotherapy drugs, potentially reducing their effectiveness or causing harmful side effects. Healthcare providers often struggle with assessing these interactions, as patients may not report their supplement use, and reliable research on supplement-drug interactions is still limited. This is where databases like NatMed come in, compiling information on natural products, their safety, and their interactions with medications. However, are these databases truly trustworthy sources of information? To answer this question, a research team led by Drs. Blake Langley and Heather Greenlee from Fred Hutchinson Cancer Center, assessed the reliability of NatMed in evaluating supplement-drug interactions. "We wanted to understand how we can leverage existing resources and databases on the potential for natural products and dietary supplement ingredients to interact with cancer treatments," Dr. Langley explained. If teams can use large data pulls with minimal processing or manipulation, analyses can potentially be run more efficiently. The researchers specifically examined interactions between dietary supplements and the chemotherapy drug doxorubicin.

One major area of concern was antioxidants, as these compounds—often marketed as protective against cell damage—could potentially interfere with chemotherapy drugs that rely on oxidative stress to kill cancer cells. The study analyzed 115 monographs for doxorubicin interactions and an additional 455 monographs for general antioxidant properties to determine whether NatMed’s reports were reliable enough for use in clinical decision-making.

To assess NatMed’s reliability, the researchers used an Application Programming Interface (API) to extract supplement monographs (detailed reports) from the database. These reports contained information on how supplements interact with five key metabolic pathways, including antioxidant effects and drug metabolism. Next, clinical pharmacists independently reviewed these monographs using five key criteria, evaluating the validity of source evidence, the reported interactions, and whether NatMed’s assessments aligned with real-world clinical knowledge. A structured agreement analysis followed, ensuring that only validated monographs were included in the final dataset. This process is illustrated in the figure below, which outlines how NatMed data was retrieved, reviewed, and validated.

The results showed that across all pathways, the pharmacists’ evaluations matched the database’s information almost 94% of the time, with strong agreement for most categories. For interactions involving doxorubicin, the agreement ranged from substantial to near perfect. For antioxidant supplements, the database achieved similarly high levels of reliability.

However, the study also highlighted areas where improvements are needed: 6.4% of the retrieved monographs were not validated by clinical pharmacists, meaning some interactions reported by NatMed may require further verification. Moreover, most of the data in NatMed were based on preclinical studies (such as lab experiments and animal models), with limited evidence from human trials. This suggests that while the database provides a good starting point, additional clinical research is necessary to confirm its findings in real-world settings. And lastly, dose-dependent interactions were not well captured. Some supplement-drug interactions may only occur at high doses, but these nuances were often missing from NatMed reports.

"This is the first step toward future analyses we have planned to better understand how dietary supplements with mechanisms of action that potentially interfere with cancer treatments. Those studies will hopefully elucidate the potential risk profile so that patients and care teams can make evidence-informed decisions on dietary supplement use during treatment," Dr. Langley stated.

The findings of this study hold significant implications for both patients and healthcare providers. First, it underscores the need for open communication about supplement use during cancer treatment. Supplements might seem harmless, but they could have unexpected effects when combined with chemotherapy.

For doctors and pharmacists, the findings suggest that NatMed is a valuable tool for evaluating these interactions. However, the study also highlights the importance of using multiple databases and consulting experts when making decisions about supplement use during treatment. While NatMed shows promise, this study is just the beginning. More research is needed to confirm the database’s findings in clinical settings and to explore the long-term effects of combining supplements with cancer treatments. Additionally, there is a need for greater education among healthcare providers about how to use these tools effectively.

For patients, the takeaway is clear: always talk to your healthcare team about any supplements you are taking. While the label on the bottle might promise big benefits, it’s essential to consider how these products interact with your treatment plan.

In the complex world of cancer care, every decision counts. This study provides much-needed clarity on the reliability of supplement interaction databases like NatMed. While it is a valuable tool, patients and healthcare professionals must remain cautious and seek multiple sources of information when evaluating supplement-drug interactions. The bottom line? What’s natural isn’t always harmless. If you are undergoing chemotherapy, talk to your doctor before taking any supplements—because when it comes to your health, it’s always better to ask.

This study was supported by grants from the National Center for Advancing Translational Sciences, the National Center for Complementary and Integrative Health, and the National Cancer Institute. The funding sources had no role in the design, analysis, or interpretation of the study.

Fred Hutch/UW/Seattle Children’s Cancer Consortium member Dr. Heather Greenlee contributed to this work.

Langley, B. O., Rillamas-Sun, E., Huang, Y., Indorf, A., Robles, M., Feaster, R., D'Addario, L., Ergas, I. J., Roh, J. M., Kushi, L. H., & Greenlee, H. 2024. Validation and Utility of Drug-Nutrient Interaction and Dietary Supplement Mechanistic Activity in the Natural Medicines Database. JCO oncology advances, 1, e2400062.