Silymarin from milk thistle research, dosage, benefit and side effects, use for liver health
February 1 2017 by Ray Sahelian, M.D.

Silymarin, the active extract from milk thistle, is a complex of several flavonolignans and polyphenols. The most active compound in slymarin is silibinin. It 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.

The fruit of the milk thistle plant contains flavonoids that are proven liver protectants. The standardized extract known as silymarin contains flavonoids of the flavonol subclass. Silybin predominates, followed by silydianin and silychristin.

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

Side effects, caution, risk
Milk thistle extracts are known to be safe and well tolerated, and toxic or adverse effects observed in clinical trials seem to be minimal.
Exacerbation of hemochromatosis by ingestion of milk thistle was a case report published in a medical journal.

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)

J Nat Prod. 2015. Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling. Silymarin, a characterized extract of the seeds of milk thistle (Silybum marianum), suppresses cellular inflammation. Natural products like silymarin may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

Antioxidant benefit
Antioxidants (Basel). 2015. Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives. Silymarin (SM), an extract from the Silybum marianum (milk thistle) plant containing various flavonolignans (with silybin being the major one), has received a tremendous amount of attention over the last decade as a herbal remedy for liver treatment. In many cases, the antioxidant properties of SM are considered to be responsible for its protective actions. Possible antioxidant mechanisms of SM are evaluated in this review. (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut. (2) Preventing free radical formation by inhibiting specific ROS-producing enzymes, or improving an integrity of mitochondria in stress conditions, are of great importance. (3) Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation is probably the main driving force of antioxidant (AO) action of silymarin. (4) Decreasing inflammatory responses by inhibiting NF-κB pathways is an emerging mechanism of SM protective effects in liver toxicity and various liver diseases. (5) Activating vitagenes, responsible for synthesis of protective molecules, including heat shock proteins (HSPs), thioredoxin and sirtuins and providing additional protection in stress conditions deserves more attention. (6) Affecting the microenvironment of the gut, including SM-bacteria interactions, awaits future investigations. (7) In animal nutrition and disease prevention strategy, SM alone, or in combination with other hepatho-active compounds (carnitine, betaine, vitamin B12, etc.), might have similar hepatoprotective effects as described in human nutrition.

Breast cancer
Acta Med Iran. 2013. The role of milk thistle extract in breast carcinoma cell line (MCF-7) apoptosis with doxorubicin. Based on silymarin's unique characteristics, its application in chemotherapy combined with doxorubicin can be effective to enhance the efficacy together with a reduced toxicity on normal tissues. The present study focus on evaluate the efficacy of silymarin in combination with doxorubicin, on viability and apoptosis of estrogen-dependent breast carcinoma cell line (MCF-7). After being cultured, MCF-7 cells were divided into 8 groups and treated as follows: 1st group received 75 μg silymarin, groups 2, 3, and 4 were treated with 10, 25, and 50 nM doxorubicin, respectively, and groups 5, 6, and 7 respectively received 10, 25, and 50 nM doxorubicin as well as 75 μg silymarin. Viability percentage and apoptosis of the cells were assessed with Trypan Blue staining after 16, 24, and 48 hours. Silymarin has a synergistic effect on the therapeutic potential of doxorubicin. Use of silymarin in combination with doxorubicin can be more effective on the therapeutic potential of doxorubicin and decreases its dose-limiting side effects.

Colon cancer
Anti-angiogenic effect of silymarin on colon cancer LoVo cell line.
J Surg Res. 2003.
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.

The efficacy of Silybum marianum (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial.
Phytother Res. 2006. 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 received a silymarin (200 mg) tablet 3 times a day plus conventional therapy. The second group 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.

Liver disease
Caspian J Intern Med. Winter 2014. Silymarin in treatment of non-alcoholic steatohepatitis: A randomized clinical trial. The patients who had taken silymarin experienced more notable fall in hepatic enzymes.

Prostate cancer
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, USA.
Cancer Res. 1998.
Recently, we showed that silymarin possesses exceptionally high to complete protective effects against experimentally induced tumor formation. Because the epidermal growth factor receptor (erbB1) and other members of the erbB family have been shown to play important roles in human prostate cancer, 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. Taken together, these results suggest that silymarin may exert a strong anticarcinogenic effect against prostate cancer and that this effect is likely to involve impairment of erbB1-SHC-mediated signaling pathway, induction of CDKIs, and a resultant G1 arrest.

Skin cancer
Silymarin prevents UV irradiation-induced A375-S2 cell apoptosis.
Biol Pharm Bull. 2004.
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.

I have read positive research regarding topical silymarin for skin cancer. I have only come across tinctures and tablets. How does one apply it topically. Can you specifically purchase topical silymarin cream?
    We did a google search in November 2010 and could only find a 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.

Silymarin Research review
Phenolics-rich extracts from Silybum marianum and Prunella vulgaris reduce a high-sucrose diet induced oxidative stress in hereditary hypertriglyceridemic rats.
Pharmacol Res. 2004.
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.
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.

Silymarin inhibits TNF-alpha-induced expression of adhesion molecules in human umbilical vein endothelial cells.
FEBS Lett. 2003.
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.
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 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. 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, to mouse skin prevents photocarcinogenesis. 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.

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.
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. A 12-month open, controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis. One group 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. 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. 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.

Milk production
Clinical efficacy, safety and tolerability of BIO-C (micronized Silymarin) as a galactagogue.
Acta Biomed. 2008; Di Pierro F, Callegari A, Carotenuto D, Tapia MM. Velleja Research, Pontenure, PC, Italy.
The authors have previously reported the use of Silymarin (a Silybum marianum standardized extract) as a promoter of milk production in cows. Due to the important psychological impact of hypogalactia in women after delivery, we evaluated the role of silymarin as a safe and effective galactogogue for human species. 50 healthy women during lactation were enrolled in order to verify the galactogogue role played by an oral treatment with micronized Silymarin (420 mg/day) in comparison with an undistinguishable placebo product. Women orally treated for 63 days with silymarin showed a clear galactagogue role for the product with an increase of 85% of the daily milk production (placebo: +32%). No drop out, nor unwanted effects were reported in both groups. Compliance and tolerability were also very good. Silymarin may be considered as a safe and effective herbal product that can be orally administered in order to improve the daily milk production in healthy women after delivery, without affecting milk quality.

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

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

Buy Silymarin, an extract from milk thistle
Supplement Facts:
Amount Per Serving
Milk thistle, dried extract 250 mg         
   (seed) standardized to 80% Silymarin

Supplement Facts
Serving Size: 1 Capsule
  Amount Per Serving %Daily Value
Milk Thistle Seed Extract (Silybum marianum) (Standardized to contain a minimum of 80% Silymarin) 250 mg **
**Daily Value not established.

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