Milk Thistle: A Comprehensive Overview for Pharmaceutical Applications

Written by Emmanuella Ogbonna, BPharm; Reviewed by Danielle Kelvas, MD, for PTcell for Pharmaceutical Industries LL.C

Milk thistle has long been used in traditional medicine to manage a range of liver and gallbladder disorders (1,2).

Current research has also found that milk thistle can boost liver function and prevent liver disorders like fatty liver disease and cirrhosis. (2) There is also evidence that milk thistle can help manage diabetes, dyspepsia, and eye disease. (3)

The demand for milk thistle is on the rise. The market size for this herb, valued at about USD 97 million in 2023, is expected to reach USD 316 million by 2033. (4)

This article will examine milk thistle extract, its classification, medicinal use, extraction techniques, and quality control.

Botanical Classification and Characteristics

Milk thistle (Silybum marianum) belongs to the family of Asteraceae, which also includes plants such as sunflowers and daisies. (5) It is also referred to as wild artichoke, blessed milk thistle, St. Mary’s thistle, and mediterranean milk. The plant is indigenous to Europe but can also be found in the United States, South America, Africa, Australia, and Asia. (1)

This plant is characterized by its distinctive reddish-purple flowers with white veins and can reach a height of approximately three feet. Due to its aggressive growth, milk thistle is often regarded as a weed.

Major bioactive compounds

Milk thistle seeds are the major components of the plant used in pharmaceutical applications. The seeds contain natural compounds called flavonolignans. (5)

Silimarin, the major active ingredient in milk thistle, is a mixture of flavonolignans, including silybin, isosilybin, silychristin A, and silydianin. (6) Silibin constitutes 50- 70% of the silymarin complex. (7) In addition to flavonolignans, silymarin also contains flavonoids such as taxifolin and quercetin. (7)

Pharmaceutical uses of Milk Thistle

Milk thistle contains antioxidants, anti-inflammatory and antifibrotic compounds that are responsible for some of its medicinal properties. (8, 9, 10). Its use in treating liver damage is well-established in Europe, especially in countries like France, Belgium, the Czech Republic, Austria, and Estonia. (11)

Although more human studies are needed, milk thistle has demonstrated medicinal properties that may have pharmaceutical applications. Some potential uses of milk thistle include:

Liver Disease

Milk thistle has a long history of use in the management and treatment of liver diseases, including fatty liver disease, hepatitis, and cirrhosis, dating back to the era of traditional medicine. (11)

The anti-inflammatory, antioxidant, and antifibrotic property of silybin makes it useful in preventing the progression of liver injury as well as shielding the liver from environmental toxins. (8)

In addition, a 2014 study suggested that milk thistle may extend the life expectancy of people with liver cirrhosis caused by alcoholic liver disease. (12)

The European Scientific Cooperative on Phytotherapy (ESCOP) also recognizes the use of milk thistle for the treatment of toxic liver damage and as supportive treatment in patients with chronic inflammatory liver conditions and hepatic cirrhosis. (11)
Other potential indications of silymarin pill in liver condition include:
● Management of hepatotoxicity caused by chemotherapy (13)
● Management of patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy (14)
● Reduce the progression of liver fibrosis (15)

AMANITA PHALLOIDES POISONING

Although not a specific antidote, silymarin may also be useful in counteracting
Amanita phalloides mushroom poisoning. (16)

A review of over 2,000 patients exposed to amatoxin in Europe and North America suggested that intravenous silibinin is the most effective available therapy for this toxin. (5) Another review of over 877 cases of amatoxin poisoning found that the use of silibinin was associated with a 90% survival rate, compared to 59% in patients receiving only supportive care. (17)

Diabetes
Some studies suggest that milk thistle is a potent agent in reducing insulin resistance and diabetes-induced hyperglycemia. (6)

In a 2020 study, researchers found that milk thistle supplements have potential benefits in reducing oxidative stress and metabolic status among patients with type-2 diabetes. (18)

Silymarin supplementation can also help decrease fasting blood glucose and haemoglobin A1C (HbA1c). (18, 19)

Treating eye diseases
Milk thistle has also been found to be beneficial in treating eye diseases like cataracts, glaucoma, and uveitis due to its anti-inflammatory, antioxidant, and antibacterial properties. (20) However, more studies are needed to confirm these benefits.

Quality Control and Standardization of Milk Thistle

The European Pharmacopoeia monograph recommends that milk thistle extract contain 90% to 110% of the normal content of silymarin, expressed as silibinin. (11)

Several analytical techniques have been developed to quantitatively measure silymarin in milk thistle extracts. These methods include: (21)
● High-performance liquid chromatography (HPLC)
● Thin-layer chromatography (TLC)
● High-performance thin-layer chromatography (HPTLC),
● Nuclear magnetic resonance (NMR)
● Ultra-high-performance liquid chromatography (UHPLC) has also been applied.

Milk thistle preparations should also be tested for the presence of high concentrations of mycotoxins and pesticides to ensure their purity. Liquid chromatography coupled with mass spectrometry is commonly used to determine the presence of mycotoxins in herbal products. (7)

One study that investigated the chemical and biological safety of 26 milk thistle supplements obtained from U.S. and Czech markets between 2016 and 2017 found concerning levels of contaminants. All preparations tested contained high concentrations of mycotoxins and several pesticides, raising serious safety issues. (22)

Regulatory Status and Safety Considerations

The European Medicines Agency (EMA) ) regulates the use of milk thistle in the management of liver disorders. (11)

Studies show that silymarin is safe and well tolerated even at doses up to 700mg, used for up to 24 weeks. (21) However, some patients may experience allergic reactions, particularly those allergic to plants in the same family, like ragweed and chrysanthemum. (1) Other side effects of milk thistle include gastroenteritis, bloating, headache and diarrhoea. (16)

Future Prospects of Milk Thistle Extract

The skincare industry is increasingly incorporating milk thistle extract into products like anti-ageing creams and sunscreens due to its antioxidant and anti- inflammatory properties. (23,24) Manufacturers of skin care products can capitalize on this market by developing innovative formulations that leverage these benefits of milk thistle.

Studies are also ongoing for using milk thistle in prostate cancer management, as well as other cancers. (13)

1. National Center for Complementary and Integrative Health. Milk Thistle 2. Bijak M. (2017). Silybin, a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)-Chemistry, Bioavailability, and Metabolism. Molecules (Basel, Switzerland), 22(11), 1942. 3. Rainone, F. (2005). Milk thistle. American Family Physician, 72(7), 1285– 1288. 4. Future Marketing Insight. Milk Thistle Market Outlook 5. Siegel, A. B., & Stebbing, J. (2013). Milk thistle: early seeds of potential. The Lancet. Oncology, 14(10), 929–930. 6. Kazazis CE., Evangelopoulos AA., Kollas A., & Vallianou NG. (2014). The therapeutic potential of milk thistle in diabetes. The review of diabetic studies: RDS, 11(2), 167–174. 7. Boško R., Pernica M., Běláková S., Bjelková M., & Pluháčková H. (2022). Determination of T-2 and HT-2 Toxins in Seed of Milk Thistle [Silybum marianum (L.) Gaertn.] Using Immunoaffinity Column by UPLC-MS/MS. Toxins, 14(4), 258. 8. Loguercio C., & Festi D. (2011). Silybin and the liver: from basic research to clinical practice. World Journal of Gastroenterology, 17(18), 2288–2301. 9. Fried MW., Navarro VJ., Afdhal N., et al. (2012). Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA, 308(3), 274–282. 10. Ted GA; Mark VP; Raj KP (2024). Milk Thistle. In: StatPearls. StatPearls Publishing. 11. European Medicines Agency. (2018). Assessment report on Silybum marianum (L.) Gaertn., fructus. EMA/HMPC/294188/2013. 12. Vargas-Mendoza N., Madrigal-Santillán E., Morales-González A. et al. (2014). Hepatoprotective effect of silymarin. World Journal of Hepatology, 6(3), 144–149. 13. Emadi SA., Ghasemzadeh RM., Mehri S., & Hosseinzadeh H. (2022). A review of therapeutic potentials of milk thistle (Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents. Iranian Journal of basic medical sciences, 25(10), 1166–1176. 14. Polyak SJ., Oberlies NH., Pécheur EI., Dahari H., Ferenci P., & Pawlotsky JM. (2013). Silymarin for HCV infection. Antiviral therapy, 18(2), 141–147. 15. Clichici S., Olteanu D., Nagy AL., Oros A., Filip A., & Mircea PA. (2015). Silymarin inhibits the progression of fibrosis in the early stages of liver injury in CCl₄-treated rats. Journal of medicinal food, 18(3), 290–298. 16. Horowitz BZ; Moss MJ. (2023). Amatoxin Mushroom Toxicity. In: StatPearls. StatPearls Publishing. 17. Tan JL., Stam J., Van den Berg AP., van Rheenen PF., Dekkers BG, & Touw DJ. (2022). Amanitin intoxication: effects of therapies on clinical outcomes – a review of 40 years of reported cases. Clinical Toxicology, 60(11), 1251– 1265. 18. Hadi A., Pourmasoumi M., Mohammadi H., Symonds M., & Miraghajani M. (2018). The effects of silymarin supplementation on metabolic status and oxidative stress in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials. Complementary therapies in medicine, 41, 311–319. 19. Mehrzadi S., Mirzaei R., Heydari M., Sasani M., Yaqoobvand B., & Huseini, HF. (2020). Efficacy and Safety of a Traditional Herbal Combination in Patients with Type II Diabetes Mellitus: A Randomized Controlled Trial. Journal of Dietary Supplements, 18(1), 31–43. 20. Tahmasbi, Z., Boroughani, M., Heidari, M. M., et al. (2025). Potential therapeutic effects of milk thistle (Silybum marianum) in eye diseases: A scoping review. Discover Applied Sciences, 7, 17. 21. Raclariu-Manolică AC., & Socaciu C. (2023). Detecting and Profiling of Milk Thistle Metabolites in Food Supplements: A Safety-Oriented Approach by Advanced Analytics. Metabolites, 13(3), 440. 22. Fenclova M., Novakova A., Viktorova J., et al. (2019). Poor chemical and microbiological quality of the commercial milk thistle-based dietary supplements may account for their reported unsatisfactory and non- reproducible clinical outcomes. Scientific Reports, 9, 11118. 23. Jadoon S., Karim S., Bin Asad MH., et al. (2015). Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity. Oxidative medicine and cellular longevity, 2015, 709628. 24. Michalak M. (2022). Plant-Derived Antioxidants: Significance in Skin Health and the Ageing Process. International journal of molecular sciences, 23(2), 585.