Silymarin from milk thistle by Ray Sahelian, M.D. Silymarin health benefit
Silymarin, the active extract from milk thistle, is a complex of 7 flavonolignans and polyphenols. The most active compound in slymarin is silibinin. Silymarin has been extensively used in patients with liver disease.
   Milk thistle is commonly found growing wild in a variety of settings, including roadsides. The seeds of the dried milk thistle flower are used.

Silymarin Benefits
Silymarin is a powerful antioxidant said to protect liver cells (and other cells in the body and brain) from toxins. Sylimarin apparently promotes liver cell protein synthesis and decreases the oxidation of glutathione. Milk thistle or silymarin may potentially be beneficial in a number of diseases involving liver disease, if in the early stages. Silymarin is not likely to work in cases of late stage cirrhosis. Early research indicates that silymarin may also have anti-cancer properties (see studies below)

Silymarin Dosage
The dose of silymarin used in studies has ranged from 200 to 800 mg per day.

Milk Thistle Extract  80% Silymarin, 60 Capsules - Club Natural

Milk Thistle Extract is standardized to 80% silymarin, the key constituent that exerts a protective effect against substances potentially harmful to the liver.

Milk Thistle Supplement Facts:
Amount Per Serving
Milk thistle, dried extract -  200 mg         
   (seed) standardized to 80% Silymarin

Recommendation: Take 1 milk thistle capsule daily or as recommended by your health care provider.

 Click here to buy Milk Thistle with silymarin, find out the latest sale price, or to see a complete list of high quality products at Physician Formulas and sign up to a FREE Supplement Research Update newsletter. Twice a month we email a brief abstract of several studies on supplements and natural medicine topics - including silymarin studies - and their practical interpretation by Dr. Sahelian.

Silymarin and diabetes
The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial.
Phytother Res. 2006 Dec;20(12):1036-9. Department of Pharmacology, Institute of Medicinal Plants, ACECR Tehran, Iran.
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. The present study was designed to investigate the effects of the herbal medicine, milk thistle seed extract (silymarin), which is known to have antioxidant properties on the glycemic profile in diabetic patients. A 4-month randomized double-blind clinical trial was conducted in 51 type II diabetic patients in two well-matched groups. The first group (n = 25) received a silymarin (200 mg) tablet 3 times a day plus conventional therapy. The second group (n = 26) received the same therapy but a placebo tablet instead of silymarin. The patients were visited monthly and glycosylated hemoglobin (HbA(1)c), fasting blood glucose (FBS), insulin, total cholesterol, LDL and HDL, triglyceride, SGOT and SGPT levels were determined at the beginning and the end of the study. The results showed a significant decrease in HbA(1)c, FBS, total cholesterol, LDL, triglyceride SGOT and SGPT levels in silymarin treated patients compared with placebo as well as with values at the beginning of the study in each group. In conclusion, silymarin treatment in type II diabetic patients for 4 months has a beneficial effect on improving the glycemic profile.

Silymarin Research Update
Silymarin prevents UV irradiation-induced A375-S2 cell apoptosis.
Biol Pharm Bull. 2004 Jul;27(7):1031-6.
Silymarin, a plant flavonoid from milk thistle (Silybum marianum)  was first evaluated for its protective effect against UV irradiation-induced apoptosis in human malignant melanoma cells. Treatment with silymarin significantly inhibited UV irradiation-induced apoptosis. Activities of caspase-9 and caspase-3 in UV-irradiated cells were effectively reduced by silymarin in a dose-dependent manner. It is suggested that the inhibitory effect of silymarin is exerted by blockage of the caspase/ICAD pathway after increased expression of Bcl-x(L) protein and activation of the ERK/MAPK pathway.

Phenolics-rich extracts from Silybum marianum and Prunella vulgaris reduce a high-sucrose diet induced oxidative stress in hereditary hypertriglyceridemic rats.
Pharmacol Res. 2004 Aug;50(2):123-30.
The study tested the effects of phenolics-rich extracts from the plants Silybum marianum (silymarin) and Prunella vulgaris on blood and liver antioxidant status and lipoprotein metabolism. These results indicate that silymarin and Prunella vulgaris improve antioxidant status in blood and liver and positively affect plasma lipoprotein profile in an experimental model of dietary induced hypertriglyceridemia.
Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons.
J Clin Gastroenterol. 2003 Oct;37(4):336-9.
Section of Liver Disease & Nutrition, Bronx VA Medical Center & Mount Sinai School of Medicine, Bronx, New York
Hepatoprotective effects of silymarin in patients with alcoholic liver disease are controversial. For strict control, this was assessed in non-human primates.  Twelve baboons were fed alcohol with or without silymarin for 3 years with a nutritionally adequate diet. RESULTS: Silymarin opposed the alcohol-induced oxidative stress and the rise in liver lipids and circulating ALT. Alcohol also increased hepatic collagen type I by 50% over the 3 years with a significant rise in mRNA for alpha1 (I) procollagen, both prevented by silymarin. There were corresponding morphologic changes: at 36 months, 2 of 6 animals fed alcohol had cirrhosis and 2 septal fibrosis, with perivenular fibrosis in 2, whereas with alcohol + silymarin, there was only 1 cirrhosis and 1 septal fibrosis, with perivenular fibrosis in 2, and virtually no lesions in the remaining 2. Silymarin retards the development of alcohol-induced hepatic fibrosis in baboons, consistent with several positive clinical trials. The negative outcome observed in other trials possibly reflects poor compliance resulting in irregular or low silymarin intake. Thus, in view of the innocuity of silymarin, it might be advisable in future clinical studies to insure the controlled administration of sufficient amounts of silymarin.

Anti-angiogenic effect of silymarin on colon cancer LoVo cell line.
J Surg Res. 2003 Jul;113(1):133-8.
This study was designed to evaluate the anti-angiogenic effect of silymarin and its major pure component silibinin, and also thalidomide (TH). A modified in vitro system using a coculture of endothelial and colon cancer cell lines was adopted in this study. Silymarin / silibinin has a strong anti-angiogenesis effect on the colon cancer cell line, and this might provide an alternative treatment option for anti-cancer treatment.

Silymarin inhibits TNF-alpha-induced expression of adhesion molecules in human umbilical vein endothelial cells.
FEBS Lett. 2003 Aug 28;550(1-3):89-93.
Silymarin is known to have an anti-atherosclerotic activity, but the mechanism responsible for it remains unclear. Here, we demonstrate a possible mechanism involved in the anti-atherosclerotic activity of silymarin. Silymarin inhibited THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs). Silymarin also suppressed the TNF-alpha-induced protein and mRNA expression of adhesion molecules, such as VCAM-1, ICAM-1 and E-selectin, in HUVECs. Moreover, silymarin suppressed the TNF-alpha-induced DNA binding of NF-kappaB/Rel in HUVECs. Taken together, these results demonstrate that silymarin exerts an anti-atherosclerotic activity, at least in part, by inhibiting the expression of adhesion molecules.

Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation.
Eur J Neurosci. 2002 Dec;16(11):2103-12.
An inflammatory response in the central nervous system mediated by activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. Silymarin is a polyphenolic flavonoid derived from milk thistle that has anti-inflammatory, cytoprotective and anti-carcinogenic effects. In this study, we first investigated the neuroprotective effect of silymarin against lipopolysaccharide (LPS)-induced neurotoxicity in mesencephalic mixed neuron-glia cultures. The results showed that silymarin significantly inhibited the LPS-induced activation of microglia and the production of inflammatory mediators, such as tumor necrosis factor-alpha and nitric oxide (NO), and reduced the damage to dopaminergic neurons. Therefore, the inhibitory mechanisms of silymarin on microglia activation were studied further. The production of inducible nitric oxide synthase (iNOS) was studied in LPS-stimulated BV-2 cells as a model of microglia activation. Silymarin significantly reduced the LPS-induced nitrite, iNOS mRNA and protein levels in a dose-dependent manner. Moreover, LPS could induce the activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase but not extracellular signal-regulated kinase. The LPS-induced production of NO was inhibited by the selective p38 MAPK inhibitor SB203580. These results indicated that the p38 MAPK signaling pathway was involved in the LPS-induced NO production. However, the activation of p38 MAPK was not inhibited by silymarin. Nevertheless, silymarin could effectively reduce LPS-induced superoxide generation and nuclear factor kappaB (NF-kappaB) activation. It suggests that the inhibitory effect of silymarin on microglia activation is mediated through the inhibition of NF-kappaB activation.

Treatment of silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin.
Int J Oncol. 2002 Dec;21(6):1213-22. Katiyar SK. University of Alabama at Birmingham, Birmingham, AL.
It is well documented that ultraviolet (UV) light-induced immune suppression and oxidative stress play an important role in the induction of skin cancers. Earlier, we have shown that topical treatment of silymarin, a plant flavonoid from milk thistle (Silybum marianum), to mouse skin prevents photocarcinogenesis, but the preventive mechanism of photocarcinogenesis in vivo animal system by silymarin is not well defined and understood. To define the mechanism of prevention, we employed immunostaining, analytical assays and ELISA which revealed that topical treatment of silymarin (1 mg/cm2 skin area) to C3H/HeN mice inhibits UVB-induced suppression of contact hypersensitivity (CHS) response to contact sensitizer dinitrofluorobenzene. Prevention of UVB-induced suppression of CHS by silymarin was found to be associated with the inhibition of infiltrating leukocytes, particularly CD11b+ cell type, and myeloperoxidase activity (50-71%). Silymarin treatment also resulted in significant reduction of UVB-induced immunosuppressive cytokine interleukin-10 producing cells and its production. Topical treatment of silymarin also resulted in significant reduction of the number of UVB-induced H2O2 producing cells and inducible nitric oxide synthase expressing cells concomitant with decrease in H2O2 (58-65%) and nitric oxide (65-68%) production. Together, these data suggest that prevention of UVB-induced immuno-suppression and oxidative stress by silymarin may be associated with the prevention of photocarcinogenesis in mice. The data obtained from this study also suggest: i) phase-I clinical trial of silymarin in high skin cancer risk human population and ii) development of sunscreen containing silymarin as an antioxidant (chemopreventive agent) or silymarin can be supplemented in skin care products.

A flavonoid antioxidant, silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells.
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Cancer Res. 1998 May 1;58(9):1920-9.
Prostate cancer (PCA) is the most common nonskin malignancy and the second leading cause of cancer deaths in United States males. One practical and translational approach to control PCA is to define a mechanism-based anti-carcinogenic agent(s). Recently, we showed that silymarin, a flavonoid antioxidant isolated from milk thistle, possesses exceptionally high to complete protective effects against experimentally induced tumorigenesis. Because the epidermal growth factor receptor (erbB1) and other members of the erbB family have been shown to play important roles in human PCA, efforts should be directed to identify inhibitors of this pathway for PCA intervention. In this study, we assessed whether silymarin inhibits erbB1 activation and associated downstream events and modulates cell cycle regulatory proteins and progression, leading to growth inhibition of human prostate carcinoma DU145 cells. Treatment of serum-starved cells with silymarin resulted in a significant inhibition of transforming growth factor alpha-mediated activation of erbB1 but no change in its protein levels. Silymarin treatment of cells also resulted in a significant decrease in tyrosine phosphorylation of an immediate downstream target of erbB1, the adapter protein SHC, together with a decrease in its binding to erbB1. In the studies analyzing cell cycle regulatory molecules, silymarin treatment of cells also resulted in a significant induction of cyclin-dependent kinase inhibitors (CDKIs) Cip1/p21 and Kip1/p27, concomitant with a significant decrease in CDK4 expression, but no change in the levels of CDK2 and CDK6 and their associated cyclins E and D1, respectively. Cells treated with silymarin also showed an increased binding of CDKIs with CDKs, together with a marked decrease in the kinase activity of CDKs and associated cyclins. In additional studies, treatment of cells grown in 10% serum with anti-epidermal growth factor receptor monoclonal antibody clone 225 or different doses of silymarin also resulted in significant inhibition of constitutive tyrosine phosphorylation of both erbB1 and SHC but no change in their protein levels. Furthermore, whereas silymarin treatment resulted in a significant increase in the protein levels of both Cip1/p21 and Kip1/p27, monoclonal antibody 225 showed an increase only in Kip1/p27. These findings suggest that silymarin also inhibits constitutive activation of erbB1 and that the observed effect of silymarin on an increase in CDKI protein levels is mediated via inhibition of erbB1 activation only in the case of Kip1/p27; however, additional pathways independent of inhibition of erbB1 activation are possibly responsible for the silymarin-caused increase in Cip1/p21 in DU145 cells. In other studies, silymarin treatment also induced a G1 arrest in the cell cycle progression of DU145 cells and resulted in a highly significant to complete inhibition of both anchorage-dependent and anchorage-independent growth of DU145 cells in a dose- and time-dependent manner. Taken together, these results suggest that silymarin may exert a strong anticarcinogenic effect against PCA and that this effect is likely to involve impairment of erbB1-SHC-mediated signaling pathway, induction of CDKIs, and a resultant G1 arrest.

Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients.
J Hepatol. 1997 Apr;26(4):871-9.
Several studies have demonstrated that diabetic patients with cirrhosis require insulin treatment because of insulin resistance. As chronic alcoholic liver damage is partly due to the lipoperoxidation of hepatic cell membranes, anti-oxidizing agents may be useful in treating or preventing damage due to free radicals. The aim of this study was to ascertain whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis. METHODS: A 12-month open, controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis. One group (n=30) received 600 mg silymarin per day plus standard therapy, while the control group (n=30) received standard therapy alone. The efficacy parameters, measured regularly during the study, included fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria levels, glycosylated hemoglobin (HbA1c) and malondialdehyde levels. RESULTS: There was a significant decrease in fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria and HbA1c levels already after 4 months of treatment in the silymarin group. In addition, there was a significant decrease in fasting insulin levels and mean exogenous insulin requirements in the treated group, while the untreated group showed a significant increase in fasting insulin levels and a stabilized insulin need. These findings are consistent with the significant decrease in basal and glucagon-stimulated C-peptide levels in the treated group and the significant increase in both parameters in the control group. Another interesting finding was the significant decrease in malondialdehyde/levels observed in the treated group. CONCLUSIONS: These results show that treatment with silymarin may reduce the lipoperoxidation of cell membranes and insulin resistance, significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration.

Silymarin questions
Q. I am looking for injectable form of silymarine and silibilin. I wonder if you could help me to find a supplier.
   A. We are not familiar with such a supplier.

Q. I have read positive research regarding topical silymarin for skin cancer. I have only come across silymarin tinctures and tablets. How does one apply it topically. Can you specifically purchase topical silymarin cream?
   A. We did a google search in August 2008 for silymarin cream and could only find a skin cream that had silymarin with MSM. We are not sure how well a silymarin tincture is absorbed through the skin or how effective it would be.

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