Shui Fei Ji
StarSilybum marianum (L.) Gaertn.
Traditionally used for
- Urinary & fluids
- Liver & jaundice
Cautions & contraindications
- Diabetes
- Allergy risk
- Toxic — professional use only
☯ TCM Properties
Clears Heat and Resolves Toxicity; Courses the Liver and benefits the Gallbladder; Clears Damp-Heat from the Liver and Gallbladder; Protects the Liver
Traditional Chinese Uses
Shui Fei Ji (milk thistle, silybum marianum) is a cool, bitter herb that in Chinese medicine clears Heat and Damp-Heat from the Liver and Gallbladder. It is used for hepatitis, jaundice, gallstones, and fatty liver conditions where Liver-Gallbladder Damp-Heat is the underlying pattern. Though originally introduced from Europe, silymarin — its active compound — has made it one of the most thoroughly researched herbs for Liver protection worldwide, validating its traditional TCM use for liver-clearing conditions.
Western Herbalism Properties
Relationships
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Botanical Description
Silybum marianum, milk thistle or Shui Fei Ji, is a stout biennial or annual herb in the Asteraceae family, native to the Mediterranean basin and naturalized widely across temperate regions. First-year plants form a large basal rosette of glossy dark green leaves boldly veined and mottled white, with deeply pinnatifid lobes ending in stiff yellow spines; in the second year flowering stems rise 60-200 cm. Solitary terminal heads 4-8 cm across are subtended by stout spine-tipped involucral bracts and bear bright red-purple tubular disc florets in summer. The shiny dark brown achenes (treated commercially as 'seeds') bear a tuft of bristly pappus and contain the silymarin flavonolignan complex.
Active Constituents
Silymarin
Flavonolignan complexConcentration: Roughly 1.5-3% of the dried fruit, reported across populations as 1 to 4.3% of achene weight; standardised extracts are concentrated to 70-80% silymarin
The name for the whole flavonolignan complex rather than a single molecule, and the entity all the clinical trials actually dose. Its composition varies between chemotypes and between extract manufacturers, which is one reason trial results across the literature are hard to pool.
Silybin A and silybin B (silibinin)
FlavonolignanConcentration: Together roughly 50-60% of silymarin, and up to about 70% of some standardised extracts
The principal and most-studied component. Silybin is the moiety responsible for the in vitro inhibition of UGT1A1, OATP1B1, BCRP and CYP2C9. Its oral bioavailability is poor: after 200 mg of milk thistle three times daily in cancer patients, peak plasma silybin was only 0.025 to 0.257 microM, which is the direct reason most of the in vitro interactions fail to appear in vivo.
Silychristin
FlavonolignanConcentration: Roughly 20% of silymarin
The second most abundant flavonolignan of the complex, contributing to its antioxidant activity.
Silydianin
FlavonolignanConcentration: Roughly 10% of silymarin
A structurally distinct flavonolignan of the complex. Its proportion varies strongly between chemotypes, and is one of the markers used to distinguish them.
Isosilybin A and isosilybin B
FlavonolignanConcentration: Roughly 5% of silymarin
Regioisomers of silybin present as minor components of the complex.
Taxifolin (dihydroquercetin)
FlavanonolThe flavonoid precursor unit from which the flavonolignans are built, by coupling to a coniferyl alcohol derived phenylpropanoid unit. Present as a minor constituent in its own right.
⚠ Drug Interactions
CYP2C9 substrates (losartan, warfarin, phenytoin, glimepiride)
This is the one CYP interaction with positive human data. In a crossover study of twelve healthy men of known genotype, silymarin 140 mg three times daily for 14 days increased losartan AUC and decreased the AUC of the active metabolite E-3174. The metabolic ratio fell significantly in CYP2C9*1/*1 subjects but not in CYP2C9*1/*3 subjects, so the size of the interaction depends on the patient's genotype: it is largest in extensive metabolisers, who have the most CYP2C9 activity to inhibit. Silymarin also increased metronidazole clearance in a separate study, so its net effect on CYP is not uniformly inhibitory.
Clinical note: Not a reason to avoid milk thistle in most patients. For warfarin, check INR one to two weeks after starting and after stopping. For losartan, expect a somewhat blunted antihypertensive effect since E-3174 carries most of the activity.
CYP3A4 substrates (midazolam, darunavir/ritonavir, indinavir, statins)
The widespread warning that milk thistle inhibits CYP3A4 rests on in vitro work and is not supported in humans. In a controlled study using rifampicin and clarithromycin as positive control inducer and inhibitor, standardised milk thistle 900 mg daily for 14 days left oral midazolam pharmacokinetics unchanged. In HIV-infected patients on darunavir/ritonavir, silymarin 150 mg every 8 hours for 14 days gave a geometric mean ratio for darunavir AUC of 0.86 (90% CI 0.70 to 1.05), with no dose adjustment needed. The explanation is pharmacokinetic: plasma silybin concentrations after ordinary oral dosing are far below the levels at which inhibition occurs in vitro.
Clinical note: Do not withhold milk thistle from patients on CYP3A4 substrates on this basis alone. The caveat is that all the negative studies used oral doses of ordinary strength; intravenous silibinin, used for amatoxin poisoning, reaches far higher concentrations and has not been studied this way.
UGT1A1 substrates (irinotecan/SN-38, raltegravir)
Silybin is a potent inhibitor of recombinant UGT1A1 in vitro, with a reported IC50 near 1.4 microM, which raised concern for irinotecan, whose active metabolite SN-38 is detoxified by UGT1A1. In six cancer patients given 200 mg milk thistle three times daily, neither 4 days nor 12 days of exposure changed irinotecan clearance or the extent of SN-38 glucuronidation. Peak silybin concentrations of 0.025 to 0.257 microM were far below the inhibitory range. The negative result is informative rather than merely absent.
Clinical note: Ordinary oral milk thistle is unlikely to alter irinotecan handling. It is still worth telling the oncology team, because the study was small and confined to standard doses.
OATP1B1 and BCRP substrates (rosuvastatin and other statins)
Silymarin inhibits OATP1B1-mediated and BCRP-mediated rosuvastatin transport in vitro with Ki values of 0.93 microM and 97 microM respectively, so on paper it should raise statin exposure and myopathy risk. In healthy men given silymarin 140 mg three times daily for 5 days before a 10 mg rosuvastatin dose, there was no significant change in AUC, half-life, apparent volume of distribution or apparent clearance. Silymarin taken as a recommended supplement is not a potent modulator of either transporter in vivo.
Clinical note: Statin therapy does not need adjusting for milk thistle. Persisting muscle symptoms should be investigated on their own merits rather than blamed on the herb.
Metronidazole
In twelve healthy volunteers, silymarin 140 mg daily for 9 days increased the clearance of metronidazole by about 29.5% and of its hydroxy metabolite by about 31.9%, with corresponding falls in half-life, Cmax and AUC and reduced urinary recovery. The authors attributed this to induction of intestinal P-glycoprotein and CYP3A4 on repeated dosing, which is the opposite direction from the inhibition predicted in vitro. This is a single small study that has not been replicated, so it is recorded as possible rather than established.
Clinical note: Suspend milk thistle during a course of metronidazole rather than risk under-treating the infection. Restart afterwards if the patient wants it.
Metformin, sulfonylureas and insulin
A meta-analysis of five randomised controlled trials in 270 patients with type 2 diabetes found that routine silymarin administration reduced fasting blood glucose by 26.86 mg/dL (95% CI -35.42 to -18.30) and HbA1c by 1.07 percentage points (95% CI -1.73 to -0.40), with no effect on lipids. The authors were explicit that the underlying trials were of low quality with high heterogeneity and that no recommendation can be made, but an effect of that size, if real, is large enough to matter alongside a sulfonylurea or insulin.
Clinical note: In a diabetic patient starting milk thistle, arrange home glucose monitoring for the first month and be ready to reduce a sulfonylurea or insulin dose.
Asteraceae (Compositae) allergy: ragweed, chrysanthemum, marigold, daisy
Silybum marianum is an Asteraceae, so patients sensitised to other members of the family can react to it. This is a hypersensitivity risk rather than a pharmacokinetic interaction, and it is the main clinically relevant adverse effect of a drug that is otherwise strikingly well tolerated: in the Cochrane meta-analysis the relative risk of adverse events versus placebo was 0.83 (95% CI 0.46 to 1.50), and in both the SyNCH hepatitis C trial and the Malaysian NASH trial the adverse event profile did not differ from placebo.
Clinical note: Ask about ragweed and chrysanthemum allergy before prescribing. Otherwise the expected adverse events are mild and gastrointestinal.
Dosage
| Form | Amount | Frequency | Duration | Population | Notes |
|---|---|---|---|---|---|
| decoction | See note — route-specific dosing | Daily | — | — | 中国药典 2020 【用法与用量】供配制成药用。 【性味与归经】苦，凉。归肝、胆经。 — Chinese Pharmacopoeia 2020, quoted verbatim; route and cautions preserved. Replaces a cleared category-filler value. |
Evidence Tier
Strong evidence · 10 studiesRecorded studies by study design, strongest design at the top. This is a study-design tier only, not a GRADE rating: it does not weigh risk of bias, consistency or precision.
Systematic review / meta-analysis
2
0 verified · 2 unverified
Randomized controlled trial
6
0 verified · 6 unverified
Show 6 studies
- Effect of Silymarin (Milk Thistle) on Liver Disease in Patients With Chronic Hepatitis C Unsuccessfully Treated With Interferon Therapy: A Randomized Controlled Trial
- A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis
- Assessing the Clinical Significance of Botanical Supplementation on Human Cytochrome P450 3A Activity: Comparison of a Milk Thistle and Black Cohosh Product to Rifampin and Clarithromycin
- Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers
- Effect of Silymarin Supplement on the Pharmacokinetics of Rosuvastatin
- Study on the Influence of Silymarin Pretreatment on Metabolism and Disposition of Metronidazole
Other clinical trial
0
Observational / case report
2
0 verified · 2 unverified
In vitro / animal
0
Other / unclassified
0
Verified: design read from PubMed for a DOI that resolves to the cited paper Unverified: taken from the study's recorded description
Clinical Studies
Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases
Eighteen randomised trials in 1088 patients. Only 28.6% of trials reported high methodological quality. Milk thistle had no significant effect on all-cause mortality (RR 0.78, 95% CI 0.53 to 1.15), complications of liver disease (RR 0.95, 95% CI 0.83 to 1.09) or liver histology. Liver-related mortality was reduced across all trials (RR 0.50, 95% CI 0.29 to 0.88) but not when restricted to high-quality trials (RR 0.57, 95% CI 0.28 to 1.19), which is the pattern expected when an apparent benefit is driven by bias. Adverse events were not increased (RR 0.83, 95% CI 0.46 to 1.50). The authors' conclusion questions the benefit of milk thistle in these conditions.
Effect of Silymarin (Milk Thistle) on Liver Disease in Patients With Chronic Hepatitis C Unsuccessfully Treated With Interferon Therapy: A Randomized Controlled Trial
The SyNCH trial: 154 patients with chronic hepatitis C and ALT of 65 U/L or more, previously failing interferon-based therapy, randomised to silymarin 420 mg, silymarin 700 mg or placebo three times daily for 24 weeks. Doses well above customary. Only 2 participants in each group met the primary ALT endpoint. Mean ALT decline did not differ across groups, nor did HCV RNA or quality of life. Adverse events matched placebo. This is the largest and most rigorous negative trial of the herb and is the reason milk thistle is not recommended for viral hepatitis.
A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis
Ninety-nine adults with biopsy-proven NASH and NAFLD activity score of 4 or more, randomised to silymarin 700 mg or placebo three times daily for 48 weeks with paired biopsies. The primary endpoint, a 30% or greater fall in NAS, was not met (32.7% versus 26.0%, p = 0.467). However, fibrosis improved by at least one stage in 22.4% on silymarin versus 6.0% on placebo (p = 0.023), and liver stiffness fell by 30% or more in 24.2% versus 2.3% (p = 0.002), with significant within-group falls in APRI, FIB-4 and NAFLD fibrosis score not seen on placebo. A negative primary endpoint with a positive antifibrotic secondary signal: hypothesis-generating, not practice-changing.
Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Five randomised trials, 270 patients. Silymarin reduced fasting blood glucose by 26.86 mg/dL (95% CI -35.42 to -18.30) and HbA1c by 1.07 (95% CI -1.73 to -0.40), with no effect on the lipid profile. Benefit on proteinuria and chronic kidney disease progression was reported in only one small study and is uncertain. The authors state that the low quality and high heterogeneity of the included trials mean no recommendation can be made.
Assessing the Clinical Significance of Botanical Supplementation on Human Cytochrome P450 3A Activity: Comparison of a Milk Thistle and Black Cohosh Product to Rifampin and Clarithromycin
Healthy volunteers took standardised milk thistle 900 mg daily for 14 days, with rifampicin and clarithromycin as positive control inducer and inhibitor, and oral midazolam as the CYP3A probe before and after each period. Midazolam pharmacokinetics were unaffected by milk thistle, while the positive controls produced the expected changes. The design is what makes the negative result credible.
Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers
Twelve healthy men of known CYP2C9 genotype (six *1/*1 and six *1/*3) in a two-phase randomised crossover, given silymarin 140 mg three times daily for 14 days. Losartan AUC rose significantly in *1/*1 subjects but not in *1/*3; E-3174 AUC fell in both. The losartan metabolic ratio fell significantly in *1/*1 (p less than 0.05) but not in *1/*3 (p = 0.065). This is the clearest positive human CYP interaction for milk thistle, and it is genotype dependent.
Effect of Silymarin Supplement on the Pharmacokinetics of Rosuvastatin
Paired in vitro and human study. Silymarin inhibited OATP1B1-mediated and BCRP-mediated rosuvastatin transport in vitro with Ki values of 0.93 microM and 97 microM. In eight healthy men randomised to silymarin 140 mg three times daily or placebo for 5 days before 10 mg rosuvastatin, no significant change in AUC, half-life, Vd/F or Cl/F was seen. The gap between in vitro potency and in vivo effect is the central lesson for this herb.
Effect of Milk Thistle on the Pharmacokinetics of Darunavir-Ritonavir in HIV-Infected Patients
Open-label fixed-sequence study in fifteen HIV-infected patients on darunavir/ritonavir 600/100 mg twice daily, with silymarin 150 mg every 8 hours added for 14 days. Geometric mean ratios for darunavir with silymarin versus alone were 0.86 (90% CI 0.70 to 1.05) for AUC0-12, 0.83 (90% CI 0.80 to 0.98) for Cmax and 0.94 (90% CI 0.73 to 1.19) for trough. Silymarin was well tolerated and no dose adjustment was judged necessary.
Effect of Milk Thistle (Silybum marianum) on the Pharmacokinetics of Irinotecan
Six cancer patients on weekly irinotecan 125 mg/m2 took milk thistle 200 mg three times daily for 14 days. Neither short-term (4 day) nor prolonged (12 day) intake significantly changed irinotecan clearance (31.2 versus 25.4 versus 25.6 L/h, p = 0.16), and the extent of SN-38 glucuronidation was unchanged (p = 0.64). Peak silybin concentrations were 0.025 to 0.257 microM, too low to inhibit CYP3A4 or UGT1A1 in vivo.
Study on the Influence of Silymarin Pretreatment on Metabolism and Disposition of Metronidazole
Twelve healthy volunteers took metronidazole 400 mg every 8 hours alone, then after a washout received silymarin 140 mg daily for 9 days with metronidazole added for the last 3 days. Silymarin increased the clearance of metronidazole by 29.51% and of hydroxy-metronidazole by 31.90%, with reduced half-life, Cmax, AUC and urinary excretion. The authors interpreted this as induction of intestinal P-glycoprotein and CYP3A4, the opposite of the inhibition predicted from in vitro data.
⚠ Safety & Contraindications
- Diabetes
- Allergy risk
- Toxic — professional use only
Contraindications
No special contraindications.
Source: Xi S, Gong Y. Essentials of Chinese Materia Medica and Medical Formulas. Academic Press/Elsevier, 2017, pp. 73–79.
Historical Texts
De Materia Medica (Dioscorides)
1st century CE, Roman eraThe English Physician (Culpeper)
17th century, England, 1652Pharmacopoeia of the People's Republic of China
Modern, 2005 editionReferences
- European Medicines Agency, Committee on Herbal Medicinal Products (HMPC). Assessment report on Silybum marianum (L.) Gaertn., fructus . European Medicines Agency
This information is for educational purposes only and is not intended to replace professional medical advice. Always consult a qualified healthcare provider before using any herbal remedy, especially if you are pregnant, nursing, or taking medications.
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