Milk Thistle

Milk Thistle

Key Points

• Before using this therapy, consult your oncology team about interactions with other treatments and therapies. Also make sure this therapy is safe for use with any other medical conditions you may have.
• Milk thistle may be useful against liver cancer.
• CancerChoices interest in milk thistle derives from its protective effects, reducing chemotherapy kidney damage in rats and liver toxicity associated with chemotherapy in children with acute lymphoblastic leukemia.
• Silibinin, one of the flavonoids in milk thistle, has demonstrated antioxidant and anti-inflammatory effects.
• Silibinin promoted the growth of liver cancer when used with alcohol in an animal study.
• Milk thistle has shown a few side effects and interactions with prescription drugs.

The natural product milk thistle is available as a supplement. Silymarin, a standardized extract of milk thistle seeds, has shown beneficial effects against liver disease, including stimulating regeneration of liver tissue.1

Treating the Cancer

Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action

Clinical Evidence

Small studies have investigated effects of silymarin in individuals with prostate cancer, although study results are not yet available.2

Lab and Animal Evidence

Managing Side Effects and Promoting Wellness

Clinical Evidence

• Milk thistle may prevent or treat liver dysfunction in patients undergoing anticancer therapy.10 Silymarin has reduced liver toxicity associated with methotrexate (MTX) chemotherapy in children with acute lymphoblastic leukemia (ALL).11
• Silymarin decreased early doxorubicin-induced left ventricular systolic function disturbances. Study authors concluded that silymarin “can be recommended as adjuvant drug in patients with ALL under doxorubicin therapy.”12
• Silymarin delayed radiodermatitis development and progression in breast cancer patients13
• Silymarin delayed mucositis development and progression in patients with head and neck cancer.14

Lab and Animal Evidence

Reducing Risk

Reducing the risk of developing cancer or the risk of recurrence

Lab and Animal Evidence

Optimizing Your Terrain

Silibinin has demonstrated antioxidant and anti-inflammatory effects in preclinical studies.19

Cautions

Silibinin exerted marginal protective effects in early stages of liver cancer in mice. However, when administered with alcohol (ethanol), it exacerbated the effects of alcohol in promoting liver cancer, but only in males.20

Milk thistle has few side effects or interactions with prescription drugs, but the most commonly reported adverse effects are a mild laxative effect and gastrointestinal upset.21

Silymarin may increase the cytotoxicity of doxorubicin.22

Both silymarin and silibinin may interfere with intestinal glucuronidation of the drug raloxifene, increasing raloxifene exposure and risk for adverse events.23

Milk thistle was associated with a modestly increased incidence of mammary tumors in rats24 but not mice.25

Other cautions are noted on the Memorial Sloan Kettering Cancer Center’s About Herbs website. Medical supervision is recommended.

Access

Milk thistle supplements are widely available.

Dosing

CancerChoices does not recommend therapies or doses, but only provides information for patients and providers to consider as part of a complete treatment plan. Patients should discuss therapies with their physicians, as contraindications, interactions and side effects must be evaluated.

Levels of active ingredients of natural products can vary widely between and even within products. See Quality and Sources of Herbs, Supplements and Other Natural Products.

Dosage recommendations are available from these sources:

• Natural Medicines Database (requires purchase)
• Also see the protocols below.

Integrative Programs, Protocols and Medical Systems

• Programs and protocols
  • Alschuler & Gazella complementary approaches26
    • Liver cancer
    • Lung cancer
    • Prostate cancer
    • Skin cancer
  • Block program27
    • Natural molecular target modification (VEGF)
    • Remission maintenance program (detoxification)
  • Lemole, Mehta & McKee protocols28
    • Bladder cancer
    • Breast cancer
    • Leukemia
    • Prostate cancer
    • Renal cancer
    • Thyroid cancer
  • MacDonald breast cancer program29
  • McKinney protocols30
    • General cancer
    • Bladder cancer
    • Carcinoid/neuroendocrine cancer
    • Colorectal cancer
    • Kidney cancer
    • Liver/gallbladder cancer
    • Melanoma
    • Myelodysplastic syndrome
    • Pancreatic cancer
    • Skin cancer
    • Stomach cancer
    • Thyroid cancer
• Traditional systems
  • Ayurveda
  • Traditional Chinese medicine

Commentary

A physician was referred to CancerChoices with a question about the safety of using milk thistle with anastrozole (Arimidex), and about the impact of milk thistle/Sylbum on the estrogen receptor.

A response from CancerChoices advisor Jen Green, ND, FABNO, September 1, 2020: Milk thistle seed tea is safe to combine with Arimidex.

It also would be safe to combine milk thistle as a standardized extract in supplement form (typically 300-900mg is used daily to deal with elevated liver enzymes) because milk thistle does not appear to affect any CYP pathways. Milk thistle is a safe herb that supports liver cell regeneration. It is likely safe concurrent with chemotherapy:

• In a randomized controlled trial of children with cancer and liver toxicity, milk thistle was associated with a trend toward significant reductions in liver toxicity. It did not antagonize the effects of chemotherapy agents used.31
• In clinical studies, milk thistle did not cause significant pharmacokinetic interactions with midazolam, irinotecan, docetaxel and imatinib.32
• In healthy volunteers, milk thistle did not affect metabolism of CYP2D6 substrates,33 CYP1A2, CYP2D6, CYP2E1, or CYP3A4 substrates.34

As for the impact on estrogen receptors, that likely comes from this review: The natural agonist of estrogen receptor Œ≤ silibinin plays an immunosuppressive role representing a potential therapeutic tool in rheumatoid arthritis. A few thoughts….in petri dishes, concentrated extract of silybin (low levels in the whole herb) bind to estrogen beta receptors in the same way that soy, flax and other phytoestrogens bind to ERbeta receptors. The blocking of estrogen beta receptors by phytoestrogens is thought to make it harder for ERalpha to be bound by estradiol, which may account for the anti-estrogen effects of phytoestrogens in human studies evaluating breast tissue (ie. lower breast density).

That being said, milk thistle has never been historically considered an herb that impacts hormone balance, so I strongly suspect that it doesn’t have the ERbeta binding ability that many other herbs and foods do. The main action of milk thistle is to decrease inflammation (VEGF specifically), and support liver cell regeneration.

CancerChoices has not conducted an independent review of research of milk thistle. This summary draws from the Memorial Sloan Kettering Cancer Center’s About Herbs and CAM-Cancer Summaries websites plus other sources as noted.

Also known by these names

• Carduus marianum
• Holy thistle
• Lady’s thistle
• Mary thistle
• Marian thistle
• Silibinin
• Silybum marianum
• Silymarin

Helpful links

• Memorial Sloan Kettering Cancer Center About Herbs: Milk Thistle
• CAM-Cancer: Milk thistle (Silybum marianum)
• Chinese Herbs: Milk Thistle: Plant Description
• TRC Natural Medicines website (subscription required): in-depth information, ratings of effectiveness and safety and evaluation of specific milk thistle products
• Cheung CW, Gibbons N, Johnson DW, Nicol DL. Silibinin—a promising new treatment for cancer. Anticancer Agents in Medicinal Chemistry. 2010 Mar;10(3):186-95.
• BCCT, KNOW Oncology and Ottawa Integrative Cancer Centre: Patient Education Brochures
• Keith Block and others: A Broad-Spectrum Integrative Design for Cancer Prevention and Therapy
• Dwight McKee, MD, editor: Clinical Pearls
• National Cancer Institute at the National Institutes of Health: PDQ® Cancer Information Summaries
• Donald I. Abrams, MD, and Andrew T. Weil, MD: Integrative Oncology, 2nd Edition
• McKinney N. Naturopathic Oncology, Fourth Edition
• Lise Alschuler, ND, FABNO, and Karolyn Gazella: The Definitive Guide to Cancer, 3rd Edition
• Keith I. Block, MD: Life over Cancer: The Block Center Program for Integrative Cancer Treatment
• National Cancer Institute: Complementary and Alternative Medicine for Health Professionals
• National Cancer Institute: Office of Cancer Complementary and Alternative Medicine
• Therapeutic Research Center: Natural Medicines Database
• American Botanical Council: HerbMed
• Cancer Research UK

References

1. Federico A, Dallio M, Loguercio C. Molecules. Silymarin/silybin and chronic liver disease: a marriage of many years. 2017 Jan 24;22(2). pii: E191.
2. PDQ Integrative, Alternative, and Complementary Therapies Editorial Board.  Milk Thistle (PDQ®): Health Professional Version. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-2018 Aug 17.
3. PDQ Integrative, Alternative, and Complementary Therapies Editorial Board.  Milk Thistle (PDQ®): Health Professional Version. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-2018 Aug 17.
4. Ting H, Deep G, Agarwal R. Molecular mechanisms of silibinin-mediated cancer chemoprevention with major emphasis on prostate cancer. AAPS J. 2013 Jul;15(3):707-16.
5. Ting H, Deep G et al. Beneficial effects of the naturally occurring flavonoid silibinin on the prostate cancer microenvironment: role of monocyte chemotactic protein-1 and immune cell recruitment. Carcinogenesis. 2016 Jun;37(6):589-599.
6. Deep G, Kumar R et al. Silibinin inhibits hypoxia-induced HIF-1α-mediated signaling, angiogenesis and lipogenesis in prostate cancer cells: In vitro evidence and in vivo functional imaging and metabolomics. Molecular Carcinogenesis. 2017 Mar;56(3):833-848.
7. Deep G, Gangar SC et al. Angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer: targeting VEGF-VEGFR signaling. PLoS One. 2012;7(4):e34630.
8. PDQ Integrative, Alternative, and Complementary Therapies Editorial Board. Milk Thistle (PDQ®): Health Professional Version. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); August 17, 2018.
9. Derry MM, Raina K, Agarwal C, Agarwal R. Identifying molecular targets of lifestyle modifications in colon cancer prevention. Frontiers in Oncology. 2013 May 14;3:119.
10. Ladas EJ, Kelly KM. Milk thistle: is there a role for its use as an adjunct therapy in patients with cancer? Journal of Alternative and Complementary Medicine. 2003 Jun;9(3):411-6.
11. Hagag AA, Elgamsy MA, El-Asy HM, Mabrouk MM. Protective role of silymarin on hepatic and renal toxicity induced by MTX based chemotherapy in children with acute lymphoblastic leukemia. Mediterranean Journal of Hematology and Infectious Diseases. 2016 Sep 1;8(1):e2016043.
12. Hagag AA, El Shehaby WA, El-Abasy AI, Mabrouk MM. Protective role of silymarin in early doxorubicin induced cardiac dysfunction in children with acute lymphoblastic leukemia. Infectious Disorders Drug Targets. 2018 Aug 3.
13. Karbasforooshan H, Hosseini S, Elyasi S, Fani Pakdel A, Karimi G. Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2018 Nov 27.
14. Elyasi S, Hosseini S, Niazi Moghadam MR, Aledavood SA, Karimi G. Effect of oral silymarin administration on prevention of radiotherapy induced mucositis: a randomized, double-blinded, placebo-controlled clinical trial. Phytotherapy Research. 2016 Nov;30(11):1879-1885.
15. PDQ Integrative, Alternative, and Complementary Therapies Editorial Board.  Milk Thistle (PDQ®): Health Professional Version. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-2018 Aug 17.
16. Rašković A, Stilinović N et al. The protective effects of silymarin against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats. Molecules. 2011 Oct 12;16(10):8601-13.
17. Post-White J, Ladas EJ, Kelly KM. Advances in the use of milk thistle (Silybum marianum). Integrative Cancer Therapies. 2007 Jun;6(2):104-9.
18. Ting H, Deep G, Agarwal R. Molecular mechanisms of silibinin-mediated cancer chemoprevention with major emphasis on prostate cancer. AAPS Journal. 2013 Jul;15(3):707-16.
19. Jahanafrooz Z, Motamed N, Rinner B, Mokhtarzadeh A, Baradaran B. Silibinin to improve cancer therapeutic, as an apoptotic inducer, autophagy modulator, cell cycle inhibitor, and microRNAs regulator. Life Sci. 2018 Nov 15;213:236-247; Derry MM, Raina K, Agarwal C, Agarwal R. Identifying molecular targets of lifestyle modifications in colon cancer prevention. Frontiers in Oncology. 2013 May 14;3:119.
20. Brandon-Warner E, Eheim AL et al. Silibinin (milk thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice. Cancer Letters. 2012 Dec 29;326(1):88-95.
21. PDQ Integrative, Alternative, and Complementary Therapies Editorial Board.  Milk Thistle (PDQ®): Health Professional Version. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-2018 Aug 17.
22. PDQ Integrative, Alternative, and Complementary Therapies Editorial Board.  Milk Thistle (PDQ®): Health Professional Version. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-2018 Aug 17.
23. Gufford BT, Chen G et al. Milk thistle constituents inhibit raloxifene intestinal glucuronidation: a potential clinically relevant natural product-drug interaction. Drug Metabolism and Disposition. 2015 Sep;43(9):1353-9.
24. Malewicz B, Wang Z et al. Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements. Carcinogenesis. 2006 Sep;27(9):1739-47.
25. Verschoyle RD, Brown K, Steward WP, Gescher AJ. Consumption of silibinin, a flavonolignan from milk thistle, and mammary cancer development in the C3(1) SV40 T,t antigen transgenic multiple mammary adenocarcinoma (TAg) mouse. Cancer Chemotherapy and Pharmacology. 2008 Jul;62(2):369-72.
26. Alschuler LN, Gazella KA. The Definitive Guide to Cancer, 3rd Edition: An Integrative Approach to Prevention, Treatment, and Healing. Berkeley, California: Celestial Arts. 2010; Alschuler LN, Gazella KA. The Definitive Guide to Thriving after Cancer: A Five-Step Integrative Plan to Reduce the Risk of Recurrence and Build Lifelong Health. Berkeley, California: Ten Speed Press. 2013.
27. Block KI. Life over Cancer: The Block Center Program for Integrative Cancer Treatment. New York: Bantam Dell. 2009.
28. Lemole G, Mehta P, McKee D. After Cancer Care: The Definitive Self-Care Guide to Getting and Staying Well for Patients with Cancer. New York, New York: Rodale, Inc. 2015.
29. MacDonald B. The Breast Cancer Companion: A Complementary Care Manual: Third Edition. 2016.
30. McKinney N. Naturopathic Oncology, Fourth Edition. Victoria, BC, Canada: Liaison Press. 2020.
31. Ladas EJ, Kroll DJ et al. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Cancer. 2009 Dec 14;116(2):506-513.
32. Goey AK, Mooiman KD, Beijnen JH, Schellens JH, Meijerman I. Relevance of in vitro and clinical data for predicting CYP3A4-mediated herb-drug interactions in cancer patients. Cancer Treatment Reviews. 2013 Nov;39(7):773-83.
33. Gurley BJ, Swain A et al. Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John’s wort, and echinacea. Molecular Nutrition & Food Research. 2008 Jul;52(7):755-63.
34. Gurley BJ, Gardner SF et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clinical Pharmacology & Therapeutics. 2004 Nov;76(5):428-40.