Milk Thistle Heath Benefits, Side Effects, Dosages
updated on February 6, 2012
Milk Thistle Safety, Side Effects, Toxicity, Dangers, Precautions and Drug Interactions

All supplements and drug products have side effects, especially at high doses. In this section, we are going to review reports about the side effects,
safety and some other issues of milk thistle.

Milk Thistle Side Effects
Milk thistle appears to be safe to healthy uses, no serious side effects are reported. In a study of 170 patients suffered from cirrhosis, no milk thistle
side effects were reported. [57] Only a few cases of milk thistle side effect have been reported in various studies. [55] Milk thistle extracts side effects
may include gastrointestinal disturbances and allergic skin rashes. [56] High dose of milk thistle may stimulate inflammatory process (from a mice
study). [61]

Milk Thistle Toxicity
Milk thistle extracts exposure did not produce any signs of overt toxicity or any changes in relative organ weights. [58] Treatment with milk thistle
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 milk thistle supplement. [59] Milk thistle was not associated with a significantly increased risk of
adverse events. [60]

Milk Thistle Precautions
Milk thistle can produce allergic reactions, which tend to be more common among people who are allergic to plants in the same family (e.g. ragweed,
chrysanthemium, marigold, and daisy}.

Milk Thistle Drug Interactions
Milk thistle decreased the trough concentrations of indinavir in humans. [53] However, another study showed milk thistle had no apparent effect on
indinavir plasma concentrations. [54]  This conflicting data might be due to different milk thistle product preparation, extraction method, product
composition, experimental design or even the purity of milk thistle.

Milk Thistle Food
Milk thistle seeds have been used as herbal medicine for many years, while milk thistle roots, leaves and stems are used as food. According to
Wikipedia.com, the roots can be eaten raw or boiled and buttered or even roasted. Milk thistle leaves can be added raw to salads.

Milk Thistle Dosage Forms
Most of milk thistle extracts available in the market in the dosage forms of capsules of standardized dried herb (each capsule contains about 120 -
140 mg silymarin), liquid extract, tincture and silymarin phosphatidylcholine complex. Phosphatidylcholine is a key element in cell membranes, it may
help the absorption of the milk thistle active ingredients.                                 
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Different people may experience different side effects and benefits of a product. You are encouraged to report adverse side effects of milk thistle to
FDA, its website is
www.fda.gov. There are always new information. Please, send me an email (zhion@zhion.com) to correct my mistake(s).
Reasonable care has been taken in preparing this document and the information provided herein is believed to be accurate. The information is not
intended to be a substitute for professional medical advice. It is important to seek the advice of a physician about any benefits and side effects of a
milk thistle supplement. Finally, please, do not transfer the article to other website. Thank you. ALL RIGHTS RESERVED.
Milk Thistle
The milk thistle is a thistle of the genus Silybum Adans., a flowering plant of the daisy family (Asteraceae). This genus contains only two species and
they are Silybum eburneum Coss. & Dur. (Silver Milk Thistle, Elephant Thistle or Ivory Thistle) and Silybum marianum (L.) Gaertner (the Blessed Milk
Thistle) [Wikipedia.com]

Milk thistle is native to the Mediterranean region. Milk thistle usually grows in dry, sunny areas. The stems branch at the top, and reach a height of 5
- 10 feet. The leaves are wide, with white blotches or veins. Milk thistle (Silybum marianum) has been considered as an important herbal remedy for
liver, kidney and gall bladder issues. Milk thistle is believed to have the benefits of protecting liver cells against toxins, alcohol, drugs, medications,
mercury and heavy metals.  Although, it should be noted that milk thistle is not a complete protector. alcohol and drug abusers may seek help with  
Intervention Support before contemplating the use of milk thistle. Consequently, milk thistle is promoted as an agent that is able to cleanse and
detoxify overburdened and stagnant livers, strengthen and tonify weak livers. Milk thistle has also used as a mild laxative to lubricate and soften the
stools.  Many animal studies have suggested the potential health benefits of milk thistle on liver, but the results in human studies are mixed. Milk
thistle may have limited side effects, and the side effects are related to gastrointestinal disturbances and allergic skin rashes.

Milk Thistle Extracts and Supplements
Traditional milk thistle extract is made from the seeds, which contain approximately 4-6% silymarin. Milk thistle extracts are standardized to a
concentration of 70-80% of flavone lignans including isosilybinin, silybinin, silychristin, and silydianin, which are collectively called
silymarin.
Silymarin may play a role in displacing toxins binding to the liver and causing the liver cells to regenerate at a faster rate. Silymarin is a strong
antioxidant, it reduces inflammation. That is why milk thistle is often suggested for people with hepatitis or other liver issues. Silymarin can be
extracted from the milk thistle seeds (fruit). The seeds are used to prepare the dosage form of capsules containing powdered herb or seed extracts;
and infusions (strong teas). In clinical studies, silymarin has typically been administered in dosages of 420–480 mg per day in two to three divided
doses. However dosages of 600 mg daily have also been used in the treatment of type II diabetes and dosage of 600 or 1200 mg daily in patients
chronically infected with hepatitis C virus. [Wikipedia.com, NCCAM]
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REFERENCES
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[2] Wallace SN Extraction of nutraceuticals from milk thistle: part II. Extraction with organic solvents. Appl Biochem Biotechnol. 2003 Spring;105
-108:891-903. [3] Wallace SN Batch solvent extraction of flavanolignans from milk thistle (Silybum marianum L. Gaertner). Phytochem Anal. 2005
Jan-Feb;16(1):7-16. [4]Duan L Silymarin extraction from milk thistle using hot water. Appl Biochem Biotechnol. 2004 Spring;113-116:559-68.[5] Lee
DY, Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J Nat
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Org Biomol Chem. 2003 May 21;1(10):1684-9.[7] 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. [8] Lee DG et al Gram-positive bacteria specific properties of silybin
derived from Silybum marianum [Milk Thistle]. Arch Pharm Res. 2003 Aug;26(8):597-600.[9] Soliman KF In vitro attenuation of nitric oxide production
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chemopreventive effects of a flavonoid antioxidant silymarin [MILK THISTLE]: inhibition of mRNA expression of an endogenous tumor promoter TNF
alpha. Biochem Biophys Res Commun. 1997 Oct 9;239(1):334-9.[12]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 [13]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.[14]
Vinh PQ et al Chemopreventive effects of a flavonoid antioxidant silymarin [MILK THISTLE] 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. [15]Tyagi AK Synergistic anti-cancer effects of silibinin
[milk thistle extract] 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.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.[17]  Kohno H et al, Silymarin [MILK THISTLE], 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.[18] 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.[19] Qi L, Epidermal growth factor receptor mediates silibinin [milk thistle]-induced cytotoxicity in a rat glioma cell line. Cancer Biol
Ther. 2003 Sep-Oct;2(5):526-31.[20] 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.[21] 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.[22] [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] [23] Singh RP A cancer chemopreventive agent silibinin [MILK THISTLE], targets
mitogenic and survival signaling in prostate cancer. Mutat Res. 2004 Nov 2;555(1-2):21-32.[23] Thelen P Silibinin down-regulates prostate
epithelium-derived Ets transcription factor in LNCaP prostate cancer cells. Planta Med. 2004 May;70(5):397-400.[24] Inhibition of telomerase activity
and secretion of prostate specific antigen by silibinin [milk thistle] in prostate cancer cells. J Urol. 2004 May;171(5):1934-8. [25] Prostate cancer
prevention by silibinin [milk thistle]. Curr Cancer Drug Targets. 2004 Feb;4(1):1-11 [26] A flavonoid antioxidant, silymarin [milk thistle], 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. 27 Silibinin [Milk Thistle] 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. 28 Dhanalakshmi S Silibinin [MILK THISTLE] 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. 29 Zi X Silibinin [MILK THISTLE] 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. [30] Singh RP Dietary feeding of [MILK THISTLE] 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. [31]Tyagi A et al, Silibinin
[MILK THISTLE] 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. [32] Tyagi A Antiproliferative and apoptotic effects of silibinin [MILK THISTLE] in rat prostate cancer cells.
Prostate. 2002 Nov 1;53(3):211-7.[33]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][34] Katiyar SK. Silymarin [milk thistle] and skin cancer prevention: anti-inflammatory,
antioxidant and immunomodulatory effects (Review). Int J Oncol. 2005 Jan;26(1):169-76.[35] 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. [36]A flavonoid antioxidant, silymarin [milk thistle], affords exceptionally high protection against tumor
promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res. 1999 Feb 1;59(3):622-32[36] Yanaida Y et al Dietary silymarin [MILK
THISTLE] suppresses 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. Carcinogenesis. 2002
May;23(5):787-94.[37]Silymarin [Milk thistle]: potent inhibitor of cyclic AMP phosphodiesterase. Methods Find Exp Clin Pharmacol. 1985
Aug;7(8):409-13.][38]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.]
[39] von Schonfeld J Silibinin [Milk thistle], 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.] [40] Maghrani M Study of the hypoglycaemic activity of Fraxinus excelsior and
Silybum marianum [Milk thistle]  in an animal model of type 1 diabetes mellitus. J Ethnopharmacol. 2004 Apr;91(2-3):309-16. [41]  Chlopcikova S
Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part I. Silymarin [Milk thistle] and its
flavonolignans. Phytother Res. 2004 Feb;18(2):107-10. [42] Katiyar SK. Treatment of silymarin [MILK THISTLE], a plant flavonoid, prevents
ultraviolet light-induced immune suppression and oxidative stress in mouse skin. Int J Oncol. 2002 Dec;21(6):1213-22. [43]Wilasrusmee C et al,
Immunostimulatory effect of Silybum Marianum (milk thistle) extract. Med Sci Monit. 2002 Nov;8(11):BR439-43.[44] 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. [45] Arteel G Advances in
alcoholic liver disease. Best Pract Res Clin Gastroenterol. 2003 Aug;17(4):625-47.[46] Lieber CS Silymarin [Milk thistle] retards the progression of
alcohol-induced hepatic fibrosis in baboons. J Clin Gastroenterol. 2003 Oct;37(4):336-9.[47]. Dehmlow C. Inhibition of Kupffer cell functions as an
explanation for the hepatoprotective properties of silibinin. Hepatology. 1996 Apr; 23 (4): 749-54. [48]. Wu DF The effects of silymarin [Milk thistle]
on hepatic microsomal and mitochondrial membrane fluidity in mice.  Zhongguo Zhong Yao Za Zhi. 2003 Sep;28(9):870-2. [49] Tanamly MD et al,
Randomised double-blinded trial evaluating silymarin [Milk thistle]  for chronic hepatitis C in an Egyptian village: study description and 12-month
results. Dig Liver Dis. 2004 Nov;36(11):752-9. [50]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.[51]  Wang MJ Silymarin [MILK THISTLE] protects dopaminergic neurons
against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation. Eur J Neurosci. 2002 Dec;16(11):2103-12 [52] Kittur S et al,
Neurotrophic and neuroprotective effects of milk thistle (Silybum marianum) on neurons in culture. J Mol Neurosci. 2002 Jun;18(3):265-9.
[53] Hu Z, Herb-drug interactions: a literature review. Drugs. 2005;65(9):1239-82.][54]DiCenzo R Coadministration of milk thistle and indinavir in
healthy subjects. Pharmacotherapy. 2003 Jul;23(7):866-70.[55]  Giese LA. Milk thistle and the treatment of hepatitis. Gastroenterol Nurs. 2001
Mar-Apr;24(2):95-7. [56] Saller R et al, The use of silymarin in the treatment of liver diseases Drugs. 2001;61(14):2035-63.[57] 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. [58]Johnson VJ
et al, Physiological responses of a natural antioxidant flavonoid mixture, silymarin, in BALB/c mice: III. [58][58]Silymarin inhibits T-lymphocyte
function at low doses but stimulates inflammatory processes at high doses. Planta Med. 2003 Jan;69(1):44-9.[59] 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.[60] 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.][61] 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.

[aa1] Raza SS, t al, Silymarin protects neurons from oxidative stress associated damages in focal cerebral ischemia: a behavioral, biochemical and
immunohistological study in Wistar rats. J Neurol Sci. 2011 Oct 15;309(1-2):45-54. [aa2] Suksomboon N et al, Meta-analysis of the effect of herbal
supplement on glycemic control in type 2 diabetes. J Ethnopharmacol. 2011 Aug 5 [aa3] Kim JL,et al, Osteoblastogenesis and osteoprotection
enhanced by flavonolignan silibinin in osteoblasts and osteoclasts.J Cell Biochem. 2011 Sep 6 [aa4] Lian R, et al, Silymarin Glyceryl
Monooleate/Poloxamer 407 Liquid Crystalline Matrices: Physical Characterization and Enhanced Oral Bioavailability. AAPS PharmSciTech. 2011
Sep 23. [D1] Lian R et al, Silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices: physical characterization and enhanced oral
bioavailability. AAPS PharmSciTech. 2011 Dec;12(4):1234-40. [D2] Varzi HN, et al, Effect of silymarin and vitamin E on gentamicin-induced
nephrotoxicity in dogs. J Vet Pharmacol Ther. 2007 Oct;30(5):477-81. [ABC1] Katiyar SK, et al, Silymarin protects epidermal keratinocytes from
ultraviolet radiation-induced apoptosis and DNA damage by nucleotide excision repair mechanism. PLoS One. 2011;6(6):e21410. [ABC2] Singh RP,
et al, Cosmeceuticals and silibinin. Clin Dermatol. 2009 Sep-Oct;27(5):479-84. [ABC3] GRAS application, JHB Inc. December 14, .2OOO [ABC4]
Kingcounty.gov. December 1, 2011
Milk Thistle Benefits
A study has demonstrated that milk thistle and S-adenosylmethionine may benefit people from alcoholic cirrhosis. [45] It may also protects liver for
patients undergoing anticancer therapy.[21] Milk thistle may protect liver from injury, in general, the protective effects of milk thistle on liver injury
may be related to the recovery of the membrane fluidities of liver microsome and mitochondria [48]Though milk thistle is popular used for the support
of a healthy liver, milk thistle may have many other benefits. For example, proper milk thistle formulations may have strong protection against
cardiovascular diseases, milk thistle-phospholipid complex showed a strong anti-atherosclerotic activity in rabbits. [10] In a test-tube study, milk
thistle extract exerted 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. [16]. In animal studies, milk thistle extracts show substantial
protection against different stages of UVB-induced carcinogenesis, possibly via its strong antioxidant properties. [33] Milk thistle also have anti-tumor
activities against skin cancer. [35]

Milk thistle may benefit people at risk from diabetes, as aqueous milk thistle extracts exhibit potent hypoglycaemic and anti-hyperglycaemic activities
in normal and streptozotocin diabetic rats without affecting insulin secretion. [40]  A study demonstrated that milk thistle was immunostimulatory in
vitro. Milk thistle increased lymphocyte proliferation in both mitogen and MLC assays. These effects of Milk Thistle 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.  [43] Further milk thistle extract may have good protection for brain too, it protected cultured rat hippocampal neurons against
oxidative stress-induced cell death. [52] The beneficial effects of milk thistle is actually dependent on its active ingredient- silymarin. The following
section discusses the key ingredients of milk thistle.
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Silymarin
Milk thistle has been used for centuries for the treatment of various liver conditions such as liver cirrhosis, alcoholic hepatitis, alcoholic fatty liver,
liver poisoning, or viral hepatitis. The key ingredient of milk thistle, silymarin, shows anti-inflammatory, cytoprotective, and anticarcinogenic activities,
and these activities are thought to be related to inhibition of activation of NF-kappa B and the kinases. [7] This milk thistle ingredient is anti-oxidative,
it is able to reduce NO production at less than 300 ppm. [9]  Study also show its ability to against chemically induced colon tumorgensis. [17]
Silymarin, protects cardiomyocytes against doxorubicin-induced oxidative stress via cell membrane stabilization effect, radical scavenging and iron
chelating potency. {41] Thus, milk thistle may support heart health. Topical treatment of milk thistle silymarin inhibited
7,12-dimethylbenz(a)anthracene-initiated and several tumor promoters in mouse models. [34] Feeding of milk thistle 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. [36] In a study, researchers treated  diabetics with 200 mg of silymarin three
times a day. After four months, patients had reductions in blood glucose levels. The results are very encouraging and the researchers planned to do
further large multi-centre studies. [Milk thistle may help diabetics -study, Reuters, October 30, 2006.] A study of mice showed silymarin could prevent
UVB-induced immuno-suppression and oxidative stress probably by inhibiting the infiltration of leukocytes, and myeloperoxidase activity. [42]
A double blind study of 170 patients with cirrhosis demonstrated that silymarin (milk thistle extract) treatment was effective in patients with alcoholic
cirrhosis. [44]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. [49] However, some researchers found that milk thistle extracts had no benefits on liver health. For instance,
milk thistle extract was found to have no hepatoprotective effect on dairy cows. [50] However, silymarin retarded the development of alcohol-induced
hepatic fibrosis in 12 baboons, consistent with several positive clinical trials. [46] Thus, milk thistle extract may have health benefits on certain liver
conditions. Further, silymarin may also benefit people suffered from certain types of neural conditions. In a cell study, silymarin 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.[51]

Silybin
Silybin may contribute to milk thistle health benefits of anti-infection and anti-cancer activities. Silybin, an important ingredient, inhibited RNA and
protein synthesis on gram-positive bacteria. [8] Silybin also shows anti-cancer activities in various studies. Silybin may benefit people suffered from
bladder cancer. Silibinin 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. [12] In another study, 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. [13] And
also, silymarin was found to be effective in preventing OH-BBN-induced bladder carcinogenesis in mice. [14] This milk thistle ingredient, may also
have synergism with cytotoxic agents for breast cancer. [15]

Isosilybin A and B
Isosilybin A and may contribute Milk thistle health benefits on 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. [22]  There are also couples of studies showing that milk thistle
benefits on prostate [24-32]. More studies are needed to understand the potential health benefits of issilybin A and B.
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Milk Thistle for Dogs
It is not sure if milk thistle is safe for dogs, limited studies have been done. A preparation of silymarin glyceryl monooleate/poloxamer 407 liquid
crystalline matrices was tested in dogs. Pharmacokinetic study in beagle dogs showed significantly increased peak concentration for silymarin
GMO/P407 LCM, and, most importantly, a 3.46-fold increase in oral bioavailability as compared with Legalon®, a commercial silymarin formulation.
[D1]

Drug-induced nephrotoxicity is an important cause of renal failure in dogs. Aminoglycoside antibiotics can produce nephrotoxicity in dogs, due to in
part to an imbalance of pro- and antioxidants. Milk thistle extract has potentially beneficial antioxidant properties. A control group was compared with
dogs that were administrated gentamicin by intramuscular injection, at dosage of 20 mg/kg, once daily for 9 days . The effects of vitamin E and milk
thistle extract - silymarin alone and in combination were compared for induced nephrotoxicity. It was found that milk thistle extract and vitamin E
decreased gentamicin-induced nephrotoxicity in dogs. [D2]

Milk Thistle, Acne and Skin
There is a rumour that milk thistle benefits people suffered from acne. It is unclear if milk thistle extract can be a cure for acne as no study has been
reported about the use of milk thistle on acne. But, there are a few studies about milk thistle' protection on skin from cancers. Solar ultraviolet (UV)
radiation is a well recognized epidemiologic risk factor for melanoma and non-melanoma skin cancers. This observation has been linked to the
accumulation of UVB radiation-induced DNA lesions in cells, and that finally lead to the development of skin cancers. A study shows treatment of
normal human epidermal keratinocytes (NHEK) with a milk thistle extract blocks UVB-induced apoptosis of NHEK in vitro. This milk thistle extract
reduces the amount of UVB radiation-induced DNA damage. One interesting finding - immunohistochemical analysis revealed that silymarin (the milk
thistle chemical) did not reduce the number of UVB-induced sunburn/apoptotic cells in the skin of NER-deficient mice, but reduced the number of
sunburn cells in their wild-type counterparts. [ABC1]
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Milk Thistle and Cosmeceuticals
Cosmeceuticals are used for nourishing and improving the appearance of the skin and are also documented as effective
agents for treating various dermatologic conditions. Cosmeceutical preparations from herbal origin are most popular
among consumers because these agents are mostly nontoxic and possess strong antioxidant activity. Because oxidative
stress is one of the major mechanisms for skin aging and dermatologic conditions, phytochemicals with proven
antioxidant activity, such as silibinin, could be useful for treating many dermatologic conditions as well as skin aging.
Silibinin possesses strong antioxidant activity and also modulates many molecular changes caused by xenobiotics and
ultraviolet radiation to protect the skin. [ABC2]

Milk Thistle and Cholesterol
Oxidative stresses are increasingly implicated in the pathogenesis of diabetic complications which may either cause
direct pancreatic beta-cell damage or lead to metabolic abnormalities that can induce or aggravate diabetes. It was
found that milk thistle seed extract has antioxidant properties on the glycemic profile in diabetic patients. In a study,
intake of milk thistle seed extract led to a significant decrease in HbA(1)c, FBS, total cholesterol, LDL, triglyceride SGOT
and SGPT levels. Thus, intake of milk thistle extracts potentially benefit people at risk of high cholesterol or even
diabetes.

Milk Thistle Mechanism
The therapeutic activity of milk thistle's active - silymarin is based on two sites or mechanisms of action: (a) It alters the
structure of the outer cell membrane of the hepatocytes in such a way as to prevent penetration of the liver toxin into the
interior of the cell (b) It stimulates the action of nucleolar polymerase A, resulting in an increase in ribosomal protein
synthesis, and thus it stimulates the regenerative ability of the liver and the formation of new hepatocytes. Milk thistle
extract provides hepatocellular protectiobny stabilizing hepatic cell membranes. Other actions include interruption of
enterohepatic recirculation of toxins, stimulation of protein synthesis and regeneration of damaged hepatocytes, as well
as antioxidant activity. Recent study on silibinin and silichristin to promote faster regeneration of diseased liver tissue
has focused on the ability of silibinin to stimulate the activity of the DNA-dependent RNA-polymerase I, causing an
increase in rRNA synthesis and an accelerated formation of intact ribosomes. This result is in a general increase in the
rate of synthesis of all cellular proteins. In vivo and in vitro molecular modeling experiments indicate that silibinin may  
mitate a steroid hormone by binding specifically to polymerase I, thus stimulating enzyme activity. This is how milk thistle
may benefit our health. [ABC3]
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Milk Thistle in Washington Sate
It is illegal to sell or buy milk thistle in Washington State and all existing plantings should be removed. Milk thistle is toxic
to livestock when consumed in large quantities. Milk thistle is a class A noxious weed in Washington State. [ABC4]
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Conclusion

1. Milk Thistle may benefit people suffered from certain liver conditions.
2. Milk Thistle may also benefit people suffered from certain types of cancers.
3. Milk Thistle side effects are mainly related to allergy and gastrointestinal disturbance.
4  Milk Thistle may also benefit people with skin cancers but more studies are needed to verify the evidence.
5. It is unclear if Milk Thistle benefit people with acne.
6. Milk Thistle may potentially benefit people with high lipid profiles.