- Holy thistle
- Lady's thistle
- Mary thistle
- Marian thistle
For Patients & Caregivers
How It Works
Milk thistle and compounds derived from it are commonly used as herbal supplements for liver problems, but study results are mixed.
Laboratory studies suggest that milk thistle or some of its compounds have protective effects on the liver, but other animal studies suggest negative effects when combined with chronic alcohol consumption.
Studies in humans are mixed, and both a large survey and multicenter trial among patients with chronic hepatitis C did not find benefit on liver function tests with milk thistle. Other studies suggest milk thistle may reduce chemotherapy-induced hepatotoxicity in children with acute lymphoblastic leukemia and cisplatin-induced nephrotoxicity, as well as improve capecitabine-induced hand-foot syndrome and radiation therapy-induced mucositis.Topical administration of a silymarin gel was reported to reduce the severity of radiodermatitis and delay its occurrence.
- To treat alcohol-induced liver damage or cirrhosis Some placebo-controlled trials suggest silymarin may be helpful in treating alcoholic liver disease or cirrhosis, but more study is needed.
- To treat hepatitis A large survey and multicenter trial among patients with chronic hepatitis C did not find benefit on liver function tests with milk thistle.
- To prevent and treat drug-induced liver damage Laboratory, animal, and clinical trials suggest this use, although the effect varies by drug.
Do Not Take If
- You are taking cytochrome P450 3A4 substrate drugs: Milk thistle may increase the risk of side effects of these drugs.
- You are taking UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrate drugs: Milk thistle may increase the risk of side effects of these drugs.
- You are taking sirolimus: Milk thistle may interfere with the clearance of this drug.
- You are taking Haloperidol or Risperidone: 7 cases of pancreatitis were reported following concomitant use of milk thistle.
- You are taking Aripiprazole: A case of hepatotoxicity was reported with combined use of milk thistle.
High doses of silibinin can elevate bilirubin and liver enzymes.
GI symptoms: A patient experienced episodes of sweating, nausea, vomiting, diarrhea, abdominal pain, weakness, and collapse. Symptoms resolved after the patient discontinued use of milk thistle.
Severe nosebleed: In a 25-year-old man, which may have been due to self-medication with aspirin, garlic, and milk thistle. His symptoms improved following treatment.
For Healthcare Professionals
Derived from the seed, pod, or fruit of milk thistle, the flavolignan silymarin is used primarily to manage various liver diseases. In vitro and animal studies suggest that flavonoids in milk thistle have antioxidant and anticancer effects (7) (8) (12) (16) (17), and may protect against Alzheimer’s disease (23) (24).
Clinical data suggest benefits of supplementation with milk thistle or silymarin for improving lipid profiles and glycemic indices in type 2 diabetic patients (18) (40). It may also be useful against alcoholic liver disease (9), cirrhosis (11) (19), and for improving fibrosis associated with nonalcoholic steatohepatitis (39). However, in both a large survey and subsequent multicenter placebo-controlled trial among patients with chronic hepatitis C, silymarin did not significantly reduce serum ALT levels (41) (42). In addition, although silymarin was associated with reduced progression from fibrosis to cirrhosis, there was no impact on clinical outcomes was (43). Milk thistle was also reported no more effective than placebo against trichotillomania in a study involving both adults and children (46).
Other studies suggest milk thistle may reduce chemotherapy-induced hepatotoxicity in children with acute lymphoblastic leukemia (20), and cisplatin-induced nephrotoxicity (28) as well as improve capecitabine-induced hand-foot syndrome (6) and radiation therapy-induced mucositis (3). Topical administration of a silymarin gel was reported to reduce the severity of radiodermatitis and delay its occurrence (47).
Both silymarin (27) and silibinin (48) have estrogenic effects with greater affinity for estrogen receptor (ER-beta), and activation of ER-beta results in suppression of cell growth.
Silibinin can exacerbate the negative effects of chronic alcohol consumption on liver cancer (10).
Mechanism of Action
Animal models suggest that silymarin confers hepatoprotection via downregulation of extracellular matrix proteins such as collagen (2). It may also be useful against liver carcinogenesis by inhibiting mast cells, a source of matrix metalloproteins that are involved in invasion and angiogenesis (29). In addition, silymarin reduced cisplatin-induced kidney damage in rats without diminishing the drug’s antitumor activity (7), and suppressed formation of amyloid beta-proteins and neurotoxicity in mice (30).
Silibinin, one of the flavonoids, demonstrated antioxidant and anti-inflammatory effects by inhibiting release of hydrogen peroxide and production of tumor necrosis factor alpha (31). Another study showed improvement in endothelial dysfunction via reduction in circulating and vascular asymmetric dimethylarginine (ADMA) levels. ADMA is an endogenous inhibitor of nitric oxide synthase (NOS) and is believed to play a role in endothelial dysfunction, associated with cardiovascular disease (32). Silibinin also inhibits the early phase of hepatitis C viral infection by affecting endosomal trafficking of virions (34).
Other studies indicate milk thistle flavonoids exert anticancer effects by arresting G1 and S phases of the cell cycle (8). Silybin inhibited hepatocellular carcinoma cell growth via the Notch signaling pathway (36). Silibinin suppressed the epidermal growth factor receptor (EGFR)-induced expression of CD44, the transmembrane receptor for hyaluronan implicated in tumor cell invasion and metastasis by inhibiting EGFR activity in breast cancer cells (33). Suggested mechanisms for reduced efficacy of silibinin in liver tumor-bearing animals that were co-administered ethanol include impaired hepatic processing of silibinin (10).
Silybin and isosilybin were shown to strongly inhibit PXR-mediated CYP3A4 induction (35).
High doses of silibinin can elevate bilirubin and liver enzymes (25).
Intermittent GI symptoms: A patient experienced intermittent episodes of sweating, nausea, vomiting, diarrhea, abdominal pain, weakness, and collapse that resolved after discontinuation of milk thistle supplementation (5).
Severe epistaxis: In a 25-year-old man, possibly due to self-medication with aspirin, garlic, and milk thistle. His symptoms improved following treatment (22).
- Cytochrome P450 3A4 substrates: Milk thistle inhibits cytochrome P450 3A4 (4) and can affect the intracellular concentration of drugs metabolized by this enzyme. However, conflicting data indicate no such effects (13) (14) (38). In another study, consumption of milk thistle did not reduce levels of indinavir, an AIDS drug (15).
- UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrates: Milk thistle modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (26).
- Sirolimus: Milk thistle may decrease clearance. Monitor therapy especially when combined with nivolumab, which may interfere with the potential to help prevent rejection of donor kidney in transplant patients (44) (45).
- Haloperidol or Risperidone: 7 cases of pancreatitis were reported following concomitant use of milk thistle (49)
- Aripiprazole: A case of hepatotoxicity was reported with combined use of milk thistle (49).