The use of dietary supplements by patients with cancer has increased significantly over the past 2 decades despite insufficient evidence of safety and effectiveness. Finding reliable sources of information about dietary supplements can be daunting. Patients typically rely on family, friends, and the Internet, often receiving misleading information.
The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on integrative and complementary therapies commonly used by patients with cancer. We chose milk thistle for this issue because of its growing popularity among cancer patients.
Compiled by Barrie R. Cassileth, PhD, and Jyothi Gubili, MS, Memorial Sloan Kettering Cancer Center. The free About Herbs website is managed by K. Simon Yeung, PharmD, MBA, LAc, Memorial Sloan Kettering Cancer Center.
Milk Thistle
Scientific names: Silybum marianum, Carduus marianum
Common names: Holy thistle, lady’s thistle, Mary thistle, Marian thistle
Overview
Milk thistle is a flowering herb native to the Mediterranean regions of Europe, Africa, and the Middle East. It also grows in many other warm climates of the world. Because it produces bright purple colored flowers, it is considered an ornamental plant.
Despite that designation, the medicinal history of milk thistle dates back more than 2,000 years. It was used as a remedy for disorders of the liver, biliary tract, and kidney. The leaves, stalks, and flowering heads of the plant were consumed as food. Today, milk thistle supplements are commonly used in many European countries to help manage liver diseases.
Silymarin, the biologically active mixture of flavonoids isolated from milk thistle seeds, has been the focus of research over recent decades. Data from clinical trials show that silymarin is useful for the treatment of alcohol-induced liver disease and for reducing liver toxicity associated with chemotherapy. Silymarin was also found to be an effective antidote to Amanita phalloides, the deathcap mushroom, which is known to cause serious liver damage.
Milk thistle is available in the form of capsules, liquid extracts, and tinctures. The products are often standardized to contain 70% to 80%
silymarin.
The Science
Preclinical studies indicate that flavonoids in milk thistle have antioxidant and anticancer effects1,2 and may protect against Alzheimer’s disease.3
Data from randomized clinical trials show that silymarin can reduce aminotransferases in alcoholic liver disease,4 and conclusions from a systematic review suggest that it helps treat liver cirrhosis.5 Silibinin, a constituent of silymarin, reduced liver toxicity associated with chemotherapy in children with acute lymphoblastic leukemia.6
A case study indicates the utility of intravenous silibinin in patients co-infected with human immunodeficiency virus and hepatitis C virus.7 However, studies in other types of hepatic disease are flawed.8,9
One of the mechanisms underlying the hepatoprotective effects of silymarin is via downregulation of extracellular matrix proteins such as collagen.10
Silymarin supplementation may also play a role in improving the glycemic profile in patients with type 2 diabetes.11
In a recent study, silymarin demonstrated estrogenic activity with mild proliferative effects in rat uteri.12 Human studies are warranted.
Adverse Effects
Intermittent episodes of sweating, nausea, vomiting, diarrhea, abdominal pain, weakness, and collapse were reported following use of milk thistle.13
A 25-year-old man developed a severe case of epistaxis, believed to have been due to self-medication with aspirin, garlic, and milk thistle.14
At high doses, silibinin can elevate bilirubin and liver enzymes.15
Herb-Drug Interactions
Cytochrome P450 3A4 substrates: Milk thistle inhibits cytochrome P450 and can affect the intracellular concentration of drugs metabolized by this enzyme.16 However, conflicting data indicate no such effects.17-19
UGT (Uridine 5´-diphospho-glucuronosyltransferase) substrates: Milk thistle modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them.20 n
Disclosure: Ms. Gubili reported no potential conflicts of interest.
References
1. Ramasamy K, Agarwal R: Multitargeted therapy of cancer by silymarin. Cancer Lett 269:352-362, 2008.
2. Verschoyle RD, Greaves P, Patel K, et al: Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse models of prostate and intestinal carcinogenesis: Relationship with silibinin levels. Eur J Cancer 44:898-906, 2008.
3. Yin F, Liu J, Ji X, et al: Silibinin: A novel inhibitor of Aâ aggregation. Neurochem Int 58:399-403, 2011.
4. Fehér J, Deák G, Müzes G, et al: Liver-protective action of silymarin therapy in chronic alcoholic liver diseases. Orv Hetil 130:2723-2727, 1989.
5. Saller R, Brignoli R, Melzer J, et al: An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch Komplementmed 15:9-20, 2008.
6. Ladas EJ, Kroll DJ, Oberlies NH, et al: A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Cancer 116:506-513, 2010.
7. Payer BA, Reiberger T, Rutter K, et al: Successful HCV eradication and inhibition of HIV replication by intravenous silibinin in an HIV-HCV coinfected patient. J Clin Virol 49:131-133, 2010.
8. Salmi HA, Sama S: Effect of silymarin on chemical, functional, and morphological alterations of the liver: A double blind study. Scand J Gastroenterol 17:517-521, 1982.
9. Ferenci P, Dragosics B, Dittrich H, et al: Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1:105-113, 1989.
10. Chen IS, Chen YC, Chou CH, et al: Hepatoprotection of silymarin against thioacetamide-induced chronic liver fibrosis. J Sci Food Agric 92:1441-1447, 2012.
11. Huseini HF, Larijani B, Heshmat R, et al: The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: A randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 20:1036-1039, 2006.
12. El-Shitany NA, Hegazy S, El-Desoky K: Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats. Phytomedicine 17:116-125, 2010.
13. Adverse Drug Reactions Advisory Committee: An adverse reaction to the herbal medication milk thistle (Silybum marianum). Med J Aust 170:218-219, 1999.
14. Shakeel M, Trinidade A, McCluney N, et al: Complementary and alternative medicine in epistaxis: A point worth considering during the patient’s history. Eur J Emerg Med 17:17-19, 2010.
15. Flaig TW, Gustafson DL, Su LJ, et al: A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs 25:139-146, 2007.
16. Venkataramanan R, Ramachandran V, Komoroski BJ, et al: Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucoronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 28:1270-1273, 2000.
17. Gurley B, Hubbard MA, Williams KD, et al: Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: Comparison of a milk thistle and black cohosh product to rifampin and clarithromycin. J Clin Pharmacol 46:201-213, 2006.
18. Fuhr U, Beckmann-Knopp S, Jetter A, et al: The effect of silymarin on oral nifedipine pharmacokinetics. Planta Med 73:1429-1435, 2007.
19. Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al: The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos 42:1611-1616, 2014.
20. Mohamed ME, Frye RF: Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med 77:311-321, 2011.
Integrative Oncology is guest edited by Barrie R. Cassileth, MS, PhD, Chief of the Integrative Medicine Service and Laurance S. Rockefeller Chair in Integrative Medicine at Memorial Sloan Kettering Cancer Center, New York.
The Integrative Medicine Service at Memorial Sloan Kettering Cancer Center developed and maintains a free website—About Herbs (www.mskcc.org/aboutherbs)—that provides objective and unbiased information about herbs, vitamins, minerals, and other dietary supplements, and unproved anticancer treatments. Each of the close to 300 and growing number of entries offer health-care professional and patient versions, and entries are regularly updated with the latest research findings.
In addition, the About Herbs app, Memorial Sloan Kettering Cancer Center’s very first mobile application, can be downloaded at http://itunes.apple.com/us/app/about-herbs/id554267162?mt=8. The app is compatible with iPad, iPhone, and iPod Touch devices.
