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

Milk thistle (Silybum marianum)

What is it?

Description

Milk thistle (Silybum marianum (L.) Gaertn.) synonym Carduus Marianus L. is a herbaceous plant belonging to the carduae tribe of the Asteraceae (daisy) family. The seeds are the part used 1.

Names

Milk thistle has many common names including lady’s thistle, St Mary’s thistle, holy thistle, and variegated artichoke 1,2. Examples of available products containing silymarin include Legalon SIL® and Thisilyn™: dried seed extracts standardized to 80% silymarin content. Siliphos™ and Silipide™ are silymarin extracts complexed with lipids. Leviaderm™ is a cream, containing silymarin amongst other herbal ingredients 2.

Ingredients / Components

The main effects of milk thistle are thought to stem from the flavonolignans combined with other ingredients 2,3. A crude extract of dried seeds of milk thistle contains 65 – 80% of a flavonolignan complex termed silymarin 4. Silymarin itself is a complex of at least seven flavonolignans (silybin A and B, isosilybin A and B, silychristin, isosilychristin and silydianin) and the flavonoid taxifolin. Silybin A and B, isosilybin A and B are isomers. Silybin, synonymous with silibin and silybinin, is the processed form of silymarin and contains the isomers silybin A and B in equal amounts. Silybin is considered the main active ingredient of the milk thistle 4,5,6. The seeds also contain fatty acids such as linoleic acid.

Application and dosage

Milk thistle is taken orally as tablets, tea or tincture 2,7. It may also be applied topically as cream. Injectable preparations have been used in research studies and are available in German speaking countries (Legalon SIL®). Various oral dosages have been used, generally relating to use for hepatoprotection, in the range 12-15g milk thistle 2,8 containing 200 - 600 mg silymarin/ day in divided doses. Silymarin is only poorly water-soluble: bio-availability has been increased by lipid formulation of silybinin in oral form such as silybinin phosphatidylcholine (Siliphos™ and Silipide™). In a phase II study the daily dosage of Siliphos™ was 13g silybinin divided up into 3 doses. These high dosages are used for achieving high plasma levels 3,9. Silybinin and silymarin have a short half-life (1.8 – 5 hours) after ingestion. The major part of orally taken silybinin is found as glucuronosised and sulfatated metabolites in blood following hepatic metabolism 10. It is not clear whether these metabolites also have anti-carcinogenic properties 3.

History and providers

Milk thistle originates from North Africa, Asia Minor and southern Europe. It is now widely naturalized across Europe, Africa, the Americas and Australasia, as a weed and cultivated plant 1. Milk thistle is so called because of the white markings (variegation) on the leaves, which have been consumed as a vegetable. Roasted seeds have been used as a coffee substitute 2. The mature untreated seeds of milk thistle have been used for 2000 years in traditional medicine to treat melancholy, headache, digestive and liver complaints, detoxification and promote lactation 2,7,8,11. In the 1960s the ingredients of milk thistle were investigated. The mixture found was named silymarin 4,12. Research concentrated primarily on the use of milk thistle in the treatment of liver disorders and protection from liver injury 2,5. In the 1990s reports based on pre-clinical models suggested preventative, and therapeutic, potential in cancer warranted further research 4,13-15.

Claims of efficacy/ alleged indications

The main claim made for milk thistle is that it protects the liver 2,8. Milk thistle fruits have a positive European Scientific Cooperative on Phytotherapy (ESCOP) monograph for the following therapeutic indications: toxic liver damage; supportive treatment in patients with chronic inflammatory liver conditions and hepatic cirrhosis 9. Orally, milk thistle is used for liver disorders including toxic liver damage caused by chemicals, Amanita phalloides mushroom poisoning, jaundice, chronic inflammatory liver disease, hepatic cirrhosis, chronic hepatitis, gallbladder complaints, hangover and indigestion 2,8,12. It has also been used in prostate cancer, pleurisy, malaria, depression, uterine complaints, allergic rhinitis, stimulating breast milk and menstrual flow 2,8,17. Intravenously, milk thistle is used as a supportive treatment for Amanita phalloides (death cap) mushroom poisoning 2,8. In cancer the claims are that milk thistle can be protective by inhibiting tumour development, and supportive in ameliorating adverse treatment effects as well as enhancing chemotherapeutic effect 14,15. These claims rest on presumed and acknowledged effects of milk thistle extracts in pre-clinical trials and case reports 16,18-20.

Mechanism(s) of action

The precise mechanism of action is unclear with silymarin considered a multi-functional, multi-target drug 17. Several mechanisms are thought to contribute to therapeutic effect in liver disease 2.Silymarin reduces hepatocyte membrane permeability to toxins 2,8. Antifibrotic action has been demonstrated by silybin in an in vitro model of human hepatic fibrogenesis 5. Silymarin demonstrates antioxidant and anti-inflammatory effects in several animal cell models 2,5. Silybinin is thought to have anti-cancer properties in different tumour types via e.g. apoptotic, tumour growth modulating, anti-carcinogenic, anti-inflammatory, anti-metastatic and anti-angiogenic mechanisms 3,5. The presumed modes of action are varied and include enhancement of pro-apoptotic molecules (e.g. caspases), enhancement of growth inhibitory proteins, presumed interaction with tumour necrosis factor (TNF), and inhibition of cell proliferation via a number of pathways including inhibition of various protein kinases (e.g. mitogen activated protein kinase MAPK), and inhibition of anti-apoptotic signalling 3,5,20.

In animal experiments and in vitro studies, anti-carcinogenic effects were seen for skin cancer, breast cancer, lung cancer, colon cancer, urinary bladder cancer, prostate cancer, ovarian cancer, leukaemia and cervical cancer 3,16,20. In in-vitro studies a synergistic action with different chemotherapeutic agents has been seen 3,21,22.

Prevalence of use

Milk thistle use has been reported in between 2% 23 and 7% 24,25 of cancer sufferers.

Legal issues

Milk thistle products are widely available in pharmacies, health food and grocery stores and on the Internet. In the US, milk thistle is included in the United States Pharmacopoeia-National Formulary. It is available as a “dietary supplement” under the Dietary Supplement Health and Education act 1994 2,8,12. In the UK it is available as a registered traditional medicine under the Traditional Herbal Medicines Directive 26. Silymarin extracts have drug status in several countries. Milk thistle is covered by a Commission E monograph 27, an ESCOP monograph 9 and the European Medicines Agency has a community monograph in preparation 28.

Cost(s) and expenditures

On the Internet prices for milk thistle tablets can vary from £8-40 for 90 capsules. A month’s dose of 7-12 g milk thistle seed containing 400-600 mg silymarin a day could cost £28 in the UK or 32 Euros: in mainland Europe silymarin extracts are more expensive.

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

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  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].
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