Milk Thistle (Silybum marianum 1)


Supporting liver function and metabolism of glucose in diabetes, metabolic syndrome, hyperglycemia, and insulin resistance.

Mechanism of Action

Nearly all of the research on Silybum has focused on the silymarin complex, a mixture of flavonolignans obtained from the seeds. Silymarin includes the individual flavonolignans silybin A and silybin B (two isomers, together referred to as silibinin1), isosilybin A, isosilybin B (two isomers), silydianin, and silychristin. Silymarin also contains fatty acids2 and a flavanone dihydroquercetin (taxifolin)3 that is credited with medicinal effects.

Silibinin is structurally similar to quercetin and credited with antihyperglycemic effects. It has been extensively explored, as silibinin inhibits gluconeogenesis in the fasting state and glycogenolysis and glycolysis in the fed state. The mechanisms of silibinin’s support of glycemic control are complex, with research emphasizing numerous effects on glucose metabolism in the liver.1 Inhibition of glucose uptake is one mechanism of silybin4; however, this may not equate to the global effects of whole Silybum extracts. The resulting glucose starvation in some susceptible cells is one proposed mechanism of the anticancer effects of silybin. Amyloid accumulates in the pancreatic islets in type II diabetes, contributing to loss of pancreatic islet beta cells. Silibinin suppresses the formation of amyloid deposits and has protective effects on pancreatic beta cells.5

Evidence-Based Research

A 2011 meta-analysis of herbs showed Silybum to be among those natural agents having the strongest evidence of improving hemoglobin A1c (HbA1c) and fasting blood sugar based on a review of nine randomized, placebo-controlled trials (n = 487 patients) identified through electronic searches (MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials).6 One study of patients with cirrhosis-related diabetes mellitus reported Silybum reduced the insulin requirement by 25%.7

A randomized controlled trial of diabetic patients investigated the effects of 200 mg of Silybum taken two times per day on glycemic indices compared with placebo. Silybum was associated with a significant decrease in HbA1c, fetal bovine serum, total cholesterol, low-density lipoprotein, and triglycerides serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase levels compared with placebo.8

Diabetic nephropathy is the major cause of end-stage renal disease worldwide, and Silybum’s antidiabetic effects may extend to the kidneys and glomeruli. Rats with induced diabetic nephropathy were dosed with silymarin at either 60 mg/kg or 120 mg/kg for 60 days and followed for effects on renal function compared with control animals. The silymarin-treated groups showed significantly lower blood glucose, glycosylated hemoglobin, urine volume, serum creatinine, serum uric acid, and urine albumin compared with the diabetic control group as well as histopathological findings further demonstrating the protective effects of silymarin.9 Silymarin’s antioxidant effect can reduce stress on renal cells and offers protective effects on the glomeruli.10 Animal studies show silymarin to protect the kidneys against ischemic and reperfusion injury, stabilizing urea and creatinine and increasing superoxide dismutase and glutathione.11

Safety in Pregnancy and Breastfeeding

Because of its long-standing history as a wild food—the leaves, the roots, and the seeds—Silybum is assumed safe during pregnancy. Silybum is considered safe in lactation and, in fact, is a folkloric galactogogue,12 with modern clinical trials showing efficacy in promoting lactation in preterm mothers with infants in the neonatal intensive care unit.13 Another study compared 429 mg of silymarin per day to placebo in nursing women with hypogalactia and reported clear galactogogue effects calculated to be an 85.94% increase in breast milk production from Silybum without side effect or difficulties in tolerance.14

General Safety

Silybum is considered to be safe in both short- and long-term applications. Because of its extensive use as a modern natural medicine, Silybum has been the beneficiary of extensive studies by the National Institute of Environmental Health Sciences. The animal investigations found no significant toxicities, no interference with reproductive functions, and no carcinogenic effects.15 Animals with long-term Silybum exposure displayed a significantly lower incidence of bile duct hyperplasia, lower mean body weights, and significantly decreased incidences of hepatocellular adenoma and hepatocellular carcinoma and decreased incidences of mammary gland neoplasms occurred in exposed groups of female rats.16
A 2-year toxicity study dosing Silybum to rats and mice found no significant toxicity and a reduction in background tumors.17

No adverse effects or toxicities were noted in any of the human trials cited. A 2007 review of clinical trials reported Silybum extracts to be safe, well tolerated, and toxic or adverse effects to be minimal.18 The main side effects of silymarin seem to be rare gastrointestinal disturbances and allergic skin rashes.8 Oral doses of silymarin up to 2.1 g/day have been shown to be well tolerated and not associated with side effects in human hepatitis C virus (HCV) patients.19

Silybum, and particularly isolated silybin, are potent inhibitors of cytochrome P2C920 and cytochrome P3A21 groups of enzymes; however, isolated silybin was not shown to have significant interactions with other drugs. At doses 16 no antagonistic interactions are noted between Silybum and vincristine, and a modest synergistic effect has been demonstrated22 No drug-related adverse events were reported.19


Silybum is generally considered safe at doses up to 700 mg/day. Because Silybum has been so widely studied, medicinal products and clinical studies are often standardized to approximately 80% silymarin content. Dosages may range from 50 to 200 mg or more of Silybum taken two or three times daily to support liver function, reduce cholesterol, and improve glycemic control.

Nonlinear pharmacokinetics of silybin A and silybin B suggests low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg.19 Pharmacokinetic studies in human HCV patients have shown a nonlinear dose–blood level curve where doses of 140, 280, and 560 mg result in similar blood levels that suddenly jump at dose of 700 mg.19

Traditional Uses

The liver is greatly involved in processing carbohydrates, and liver herbs can be an important component of treatments for diabetes, metabolic syndrome, and hyperglycemia. Silybum has been used historically in the treatment of diabetes,23,24 liver disease, and liver cirrhosis and to prevent liver cancer in Europe and Asia since ancient times. Silybum seeds are used in tinctures and encapsulations primarily to support liver function; help the liver to process glucose, lipids and hormones; treat hepatitis and viral-induced inflammation; and help process and protect from exogenous chemicals and toxins.25 Parenteral Silybum preparations have become established as a viable treatment to save the liver after acute ingestion of hepatotoxins such as poison mushrooms.26,27

Silybum has also been used to treat gallbladder and biliary disease, jaundice, peritonitis, malarial fevers, bronchitis, insufficient lactation, and varicose veins and to reduce insulin resistance. The roots of Silybum have been prepared as a medicinal food, and the spines can be cut from leaves and used a salad greens and pot herbs. Silybum seeds have been roasted brewed into teas and coffee substitutes. Recent research is also showing the Silybum can be useful for renal disease and inflammation and may have efficacy against hormonal cancers including breast, cervical, and prostate.



Chem Biol Interact. 2012;195(2):119–32. Metabolic effects of silibinin in the rat liver. Colturato CP, Constantin RP, Maeda AS Jr, Constantin RP, Yamamoto NS, Bracht A, Ishii-Iwamoto EL, Constantin J.

2 Pharmacogn Mag. 2014;10(Suppl 1):S92–9. Silybum marianum oil attenuates oxidative stress and ameliorates mitochondrial dysfunction in mice treated with D-galactose. Zhu SY, Dong Y, Tu J, Zhou Y, Zhou XH, Xu B.

3 Eur J Pharmacol. 2012;684(1–3):19–26. Dihydroquercetin: More than just an impurity? Weidmann AE.

4 J Cell Biochem. 2011;112(3):849–59. Silybin and dehydrosilybin decrease glucose uptake by inhibiting GLUT proteins. Zhan T, Digel M, Küch EM, Stremmel W, Füllekrug J.

5 Biochem Biophys Res Commun. 2012;419(3):495–9. Silibinin inhibits the toxic aggregation of human islet amyloid polypeptide. Cheng B, Gong H, Li X, Sun Y, Zhang X, Chen H, Liu X, Zheng L, Huang K.

6 J Ethnopharmacol. 2011;137(3):1328–33. Meta-analysis of the effect of herbal supplement on glycemic control in type 2 diabetes. Suksomboon N, Poolsup N, Boonkaew S, Suthisisang CC.

7 Drugs. 2001;61(14):2035–63. The use of silymarin in the treatment of liver diseases. Saller R, Meier R, Brignoli R.

8 Phytother Res. 2006;20(12):1036–9. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M.

9 Iran J Kidney Dis. 2013;7(2):117–23. Effect of silymarin on streptozotocin-nicotinamide-induced type 2 diabetic nephropathy in rats. Sheela N, Jose MA, Sathyamurthy D, Kumar BN.

10 J Renal Inj Prev. 2012;1(1):3–5. Silymarin and diabetic nephropathy. Rafieian-Kopaie M, Nasri H.

11 Int Urol Nephrol. 2008;40(2):453–60. Antioxidant and protective effects of silymarin on ischemia and reperfusion injury in the kidney tissues of rats. Turgut F, Bayrak O, Catal F, Bayrak R, Atmaca AF, Koc A, Akbas A, Akcay A, Unal D.

12 Ann Pharmacother. 2012;46(10):1392–404. The use of galactogogues in the breastfeeding mother. Forinash AB, Yancey AM, Barnes KN, Myles TD.

13 Minerva Pediatr. 2014;66(5):375–80. Silymarin/galega administration in term and preterm mothers to sustain breast feeding: an observational study. Castoldi F, Pivetti V, Moiraghi L, Marangione P, Lista G.

14 Acta Biomed. 2008;79(3):205–10. Clinical efficacy, safety and tolerability of BIO-C (micronized Silymarin) as a galactagogue. Di Pierro F, Callegari A, Carotenuto D, Tapia MM.

15 World J Gastroenterol. 2011;17(18):2288–301. Silybin and the liver: from basic research to clinical practice. Loguercio C, Festi D.

16 Natl Toxicol Program Tech Rep Ser. 2011;(565):1–177. Toxicology and carcinogenesis studies of milk thistle extract (CAS No. 84604-20-6) in F344/N rats and B6C3F1 mice (Feed Studies). National Toxicology Program. Collaborators (45).

17 Toxicol Pathol. 2011;39(2):398–409. Investigating the potential for toxicity from long-term use of the herbal products, goldenseal and milk thistle. Dunnick JK, Singh B, Nyska A, Peckham J, Kissling GE, Sanders JM.

18 Integr Cancer Ther. 2007;6(2):146–57. Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.). Tamayo C, Diamond S.

19 J Clin Pharmacol. 2010;50(4):434–49. Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C. Hawke RL, Schrieber SJ, Soule TA, Wen Z, Smith PC, Reddy KR, Wahed AS, Belle SH, Afdhal NH, Navarro VJ, Berman J, Liu QY, Doo E, Fried MW; SyNCH Trial.

20 J Pharm Pharmacol. 2014;66(9):1339–46. The in-vitro effect of complementary and alternative medicines on cytochrome P450 2C9 activity. Mooiman KD, Goey AK, Huijbregts TJ, Maas-Bakker RF, Beijnen JH, Schellens JH, Meijerman I.

21 Drug Metab Dispos. 2013;41(9):1662–70. A systematic approach to evaluate herb-drug interaction mechanisms: investigation of milk thistle extracts and eight isolated constituents as CYP3A inhibitors.Brantley SJ, Graf TN, Oberlies NH, Paine MF.

22 Cancer. 2010;116(2):506–13. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Ladas EJ, Kroll DJ, Oberlies NH, Cheng B, Ndao DH, Rheingold SR, Kelly KM.

23 Pak J Biol Sci. 2013;16(9):401–11. Iranian medicinal plants for diabetes mellitus: a systematic review. Rashidi AA, Mirhashemi SM, Taghizadeh M, Sarkhail P.

24 Acta Med Iran. 2011;49(10):637–42. Antidiabetic plants of Iran. Shojaii A, Dabaghian FH, Goushegir A, Fard MA.

25 J Sci Food Agric. 2012;92(7):1441–7. Hepatoprotection of silymarin against thioacetamide-induced chronic liver fibrosis. Chen IS, Chen YC, Chou CH, Chuang RF, Sheen LY, Chiu CH.

26 Przegl Lek. 2012;69(8):541–3. Silibinin and its hepatoprotective action from the perspective of a toxicologist. Kostek H, Szponar J, Tchórz M, Majewska M, Lewandowska-Stanek H.

27 Curr Pharm Biotechnol. 2012;13(10):1964–70. Legalon® SIL: the antidote of choice in patients with acute hepatotoxicity from amatoxin poisoning. Mengs U, Pohl RT, Mitchell T.