A closeup of Silymarin (Milk Thistle)

Silymarin, A Consistently Amazing Therapeutic Agent

Reviewed By: Paul Anderson, NMD

This post originally appeared on Emerson Ecologics

Reference: Karimi G. et.al. “Silymarin”, a Promising Pharmacological Agent for Treatment of Diseases. Iranian Journal of Basic Medical Sciences. Vol. 14, No. 4, July-Aug 2011, 308-317. Received: Oct 23, 2010; Accepted: May 5, 2011

Most integrative health practitioners know of the potential benefits of Silymarin (Milk Thistle) in liver protection and other health promoting areas. As someone who studies plant compounds for their immunologic potentials to expand my understanding of potential uses in immune and cancer therapies, I am consistently amazed by silymarin.
The authors of this paper set up the broader view of silymarin in the abstract:

These protective effects have been illustrated in the fields of nephrotoxicity, hepatotoxicity, viral hepatitis, cancer, in vitro fertilization, neurotoxicity, depression, lung diseases, prostate diseases etc. Silymarin has cytoprotection activities due to its antioxidant activity and radical scavenging. The possible known mechanisms of action of silymarin protection are blockade and adjustment of cell transporters, p-glycoprotein, estrogenic and nuclear receptors. Moreover, silymarin anti-inflammatory effects through reduction of TNF-α, protective effects on erythrocyte lysis and cisplatin-induced acute nephrotoxicity have been indicated in some studies. Silymarin has also inhibited apoptosis and follicular development in patients undergoing IVF.


Different mechanisms of action of silymarin are as follows:
Increasing the regenerative ability of the liver cells by enhancing the synthesis of DNA and RNA, as silymarin has a steroid structure
Altering the structure of the hepatocyte external membrane, that prevents entrance of the xenobiotics into the cell (poisoning with Amanita mushroom is a noteworthy example of such mechanism)Scavenging free radicals and increasing the cellular content of glutathione that leads to the inhibition of lipid peroxidation

Scavenging free radicals and increasing the cellular content of glutathione that leads to the inhibition of lipid peroxidation
And modifying the transporters and receptors of cell membranes.

Liver is the key organ of metabolism and excretion, and is continuously and variedly exposed to xenobiotics. Liver diseases remain a primary health problem. Damage ranges from acute hepatitis to hepatocellular carcinoma, being caused through apoptosis, necrosis, inflammation, immune response, fibrosis, ischemia, altered gene expression, and even in regeneration.

Effects of silymarin or silybinin on multiple cancers have been reported. Please see this excellent paper for detailed lists of cancers and potential mechanisms by which silymarin may help in those cancers. Some of the many mechanisms of the cytoprotective activity of silybin related to antioxidative and radical scavenging effects. In addition to this specific receptor interaction and modulation of a variety of cell-signaling pathways e.g. NFkappa B, suppression of EGFRMAPK/ ERK1/2 signaling and IGF-receptor signaling. Protective effects in skin cancer are likely driven via the anti-apoptotic effect of silymarin against UV irradiation by up-regulation of tumor-suppressor genes p53- and p21CIP1.

Other mechanisms in oncology which silymarin possess are: antiangiogenic properties, down-regulation of EGFR(epidermal growth factor receptor) signaling, considerable reduction in the generation of MDA-DNA adducts and hepatocellular carcinoma serum markers such as alpha-fetoprotein, carcinoembryonic antigen, aminotransferase, alkaline phosphatase, lactate dehydrogenase, gammaglutamyltransferase and 5´-nucleotidase and inhibits β-catenin increase, which will suppress the proliferation of hepatocellular carcinoma HepG2 cells.
Multidrug resistance is one of the main problems of successful cancer treatment, and silymarin elevates absorption and bioavailability of chemopharmaceutics such as daunomycin, vinblastine, and doxorubicin in cancerous cells by inhibition of P-glycoprotein (P-gp), MRP1 -mediated drug carrier and breast cancer resistance protein.

Silymarin can be applied as a co-treatment with the other chemotherapeutics agents while silybin is mainly useful as a hepatoprotective substance against chemotherapeutics-induced oxidative stress.

Renal protection:
It has antioxidant effects via increase of gene expression of antioxidant enzymes and a number of the most important protection mechanisms against free radicals damage containing super- oxide dismutase, glutathione peroxidase, and catalase. Therefore, silymarin can be used as a drug for diabetic nephropathy therapy. Oxidative stress (ROS) reduces glomerular filtration. Treatment with silymarin or vitamin E improved alteration in serum creatinine concentrations in an animal renal injury model. In another study, cisplatin and ifosfamide induced renal toxicity can be antagonized by silymarin without reducing anti-tumor efficacy of these drugs.

Neuronal effect:
High oxygen utilization, huge amounts of polyunsaturated fatty acids, elevated levels of free iron ions and low antioxidants defenses all together make the brain tissue vulnerable to reactive oxygen species injuries. Silymarin when administered at a dose of 200 mg/kg/day, strongly reduced the proteins oxidation in the hippocampus and cortex of elderly rats in comparison to the young ones. Additionally it shows promise as a choice compound against Alzheimer’s disease in which the protein oxidation is an important early occasion. According to previous studies, silymarin has antioxidant activities in the central nervous system.

In an extensive description in the original paper the authors describe study after study showing silymarin modulating immune signaling molecules, and doing so in a generally immune balancing and optimizing pattern. These effects have differing directions which are dose dependent, which may lead to varied dose strategies in autoimmunity.

Protective effect on pancreas:
Silymarin can increase serum insulin, reduce serum glucose and elevate antioxidant enzymes and glutathione. In addition, silybin has chemoprotectant effects and can improve pancreatic function after exposure to toxic agents leading to damages. In a chemical toxin model which provokes diabetes mellitus by necrosing beta pancreatic cells and production of free radicals, concurrent treatment with silymarin, in an animal model, prevented high plasma glucose levels and damages in pancreatic cells within 3 days of the first dose of silymarin administration and 5 days later the mentioned changes were completely prevented.

Preventing effect against hemolysis:
Membranes of erythrocytes are sensitive to lipid peroxidation in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, sickle cell anemia and β-thalasemia disease. In studies, silymarin increased the lag time of hemolysis and stabilized the cell membrane by reducing the rate and the total content of glutathione loss in erythrocytes.

Protective effect against environmental toxins:
In a study cited in healthy volunteers, the cytotoxic effect of Benzo(a) pyrene on peripheral blood mononuclear cells was prevented by silymarin through stabilizing cell membranes, increasing the GSH/GSSG ratio, restoration of glutathione metabolizing enzymes, elimination agents produced from lipid peroxidation and protein oxidation and functional stimulation of the antioxidant enzymes such as catalase and superoxide dismutase.

An effective oral hepatoprotective dose is 420 mg/day of extract (standardized to 70-80% silymarin) three times a day for 6-8 weeks. Maintenance dose is 280 mg/day.
Intravenous solution is used for cyclopeptid mushroom poison in dose of 33 mg/kg/day for approximately four days. In my personal experience, one must assure a sterile and stable intravenous source of silibinin (the IV form) and use small test doses prior to IV administration. The reactions people have to IV silibinin are mostly due to the solutions the molecule must be stabilized in for IV use as opposed to the silibinin itself.

Most common adverse effects reported are headaches, gastroenteritis and dermatological symptoms, among them gastrointestinal symptoms are the most common. In animal studies, silymarin has been reported to be nontoxic and symptom free with the maximum oral doses of 2500 and 5000 mg/kg. It has been also illustrated that silymarin is not a teratogen and had no post-mortem toxicity. As there was not significant toxicity of silymarin reported in human studies, this substance can be used with anti-tuberculosis drugs as a supplement added to the diet.


  1. Anderson P, Cochran B. Personal experiences with the clinical use of intravenous Silibinin. AMSA, AMT, BIORC and Private clinic data. Seattle Washington, 2010 – 2017.


This article first appeared on Dr. Anderson’s monthly review for Emerson Ecologics.

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