Milk Thistle

David McCluggage, D.V.M., C.V.A.

Silybum marianum (milk thistle) is a flavonoid having an affinity for the liver. Its hepatoprotective and hepatorestorative effects make silymarin one of the best nutraceutical for many liver disorders. It is primarily used to regenerate hepatocytes, where it improves the flow of bile and fat to and from the liver as well as heal liver cells. Less known, but of equal value, is that it is also an excellent antioxidant. Its antioxidant properties make it valuable in a wide variety of degenerative diseases.

Active ingredients:

The major active ingredient is considered to be the flavonolignan , silybin , a lipid soluble, poorly absorbed compound. Betaine, which has been shown to be a liver protectant, is also found in the plant. There are other flavonolignans in milk thistle, but they appear less significant. Perhaps of more importance are the essential oils and trace minerals found in the herb.

Modes of Action:

As an antioxidant silymarin, inhibits benzoyl peroxide-induced tumor promotion, oxidative stress and inhibits the inflammatory responses with certain types of tumors.Zhao J, Lahiri-Chatterjee M, Sharma Y, Agarwal R. Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. Carcinogenesis. 2000 Apr;21(4):811-816. Silymarin increases the biliary excretion and the endogenous pool of bile salts by stimulating the synthesis of hepatoprotective bile salts, such as beta- muricholate and ursodeoxycholate. Crocenzi FA, Pellegrino JM, Sanchez Pozzi EJ, Mottino AD, Garay EA, Roma MG. Effect of silymarin on biliary bile salt secretion in the rat. Biochem Pharmacol . 2000 Apr 15;59(8):1015-22.

It enhances Phase II and inhibits Phase I liver detoxification, which can effectively balance detoxification since the by-products of Phase I detoxification are often more toxic than the original products from which they are produced.Zhao J, Agarwal R. Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention. Carcinogenesis. 1999 Nov;20(11):2101-8.

Phase I detoxification, the Cytrochrome P450 enzymes, often produce free radicals which must be removed by Phase II detoxification. Silymarin, allowing for greater conjugation of these free radicals, enhances Glucuronic acid, a part of Phase II detoxification. Once conjugated the can be removed from the body through the bile ducts.

Silymarin has been shown to lower elevated levels of bilirubin, aspartate aminotransferase (AST), and alanine amino-transferase (ALT). In part this is due to its ability to stimulate the production of heplatocellular proteins.Neuman MG, Cameron RG, Haber JA, Katz GG, Malkiewicz IM, Shear NH. Inducers of cytochrome P450 2E1 enhance methotrexate-induced hepatocytoxicity . Clin Biochem . 1999 Oct;32(7):519-36.

Adding to the long list of beneficial effects of this nutraceutical is its anti-lipid peroxidation effect. Silymarin will inhibit the formation of leukotrienes from polyunsaturated fatty acids in the liver, via its inhibition of the enzyme lipoxygenase, stabilized mast cells, modulated immune functions, and is anti-inflammatory. Sonnenbichler J, Goldberg M, Hane L, et al. Stimulatory effect of silibinin on the DNA synthesis in partially hepatectomized rat livers: non-response in hepatoma and other malignant cell lines. Biochem Pharmacol 1986;35:538-541.

The anti- iflammatory effect of silymarin is significant, and has been proven in studies. This allows the practitioner to elect not to use Western antiinflammatories such as prednisone.Luper S. A review of plants used in the treatment of liver disease: part two. Altern Med Rev. 1999 Jun;4(3):178-88. Review.

Amanita Mushroom Poisoning

Some species of Amanita mushrooms have powerful hepatotoxins, including amanitin and phalloidin. Milk thistle has gained much recognition in its ability to reducing death rates from exposure to Amanita mushrooms up to 100%.Dehmlow C, Murawski N, de Groot H, et al. Scavenging of reactive oxygen species and inhibition of arachidonic acid metabolism by silibinin in human cells. Life Sci 1996;58:1591-1600.Hruby K, Csomos G, Fuhrmann M, Thaler H. Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 1983;2:183-195.

Liver enzyme studies and liver biopsies in studies involving dogs shows a significant hepatoprotective effect for silymarin when given toxic doses of Amanita mushrooms.Sabeel AI, Kurkus J, Lindholm T. Intensive hemodialysis and hemoperfusion treatment of Amanita mushroom poisoning. Mycopathologia 1995;131:107-114.

Other Clinical Uses

Silymarin has been shown to be of some benefit is treatment of liver disease in alcoholics, although it is not as effective as one might expect.Vogel G, Tuchweber B, Trost W. Protection by silibinin against Amanita phalloides intoxication in beagles. Toxicol Appl Pharmacol 1984;73:355-362.

Silymarin is very helpful in the treatment of liver cirrhosis. One study is indicative of this beneficial aspect of the herb. This study, involving 170 patients with liver cirrhosis, were given 420 mg/day of silymarin for an average of 41 months. These patients showed a significant improvement in survival (58% in silymarin-treated patients and 39% in the placebo group). Trinchet IC, Coste T, Levy VG. Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients. Gastroenterol Clin Biol 1989;13:120-124.

In Western medicine, colchicine is often used to inhibit liver fibrosis. This is, however, of questionable value, especially when considering the potential toxicity of colchicineFerenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989;9:105-113.

In one study the use of silymarin was as effective as colchicine in the treatment of liver disease, and had none of the untoward effects exhibited with colchicine.Wang RY, Morasco R, Henry GC, Hoffman RS, Goldfrank Antidotal efficacy of glutamate and aspartate for colchicine toxicity. Vet Hum Toxicol .1997 Aug;39(4):207-10.

Silymarin also inhibits fibrosis in lung tissue, kidney tissue, pancreas and other organs throughout the body.Favari L, Perez-Alvarez V. Comparative effects of colchicine and silymarin on CCl4-chronic liver damage in rats. Arch Med Res 1997;28:11-17. Soto CP, Perez BL, Favari LP, Reyes JL. Prevention of alloxan-induced diabetes mellitus in the rat by silymarin. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol . 1998 Feb;119(2):125-9.

Being a powerful Antioxidant, it can help improve many degenerative conditions throughout the body, including kidney disease, heart disease, and diabetes.Zima T, Kamenikova L, Janebova M, Buchar E, Crkovska J, Tesar V. The effect of silibinin on experimental cyclosporine nephrotoxicity. Ren Fail. 1998 May;20(3):471-9.

Silymarin is found throughout the entire plant, but is concentrated in the fruit and seeds. Since the seeds have a high content of silymarin, it is an excellent seed to feed birds that have liver disease.

If used in too high a dose, it can cause a loose stool due to the increase in bile it produces.