Bulk Nutrition - Milk Thistle Information by David Tolson

Milk Thistle Information

Introduction

Milk thistle (silybum marianum) is a plant that has been used for centuries. It is presently one of the most commonly used medicinal plants worldwide [1]. The extract of the active components of milk thistle, consisting of various flavonolignans and the isoflavanoid taxifolin, is known as silymarin. The flavanolignans in silymarin include silybinin (also spelled silibinin), isosilybinin, silydianin, silychristin, and dehydrosilibinin [2-3]. Silibinin is generally seen as the primary active component, although the other flavanolignans may also contribute to the therapeutic activity of silymarin [4-5].

The biological activity of silymarin can be attributed to many factors. One of the most important is its action as an antioxidant, and many of the other biological effects are downstream of this action. Silymarin scavenges free radicals and causes a significant reduction in lipid peroxidation, protecting and stabilizing cell membranes [2, 4]. Silymarin stimulates RNA and protein synthesis in the liver, leading to faster regeneration after injury [5-6]. [2]. Silymarin may also bind directly to receptor sites in liver cells, prevent toxins from binding to those sites [8]. The effects are many, and the protective effect of milk thistle can be seen as the sum of many different mechanisms [5].

Liver protection

There is a large body of literature discussing experimental studies on the hepatoprotective (liver protecting) properties of silymarin. In rodent models, silymarin (or silibinin) reduced or prevented liver toxicity caused by chroquine (an antimalarial and antirheumatoid agent), amiodarine (an anti-arrhytmic drug), D-galactosamine, carbon tetrachloride, acetaminophen, paracetamol, heavy metals, ethanol, pyrogallol, phenylhydrazine, radiation, and Amanita phalloides (a toxic mushroom species) [4, 6, 8-12]. These benefits have been measured by changes in liver enzymes (such as AST, ALT, and ALP), changes in serum bilirubin, decreased free radical generation, and other methods [4, 6, 9, 13-14].

Other effects

A number of other possible benefits of silymarin supplementation have been identified, related to its antioxidant effects. In humans, supplementation with silymarin significantly increases plasma antioxidant capacity [2]. In addition to protecting the liver from heavy metals, silymarin (or silibinin) may reduce other toxic effects of iron and mercury buildup [2, 31].

Dosage & toxicity

The majority of the literature indicates that silymarin is virtually non-toxic and associated with few side effects [2, 22]. No significant adverse effects with silymarin as monotherapy, and few negative drug interactions have been reported [2, 8]. In clinical trials, reports of side effects are similar to those reported with placebo treatment [8, 10]. There are some a few case reports of gastrointestinal disturbances and allergic skin rashes [17]. In vitro studies indicate that silymarin may actually be hepatotoxic in high enough concentrations, and high concentrations of silymarin inhibit some drug metabolizing enzymes, but these are not significant concerns with normal supplemental doses [5, 33].

Although there are many references to the low oral bioavailability of silymarin, supplementation in sufficient quantities results in increased silymarin concentrations in various tissues, especially the liver [4, 34]. The dose used in most clinical trials is 420 mg, with a range of 210-800 mg [8]. Assuming the milk thistle being used is 70-80% silymarin, 200-400 mg of milk thistle daily is recommended as a general supplement to maintain good liver health, and 500-1000 mg is recommended in situations of high liver stress.

If you have any questions or comments regarding this article, please email dvdtlsn@bulknutrition.com.

This article is for informational purposes only. Always consult a doctor before taking any supplement or starting a new diet or training program.

No part of this article may be reproduced in any form without the permission of David Tolson or Mike McCandless.

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References

1. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Sep 5;794(2):303-10. Application of liquid chromatography-electrospray ionization-ion trap mass spectrometry to investigate the metabolism of silibinin in human liver microsomes. Gunaratna C, Zhang T.

2. Phytother Res. 2004 Feb;18(2):107-10. Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part I. Silymarin and its flavonolignans. Chlopcikova S, Psotova J, Miketova P, Simanek V.

3. J Steroid Biochem Mol Biol. 2003 Aug;86(2):179-88. Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx) rats. Seidlova-Wuttke D, Becker T, Christoffel V, Jarry H, Wuttke W.

4. J Appl Toxicol. 2004 Jan-Feb;24(1):21-6. Protective effect of alpha-lipoic acid against chloroquine-induced hepatotoxicity in rats. Pari L, Murugavel P.

5. Toxicol Lett. 2003 Feb 3;137(3):201-12. Primary cultures of human hepatocytes as a tool in cytotoxicity studies: cell protection against model toxins by flavonolignans obtained from Silybum marianum. Dvorak Z, Kosina P, Walterova D, Simanek V, Bachleda P, Ulrichova J.

6. J Hepatol. 2003 Sep;39(3):333-40. Silibinin protects mice from T cell-dependent liver injury. Schumann J, Prockl J, Kiemer AK, Vollmar AM, Bang R, Tiegs G.

7. Planta Med. 2003 Jan;69(1):44-9. 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. Johnson VJ, He Q, Osuchowski MF, Sharma RP.

8. Am J Med. 2002 Oct 15;113(6):506-15. Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. Jacobs BP, Dennehy C, Ramirez G, Sapp J, Lawrence VA.

9. Toxicology. 2003 Sep 30;191(2-3):179-87. Antioxidants protect primary rat hepatocyte cultures against acetaminophen-induced DNA strand breaks but not against acetaminophen-induced cytotoxicity. Lewerenz V, Hanelt S, Nastevska C, El-Bahay C, Rohrdanz E, Kahl R.

10. J Pharm Belg. 2003;58(1):28-31. [St. Mary's Thistle: an overview] [Article in French] Laekeman G, De Coster S, De Meyer K.

11. J Med Food. 2002 Winter;5(4):197-204. Influence of Piper betle on hepatic marker enzymes and tissue antioxidant status in ethanol-treated Wistar rats. Saravanan R, Prakasam A, Ramesh B, Pugalendi KV.

12. Methods Find Exp Clin Pharmacol. 2002 Oct;24(8):497-500. Pyrogallol-induced hepatotoxicity in rats: a model to evaluate antioxidant hepatoprotective agents. Gupta YK, Sharma M, Chaudhary G.

13. Hepatol Res. 2003 Jul;26(3):217-224. Protection against post-ischemic mitochondrial injury in rat liver by silymarin or TUDC. Rolo AP, Oliveira PJ, Moreno AJ, Palmeira CM.

14. J Clin Gastroenterol. 2003 Oct;37(4):336-9. Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. Lieber CS, Leo MA, Cao Q, Ren C, DeCarli LM.

15. Dtsch Med Wochenschr. 2004 Jan 23;129(4):137-40. [The development of a toxic megacolon due to Amanita phalloides poisoning. A rare complication] [Article in German] Eyer F, Felgenhauer N, Zilker T.

16. Mol Cancer Ther. 2002 May;1(7):525-32. Inhibition of retinoblastoma protein (Rb) phosphorylation at serine sites and an increase in Rb-E2F complex formation by silibinin in androgen-dependent human prostate carcinoma LNCaP cells: role in prostate cancer prevention. Tyagi A, Agarwal C, Agarwal R.

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

18. BioDrugs. 2001;15(7):465-89. Silymarin: a review of its clinical properties in the management of hepatic disorders. Wellington K, Jarvis B.

19. Am J Gastroenterol. 2003 Mar;98(3):538-44. Medicinal herbs for hepatitis C virus infection: a Cochrane hepatobiliary systematic review of randomized trials. Liu J, Manheimer E, Tsutani K, Gluud C.

20. Curr Cancer Drug Targets. 2004 Feb;4(1):1-11. Prostate cancer prevention by silibinin. Singh RP, Agarwal R.

21. Biochem Biophys Res Commun. 2003 Dec 26;312(4):1178-84. Silibinin down-regulates survivin protein and mRNA expression and causes caspases activation and apoptosis in human bladder transitional-cell papilloma RT4 cells. Tyagi AK, Agarwal C, Singh RP, Shroyer KR, Glode LM, Agarwal R.

22. Oncogene. 2003 Nov 13;22(51):8271-82. Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells. Agarwal C, Singh RP, Dhanalakshmi S, Tyagi AK, Tecklenburg M, Sclafani RA, Agarwal R.

23. Carcinogenesis. 2004 Mar 19 [Epub ahead of print]. 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. Dhanalakshmi S, Mallikarjuna GU, Singh RP, Agarwal R.

24. Carcinogenesis. 2002 May;23(5):787-94. Dietary silymarin suppresses 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. Yanaida Y, Kohno H, Yoshida K, Hirose Y, Yamada Y, Mori H, Tanaka T.

25. Oncol Rep. 2004 Feb;11(2):493-9. Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Tyagi AK, Agarwal C, Chan DC, Agarwal R.

26. Cancer Biol Ther. 2003 Sep-Oct;2(5):526-31. Epidermal growth factor receptor mediates silibinin-induced cytotoxicity in a rat glioma cell line. Qi L, Singh RP, Lu Y, Agarwal R, Harrison GS, Franzusoff A, Glode LM.

27. Anticancer Res. 2003 May-Jun;23(3B):2649-55. Silibinin induces growth inhibition and apoptotic cell death in human lung carcinoma cells. Sharma G, Singh RP, Chan DC, Agarwal R.

28. Phytother Res. 2003 May;17(5):524-30. Plasma lipoproteins in transport of silibinin, an antioxidant flavonolignan from Silybum marianum. Svagera Z, Skottova N, Vana P, Vecera R, Urbanek K, Belejova M, Kosina P, Simanek V.

29. Biochem Pharmacol. 2004 Jan 1;67(1):175-81. Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1beta and prostaglandin E2 synthesis by silymarin. Kang JS, Jeon YJ, Park SK, Yang KH, Kim HM.

30. Phytother Res. 2002 Mar;16 Suppl 1:S63-7. Influence of silymarin and its flavonolignans on doxorubicin-iron induced lipid peroxidation in rat heart microsomes and mitochondria in comparison with quercetin. Psotova J, Chlopcikova S, Grambal F, Simanek V, Ulrichova J.

31. Toxicol In Vitro. 2003 Aug;17(4):385-95. Cytotoxicity of inorganic mercury in murine T and B lymphoma cell lines: involvement of reactive oxygen species, Ca(2+) homeostasis, and cytokine gene expression. Kim SH, Sharma RP.

32. Phytomedicine. 2000 Mar;7(1):21-4. Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase. Gupta OP, Sing S, Bani S, Sharma N, Malhotra S, Gupta BD, Banerjee SK, Handa SS.

33. Phytother Res. 2002 Nov;16(7):632-8. Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Zuber R, Modriansky M, Dvorak Z, Rohovsky P, Ulrichova J, Simanek V, Anzenbacher P.

34. FEBS Lett. 2003 Aug 28;550(1-3):89-93. Silymarin inhibits TNF-alpha-induced expression of adhesion molecules in human umbilical vein endothelial cells. Kang JS, Park SK, Yang KH, Kim HM.