Effects of common nutraceutical supplements marketed for cancer prevention on tumor cell growth.
Authors: Kwok Yue Faat Raymond , Einbond Linda Saxe , Tantawi Hoda , Strange Theodore , Smith Christina , Dhar Meekoo , Bershadskiy Alexander , Castellanos Mario R 
Published: June 2024

e22504 Background: In 2022, there were 1.9 million new cancer cases in the US. Data indicates that many patients receiving a cancer diagnosis begin taking supplements, believing that these products improve health. Unfortunately, most supplements lack sufficient clinical trial data to substantiate their use. Our team explores the anticancer effects of natural compounds in common nutraceuticals. We have confirmed that six compounds induce cancer cell death in vitro. However, at sublethal doses, they exhibit a biphasic effect and promote cancer cell growth. Additionally, we conduct a systematic review of these compounds to aggregate data from clinical trials on their effects in a cancer context. Methods: From the medical literature, common phytochemicals reported to have anticancer properties & sold in nutraceutical products were tested using established cancer cell lines, which include the breast, liver, colon, and ovary as the tissues of origin—cellular proliferation was measured by MTT assays. Half-maximal inhibitory concentration (IC50) was calculated, and in vitro assays described in the literature were modified to test low doses of the compounds over 96 hours. Chemicals identified to promote cell proliferation were used to conduct a systematic literature review in the PubMed database from all time through December 2023, using MeSH terms with the keywords "cancer" and "clinical trial" to tabulate compound effects in clinical trials. Results: 6 phytochemicals, reported to have anticancer properties, exhibited biphasic effects. High doses effectively suppressed cancer cells, while sublethal low doses (fractions of the IC50) induced the proliferation of cancer cells. These compounds & enriched extracts include Curcumin, Resveratrol, Rosemary extract, Rosmarinic acid, Hederagenin, & Kava extract. Curcumin & Resveratrol, which dominate the nutraceutical market, were specifically chosen for a systematic literature review. Despite their widespread use, relatively few formal clinical trials have been conducted in the cancer setting, and most showed negative or minimal anticancer effects in treated patients. No pro-growth tumor effects were reported in these trials. However, the follow-up periods were short, and the study sample sizes were small. Conclusions: We discovered 6 compounds & enriched extracts, widely marketed for anti-cancer properties, actually promote cancer cell growth at low doses. Curcumin & Resveratrol, which are prevalent in the U.S. supplement market, have insufficient clinical trial data to validate their efficacy and safety. Furthermore, our findings raise concerns about the typical milligram-level consumption of these compounds. Clinical trials indicate that such dosages result in sublethal blood concentrations, which our study has shown can be problematic. Given these findings, we advise against using these supplements until more comprehensive data is available.