Key Interactions Between Anastrozole and Herbal Supplements

Understanding Anastrozole Interactions with Herbal Supplements: A Guide for Safe Usage

Disclaimer: This article is for educational purposes only and does not constitute medical advice. Always consult your oncologist or a licensed medical professional before introducing any supplement into your regimen.

Anastrozole (brand name Arimidex) is a non-steroidal aromatase inhibitor used as adjuvant treatment in post-menopausal women with oestrogen-receptor positive (ER+) breast cancer. It reduces oestrogen biosynthesis by inhibiting the aromatase enzyme that converts androgens to oestrogens, thereby limiting stimulation of ER-dependent tumour growth.

Metabolic Pathway: Anastrozole is metabolised primarily in the liver by cytochrome-P450 (CYP) enzymes. CYP3A4 is the major metabolic pathway, with contributions from CYP2B6, CYP2D6, CYP2C8 and UGT1A4. Supplements that induce or inhibit CYP3A4, or act on P-glycoprotein (P-gp), may alter the drug's plasma concentration. Any product with oestrogenic activity could also counteract anastrozole's core mechanism.

Overview of Herbal-Drug Interactions

Types of Interactions

1. Phytoestrogenic herbs: These may increase circulating oestrogens. Examples: red clover, soy isoflavones, flaxseed, dong quai, ginseng, licorice, kudzu and maca.
2. CYP450 modulators: Herbs that induce CYP3A4 (St. John's Wort) decrease drug levels; inhibitors (grapefruit juice, ginseng, echinacea) may increase toxicity.
3. P-glycoprotein (P-gp) modulators: P-gp is an efflux transporter that influences oral drug absorption. St. John's Wort induces P-gp, which can significantly reduce drug bioavailability.
4. Herbs increasing bleeding risk: Some herbs have antiplatelet or anticoagulant properties. Combined with anastrozole, these may increase the risk of bruising or haemorrhage — examples include high-dose turmeric, ginseng, ginkgo biloba, garlic, and ginger.
5. Hepatotoxicity: Since anastrozole is metabolised in the liver, hepatotoxic herbs (e.g., high-dose green tea extract, kava) may compound hepatic stress. The Oncology Nursing Society specifically notes that green tea extract may increase anastrozole hepatotoxicity.

Evidence for Specific Herbs and Supplements

1. St. John's Wort (Hypericum perforatum)

St. John's Wort is a popular herbal antidepressant. It strongly induces CYP3A4 and P-gp, leading to reduced plasma levels of many drugs. It may similarly reduce anastrozole concentration, lowering its clinical efficacy. Because enzyme induction persists for weeks after discontinuation, most guidelines recommend waiting at least 14 days after stopping St. John's Wort before starting anastrozole. Do not use without oncologist approval.

2. Ginseng (Panax ginseng and other species)

Ginseng is used for energy but poses multiple concerns in hormone-sensitive cancers. Panax ginseng contains ginsenosides that exhibit weak oestrogenic activity; studies suggest they may stimulate ER-positive tumour cells. Ginseng also inhibits or induces CYP3A4 and CYP2C9, and its antiplatelet activity adds further risk when combined with anticoagulants. Patients on anastrozole should avoid ginseng products.

3. Red Clover, Soy Isoflavones, Flaxseed and Other Phytoestrogens

Red clover (Trifolium pratense) and soy contain isoflavones (genistein, daidzein) that act as selective oestrogen receptor modulators. High doses of soy isoflavones can stimulate ER-positive breast cancer cells, potentially counteracting the therapeutic goal of anastrozole. A wide range of supplements — including flaxseed, guggul, kudzu, licorice, maca, and red raspberry leaf — contain plant oestrogens that should be avoided during aromatase inhibitor therapy.

4. Black Cohosh (Actaea racemosa)

Black cohosh is frequently used for menopausal symptoms, but case reports of hepatotoxicity and concerns over CYP450 activity modulation make it a risk. While its oestrogenic activity is debated, it is listed among herbs that can alter drug metabolism and increase bleeding risk when combined with anticoagulants. Most clinical handouts advise avoiding black cohosh during anastrozole therapy.

5. Dong Quai (Angelica sinensis)

Used in traditional Chinese medicine, Dong Quai contains coumarins and ferulic acid with potential oestrogenic effects. It is also known to potentiate anticoagulants, significantly increasing bleeding risk. Because it may stimulate oestrogen receptors, it is best avoided for patients with ER+ cancer.

6. Ginkgo Biloba

Promoted for cognitive health, Ginkgo is a weak CYP3A4 inhibitor and can also inhibit CYP2C9. Combined with anastrozole, it could increase drug concentrations or exacerbate bleeding risk. Given the lack of proven benefit for cancer patients, its use is generally discouraged.

7. Licorice (Glycyrrhiza species)

Licorice contains glycyrrhizin, which possesses weak oestrogenic activity. It may also raise blood pressure and cause hypokalaemia. Due to these phytoestrogenic effects, licorice supplements (including DGL) should be avoided by patients on anastrozole.

8. Milk Thistle (Silybum marianum)

Silymarin, the active complex in milk thistle, can inhibit CYP3A4 and other hepatic enzymes. While clinical data are limited, some evidence suggests it can alter the pharmacokinetics of drugs metabolised by the liver. Milk thistle seeds may also contain phytoestrogens, leading many clinicians to recommend abstaining from high-dose supplements during anastrozole therapy.

9. Turmeric / Curcumin (Curcuma longa)

Curcumin has anti-inflammatory properties but also exhibits significant antiplatelet activity. High-dose curcumin supplements should not be taken with anastrozole because they may increase bleeding risk and potentially lead to gallbladder obstruction. Culinary use of turmeric in cooking is generally considered safe at normal food amounts.

10. Valerian (Valeriana officinalis) and Other Sedatives

Valerian is commonly used for insomnia but may inhibit CYP3A4 and enhance the sedative effects of other medications. Other sedative herbs, like kava, have been linked to severe hepatotoxicity. Unless supervised by a healthcare provider, these should be avoided during endocrine therapy to prevent metabolic interference.

11. Green Tea (Camellia sinensis)

Brewed tea is generally safe. However, concentrated green tea extracts (EGCG) can induce or inhibit CYP enzymes and are associated with liver stress. The Oncology Nursing Society warns that green tea extract may increase the hepatotoxicity of anastrozole. Weight-loss products containing high doses of green tea extract are a particular concern.

12. Garlic, Ginger and Other Bleeding-Risk Herbs

In concentrated supplement form, these culinary herbs possess antiplatelet properties and may inhibit CYP enzymes. High doses of garlic, ginseng, ginkgo, and ginger can exacerbate bleeding or bruising when combined with aromatase inhibitors. At normal culinary doses in cooking, they are safe.

Supplements Generally Considered Safe During Anastrozole Therapy

Always confirm doses with your oncologist — but the following are frequently recommended or considered low-risk alongside anastrozole:

Other Vitamins and Dietary Supplements

While standard multivitamins are generally safe, avoid supplements containing phytoestrogens such as red clover, wild yam and soy isoflavones — they might oppose the drug's oestrogen-lowering effect. High-dose antioxidants or "bioidentical hormone" products should also be avoided unless specifically recommended by a clinician.

Practical Guidance for Patients

1. Tell your healthcare team about everything you take: Include herbal teas, multivitamins, and supplements from health food stores — not just prescription medications.
2. Avoid high-dose phytoestrogenic herbs: Concentrated extracts of red clover, soy, flaxseed oil, and maca can counteract the oestrogen-lowering effect of anastrozole.
3. Beware of CYP3A4 and P-gp modulators: Avoid St. John's Wort, ginseng, and grapefruit juice to prevent altered drug concentrations.
4. Limit herbs that increase bleeding or hepatotoxicity: Turmeric, ginger, and garlic supplements at high doses increase bleeding risk; kava can cause liver injury.
5. Use reputable resources: Consult evidence-based databases such as the Memorial Sloan Kettering About Herbs database for specific ingredient queries.

Conclusion: Navigating Anastrozole–Herbal Interactions

Anastrozole is a cornerstone of endocrine therapy, but its efficacy relies on maintaining specific CYP3A4 metabolic pathways and low oestrogen levels. Herbal supplements with oestrogenic activity or those that modulate drug-metabolising enzymes can interfere with safety and treatment success. Following the precautionary principle, avoid high-dose herbal supplements during therapy unless supervised by an oncologist.

Bibliography

Rutherford DV, et al. Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226. Pharmacogenomics. 2023;24(12):665–673. PMC.

Hartmann KE, et al. Precautions for Patients Taking Aromatase Inhibitors. Journal of Advanced Practitioner in Oncology. 2023.

National Health Service (NHS). Taking anastrozole with other medicines. Updated 2024. NHS.uk.

Oncology Nursing Society. Herb–drug interactions: guidance for oncology nurses. October 2024. ONS Voice.

Siegel RL, et al. Are Your Patients Taking Herbs That May Interact With Their Cancer Drugs? Oncology Nursing Society. 2017.

Jameson JL, et al. Oral antineoplastic agent interactions with medicinal plants and food. Journal of Cancer Research & Clinical Oncology. 2016.

Massachusetts General Hospital Cancer Center. Aromatase Inhibitors patient teaching handout. March 2024.

CancerChoices (Healwell). Turmeric and curcumin safety. Updated 2025.

Medical News Today. Interactions and contraindications for Arimidex. April 2025.