By Nikita Agarwal
Milk thistle has been known for its liver protective activity for many centuries now. Its reference first appeared in 1626 in Matthiolus’ Book of Herbs. The species name “marianum” is believed to come from the legend of the Virgin Mother Mary fleeing to Egypt. The white spots on the leaves represent her milk while nursing Jesus. The seed extracts of the plant are widely studied. The constituent silymarin is said to be the active ingredient. Silymarin is shown to exert hepatoprotective, anti-fibrotic, anti-inflammatory and anti-oxidant properties. Both animal and human studies have shown that silymarin is not toxic. At higher doses (>1500 mg per day) a laxative effect is possible. Only a few well-designed clinical trials exist to prove its effectiveness. This monograph aims to describe the plant holistically from an interdisciplinary perspective.
Silybum marianum (L.) Gaertn. or milk thistle with its purple flowers stands out in the Mecklenburgh square garden. It is a very attractive plant with white veins and dark green leaves. The flowers are in bloom from July to September. As a garden plant, it is rather troublesome. It spreads aggressively, placement of the plant is therefore challenging. Since the leaves and stems are spiny and exude a milky sap when cut, the collection and disposal of them are time-consuming.  Milk thistle is also found to be toxic to livestock. 
It belongs to the family Asteraceae (formerly Compositae) with a composite flower head and solitary flowers. It is an annual or biennial plant that grows up to a height of 150 cm.  The appearance is like a thistle owing to its outer husk of blossoms with sharp hard thorns. The leaves also end in sharp yellow spines, they are usually marbled in white. The fruits are hard-shelled egg-shaped and light to dark brown in colour.  The fruit falls off easily and is therefore self-seeding.
The plant is indigenous to the Mediterranean region and has been widely used in Europe for over 20 centuries. It can now be found growing all over the world, in most temperate areas. It prefers rocky slopes, edges of paths, sunny fields, waste and pasture lands with any type of soil. 
Traditionally, the whole plant including the leaves, young shoots, flowers and stem were consumed after baking or boiling. Powdered dried leaves were added to tea to treat headaches. The roots and seeds were used in tinctures (dissolved in alcohol). Herbalists from the time of Dioscordes made decoctions of the plant and used it as an antidote for snake bites.  It was also used in supportive therapy in food poisoning due to the death cap mushroom (Amanita phalloides).  Hepatitis, gallbladder problems and cirrhosis were all treated with milk thistle historically. Presently, silymarin is the most popular herbal supplement sold in the United States for liver disorders. The supplements are available as powders, extracts and capsules. 
Why the name?
Silybum marianum (L.) Gaertn. is the accepted name. Although, it is also sometimes referred to as Carduus marianus L.  Its common names include milk thistle, blessed milkthistle and Mediterranean milk thistle. The genus name is derived from the Greek word sillybon meaning ‘tufts’ or ‘tassel’ which is a reference to the spiny bracts found in the inflorescence. The species name “marianum” is believed to come from the legend of the Virgin Mother Mary fleeing to Egypt. The white spots on the leaves represent her milk while nursing Jesus.
The plants’ chemistry
Silymarin is considered the main phytoconstituent of the plant. It comes from its seed. The terms “silymarin” and ‘milk thistle” are confused and often used interchangeably.  Silymarin is a collection of compounds that include silybin, isosilybin, silychristin and silydianin  It is found in 80% of the extracts sold in the market. These are also known as flavonolignans, as they are part flavonoid and part lignan. As shown below:
Additionally, the seed also contains oleic acid and palmitic acid, these are common fatty acids found naturally in various animal and vegetable fats / oils. Fixed oils, tocopherol (Vitamin E activity), sterols, sitosterol, cholesterol, mucilage and stigmasterol can also be found in the seeds. [10,11] Kren V, et al have isolated quercetin, taxifolin, silybonol and betaine from the plant. 
The drug can is characterized and identified by microscopic techniques, thin layer chromatography (TLC), high-performance chromatography (HPLC) or using spectrophotometry. 
Silymarin or the flavonolignans are reported to be responsible for the pharmacological activity. These are insoluble in water. Hence the teas or infusions that claim to have a hepatoprotective function (liver protective) do not hold water.  The preferred form of administration is encapsulated 70-80% extract. Silymarin is absorbed when given orally. The absorption of silymarin is about 20-50% only.
What is it good for?
The medicinal value of milk thistle has been known for ages. Since 23 AD the time of Pliney The Elder, he noted that the juice of the plant along with honey was excellent in “carrying away bile” . Milk thistle is regarded as a treatment of liver diseases by many scientists from Otto Brunfels in 1534 to Adam Lonicerus in 1697. In 1787 Culpeppers reported that milk thistle works well against obstructions of the liver and spleen. Infusions of the seeds along with the fresh root could break / expel stones and cure jaundice. 
Silymarin is said to have anti-oxidant properties.  It increases the glutathione levels in the body which is crucial for liver detoxification and may also play a role in regenerating liver cells.  The effects of high-cholesterol and high-fat diets can also be modulated by milk thistle as it prevents the development of a fatty liver. 
To say that silymarin is only used to treat liver problems associated with alcohol would be wrong. It is a powerful treatment against several environmental toxins and drugs. To name a few, iron overload, overdose of acetaminophen, poisonous liquids like phenylhydrazine and carbon tetrachloride. It is used to protect the liver against chemotherapy and psychotropic medication as well. 
Beyond the liver
Recent research shows that milk thistle has excellent anti-inflammatory action as well. It has been compared to other powerful natural compounds like curcumin (from turmeric) and epigallocatechin (from green tea). 
The American Botanical Council (ABC) reports that several studies on milk thistle both in vivo and in vitro suggest that it is a potential cancer treatment. As it exhibits inhibition in prostate cancer cells and increases apoptosis (programmed cell death). It is beneficial as a topical application against skin tumours by inhibiting the growth of the tumour.  Topical formulation of silymarin demonstrates protection against ultraviolet-B radiations from the sun i.e. a photoprotectant.
Milk thistles effect on the kidney closely resembles its effect on the liver. It stimulates cell regeneration and protein synthesis in the kidney as well. The plant has a mild diuretic effect in rats with a significant decrease in potassium excretion. 
Herbalists report milk thistle to have potential as a neuroprotectant. Neurological problems like myalgias, carpal tunnel syndrome and multiple sclerosis cases have been backed up by in-vitro studies. 
Does it really work?
Anti-inflammatory and immunomodulatory activities have been demonstrated by silymarin in multiple pathways and structures of the cell. Silibin in a pre-clinical study prevented cancer in liver cells by reactive oxygen species (ROS) dependent mechanisms.  The compound does not have the ability to scavenge for free radicals (highly reactive molecules) such as superoxide (O2-) and hydrogen peroxide (H2O2) but rapidly reacted with hydroxyl radical (HO-). 
Despite popular belief, silymarin is not found to directly affect the bodies ethanol metabolism, cause reduction in ethanol levels nor affect the rate at which ethanol is excreted from the body. Hence, the anti-toxic effects attributed to the medicinal plant are due to its anti-oxidant and free radical scavenging properties. 
Silymarin protects the liver with its antifibrotic activity. Which means it works by preventing tissue scarring. It is believed to block toxins by inhibiting them from binding to the liver’s cell membrane receptors. 
A majority of the clinical trials designed to prove the plants’ efficacy is difficult to interpret. As they either have a small number of test subjects, vary in severity of the disease, inconsistent with the consumption of alcohol in patients, inadequately defined endpoints and unequal control groups. Although the histological and biochemical improvements have been demonstrated fairly well. 
Is it toxic or harmful in any way?
Silymarin extracts with concentrations even up to 80% have very low toxicity. As far as known, milk thistle is not embryotoxic. Some studies with isolates of silybin or silymarin have shown negative effects on cell cultures when applied for a long period. Hence, the isolated constituents cannot be regarded as completely safe.  The herb is believed to interact and inhibit certain drugs that are metabolized by cytochrome enzymes. However, the concentrations necessary for this effect may not be reached the therapeutic doses.
Caution needs to be taken when consuming newer supplements that have increased bioavailability. There is a possibility that higher doses of the flavonolignans could result in interference with prescription medications. 
There are no serious side effects reported with milk thistle. Mild nausea and diarrhea may occur at higher doses (>1500 mg per day). Allergic reactions may be a problem with some individuals, especially those who are allergic to plants from the Asteraceae family (daisies, thistles and artichokes). 
All parts of Silybum marianum have traditionally been used as medicine. Now, it is most commonly traded as a food supplement. Silymarin, that is a group of flavonolignans, are said to be responsible for the plant’s liver protective activity. Apart from its beneficial effects to the liver, the compound is useful in cells regeneration and protein synthesis in the kidney, for anti-inflammation, tumour suppression and as a neuroprotectant. The data generated through clinical trials for the compound are not very reliable. The plant and its extracts are not toxic and shows no serious side effects even at high doses.
Disclaimer: In this essay we do not to advise or recommend herbs for medicinal or health use. This information is intended for educational purposes only and should not be considered as a recommendation or an endorsement of any particular medical or health treatment. The use of any such product should be based on the appropriate advice of a health care professional or based on the information available in the patient information leaflets (i.e. for THR products).
© Nikita Agarwal 2019. All rights reserved.
Nikita Agarwal is a MSc. student in Medicinal Natural Products and Phytochemistry at the UCL School of Pharmacy.
To contact Nikita, you can write to her at firstname.lastname@example.org
- Khan, M.A., Blackshaw, R.E. and Marwat, K.B., 2009. Biology of milk thistle (Silybum marianum) and the management options for growers in north‐western Pakistan. Weed Biology and Management, 9(2), pp.99-105.
- Ross, S.M., 2008. Milk thistle (Silybum marianum): an ancient botanical medicine for modern times. Holistic Nursing Practice, 22(5), pp.299-300.
- Abenavoli, L., Izzo, A.A., Milić, N., Cicala, C., Santini, A. and Capasso, R., 2018. Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytotherapy Research, 32(11), pp.2202-2213.
- Boh, M. and Breakspear, I., 2015. Silybum marianum–ancient medicine for modern times. Australian Naturopathic Practitioners Association Inc. pp. 1-13.
- Koop-phyto.org. (2019). Milk Thistle (Milk Thistle – Silybum marianum (L.) Gaertn. (syn. Carduus marianus L.)) – Medicinal Plants – Kooperation Phytopharmaka. [online] Available at: https://www.koop-phyto.org/en/medicinal-plants/milk-thistle.php [Accessed 1 Apr. 2019].
- Abenavoli, L., Capasso, R., Milic, N. and Capasso, F., 2010. Milk thistle in liver diseases: past, present, future. Phytotherapy Research, 24(10), pp.1423-1432.
- The Plant List (2013). Version 1.1. Published on the Internet; http://www.theplantlist.org/ (accessed 1st April)
- Vogel, G., Tuchweber, B., Trost, W. and Mengs, U., 1984. Protection by silibinin against Amanita phalloides intoxication in beagles. Toxicology and Applied Pharmacology, 73(3), pp.355-362.
- Kumar, T., Larokar, Y.K., Iyer, S.K., Kumar, A. and Tripathi, D.K., 2011. Phytochemistry and pharmacological activities of Silybum marianum: a review. Apex, 10, p.12.
- Khan, S.A., Ahmed, B. and Alam, T., 2003. Phytochemical and pharmacological investigation of Silybum marianum. Hamdard Medicus (Pakistan).
- Zahra, N. (2017). A Short Review on Ethnomedicinal Uses and Phytochemistry of Silybum marianum. Natural Products Chemistry & Research, 05(07).
- Arviv, A., Muklada, H., Kigel, J., Voet, H., Glasser, T., Dvash, L., Ungar, E.D. and Landau, S.Y., 2016. Targeted grazing of milk thistle (Silybum marianum) and Syrian thistle (Notobasis syriaca) by goats: Preference following preconditioning, generational transfer, and toxicity. Applied Animal Behaviour Science, 179, pp.53-59.
- Křen, V. and Walterova, D., 2005. Silybin and silymarin–new effects and applications. Biomed papers, 149(1), pp.29-41.
- Dixit, N., Baboota, S., Kohli, K., Ahmad, S. and Ali, J., 2007. Silymarin: A review of pharmacological aspects and bioavailability enhancement approaches. Indian Journal of Pharmacology, 39(4), p.172.
- Flora, K., Hahn, M., Rosen, H. and Benner, K., 1998. Milk thistle (Silybum marianum) for the therapy of liver disease. The American Journal of Gastroenterology, 93(2), pp.139-143.
- Anthony, K., Subramanya, G., Uprichard, S., Hammouda, F. and Saleh, M., 2013. Antioxidant and anti-hepatitis c viral activities of commercial milk thistle food supplements. Antioxidants, 2(1), pp.23-36.
- Mercola.com. (2019). Magnificent Milk Thistle Benefits. [online] Available at: https://articles.mercola.com/sites/articles/archive/2015/09/14/milk-thistle-benefits.aspx [Accessed 2 Apr. 2019].
- Lovelace, E.S., Wagoner, J., MacDonald, J., Bammler, T., Bruckner, J., Brownell, J., Beyer, R.P., Zink, E.M., Kim, Y.M., Kyle, J.E. and Webb-Robertson, B.J.M., 2015. Silymarin suppresses cellular inflammation by inducing reparative stress signalling. Journal of Natural Products, 78(8), pp.1990-2000.
- Das, S.K. and Vasudevan, D.M., 2006. Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver.
- Cms.herbalgram.org. (2019). HerbClip: Beyond Liver Conditions: Other Uses for Milk Thistle with Clinical Guidelines. [online] Available at: http://cms.herbalgram.org/herbclip/262/review43858.html?ts=1554831164&signature=761d5d49e8464bae386b2291efe5cfcf [Accessed 3 Apr. 2019].
- Greenlee, H., Abascal, K., Yarnell, E. and Ladas, E., 2007. Clinical applications of Silybum marianum in oncology. Integrative cancer therapies, 6(2), pp.158-165.
- Jacobs, B.P., Dennehy, C., Ramirez, G., Sapp, J. and Lawrence, V.A., 2002. Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. The American journal of medicine, 113(6), pp.506-515.
- Detaille, D., Sanchez, C., Sanz, N., Lopez-Novoa, J.M., Leverve, X. and El-Mir, M.Y., 2008. Interrelation between the inhibition of glycolytic flux by silibinin and the lowering of mitochondrial ROS production in perifused rat hepatocytes. Life sciences, 82(21-22), pp.1070-1076.
- Miguez, M.P., Anundi, I., Sainz-Pardo, L.A. and Lindros, K.O., 1994. Hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1. Chemico-biological interactions, 91(1), pp.51-63.