Silybum Marianum (Milk Thistle) benefits and side effects have been studied extensively. This article reviews on
published reports pertaining to milk thistle benefits and side effects.

INTRODUCTION

Silybum Marianum has been used for centuries for the treatment of liver disease. Milk thistle appears to be safe
and the available evidence on the mechanisms of action appears promising [1]. Traditionally, milk thistle is
commonly used for liver cirrhosis, alcoholic hepatitis, alcoholic fatty liver, liver poisoning, and viral hepatitis. Silybum
Marianum plays a role in displacing toxins binding to the liver and causing the liver cells to regenerate at a faster
rate.

PREVALENCE OF SILYBUM MARIANUM

The most common herbal medications taken by hepatitis C patients were silybum Marianum (12.2%), ginseng
(4.6%), and echinacea (3.0%).
Siddiqui U Prevalence and predictors of herbal medication use in veterans with chronic hepatitis C. J Clin
Gastroenterol. 2004 Aug;38(7):605-10.

MAIN ACTIVE INGREDIENTS OF SILYBUM MARIANUM

Silybum Marianum extracts are standardized to a concentration of 70-80% of flavone lignans including isosilybinin,
silybinin, silychristin, and silydianin, which are collectively called silymarin.

SILYBUM MARIANUM EXTRACTION METHOD

The extraction of Silybum Marianum compounds usually involves a two-step defatting and extraction process using
organic solvents. Lipid removal is an important extraction step for Silybum Marianum compounds, because defatted
material yields twice the silymarin concentration.
Wallace SN Extraction of nutraceuticals from milk thistle: part II. Extraction with organic
solvents. Appl Biochem Biotechnol. 2003 Spring;105 -108:891-903.

Bioling water is an effective method to extract more polar silymarins such as taxifolin and silychristin from Silybum
Marianum seed. The yield of silymarin of Silybum Marianum extraction increases with increasing temperature.
While, boling alcohol is an effective way to extract taxifolin, silychristin, silybinin A and silybinin B from defatted milk
thistle seed meal.
[Wallace SN Batch solvent extraction of flavanolignans from milk thistle (Silybum marianum L. Gaertner). Phytochem Anal. 2005
Jan-Feb;16(1):7-16.

Severe degradation of Silybum Marianum compounds occurred under hot water extraction at 140 degrees C. Duan L
Silymarin extraction from milk thistle using hot water. Appl Biochem Biotechnol. 2004 Spring;113-116:559-68.

SILYBUM MARIANUM INGREDIENTS ISOLATION AND CHARACTERIZATION METHODS

Silybin A, silybin B, isosilybin A, and isosilybin B, could be separated from Silybum Marianum by sequential silica gel
column chromatography, preparative reversed-phase HPLC, and recrystallization.
Lee DY, Molecular structure and
stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J Nat Prod. 2003 Dec;66(12):1632.

Silybum Marianum ingredients include silybins A (1) and B (2), and isosilybins A (3) and B (4) silychristin (5)
isosilychristin (6) and silydianin (7), and a flavonoid, taxifolin (8). Methods used are preparative reversed-phase
HPLC, 2D NMR and CD spectroscopy.
Kim NC Complete isolation and characterization of silybins and isosilybins from milk thistle (Silybum
marianum). Org Biomol Chem. 2003 May 21;1(10):1684-9.

SILYBUM MARIANUM DRUG INTERACTION

Silybum Marianum decreased the trough concentrations of indinavir in humans. [Hu Z, Herb-drug interactions: a literature
review. Drugs. 2005;65(9):1239-82.]

However, another study showed Silybum Marianum had no apparent effect on indinavir plasma concentrations.
DiCenzo R Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy. 2003 Jul;23(7):866-70.

This conflicting data might be due to different Silybum Marianum product preparation, extraction method, product
composition, experimental design or even the purity of Silybum Marianum.

SILYBUM MARIANUM SIDE EFFECTS

Silybum Marianum appears to be safe and accepted by patients. Only a few cases of Silybum Marianum side effect
have been reported. Citations about Silybum Marianum side effects and safety issues from various researchers are
summarized as follows:

Silymarin (Silybum Marianum) with few side effects that has been safely used for centuries to treat liver ailments.
Giese LA. Milk thistle and the treatment of hepatitis. Gastroenterol Nurs. 2001 Mar-Apr;24(2):95-7.

Silymarin (Silybum Marianum) side effects include gastrointestinal disturbances and allergic skin rashes. Saller R et al,
The use of silymarin in the treatment of liver diseases Drugs. 2001;61(14):2035-63.

In a study of 170 patients with cirrhosis, researchers observed no Silybum Marianum side effect. Ferenci P. et al,
Randomized controlled trial of silymarin (milk thistle) treatment in patients with cirrhosis of the liver. J Hepatol. 1989 Jul;9(1):105-13.

Silymarin (Silybum Marianum) exposure did not produce any signs of overt toxicity or any changes in relative organ
weights.
Johnson VJ et al, Physiological responses of a natural antioxidant flavonoid mixture, silymarin, in BALB/c mice: III. Silymarin inhibits T-
lymphocyte function at low doses but stimulates inflammatory processes at high doses. Planta Med. 2003 Jan;69(1):44-9.

Treatment with Silybum Marianum appears to be safe and well tolerated. No reduction in mortality, but
improvements in histology and in biochemical markers of liver function among patients with chronic liver disease
were found with Silybum Marianum supplement.
Jacobs BP, Milk thistle for the treatment of liver disease: a systematic review and meta-
analysis. Am J Med. 2002 Oct 15;113(6):506-15.

Silybum Marianum was not associated with a significantly increased risk of adverse events. [Rambaldi A. et al, Milk thistle
for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD003620.]

High dose of Silybum Marianum may stimulate inflammatory process (from a mice study). Physiological responses of a natural
antioxidant flavonoid mixture, silymarin, in BALB/c mice: III. Silymarin inhibits T-lymphocyte function at low doses but stimulates inflammatory processes
at high doses. Planta Med. 2003 Jan;69(1):44-9.

SILYBUM MARIANUM EXTRACT BENEFITS

Silybum Marianum silymarin has anti-inflammatory, cytoprotective, and anticarcinogenic effects. These effects are
probably related to inhibition of activation of NF-kappa B and the kinases.  
Manna SK Silymarin [MILK THISTLE] suppresses TNF-
induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. J Immunol. 1999 Dec 15;163(12):6800-9.

ANTI-MICROBIAL ACTIVITIES

Silybum Marianum silybin inhibited RNA and protein synthesis on gram-positive bacteria. Lee DG et al Gram-positive bacteria
specific properties of silybin derived from Silybum marianum [Silybum Marianum]. Arch Pharm Res. 2003 Aug;26(8):597-600.

ANTI-OXIDANT

Silybum Marianum silymarin reduced NO production at less than 300 ppm. Soliman KF In vitro attenuation of nitric oxide
production in C6 astrocyte cell culture by various dietary compounds. Proc Soc Exp Biol Med. 1998 Sep;218(4):390-7.

ARTHEROSCLEROSIS

Silybum Marianum and lecithin have found to have anti-atherosclerotic activity in rabbits. Silybum Marianum-
phospholipid complex showed a strong anti-atherosclerotic activity.
Bialecka M. The effect of bioflavonoids and lecithin on the
course of experimental atherosclerosis in rabbits Ann Acad Med Stetin. 1997;43:41-56.

CANCER

Silybum Marianum silibinin and Silybum Marianum silymarin, have shown the anticancer effects in different cancer
cells.

Silybum Marianum silymarin exerts chemopreventive effects against tumorigenicity by inhibiting endogenous tumor
promoter TNF alpha.
Zi X, Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin [Silybum Marianum]: inhibition of mRNA
expression of an endogenous tumor promoter TNF alpha. Biochem Biophys Res Commun. 1997 Oct 9;239(1):334-9.

BLADDER Silybum Marianumsilibinin modulates cyclin-dependent kinase inhibitors - cyclin-dependent kinases -
cyclin cascade and activates caspase 3 causing growth inhibition and apoptotic death of human bladder transitional
cell carcinoma cells.
Tyagi A Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-
CDK-cyclin cascade, and caspase 3 and PARP cleavages. Carcinogenesis. 2004 Sep;25(9):1711-20. Epub 2004 Apr *milk thistle

Silybum Marianum silibinin decreased survivin levels and caspases-PARP cleavages, in accord with a strong
apoptotic death and growth inhibition of Human bladder transitional-cell papilloma cells.
Tyagi AK Silibinin down-regulates
survivin protein and mRNA expression and causes caspases activation and apoptosis in human bladder transitional-cell papilloma RT4 cells. Biochem
Biophys Res Commun. 2003 Dec 26;312(4):1178-84.

Silybum Marianum silymarin was found to be effective in preventing OH-BBN-induced bladder carcinogenesis in
mice.
Vinh PQ et al Chemopreventive effects of a flavonoid antioxidant silymarin [Silybum Marianum] on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced
urinary bladder carcinogenesis in male ICR mice. Jpn J Cancer Res. 2002 Jan;93(1):42-9.

BREAST An in vitro study has suggested a possible synergism between Silybum Marianum silibinin and
conventional cytotoxic agents for breast cancer treatment.
Tyagi AK Synergistic anti-cancer effects of silibinin [Silybum Marianum]
with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Oncol Rep.
2004 Feb;11(2):493-9.

Silybum Marianum extract may exert a strong anticarcinogenic effect against breast cancer involving inhibition the
threshold kinase activities of cyclin-dependent kinases and associated cyclins, leading to a G1 arrest in cell cycle
progression.
Zi X. Anticarcinogenic effect of a flavonoid antioxidant, silymarin [milk thistle], in human breast cancer cells MDA-MB 468: induction of
G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins. Clin Cancer
Res. 1998 Apr;4(4):1055-64.

COLON Study showed a chemopreventive ability of Silybum Marianum silymarin against chemically induced colon
tumorigenesis.
Kohno H et al, Silymarin [Silybum Marianum], a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-
induced colon carcinogenesis in male F344 rats. Int J Cancer. 2002 Oct 10;101(5):461-8.

ENDOTHELIAL CELLS Silybum Marianumsilibinin may exert, at least partly, its anti-cancer effect by inhibiting
angiogenesis through induction of endothelial apoptosis via modulation of NF-kappaB, Bcl-2 family and caspases.
Yoo HG Involvement of NF-kappaB and caspases in silibinin-induced apoptosis of endothelial cells. Int J Mol Med. 2004 Jan;13(1):81-6.

Silybum Marianum silibinin toxicity to cancer cells involves the epidermal growth factor receptor signaling pathway.
Qi L, Epidermal growth factor receptor mediates silibinin [Silybum Marianum-induced cytotoxicity in a rat glioma cell line. Cancer Biol Ther. 2003 Sep-
Oct;2(5):526-31.

LUNG Silybum Marianum containing Silibinin exerted a dose-dependent inhibitory effect on the invasion and motility
of human lung cancer cells.
Chu SC Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-
plasminogen activator and matrix metalloproteinase-2. Mol Carcinog. 2004 Jul;40(3):143-9.

LIVER Silybum Marianum may be useful in the prevention or treatment of liver dysfunction in patients undergoing
anticancer therapy.
Ladas EJ Milk thistle: is there a role for its use as an adjunct therapy in patients with cancer? J Altern Complement Med. 2003
Jun;9(3):411-6.

PROSTATE Silybum Marianum extracts possess anticancer activities on human prostate carcinoma. Isosilybin A
and B might be the most effective suppressors of prostate-specific antigen secretion by androgen-dependent
LNCaP cells. Researchers suggested that milk thistle extracts enriched for isosilybin A or B might possess improved
potency in prostate cancer prevention and treatment.
[Davis-Searles PR, Milk thistle and prostate cancer: differential effects of pure
flavonolignans from Silybum marianum [MILK THISTLE] on antiproliferative end points in human prostate carcinoma cells. Cancer Res. 2005 May 15;65
(10):4448-57]

In prostate cancer, Silybum Marianum silibinin exerts its anti-cancer effect probably via epidermal growth factor
receptor, insulin-like growth factor receptor type I and nuclear factor kappa B signaling
Singh RP A cancer chemopreventive
agent silibinin [Silybum Marianum], targets mitogenic and survival signaling in prostate cancer. Mutat Res. 2004 Nov 2;555(1-2):21-32.

Silybum Marianum silibinin was able to down regulate 5alpha-dihydrotestosterone, thus, milk thistle may be
beneficial to prostate health.
Thelen P Silibinin down-regulates prostate epithelium-derived Ets transcription factor in LNCaP prostate cancer
cells. Planta Med. 2004 May;70(5):397-400.

Other studies show the anti-tumor activities of Silybum Marianum extracts on prostate cancer: [1] Inhibition of
telomerase activity and secretion of prostate specific antigen by silibinin [Silybum Marianum] in prostate cancer
cells. J Urol. 2004 May;171(5):1934-8. [2] Prostate cancer prevention by silibinin [milk thistle]. Curr Cancer Drug
Targets. 2004 Feb;4(1):1-11 [3] A flavonoid antioxidant, silymarin [Silybum Marianum], inhibits activation of erbB1
signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate
carcinoma DU145 cells. Cancer Res. 1998 May 1;58(9):1920-9. Silibinin [Silybum Marianum] decreases prostate-
specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells:
implications for prostate cancer intervention. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7490-5. Dhanalakshmi
S Silibinin [Silybum Marianum] sensitizes human prostate carcinoma DU145 cells to cisplatin- and carboplatin-
induced growth inhibition and apoptotic death. Int J Cancer. 2003 Sep 20;106(5):699-705. Zi X Silibinin [Silybum
Marianum] up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-
independent prostate cancer cells Cancer Res. 2000 Oct 15;60(20):5617-20. Singh RP Dietary feeding of [Silybum
Marianum] silibinin inhibits advance human prostate carcinoma growth in athymic mice and increases plasma insulin-
like growth factor-binding protein-3 levels. Cancer Res. 2002 Jun 1;62(11):3063-9. Tyagi A et al, Silibinin [Silybum
Marianum] strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-
M arrest, and apoptosis. Clin Cancer Res. 2002 Nov;8(11):3512-9. Tyagi A Antiproliferative and apoptotic effects of
silibinin [Silybum Marianum] in rat prostate cancer cells. Prostate. 2002 Nov 1;53(3):211-7
.

SKIN In studies of rats, Silybum Marianum extracts provided substantial protection against different stages of UVB-
induced carcinogenesis, possibly via its strong antioxidant properties.
Katiyar SK et al, Protective effects of silymarin [milk thistle]
against photocarcinogenesis in a mouse skin model. J Natl Cancer Inst. 1997 Apr 16;89(8):556-66]

Topical treatment of Silybum Marianum silymarin inhibited 7,12-dimethylbenz(a)anthracene-initiated and several
tumor promoters in mouse models. Katiyar SK.
Silymarin [Silybum Marianum] and skin cancer prevention: anti-inflammatory, antioxidant
and immunomodulatory effects (Review). Int J Oncol. 2005 Jan;26(1):169-76.

Other studies show the anti-tumor activities of Silybum Marianum extracts on skin cancer: Silibinin prevents
ultraviolet radiation-caused skin damages in SKH-1 hairless mice via a decrease in thymine dimer positive cells and
an up-regulation of p53-p21/Cip1 in epidermis. Carcinogenesis. 2004 Aug;25(8):1459-65. Epub 2004 Mar 19. A
flavonoid antioxidant, silymarin [Silybum Marianum], affords exceptionally high protection against tumor promotion in
the SENCAR mouse skin tumorigenesis model. Cancer Res. 1999 Feb 1;59(3):622-32

TONGUE Feeding of Silybum Marianum silymarin (500 p.p.m.) during the promotion phase of 4-NQO-induced rat
tumorigenesis exerts chemopreventive ability against tongue squamous cell carcinoma through modification of
phase II enzymes activity, cell proliferation, and/or PGE(2) content.
Yanaida Y et al Dietary silymarin [Silybum Marianum] suppresses
4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. Carcinogenesis. 2002 May;23(5):787-94.

CHOLESTASIS

In 1985, Koch HP reported that Silybum Marianum was a very potent inhibitor of cyclic AMP phosphodiesterase. Milk
thistleÂ’s constituents, silybin, silydianin and silychristin, are 12.66 to 52.06 times more active than theophylline.
[Silymarin [Silybum Marianum]: potent inhibitor of cyclic AMP phosphodiesterase. Methods Find Exp Clin Pharmacol. 1985 Aug;7(8):409-13.]

Silybum Marianum prevents cholestasis induced by estrogens and taurolithocholate via inhibiting cAMP-
phosphodiesterase.
[Crocenzi FA et al, Silibinin [Milk thistle] prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated
rat hepatocyte couplets: possible involvement of cAMP. Biochem Pharmacol. 2005 Apr 1;69(7):1113-20.]

DIABETES

Silybum Marianumextracts may be useful in treatment of non-insulin-dependent diabetes mellitus, as silibinin inhibits
glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo.
von Schonfeld J
Silibinin [Silybum Marianum], a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A
toxicity. Cell Mol Life Sci. 1997 Dec;53(11-12):917-20.]

Aqueous extracts of Silybum Marianum exhibit potent hypoglycaemic and anti-hyperglycaemic activities in normal
and streptozotocin diabetic rats without affecting insulin secretion.
Maghrani M Study of the hypoglycaemic activity of Fraxinus
excelsior and Silybum marianum [Silybum Marianum]  in an animal model of type 1 diabetes mellitus. J Ethnopharmacol. 2004 Apr;91(2-3):309-16.

HEART
Silybum Marianum extract, silymarin, protects cardiomyocytes against doxorubicin-induced oxidative stress via cell
membrane stabilization effect, radical scavenging and iron chelating potency.
Chlopcikova S Chemoprotective effect of plant
phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part I. Silymarin [Silybum Marianum] and its flavonolignans. Phytother Res. 2004
Feb;18(2):107-10.

IMMUNE MODULATION

A study of mice showed Silybum Marianum silymarin could prevent UVB-induced immuno-suppression and oxidative
stress probably by inhibiting the infiltration of leukocytes, and myeloperoxidase activity.
Katiyar SK. Treatment of silymarin
[Silybum Marianum], a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin. Int J Oncol. 2002 Dec;21
(6):1213-22.

A study demonstrated that Silybum Marianum was immunostimulatory in vitro. Milk thistle increased lymphocyte
proliferation in both mitogen and MLC assays. These effects of Silybum Marianum were associated with an increase
in interferon gamma, interleukin (IL)-4 and IL-10 cytokines in the MLC (table). This immunostimulatory effect
increased in response to increasing doses of Milk Thistle.  
Wilasrusmee C et al, Immunostimulatory effect of Silybum Marianum
(Silybum Marianum) extract. Med Sci Monit. 2002 Nov;8(11):BR439-43.


LIVER

CIRRHOSIS A double blind study of 170 patients with cirrhosis demonstrated that silymarin (Silybum Marianum
extract) treatment was effective in patients with alcoholic cirrhosis.
Ferenci P et al, Randomized controlled trial of silymarin [Silybum
Marianum]  treatment in patients with cirrhosis of the liver. J Hepatol. 1989 Jul;9(1):105-13.

Silybum Marianum and S-adenosylmethionine may be effective in alcoholic cirrhosis. Arteel G Advances in alcoholic liver
disease. Best Pract Res Clin Gastroenterol. 2003 Aug;17(4):625-47.

FIBROSIS Silybum Marianum silymarin retarded the development of alcohol-induced hepatic fibrosis in 12 baboons,
consistent with several positive clinical trials.
Lieber CS Silymarin [Silybum Marianum] retards the progression of alcohol-induced hepatic
fibrosis in baboons. J Clin Gastroenterol. 2003 Oct;37(4):336-9.

INJURY The hepatoprotective properties of milk thistle extracts in acute and chronic liver injury is probably related
to inhibition of leukotriene B (4) formation by silibinin [Silybum Marianum].
Dehmlow C. Inhibition of Kupffer cell functions as an
explanation for the hepatoprotective properties of silibinin. Hepatology. 1996 Apr; 23 (4): 749-54.

The protective effects of Silybum Marianum on liver injury may be related to the recovery of the membrane fluidities
of liver microsome and mitochondria.
Wu DF The effects of silymarin [Silybum Marianum] on hepatic microsomal and mitochondrial
membrane fluidity in mice.  Zhongguo Zhong Yao Za Zhi. 2003 Sep;28(9):870-2.

HEPATITIS C A double-blinded trial of 141 subjects demonstrated that milk thistle extract, silymarin, could improve
symptoms and general well-being of patients suffered from hepatitis C.
Tanamly MD et al, Randomised double-blinded trial
evaluating silymarin [Silybum Marianum]  for chronic hepatitis C in an Egyptian village: study description and 12-month results. Dig Liver Dis. 2004 Nov;36
(11):752-9.

However, some researchers found milk thistle extracts had no benefits on liver health.

Silybum Marianum extract was found to have no hepatoprotective effect on dairy cows.
Tedesco D Silymarin, a possible
hepatoprotector in dairy cows: biochemical and histological observations. J Vet Med A Physiol Pathol Clin Med. 2004 Mar;51(2):85-9.

NERVOUS SYSTEM

In a cell study, Silybum Marianumsilymarin significantly inhibited the LPS-induced activation of microglia and the
production of inflammatory mediators, such as tumour necrosis factor-alpha and nitric oxide (NO), and reduced the
damage to dopaminergic neurons.
Wang MJ Silymarin [Silybum Marianum] protects dopaminergic neurons against lipopolysaccharide-
induced neurotoxicity by inhibiting microglia activation. Eur J Neurosci. 2002 Dec;16(11):2103-12

Silybum Marianum extract protected cultured rat hippocampal neurons against oxidative stress-induced cell death.
Kittur S et al, Neurotrophic and neuroprotective effects of Silybum Marianum (Silybum marianum) on neurons in culture. J Mol Neurosci. 2002 Jun;18(3):
265-9.


This Silybum Marianum article is for your information only. If you have any question, please, consult with your doctor.
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