What is it?


The seeds and fruit of Silybum marianum (SM), also known as milk thistle (not to be confused with blessed thistle), have been used to treat liver conditions since the 16th century. (Gillessen 2020) The World Health Organization (WHO) recognized it as an official hepatoprotective medicine in 1970. (Bijak 2017) Silymarin, the main extract from SM, is composed mostly of flavonolignans, flavonoids (i.e., taxifolin, quercetin) and polyphenols. Silybin is the main bioactive component of silymarin that appears to be responsible for any hepatoprotective effects. (Bijak 2017

SM’s mechanisms of action are not fully understood, but it may act as an antioxidant, antifibrotic agent, insulin resistance modulator, glutathione production inducer, and anti-inflammatory agent through the downregulation of cyclooxygenase and tumor necrosis factor-alpha (TNF-ɑ). (de Avaler 2017)(Gillessen 2020)(Saller 2007)

Main uses

Cardiometabolic modulation
Hormonal modulation


Bioavailability & safety
Non-proprietary standardized extracts
20-50% bioavailability for standardized extracts
Up to 2,100 mg for up to 48 weeks, and 420 mg per day for up to four years has been shown to have only minor adverse effects that are less or equal to placebo (Gillessen 2020)
Eurosil 85®/Legalon®
30% greater area under the curve (AUC) versus standardized extracts (Kim 2003)
Has been shown to have no serious adverse effects in studies up to 15 months in duration (Gillessen 2020)
Realsil® (silybin 94 mg, phosphatidylcholine 194 mg, vitamin E acetate 50% (α-tocopherol 30 mg) 89.28 mg)
Higher bioavailability reported with the addition of phosphatidylcholine and vitamin E (Derakhshandeh-Rishehri 2020)
Magnitude of effect with addition of phosphatidylcholine may be 10x (Mendez-Sanchez 2019)
Has been shown to have no serious adverse effects in studies up to 12 months in duration (Derakhshandeh-Rishehri 2020)
Silipide® (1:2 silybin to phosphatidylcholine)
4-10x greater bioavailability of silybin than standard SM preparations (Abenavoli 2010)(Barzaghi 1990)
Has been shown to have no serious adverse effects in studies up to 12 months in duration (Federico 2006)

Dosing & administration

Adverse effects

A 2005 Cochrane review found no significant increase in adverse effects from SM supplementation. (Rambaldi 2005) Silymarin extracts have been used at doses up to 420 mg per day for up to four years and for up to 48 weeks at 2,100 mg per day. Adverse effects reported have been rare and minor and tend to occur as often or less often than with placebo. (Gillessen 2020)(Jacobs 2002) For example, in placebo-controlled trials of over 600 participants, the most common adverse effects were pruritus (in 1.01% and 1.35% of the SM and placebo groups, respectively) and headache (in 1.35% and 3.7% of the SM and placebo groups, respectively). (Saller 2007) Less common effects were diarrhea (0.20%), irregular stools (0.10%), nausea (0.13%), and dyspepsia (0.08%). (Saller 2007) Milk thistle is a member of the Asteraceae family of plants, so those with allergies to plants such as ragweed may also have a sensitivity to milk thistle. Therefore, caution is urged in these patients. (Gillessen 2020)

With regards to drug interactions, no evidence was found of induction or inhibition of cytochrome P450 enzymes CYP 1A2, 2C9, 2D6, 2E1, 3A4, or 3A5 in healthy volunteers. (Doehmer 2008) SM was theorized to interact with statins as they may inhibit transport into the liver; however, a human trial found no impact of SM on rosuvastatin pharmacokinetics in healthy males. (Gillessen 2020)



  • Oral bioavailability of SM’s flavonolignans is low due to their rapid conjugation in the intestines and liver and rapid excretion back into the gastrointestinal tract by the liver through bile (Tvrdy 2021)
  • The nonlinear pharmacokinetics of silybin A and silybin B suggest silymarin has low bioavailability; only 20 to 50% appears to be absorbed (Gillessen 2020)(Hawke 2010)
  • Peak plasma levels of silybin were reached two hours after administration (Saller 2007)


  • No data is currently available


  • Silybin is rapidly metabolized by phase I and II biotransformation, undergoing extensive enterohepatic circulation (Gillessen 2020)
  • It is not clear which cytochromes are primarily responsible for SM’s metabolism (Bijak 2017)
  • SM has a half-life of two to six hours, so it is frequently dosed two to three times per day (Hawke 2010)(Saller 2007)


  • 1 to 8% of the administered dose of SM is eliminated by the kidneys, with the majority being eliminated into the gastrointestinal tract as bile (Tvrdy 2021)(Saller 2007)
  • 80% of silybin is excreted as glucuronide and sulfate conjugates with bile; 20 to 40% is recovered, whereas the remainder is excreted in feces (Gillessen 2020)
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