How Herbal and Dietary Supplements Affect Oncologic Drugs

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Susan Egbert

Statistics show that about 80 percent of the world’s population consume herbal/dietary supplements without specific recommendations to take them¹, with some cancer patients using herbal/dietary supplements to alleviate their symptoms (e.g. pain, nausea, etc)^,2,3,4,5.  Generally, patients consider herbal/dietary supplements “safe” since they are “natural,” however, herb-drug interactions (HDI) (e.g. St. John’s wort and docetaxel) have been reported in 8% of patients taking one or two herbal products while on oral chemotherapy⁶.  Despite the increasing use of herbal/dietary supplements, there is not a significant amount of research trying to understand how these products can affect oncology regimens specifically. Some interactions that could be harmful include increase of drug levels in the blood which can cause patients to be at a higher dose than needed or drugs not being able to perform correctly because the herb is prohibiting the drug from reaching where it’s supposed to be.This article will not only dive into what has been done to understand herb-drug interactions in the world of oncology but also to emphasize how much is missing.

In a study done by Prely et al (2022), four online drug interaction databases (Thériaque®, Drugs.com®, Hédrine, and Memorial Sloan Kettering Cancer Center (MSKCC) database) were evaluated to assess their accuracy. These databases contain previously published studies of drug interactions, detailing the interactions and their effects.  In studies evaluated from 2017 to 2019, at least one interaction was found for 267 patients: 263 with drug-drug interaction (DDI-where drugs interact with each other), 68 with HDI (where any herbal compounds interact with drugs), and 64 with both⁷.  Hédrine® identified 36 high-risk HDI, and 10 weak risk interactions⁷. For HDI, 83 pharmaceutical interventions (any changes made to drugs because of another agent) that were performed in 60 patients: 75 led to herb discontinuation, 3 to therapeutic monitoring, 3 to pharmaceutical advice and 1 to drug intake optimization (making changes to the dosage of the drug in order to get the most beneficial effect from it). This analysis suggests care is needed when mixing herbal products with prescription medications.  Patients should mention every supplement and herbal product being used to their prescriber so that the prescriber can understand the full picture.

Gougis et al. 2021 also brought emphasis to understanding HDI in their review paper. Table 1 summarizes the herbal products and studies they discuss along with the conclusions. Although the use of some herbal products such as grapefruit and St John’s Wort has been well known to affect cancer treatment, it is noteworthy that other interactions were found. This included the combination of curcumin+piperine which modified the active metabolite of tamoxifen (a commonly used breast cancer drug).

Herbal product	Anticancer Drug	Number of patients	Conclusion
cannabis	irinotecan	17	no significant modification of drug concentration
docetaxel	14	no significant modification of drug concentration
curcumin alone	tamoxifen	16	drug concentration decrease
curcumin+piperin	tamoxifen	16	drug concentration decreased by 12.4%
everolimus	1 (x2)	Concentration of drug decreased between 2 and 3 folds
echinacea	docetaxel	10	no significant modification of drug concentration
garlic	docetaxel	10	no significant modification of drug concentration
grapefruit	docetaxel	1	drug concentration increased by 2.6 fold
Oral etoposide	6	drug concentration decreased by 26%
ibrutinib	8	drug concentration of ibrutinib increased by 2.1 fold
sunitinib	8	drug concentration increased by 11%
imatinib	4	no significant modification for drug concentration
Milk thistle	irinotecan	6	no significant modification of drug concentration
St John’s wort	irinotecan	5	drug concentration decreased by 42%
docetaxel	10	drug concentration decreased by 11%
imatinib	10	drug concentration decreased by 32%
imatinib	12	drug concentration decreased by 30%
soy	tamoxifen	136 vs. 154controls	no significant modification of drug concentration

There is a need for more herbal drug interaction studies so that we can fully comprehend the interactions amongst them, which will also take us a step further in understanding any potential use as treatment for cancer patients. Limitations of current reviews/studies is the small sample sizes and the lack of diversity in the patients that were selected to undergo analysis.  Although there is more data appearing for non-Caucasian individuals, the majority of the clinical trials and studies still mostly have Caucasian patients that are participating in the study.  People with different ethnic backgrounds, age groups or comorbidities may have varying rates of metabolizing drugs and therefore need different therapies. 

Edited by Maha Said

References

1. Clement YN, Williams AF, Khan K, Bernard T, Bhola S, Fortuné M, et al. A gap between acceptance and knowledge of herbal remedies by physicians: the need for educational intervention. BMC Complement Altern Med. 2005 Nov 18;5:20. Pmid:16297236
2. Bahall M (2017) Prevalence, patterns, and perceived value of complementary and alternative medicine among cancer patients: a cross-sectional, descriptive study. BMC Complement Altern Med. https://doi.org/10.1186/s12906-017-1853-6
3. Berretta M, Pepa CD, Tralongo P et al (2016) Use of Complementary and Alternative Medicine (CAM) in cancer patients: an Italian multicenter survey. Oncotarget 8:24401–24414. https://doi.org/10.18632/oncotarget.14224
4. Laurent V, Justine S, Thierry M et al (2020) Anticancer agents and phytotherapy: interactions that are often unrecognized. J Oncol Pharm Pract. https://doi.org/10.1177/1078155220920363
5. Tuna S, Dizdar O, Calis M (2013) The prevalence of usage of herbal medicines among cancer patients. J BUON 18:1048–1051
6. Clairet A-L, Boiteux-Jurain M, Curtit E et al (2019) Interaction between phytotherapy and oral anticancer agents: prospective study and literature review. Med Oncol 36:45. https://doi.org/10.1007/s12032-019-1267-z
7. Prely, H., Herledan, C., Caffin, A. G., Baudouin, A., Larbre, V., Maire, M., … & Rioufol, C. (2022). Real-life drug–drug and herb–drug interactions in outpatients taking oral anticancer drugs: comparison with databases. Journal of Cancer Research and Clinical Oncology, 148(3), 707-718.
8. Gougis P, Hilmi M, Geraud A, Mir O, Funck-Brentano C. Potential cytochrome P450-mediated pharmacokinetic interactions between herbs, food, and dietary supplements and cancer treatments. Crit Rev Oncol Hematol. 2021;166:103342. oi:10.1016/j.critrevonc.2021.103342