Written by Julia Green, Alexander Kalisch and the CAM-Cancer Consortium.
Updated January 29, 2015

Milk thistle (Silybum marianum)

Is it safe?

Adverse events

Orally milk thistle is usually well-tolerated 2,3,30. The rate of adverse events of milk thistle was low in clinical trials and in one randomized controlled trial equal to the placebo group 9-11,31-36. Described adverse effects were difficult to distinguish from symptoms of the underlying condition. In rare cases there were complaints of intestinal symptoms, headache and dizziness 2,10,31,33. In a phase I trial in which high doses of silybin phytosome (up to 20g) were given mild transient elevation of bilirubin, and the liver enzymes aspartate transaminase and alanine transaminase (AST and ALT) were reported 36. One participant receiving high dose silybin phytosome who subsequently had surgery developed a thrombo-embolism: this could have been due to the surgery 10.

Contraindications

Milk thistle has been assessed as likely safe when used orally and appropriately 2. There is insufficient information to assess safety in pregnancy and lactation 2.

Interactions

Milk thistle extract might work as an inhibitor of CYP2C9 2,6,36. There is contradictory evidence about the effect of milk thistle on CYP3A4 2,29,35. A phase II clinical trial of 600mg silymarin in cancer patients found no in vivo effect on irinotecan, CYP34A or UGT1A1 pharmacokinetics 35.

Warnings

In an animal experiment and in an experiment with an oestrogen responsive breast cancer cell line (MCF-7) a tumour growth was seen when adding silymarin 3. This raises the theoretical risk silymarin could have an oestrogen-like action in women with oestrogen-responsive breast cancer. However the more commonly used milk thistle seed extracts are not known to have oestrogenic effects in vivo 2 ,8. Cautions have been recommended in patients with a known hypersensitivity to plants in the Asteraceae family 2,8,12.

Citation Julia Green, Alexander Kalisch, CAM-Cancer Consortium. Milk thistle (Silybum marianum) [online document]. http://ws.cam-cancer.org/The-Summaries/Herbal-products/Milk-thistle-Silybum-marianum. January 29, 2015.

References

  1. USDA dARS, National Genetic Resources Program. Germplasm Resources Information Network (GRIN) [Online Database]. 2012. National Germplasm Resources Laboratory, Beltsville, Maryland. Available at: http://www.ars-grin.gov/cgi-bin/npgs/html/index.pl [Accessed 7th November 2012].
  2. Natural Medicines Comprehensive Database: professional version. Milk Thistle monograph. Stockton (CA): Therapeutic Research Faculty. 2012. Available at: http://naturaldatabase.therapeuticresearch.com. [Accessed 12th November 2012].
  3. Cheung CW, Gibbons N, Johnson DW, Nicol DL. Silibinin-a promising new treatment for cancer. Anticancer Agents Med Chem. 2010;10:186-95.
  4. Kroll DJ, Shaw HS, Oberlies NH. Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integrative cancer therapies 2007;6(2):110-119.
  5. Loguercio C, Festi D. Silybin and the liver: from basic research to clinical practice. World J Gastroenterol. 2011;17:2288-301.
  6. Brantley SJ, Oberlies NH, Kroll DJ, Paine MF. Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations. J Pharmacol Exp Ther. 2010;332:1081-87.
  7. Wichtl M. Cardui mariae fructus in: Herbal drugs and phytopharmaceuticals. Medpharm Scientific Publishers; 2004.
  8. Braun L, Cohen M. Herbs & natural supplements: an evidence-based guide. 3rd ed: Churchill Livingstone; 2010.
  9. European Scientific Cooperative on Phytotherapy. ESCOP MONOGRAPHS The Scientific Foundation for Herbal Medicinal Products. 2nd edition supplement. Thieme, 2009: 222-248.
  10. Flaig TW, Glode M, Gustafson D, van BA, Tao Y, Wilson S et al. A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer. Prostate. 2010;70:848-55.
  11. Hoh C, Boocock D, Marczylo T, Singh R, Berry DP, Dennison AR et al. Pilot study of oral silibinin, a putative chemopreventive agent, in colorectal cancer patients: silibinin levels in plasma, colorectum, and liver and their pharmacodynamic consequences. Clin Cancer Res. 2006;12:2944-50.
  12. Mills S, Bone K. Principles and practice of phytotherapy. Modern herbal medicine. : Churchill Livingstone; 2000.
  13. Phytopharmaka II - Forschung klinische Anwendung. Darmstadt: Stinkopff; 1996
  14. Greenlee H, Abascal K, Yarnell E, Ladas E. Clinical applications of Silybum marianum in oncology. Integrative cancer therapies 2007;6(2):158-165.
  15. Post-White J, Ladas EJ, Kelly KM. Advances in the use of milk thistle (Silybum marianum). Integrative cancer therapies 2007;6(2):104-109.
  16. Deep G, Agarwal R. Antimetastatic efficacy of silibinin: molecular mechanisms and therapeutic potential against cancer. Cancer Metastasis Rev 2010;29(3):447-463.
  17. Saller R, Melzer J, Reichling J, Brignoli R, Meier R. An updated systematic review of the pharmacology of silymarin. Forschende Komplementärmedizin/Research in Complementary Medicine 2007;14(2):70-80.
  18. Olaku O, White JD. Herbal therapy use by cancer patients: A literature review on case reports. Eur J Cancer 2011 3;47(4):508-514.
  19. McBride A, Augustin KM, Nobbe J, Westervelt P. Silybum marianum (milk thistle) in the management and prevention of hepatotoxicity in a patient undergoing reinduction therapy for acute myelogenous leukemia. Journal of Oncology Pharmacy Practice 2012;18(3):360-365.
  20. Deep G, Agarwal R. Chemopreventive efficacy of silymarin in skin and prostate cancer. Integr Cancer Ther. 2007;6:130-145.
  21. Colombo V, Lupi M, Falcetta F, Forestieri D, D’Incalci M, Ubezio P. Chemotherapeutic activity of silymarin combined with doxorubicin or paclitaxel in sensitive and multidrug-resistant colon cancer cells. Cancer Chemother Pharmacol 2011;67(2):369-379.
  22. Scambia G, De Vincenzo R, Ranelletti P, Benedetti Panici P, Ferrandina G, D'Agostino G, et al. Antiproliferative effect of silybin on gynaecological malignancies: Synergism with cisplatin and doxorubicin. Eur J Cancer 1996;32(5):877-882.
  23. Bright-Gbebry M, Makambi K, Rohan J, Llanos A, Rosenberg L, Palmer J, et al. Use of multivitamins, folic acid and herbal supplements among breast cancer survivors: the black women's health study. BMC Complementary and Alternative Medicine 2011;11(1):30
  24. Damery S, Gratus C, Grieve R, Warmington S, Jones J, Routledge P, et al. The use of herbal medicines by people with cancer: a cross-sectional survey. Br J Cancer 2011;104(6):927-933
  25. Werneke U, Earl J, Seydel C, Horn O, Crichton P, Fannon D. Potential health risks of complementary alternative medicines in cancer patients. Br J Cancer 2004;90(2):408-413.
  26. MHRA. Traditional Herbal Medicines Registration Scheme: Guidance for Retailers, Wholesalers, Importers and Manufacturers on the Requirements of the THMRS. 2007 Available from: <http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con2030651.pdf> [Accessed 29 October 2012]
  27. Blumenthal M, Goldberg A, Brinckmann J. Herbal Medicine. Expanded Commission E monographs. : Integrative Medicine Communications; 2000.
  28. European Medicines Agency. Community monographs: call for evidence 22/3/2010. Available at: http://www.ema.europa.eu/ [Accessed 13th November 2012]
  29. Rambaldi A, Jacobs BP, Iaquinto G, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C liver diseases--a systematic cochrane hepato-biliary group review with meta-analyses of randomized clinical trials. Am J Gastroenterol. 2005;100:2583-91.
  30. Tamayo C, Diamond S. Review of Clinical Trials Evaluating Safety and Efficacy of Milk Thistle (Silybum marianum [L.] Gaertn.). Integrative Cancer Therapies 2007 June 01;6(2):146-157
  31. Ladas EJ, Kroll DJ, Oberlies NH, Cheng B, Ndao DH, Rheingold SR et al. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Cancer. 2010;116:506-13.'Schröder FH, Roobol MJ, Boevé ER, de Mutsert R, Zuijdgeest-van Leeuwen SD, Kersten I, et al. Randomized, Double-Blind, Placebo-Controlled Crossover Study in Men with Prostate Cancer and Rising PSA: Effectiveness of a Dietary Supplement. Eur Urol 2005 12;48(6):922-931.
  32. Vidlar A, Vostalova J, Ulrichova J, Student V, Krajicek M, Vrbkova J, et al. The safety and efficacy of a silymarin and selenium combination in men after radical prostatectomy–a six month placebo-controlled double-blind clinical trial. Biomedical Papers 2010;154(3):239-244.
  33. Becker-Scheibe, M., Mengs, M., Schaefer, M., Bulitta, M/ and Hoffman, W. Topical use of a silymarin-based preparation to prevent radiodermatitis: results of a prospective study in breast cancer patients. Strahlentherapie und Onkologie. 2011;187(8):485-491
  34. van Erp NPH, Baker SD, Zhao M, Rudek MA, Guchelaar HJ, Nortier JWR, et al. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clinical cancer research 2005;11(21):7800-7806.
  35. Han Y, Guo D, Chen Y, Chen Y, Tan ZR, Zhou HH. Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers. Eur J Clin Pharmacol. 2009;65:585-91.
  36. Flaig TW, Gustafson DL, Su LJ, Zirrolli JA, Crighton F, Harrison GS et al. A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs. 2007;25:139-46.