Milk Thistle extract supplement benefits and side effects, use for liver health, the right dosage
February 1 2017 by Ray Sahelian, M.D.

Milk thistle is commonly found growing wild in a variety of settings, including roadsides. The Latin name is Silybum marianum. The seeds of the dried flower are used. The active ingredient in the plant is a flavonoid called silymarin, an antioxidant said to protect liver cells from toxins. Silymarin apparently promotes liver cell protein synthesis and decreases the oxidation of glutathione. The plant's flowers and seeds have been used for more than 2,000 years to treat disorders of the liver and gallbladder.

Milk Thistle benefit in health and disease
Studies show silymarin, silibinin, and other flavonoids found in milk thistle may benefit in a number of conditions including alcoholic cirrhosis and tumors. Many compounds in milk thistle, for instance silibinin, have shown potent anti- prostate and anti-lung cancer activity. Milk thistle herbal supplements are mostly used for liver health.

Anti-inflammatory benefit
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.

Cancer treatment of prevention
Milk thistle (Silybum marianum) is an herb that is increasingly used in oncology research and treatment settings. Historically, it has been used to treat liver and biliary disorders and has been used in detoxification and cleansing protocols. However, milk thistle is increasingly being investigated for its use in adult and pediatric populations for oncology indications. Possible indications during cancer treatment include cleansing and detoxification after chemotherapy, preventing hepatotoxicity during chemotherapy, treating hepatotoxicity after chemotherapy, and potentiating chemotherapy and radiation therapy as an adjunctive treatment. Milk thistle may also have applications in ameliorating long-term hepatic and cardiovascular effects of cancer treatment. Preliminary studies are investigating its use as a chemopreventive agent and possibly to treat cancer directly. Much of milk thistle's current clinical use grows out of historical uses but is informed by an increasing number of clinical trials and animal studies.

Number of studies has established the cancer chemopreventive role of silymarin in both in vivo and in vitro models. Silymarin modulates imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis. In addition, silymarin also showed anti-inflammatory as well as anti-metastatic activity. Further, the protective effects of silymarin and its major active constituent, silibinin, studied in various tissues, suggest a clinical application in cancer patients as an adjunct to established therapies, to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity.

Bladder cancer
Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-CDK-cyclin cascade, and caspase 3 and PARP cleavages. Carcinogenesis. 2004.

Silibinin modulates CDKI-CDK-cyclin cascade and activates caspase 3 causing growth inhibition and apoptotic death of human TCC cells, providing a strong rationale for future studies evaluating preventive and/or intervention strategies for silibinin in bladder cancer pre-clinical models. Carcinogenesis. 2004.

In a study of 50 children undergoing chemotherapy for acute lymphoblastic leukemia (ALL), milk thistle appeared to reduce treatment-related liver inflammation. Dr. Kara M. Kelly, a pediatric oncologist at Columbia University Medical Center in New York randomly assigned 50 children with ALL to take either milk thistle capsules or placebo (inactive) capsules for one month while undergoing their "maintenance" round of chemotherapy. Going into the study, all of the children had signs of liver inflammation from their previous round of treatment. After one month, however, children taking milk thistle had lower levels of two liver enzymes than those in the placebo group -- a sign of lesser liver inflammation. Kara M. Kelly reports that children on milk thistle were also somewhat less likely to need their chemotherapy dose lowered at any point. Cancer, 2009.

Depression and mood disorders
Comparison of Silybum marianum with fluoxetine in the treatment of Obsessive-Compulsive Disorder.
Prog Neuropsychopharmacol Biol Psychiatry. 2009.
Obsessive-Compulsive Disorder (OCD) is a common neuropsychiatric condition. Although a variety of pharmaceutical agents is available for the treatment of OCD, psychiatrists often find that many patients cannot tolerate the side effects of these medications; do not respond properly to the treatment; or the medications lose their effectiveness after a period of treatment. Herbal medicine can be a solution to some of these problems. In fact many herbs with psychotropic effects exist which can have fewer side effects. They can provide an alternative treatment. Silybum marianum is a well-known medicinal plant with a long history of usage in Iran. Our objective in this study was to compare the efficacy of the extract of milk thistle with fluoxetine in the treatment of OCD. The study was an 8-week pilot double-blind randomized trial. Thirty five adult outpatients who met the DSM-IV-TR criteria for OCD based on the structured clinical interview participated in the trial. The minimum score of Yale-Brown Scale for OCD was 21 for all patients. In this double-blind and randomized trial, patients were randomly assigned to receive either capsule of the extract (600mg/day) or fluoxetine (30mg/day) for 8weeks. The results showed no significant difference between the extract and fluoxetine in the treatment of OCD. There was also no significant difference between the two groups in terms of observed side effects.

Milk thistle and diabetes
The efficacy of Silybum marianum in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial.
Phytother Res. 2006.
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 results showed a significant decrease in HbA(1)c, FBS, total cholesterol, LDL, triglyceride SGOT and SGPT levels in milk thistle silymarin treated patients compared with placebo as well as with values at the beginning of the study in each group. In conclusion, milk thistle silymarin treatment in type II diabetic patients for 4 months has a beneficial effect on improving the glycemic profile.

Milk thistle and liver disease, alcoholic and/or hepatitis B or C virus liver conditions
Is there scientific evidence that milk thistle protects the liver or is helpful as a treatment for liver disease?
   As of 2017, I believe more research is needed in order to know such benefits.
There are many types of liver disease and perhaps milk thistle or extracts will be found to be of benefit in certain types of liver conditions.
Silymarin, a flavonolignan from milk thistle plant, is used for the protection against various liver conditions in both clinical settings and experimental models.

J Vet Intern Med. 2013. Milk thistle and its derivative compounds: a review of opportunities for treatment of liver disease. Hackett ES, Twedt DC, Gustafson DL. Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.
Milk thistle extracts have been used as a "liver tonic" for centuries. In recent years, silibinin, the active ingredient in milk thistle extracts, has been studied both in vitro and in vivo to evaluate the beneficial effects in hepatic disease. Silibinin increases antioxidant concentrations and improves outcomes in hepatic diseases resulting from oxidant injury. Silibinin treatment has been associated with protection against hepatic toxins, and also has resulted in decreased hepatic inflammation and fibrosis. Limited information currently is available regarding silibinin use in veterinary medicine. Future study is justified to evaluate dose, kinetics, and treatment effects in domestic animals.

Dr. Christian Gluud of Copenhagen University Hospital in Denmark, reviewed 13 clinical trials of milk thistle for liver disease due to alcoholism or hepatitis B or C. The gold standard for clinical trials is for them to be placebo-controlled and double-blind, meaning neither patients nor the study administrators know whether a patient is taking the real drug or placebo. Just six of the trials analyzed met this standard. The researchers found no effect of milk thistle versus placebo on mortality rates or liver disease complications. While the remedy appeared to reduce death from liver-related causes when all data was included, an analysis limited to the best-quality studies found no effect. No increased risk of adverse events was seen with milk thistle. The American Journal of Gastroenterology, November 2005.

The Clinical Utility of Milk Thistle in Cirrhosis of the Liver.
J Herb Pharmcother. 2002.
Silybum marianum is a flowering herb utilized for its potentially protective effects on the liver. Although the mechanism of action is not fully understood, one explanation may be that it concentrates in the hepatocytes and competes with toxins for hepatocyte binding and penetration. Preliminary clinical evaluations of milk thistle for cirrhosis of the liver indicate potential benefits in healthier patients with alcoholic cirrhosis. However, major flaws in many of the studies make it difficult to draw solid conclusions. Milk thistle appears to be relatively safe, even with long-term use.

Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver.
Hepatol. 1989.
To determine the effect of silymarin on the outcome of patients with cirrhosis, a double blind, prospective, randomized study was performed in 170 patients with cirrhosis. 87 patients (alcoholic 46, non-alcoholic 41) received 140 mg silymarin three times daily. 83 patients (alcoholic 45, non-alcoholic 38) received a placebo. The mean observation period was 41 months. The 4-year survival rate was 58% in silymarin-treated patients and 39% in the placebo group. Analysis of subgroups indicated that treatment with silymarin in milk thistle was effective in patients with alcoholic cirrhosis. No side effects of drug treatment were observed.

Q. I am just wondering what form of milk thistle I should order for my husband who has always had elevated levels in blood test. AST 138 and ALT 60. I don't know whether to get a liver cleanse or just milk thistle supplements.
   A. There are many causes for elevated AST and ALT and it is not possible to predict the role of this herb would have on the liver when the diagnosis is not clear.

Biomed Res Int. 2013. Antiosteoclastic activity of milk thistle extract after ovariectomy to suppress estrogen deficiency-induced osteoporosis. Bone integrity abnormality and imbalance between bone formation by osteoblasts and bone resorption by osteoclasts are known to result in metabolic bone diseases such as osteoporosis. Silymarin-rich milk thistle extract (MTE) and its component silibinin enhanced alkaline phosphatase activity of osteoblasts but reduced tartrate-resistant acid phosphatase (TRAP) activity of osteoclasts. The osteoprotective effects of MTE were comparable to those of estrogenic isoflavone. Low-dose combination of MTE and isoflavone had a pharmacological synergy that may be useful for osteogenic activity. This study attempted to reveal the suppressive effects of MTE on bone loss. C57BL/6 female mice were ovariectomized (OVX) as a model for postmenopausal osteopenia and orally administered 10 mg/kg MTE or silibinin for 8 weeks. The sham-operated mice served as estrogen controls. The treatment of ovariectomized mice with nontoxic MTE and silibinin improved femoral bone mineral density and serum receptor activator of nuclear factor- κB ligand/osteoprotegerin ratio, an index of osteoclastogenic stimulus. In addition, the administration of MTE or silibinin inhibited femoral bone loss induced by ovariectomy and suppressed femoral TRAP activity and cathepsin K induction responsible for osteoclastogenesis and bone resorption. Collectively, oral dosage of milk thistle extract containing silibinin in the preclinical setting is effective in preventing estrogen deficiency-induced bone loss.

Compounds in the plant and their ability to be absorbed
There are many compounds in the herb, mostly flavonoids, including silymarin, silybin, isosilybin, and silibinin.

Phytomedicine. 2012. Absorption and metabolism of milk thistle flavanolignans in humans. This study evaluated the absorption and metabolism of milk thistle flavonolignans silychristin, silydianin, silybin and isosilybin isomers (all together known as silymarin) in humans. Fourteen volunteers consumed an extract of milk thistle and urine was collected up to 48 h after consumption. Thirty-one metabolites were identified in urine by means of HPLC-MS/MS, monoglucuronides being the most common excreted form, followed by sulphate-glucuronides and diglucuronides, respectively. These flavonolignans are extensively modified after ingestion and recovered in urine as sulpho- and glucuronyl-conjugates, indicating a strong affinity for hepatic phase II enzymes. All future studies (in vitro and in vivo) dealing with the effects of milk thistle should start by considering the modification of its flavonolignans after ingestion by humans.

Milk thistle dosage
The dose of silymarin used in studies has ranged from 200 to 800 mg per day.
Milk Thistle extract is sold in a variety of concentrations including 70 percent silymarin, 80% or a 10 to 1 milk thistle extract. One option is 80 to 200 mg extract (80% sylmarin) once or twice daily.

Milk thistle side effects, risk, danger
No significant milk thistle side effects have yet been reported thus far with milk thistle extract but it is possible that, as more people take this herb, potential side effects could be uncovered. It is unlikely that milk thistle side effects exist in drinking the tea, but perhaps using several milk thistle extract capsules daily for prolonged periods could cause problems.

Combining with other herbs and nutrients
I've heard that milk thistle and alpha lipoic acid can be taken together to fight fatty liver and high liver enzimes. Is this true? What are the correct dosages and do they hurt the kidneys?

    I have not seen human studies that have evaluated the combination of the herb and alpha lipoic acid as a treatment for liver damage so it is not easy to say what the right dosage would be when taken together and whether they have any effect on kidney function. I personally prefer using lower dosages than other people recommend.

Milk Thistle research review
Drug Metab Dispos. 2013. Milk thistle's active components silybin and isosilybin: novel inhibitors of PXR-mediated CYP3A4 induction.

Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells.
J Urol. 2004.
The down-regulation of PSA by silibinin and its counteraction on DHT effects indicate that this compound can interact with the expression of genes that are regulated through the androgen receptor. Silibinin can also inhibit the telomerase activity that mediates cell immortality and carcinogenesis. The 2 effects underline the possible therapeutic use of silibinin as an antiproliferative agent in intervention for prostate cancer.

Q. Is is safe to take vitamin-E with C and milk thistle? What about taking it with serrapeptase?
   A. No one can definitely promise 100 percent safety with the use of vitamin combinations, but milk thistle and vitamin C and E you mention are relatively benign and should be fine to use together if not used in excess. As to serrapeptase, we don't know enough about this enzyme to be certain how it interacts with medicines and herbs and vitamins.

Q. I know it is difficult to predict, but do you foresee any problems taking small amounts of milk thistle extract with chrysin supplements?
   A. I would suggest at first trying them separately each for a week before combining. Use low dosages when combining many herbs or supplements.

Q. Milk thistle is a well-known liver cleanser but is it also a diuretic, and as such, could it cause frequent urination, especially for long term use? And possible cause some dehydration?
   A. I am not aware of studies that show it to cause dehydration.

Nature's Bounty, Milk Thistle, 250 mg, 200 Capsules
buy 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 Milk thistle extract
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 or two milk thistle capsules daily or as recommended by your health care provider.

Additional products
Nature's Answer, Milk Thistle, Alcohol-Free, 2,000 mg, 1 fl oz (30 ml) - liquid extract