Milk Thistle (Silybum marianum) - a monograph

Updated: Jan 20

Silybum marianum is a medicinal herb from the Asteraceae family, which has been used for centuries. The seed contains the following constituents; Flavanolignans which are mutually known as silymarin (1.5-3%); silybin (silibinin), silychristin, silydianin, and 2,3-dehyfro derivatives.  There is also a fixed oil content of 20-30%; falavonoids, taxifolin and sterols (Bone & Mills, 2013). Further Fisher adds Flavonoid called apigenin, Amines; tyramine, histamine and trimethylglycine  as well as Polyacetylenes (2009)

The major actions, which are discussed here, are: Hepatoprotective, hepatic trophorestorative, antioxidant, anti-tumour, anti-inflammatory, anti-fibriotic, anti-hypercholesteraemic, anti-diabetic, immunomodulatory, and anti-viral.

These actions are discussed relating to therapeutic indications.

Therapeutic Indications

Rademacher, successfully treated a woman with a yellowish colour using the Lady’s Thistle in approximately 1810, after which he continued to discover therapeutic uses to include spleen as well as liver (1909). He especially found great effects on gall stones.

Culpeper agreed with Rademacher, but then suggested Milk Thistle was effective against the plague, whilst furthermore prescribed for the kidneys (1880). He also prescribed it as a general anodyne for abdominal pain, ostensibly by topical application, as well as prescribing an infusion as a depurative.  An eclectic named Petersen adds the use for varicose veins where nothing else worked(1905), which supports the purported action of circulatory stimulation by Felt & Lloyd (1898), in table above.

Ellingwood summarised the evidence above in his writings, before he added some peer reported observations in regards to the effectiveness of improving venous return(1919).

There has been a possible explosion of research in modern times on Milk thistle’s, as a review article from 2001 reported finding 525 references (Saller, Meier, & Brignoli), but a 2013 review article claims to have found over 12,000 scientific publications relating to Milk Thistle (Hackett, Twedt, & Gustafson).  Most of the research relates to liver disease. Research has been found to focus mostly on the extracted constituents grouped as Silymarin, sometimes singling out Silybinin. Heinrich, Barnes, Gibbons and Williamson describes these components to be antihepatotoxins (2012).

Liver disease

Milk thistle has an extensive hepatoprotective action, claims  Bone, stating that this action is both prophylactic as well as curative (2003). It’s supporter by a study, where a woman had high liver toxicity from unknown source before being treated with chemotherapy (McBride, Augustin, Nobbe, & Westervelt, 2012). The patient showed improved liver function tests after receiving Milk Thistle before and during her chemotherapy; however with only one patient in the study it doesn’t necessarily prove the efficacy of Milk Thistle.


A larger study on women receiving treatment for breast cancer suggested evidence for Milk thistle to be hepato-trophorestorative, since it reports a positive effect on hepatic function after treatment with the herb (Mohaghegh, Solhi, & Kazemifar, 2015). This study also suggested further research into Milk thistle as an adjunct cancer treatment.

A study on rats found Silymarin to have a therapeutical role in controlling either the onset or the progression of non-alcoholic steatohepatitis, which is a fatty liver disease characterised by inflammation, fatty  deposits and cellular damage, suggesting it to be anti-inflammatory  (Pais & D’Amato, 2014). This is supported by the findings of Barnes, Anderson, & Phillipson as they discuss their findings of the anti-inflammatory action of Milk Thistle (2007).


Silymarin was found to prevent alcoholic fibrosis in baboons in a study from 2003 (Lieber, Leo, Cao, Ren, & DeCarli). It can be argued that the sample size was too low to prove the anti-fibriotic action of the herb, with only a 12 baboons in total. However, the results are supported by a study on rats from 2015 which concludes that Silymarin will inhibit liver fibrosis progression and the fibrogenetic mechanism (Clichici et al.). This study also supports the findings of Silymarin being an effective antioxidant, which according to Clichici et al. seems to be part of the anti-fibriotic action.


Numerous human studies were found which specifically focussed on Hepatitis C and the anti-viral activity of Silymarin. Hawke et al discuss how prolonged oral treatment may result in anti-viral activity (2010).They continue to state that Silymarin will target the liver effectively and may provide immunomodulatory and anti-inflammatory effects on the hepatic cells. However, Ferenci et al. disagree and suggest that oral Silymarin is metabolised too quickly and that intravenous Silibinin, a water-soluble component of Silymarin, has a much higher success rate as an anti-viral (2008).


Cardiac vascular disease

Silymarin is reported to inhibit the absorption of cholesterol in the intestine, therefore making a positive effect on the overall cholesterol profile of the murine subjects, indicating anti-hypercholesterolemic (Sobolová, Škottová, Večeřa, & Urbánek, 2006). Additionally, a Berberis aristata and Silybum marianum combination has been shown to maintain lipid profile on patients which have been taken off statins (due to being intolerant) compared to the placebo group(Derosa, Romano, D ’angelo, & Maffioli, 2015).


Diabetes

Fisher presents the possibility of Silybum marianum being beneficial for cirrhosis induced diabetes, thus being anti-diabetic (2009), this is supported by the following studies; Ebrahimpour koujan, Gargari, Mobasseri, Valizadeh, & Asghari-Jafarabadi found Silymarin to have beneficial effect on complications in Type 2 diabetes mellitus (T2DM), by suppressing several inflammatory pathways and having a restorative effect on the pancreatic cells (2015).  A combination of Berberis aristata and Silybum marianum was studied for effect on type 1 diabetes mellitus patients for 6 months, and results show a decrease in insulin needed, as well as a slowed progression of destruction of pancreatic cell mass (Derosa, D’Angelo, & Maffioli, 2016).  Authors note: These studies indicate that Silymarin could be trophorestorative to other cells than just the hepatic cells.


Cancer

Bone and Mills discuss the concept of adjunct treatment to chemotherapy and radiotherapy (2013). Supporting this Post-White, Ladas, and Kelly found the potent antioxidant function of Silymarin to have anti-tumour effects by inhibiting the growth of cancer cell lines, and stabilising cell membranes  (2007). Other studies have found Silibinin to have additive and synergistic activity when combined with chemotherapy (Gustafson et al., 2010).


Safety data


Side effects

Milk thistle is generally reported to be well tolerated, however a small population of study objects have reported nausea or headaches (Hawke et al., 2010). Whilst a meta-analysis reported other events such as dermatologic, musculoskeletal pain, infection and fatigue, these were all reported to be mild (Yang, Zhuang, Lu, Xu, & Chen, 2014).

Intravenously administered Silybinin was reported to be well tolerated, some of the above side effects were reported during infusions, but subsided as soon as administration finished (Ferenci et al., 2008).


Contraindications

Bone and Mills have reviewed safety in children and found it safe (2013). Smith identifies the risk of lowered blood sugar levels and the potential risk for diabetic patients (2013). People with a known allergy to Asteraceae family of plants, can react to Silybum marianum (Braun & Cohen, 2015). Barnes et al. want mothers to avoid Milk Thistle during pregnancy and lactation (2007)


Drug interactions

Fisher explores how flavolignans affect the hepatic enzymes, which gives rise to herb/drug interactions (2009). One study from 2009 found evidence of Silymarin having an effect on the metabolism of drugs  due to its impact on the phase I and II enzymes in the liver (Wu, Lin, & Tsai, 2009). Spiteri specifies the drug interactions to Cisplatin, metronidazole, nifedipine, protease inhibitors, pyrazinamide and warfarin (2011).


Prescriptive forms




Higher doses are said to be needed for more severe liver damage, also worth noting that this herb should be taken over a long period of time for definitive effect (Mills & Bone, 2000). Lecithin is claimed to enhance absorption, but no supporting evidence of this claim has been found.


NOTE: always seek help from a accredited Naturopath before starting on a herbal regime, as the side effects needs to be monitored, as well as all contraindications considered in your individual case.


References:

image source: http://www.liversupport.com/milkthistle.htm

Barnes, J., Anderson, L., & Phillipson, D. (2007). Herbal Medicine (3rd ed.). London: Pharmaceutical Press.


Bone, K. (2003). A Clinical Guide to Blending Liquid Herbs : Herbal Formulations for the Individual Patient. St. Louis: Churchill Livingstone. Retrieved from http://web.b.ebscohost.com.ezproxy.endeavour.edu.au/ehost/detail/detail/bmxlYmtfXzQ0NTUyNl9fQU41?sid=1eccddb7-dda0-4b75-9240-6b923d8c137e@sessionmgr101&vid=0#AN=445526&db=nlebk

Bone, K., & Mills, S. (2013). Principles and practice of phytotherapy : modern herbal medicine. Sydney: Churchill Livingstone.


Braun, L., & Cohen, M. (2015). Herbs & Natural Supplements - An Evidence based guide (4th ed., Vol. 1). Chatswood, NSW: Elsevier Health Sciences APAC.


Clichici, S., Olteanu, D., Nagy, A.-L., Oros, A., Filip, A., & Mircea, P. A. (2015). Silymarin Inhibits the Progression of Fibrosis in the Early Stages of Liver Injury in CCl 4 -Treated Rats. Journal of Medicinal Food, 18(3), 290–298. http://doi.org/10.1089/jmf.2013.0179


Culpeper, N. (1880). Complete Herbal. London: W. Foulsham and Co. Ltd.


Derosa, G., D’Angelo, A., & Maffioli, P. (2016). The role of a fixed Berberis aristata/Silybum marianum combination in the treatment of type 1 diabetes mellitus. Clinical Nutrition, 35(5), 1091–1095. http://doi.org/10.1016/j.clnu.2015.08.004


Derosa, G., Romano, D., D ’angelo, A., & Maffioli, P. (2015). Berberis aristata combined with Silybum marianum on lipid profile in patients not tolerating statins at high doses. Atherosclerosis, 239, 87–92. http://doi.org/10.1016/j.atherosclerosis.2014.12.043


Ebrahimpour koujan, S., Gargari, B. P., Mobasseri, M., Valizadeh, H., & Asghari-Jafarabadi, M. (2015). Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus. Phytomedicine, 22, 290–296. http://doi.org/10.1016/j.phymed.2014.12.010


Ellingwood, F. (1919). American Materia Medica Therapeutics and Pharmacognosy (2nd ed.). Bisbee, AZ: unknown. Retrieved from http://www.swsbm.com/Ellingwoods/Ellingwoods_plants_only.pdf


Felter, H. W., & Lloyd, J. U. (1898). King’s American Dispensatory (18th ed.). Cincinnatti: Ohio Valley Co. Retrieved from http://www.henriettes-herb.com/eclectic/kings


Ferenci, P., Scherzer, T.-M., Kerschner, H., Rutter, K., Beinhardt, S., Hofer, H., … Steindl-Munda, P. (2008). Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology, 135(5), 1561–7. http://doi.org/10.1053/j.gastro.2008.07.072


Fisher, C. (2009). Materica Medica of Western Herbs. Nelson, NZ: Carole Fisher.

Gustafson, D., Bokhoven, A. Van, Flaig, T. W., Glode, M., Tao, Y., Wilson, S., … Pollak, M. (2010). A Study of High-Dose Oral Silybin-Phytosome Followed by Prostatectomy in Patients With Localized Prostate Cancer, 855(December 2009), 848–855. http://doi.org/10.1002/pros.21118


Hackett, E. S., Twedt, D. C., & Gustafson, D. L. (2013). Milk Thistle and Its Derivative Compounds: A Review of Opportunities for Treatment of Liver Disease. Journal of Veterinary Internal Medicine, 27(1), 10–16. http://doi.org/10.1111/jvim.12002


Hawke, R. L., Schrieber, S. J., Soule, T. A., Wen, Z., Smith, P. C., Reddy, K. R., … SyNCH Trial Group. (2010). Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C. Journal of Clinical Pharmacology, 50(4), 434–49. http://doi.org/10.1177/0091270009347475


Heinrich, M., Barnes, J., Gibbons, S., & Williamson, E. M. (2012). Fundamentals of Pharmacognosy and Phytotherapy E-Book (2nd ed.). Sydney: Churchill Livingstone. Retrieved from http://ebookcentral.proquest.com.ezproxy.endeavour.edu.au/lib/endeavour/reader.action?docID=1724052


Heinrich, M., Kinghorn, A. D., Phillipson, J. D., Maizels, D., & Gibbons, S. (2012). Fundamentals of pharmacognosy and phytotherapy (2nd ed.). Edinburgh: Elsevier.

Lieber, C. S., Leo, M. A., Cao, Q., Ren, C., & DeCarli, L. M. (2003). Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. J Clin Gastroenterol, 37(4), 336–339. http://doi.org/10.1097/00004836-200310000-00013


McBride, A., Augustin, K. M., Nobbe, J., & Westervelt, P. (2012). 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 : Official Publication of the International Society of Oncology Pharmacy Practitioners, 18(3), 360–5. http://doi.org/10.1177/1078155212438252


Mills, S., & Bone, K. (2000). Principles and Practice of Phytotherapy (1st ed.). Sydney: Harcourt Publishers Limited.


Mohaghegh, F., Solhi, H., & Kazemifar, A. M. (2015). Silymarin (Milk Thistle) can revoke liver enzyme changes during chemotherapy of breast cancer with Taxanes. European Journal of Integrative Medicine. http://doi.org/10.1016/j.eujim.2015.10.012


Pais, P., & D’Amato, M. (2014). In Vivo Efficacy Study of Milk Thistle Extract (ETHIS-094(TM)) in STAM(TM) Model of Nonalcoholic Steatohepatitis. Drugs in R and D, 14(4), 291–299. http://doi.org/10.1007/s40268-014-0068-2


Petersen, F. J. (1905). Materia Medica and Clincal Therapeutics. Los Olivos, California: F. J. Petersen, M. D. Retrieved from http://www.henriettes-herb.com/eclectic/petersen/intro.html


Post-White, J., Ladas, E. J., & Kelly, K. M. (2007). Advances in the use of milk thistle (Silybum marianum). Integrative Cancer Therapies, 6(2), 104–9. http://doi.org/10.1177/1534735407301632


Rademacher, J. (1909). Universal and organ remedies. (A. A. Ramseyer, Trans.). Philadelphia: Boericke & Tafel. Retrieved from https://archive.org/stream/rademachersuniv00radegoog#page/n7/mode/2up/search/thistle


Saller, R., Meier, R., & Brignoli, R. (2001). The use of silymarin in the treatment of liver diseases. Drugs, 61(14), 2035–63. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11735632


Smith D., G. (2013). The use of milk thistle in hepatitis. Gastrointestinal Nursing, 11(6), 13–14. Retrieved from https://login.ezproxy.endeavour.edu.au:2443/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=rzh&AN=2012206423&site=eds-live&scope=site


Sobolová, L., Škottová, N., Večeřa, R., & Urbánek, K. (2006). Effect of silymarin and its polyphenolic fraction on cholesterol absorption in rats. Pharmacological Research, 53(2), 104–112. http://doi.org/10.1016/j.phrs.2005.09.004


Spiteri, M. (2011). Herbal Monographs. Malta: Department of Pharmacy, University of Malta.


The Council of Heads of Australasian Herbaria. (2011). Vascular Plants APC - Silybum marianum. Retrieved March 20, 2017, from https://biodiversity.org.au/nsl/services/search?product=APNI&tree.id=&name=Silybum+marianum+%28L.%29+Gaertn.&inc._scientific=&inc.scientific=on&inc._cultivar=&inc.cultivar=on&inc._other=&inc.other=on&max=100&display=&search=true


Wu, J.-W., Lin, L.-C., & Tsai, T.-H. (2009). Drug–drug interactions of silymarin on the perspective of pharmacokinetics. Journal of Ethnopharmacology, 121, 185–193. http://doi.org/10.1016/j.jep.2008.10.036


Yang, Z., Zhuang, L., Lu, Y., Xu, Q., & Chen, X. (2014). Effects and tolerance of silymarin (milk thistle) in chronic hepatitis C virus infection patients: a meta-analysis of randomized controlled trials. BioMed Research International, 2014, 941085. http://doi.org/10.1155/2014/941085

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