Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review

Phytother Res. 2019 Jun;33(6):1627-1638. doi: 10.1002/ptr.6361. Epub 2019 May 8.


Milk thistle (Silybum marianum) is a medicinal plant from the Asteraceae family. Silymarin is the major constituent of milk thistle extract and is a mixture of some flavonolignans such as silybin, which is the most active component of silymarin. It is most commonly known for its hepatoprotective effect. Also, studies have shown other therapeutic effects such as anticancer, anti-Alzheimer, anti-Parkinson, and anti-diabetic, so its safety is very important. It has no major toxicity in animals. Silymarin was mutagen in Salmonella typhimurium strains in the presence of metabolic enzymes. Silybin, silydianin, and silychristin were not cytotoxic and genotoxic at concentration of 100 μM. Silymarin is safe in humans at therapeutic doses and is well tolerated even at a high dose of 700 mg three times a day for 24 weeks. Some gastrointestinal discomforts occurred like nausea and diarrhea. One clinical trial showed silymarin is safe in pregnancy, and there were no anomalies. Consequently, caution should be exercised during pregnancy, and more studies are needed especially in humans. Silymarin has low-drug interactions, and it does not have major effects on cytochromes P-450. Some studies demonstrated that the use of silymarin must be with caution when co-administered with narrow therapeutic window drugs.

Keywords: Silybum marianum; Silymarin; adverse reactions; safety; toxicity.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / adverse effects
  • Antioxidants / isolation & purification
  • Antioxidants / therapeutic use
  • Antioxidants / toxicity
  • Asteraceae / chemistry
  • Asteraceae / classification
  • Cytochrome P-450 Enzyme System / metabolism
  • Cytoprotection / drug effects
  • DNA Damage / drug effects
  • Drug Interactions
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Liver / drug effects
  • Milk Thistle / adverse effects
  • Milk Thistle / chemistry*
  • Nerve Degeneration / prevention & control
  • Plant Extracts / adverse effects
  • Plant Extracts / therapeutic use*
  • Pregnancy
  • Silymarin / adverse effects
  • Silymarin / therapeutic use*


  • Antioxidants
  • Hypoglycemic Agents
  • Plant Extracts
  • Silymarin
  • Cytochrome P-450 Enzyme System