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Silymarin (Milk Thistle)
Silymarin, the active extract from milk thistle, is a complex of 7 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 to extract this compound. Milk thistle has been used for over 2,000 years, so a lot has been written about its health benefits. There have been over 300 scientific studies on silymarin that document its benefits as:

arw Antioxidant effects

arw Treatment of cirrhosis of the liver caused by alcoholism

arw Treatment of chronic hepatitis

arw Treatment of poisoning due to eating wild mushrooms

arw Helping the liver repair itself
What is Silymarine?

Systematic (IUPAC) name

Silibinin (INN), also known as silybin, is the major active constituent of silymarin, the mixture of flavonolignans extracted from milk thistle (Silybum marianum) consisting of silibinin A and B, isosibilinin A and B, silicristin, silidianin. It is used to protect the liver from a variety of toxic substances. It prevents toxins from penetrating the interior of liver cells while promoting the growth of healthy new cells to repair liver damage.

Where is it Found?
Silymarin is an extract of the seeds of the milk thistle plant.

See Silymarin related videos:
video icon Helpful for various liver disease
(video module – 6.57 minutes)

Product related PDF file
Milk thistle- A Remarkable Flavonoid, Antioxidant And Liver Protectant
Milk Thistle Facts
Milk Thistle
The Efficacy of Silymarin in treating Type II Diabetes

Benefits / Uses
Milk thistle provides hepatocellular protection by stabilizing hepatic cell membranes. It alter the structure of the outer cell membrane of the hepatocytes in such a way as to prevent the penetration of the liver toxins into interior of the cell. The stimulation effect on nucleolar polymerase A results in an increase in ribosomal protein synthesis, and thus increase the regenerative ability of the liver and the formation of new hepatocytes. Other actions include interruption of enterohepatic recirculation of toxins and regeneration of damaged hepatocytes.

An animal study performed in rats demonstrated a reduction in kidney damage following administration of cisplatin without diminished anti-tumor activity. Other studies indicate the flavonoids in milk thistle has anticancer effects by inducing G1 and S phase arrest in cells. Anecdotal data suggests that milk thistle may prevent liver damage from hepatotoxic medications including butyrophenones, phenothiazines, and phenytoin.

Antioxidant and Anti-Cancer
Silymarin is a powerful antioxidant said to protect liver cells (and other cells in the body and brain) from toxins. Silymarin 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.

Liver Cell Growth
Silymarin from milk thistle appears to promote the growth of some types of cells in the liver. Milk thistle is not used to prevent Hepatitis C Virus from causing liver disease. Rather, milk thistle is used with the hope that it would minimize the damage to the liver that HCV can cause.

Antihepatotoxic Activity
Studies suggest that silymarin from milk thistle can block various types of toxins from entering and injuring liver cells.

Milk thistle Silymarin may be an effective "antioxidant," which means milk thistle may help fight a destructive chemical process in the body known as "oxidation." In oxidation, harmful substances produced in the body (called free radicals) can damage cells. Some studies suggest that milk thistle silymarin can prevent these substances from damaging liver cells.

Inflammation Inhibition
Milk thistle's Silymarin is thought to prevent inflammation (swelling) of the liver; this may be described as displaying anti-inflammatory properties.

Especially How It Works for Liver
Milk thistle prevents toxins from entering the liver by guarding the organ's numerous doorways-the membranes of liver cells. By slowing the rate at which the liver absorbs harmful substances, the toxins are excreted through the kidneys before they can cause liver damage. The most dramatic example of this is Milk Thistle's ability to block poisons from the deathcap, mushroom (Amanita phalloides), one of the most notorious liver toxins known to humans. In a group of 49 patients with Amanita poisoning, physicians rated the results ¡°amazing¡± and ¡°spectacular,¡± after patients were given injections (20 mg/kg daily) of silybin, a major constituent in Milk Thistle. All of the patients survived, even though they were treated 24 to 36 hours after poisoning, when liver and kidney damage had already occurred. The death rate in emergency rooms from Amanita poisoning is usually 30 to 40 percent.8 Milk thistle acts in a similar fashion to detoxify other synthetic chemicals that find their way into our bodies, from acetaminophen and alcohol to heavy metals and radiation.

Much of Milk Thistle's protective effect is due to the flavonoid complex silymarin, which acts as a powerful antioxidant, combining with and thus neutralizing harmful free radicals that result from normal metabolic processes and from the breakdown of toxic substances. At least 10 times as potent as vitamin E, silymarin also helps increase levels of two additional antioxidants, glutathione and superoxide dismutase (SOD). A laboratory study showed that silymarin may increase glutathione content in the liver and intestines by up to 50 percent. Silymarin also increases the activity of SOD in erythrocytes (red blood cells) and lymphocytes (white blood cells) formed in the lymphatic tissue in patients with liver disease. Because silymarin is a potent antioxidant in the stomach and intestines, it may also have a role to play in treating inflammatory conditions such as colitis and ulcers.

When damage has already been done, Milk Thistle aids the liver in repairing injured cells and generating new ones. It does this by stimulating protein synthesis through the enzyme RNA polymerase I. Protein is a basic building block of cell walls, cell structures, and enzymes that are vital to all body processes. Recent evidence (molecular modeling) suggests that the constituent silybin may be responsible for stimulating protein synthesis, because it imitates a steroid hormone. Silybin increases protein synthesis by up to 25 to 30 percent, compared with controls. Milk thistle's regenerative ability is essential for treating serious conditions such as chronic hepatitis, cirrhosis, and toxic fatty deposits in the liver.

Kidney Cleansing
Silybin has also been tested in animals for its ability to protect the kidney from damage due to drugs such as the chemotherapeutic agent cisplatin. Silybin reduces oxidative damage to kidney cells in vitro. In rats, silybin prevented cisplatin induced nephrotoxicity, but did not prevent cyclosporine-induced glomerular damage except for lipid peroxidation.

Acne and Inflammation
Milk Thistle is also a Demulcent, meaning that it soothes and moistens the mucus membranes, kidney and bladder irritations and inflammations in general. Being a demulcent, it also greatly softens and moistens the skin. Patients with skin problems ranging from acne to severe eczema have reported a clearing of skin impurities, healing of redness and inflammation, a dramatic softening and moistening of dry, cracking skin, and a noticeable glow and radiance to the skin quality.

Improved Liver function leads to improved diabetes control. The liver is the first and most important tissue involved with insulin utilization. In secondary diabetes due to liver damage, insulin resistance is particularly pronounced. The reduction in lipid per oxidation produced by silymarin can lead to improved metabolic control and a reduced requirement for endogenous insulin in such patients, as demonstrated by this investigation conducted in Italy.

Enzymes in the liver break down many of the substances that we eat and drink, including medications. If the activity of these enzymes are reduced, then drugs remain in the blood longer than they otherwise might. This could lead to having higher-than-expected levels of drugs in the body, causing side-effects or intensifying already-existing side-effects. Indeed, in recent experiments using milk thistle and human liver cells, the researchers found that relatively small concentrations of milk thistle did significantly slow down the activity of the liver enzyme CYP3A4 by 50% to 100%.
Milk thistle also has the potential to lower levels of the following drugs:

arw anti-parasite drugs -- Mepron (atovaquone)

arw sedatives/sleeping pills -- Ativan (lorazepam)

arw hormones - estrogen
The research by the scientists in Pittsburgh should emphasize to readers that simply because a product is "natural" it does not mean it is safe when taken with other substances. This research also shows the need to conduct further research on herb-drug interactions on liver cells as well as in people. Such studies may find combinations of herbs and drugs that can be safely used together.
The Pittsburgh researchers noted that "patients and health care professionals must be encouraged to discuss the use of herbs and be educated about the potential interactions between herbs and drugs." This cannot be stressed enough.

Silymarin and Other Diseases
Blood lipids - silymarin may inhibit hepatic synthesis of cholesterol and reduce blood lipids, as shown in vitro, animal studies, and human trials.

Milk Thistle and Gall Bladder Disease - Because Milk Thistle is both a demulcent and it stimulates bile flow, it is a natural for treating a wide array of Gall Bladder diseases and Symptoms. Milk Thistle can calm down an inflamed Gall Bladder while at the same time clearing out any stagnation that might be present. When using Milk Thistle to combat Gall Bladder symptoms, it is important to verify that there are no Gall Stones present which would be too large for the gall bladder to pass. The only way that this can be known is to visit your local physician and get a clearance from them to proceed.

Deathcap Poisoning - In Amanita mushroom poisoning, silybinin appears to dramatically reduce death rates, which are typically from 30 to 50%, down to less than 10%.13 This mushroom destroys the liver if left untreated. In conditions like this one, it isn't ethical to perform double-blind studies. However, Milk Thistle seems to be so dramatically effective that its value is not disputed.

Milk Thistle and the Bowels - Milk Thistle is a gentle and mild laxative due to its ability to increase bile secretion and flow in the intestinal tract. This herb can have actions ranging from lubrication and softening of the stools to a mild laxative effect, to actually balancing individuals that alternate between diarrhea and constipation. (In patients with stools that alternate between constipation and diarrhea, Oriental Medicine would most likely suspect liver involvement.) This formula has been seen to improve bowel regularity and stool consistency in individuals with this type of alternating presentation. This is due to the astringent nature of the Dandelion Root combined with the softening and moistening nature of the Milk Thistle).

A standardized extract should be 80% silymarin (the active ingredient). The shelf life of silymarin is only about three months. The usual dosage of milk thistle extract is between 300 milligrams (mg) and 600 mg daily. Milk thistle does not dissolve easily in water, so milk thistle tea is not recommended.

Possible Side effects / Precautions / Possible Interactions:
There are no clearly documented serious side effects of milk thistle. Even very high doses do not seem to have any negative effects. However, some people get an upset stomach, diarrhea, bloating, or more gas when they start using silymarin. If this happens, cut back on your dosage and then increase it slowly.
A few people have allergic reactions to milk thistle. This is more common for people who have an allergy to another plant in the same family, like ragweed.

Possible Interactions:
Many medications taken by people with HIV/AIDS (PHAs) such as protease inhibitors and non-nukes are processed by this liver enzyme. If milk thistle is taken by someone using protease inhibitors or non-nukes, it has the potential to raise levels of these drugs, causing unpleasant or even dangerous side effects. Below is a short list of some other medications that are processed through the CYP3A4 enzyme. Levels of these medications may increase if taken by people who are also using milk thistle. This list is not exhaustive:

arw drugs -- carbamazepine (Tegretol)

arw antidepressants -- St. John's wort, Zyban/Wellbutrin (bupropion), Paxil (paroxetine), Prozac (fluoxetine), Luvox (fluvoxetine) Serzone (nefazodone), Zoloft (sertraline), Effexor (venlafaxine)

arw antihistamines -- Hismanal (astemizole), Seldane (terfenadine)

arw antifungals -- itraconazole (Sporanox), Ketoconazole (Nizoral)

arw gastrointestinal motility methadone

arw heart drugs -- Tambocor (flecainide), Rythmol (propafenone)

arw antibiotics -- erythromycin, rifampin
arw anti-seizure agents -- Prepulsid (Cisapride)
arw ergot drugs -- Ergonovine, Ergomar (ergotamine)
arw anti-psychotics -- Clozaril (clozapine), Orap (pimozide)
arw sedatives/sleeping pills -- Ambien (zolpidem), Halcion (triazolam), Versed (midazolam)
arw lipid-lowering drugs (statins) -- Lescol (fluvastatin), Mevacor (lovastatin), Pravachol (pravastatin) and Zocor (simvastatin), Baycol (cerivastatin)

arw transplant drugs -- cyclosporine (Neoral, Sandimmune), ProGraf (tacrolimus)

Research Studies / References
Clinical Study: Silymarin provided protection against the toxic effects of long-term treatment with psychotropic drugs (used in mental illness) in a randomized, double-blind, placebo controlled clinical study of 60 people. Before the study began, all of the participants had been taking the psychotropic drugs phenothiazine or butyrophenone, or both, for at least 5 years. Subjects were divided into four groups for the 3-month trial: group I took psychotropic drugs and a high dose of silymarin (800 mg per day), group 11 took psychotropics with placebo, group III took silymarin only (800 mg per day), and group IV took placebo. Silymarin provided liver protection to group I by reducing blood levels of malondialdehyde (MDA), an indicator of liver damage that increases during long-term treatment with psychotropics. Not surprisingly, the decrease in MDA levels was even greater in the group taking silymarin alone (group III ). Patients in group II continued to experience rising levels of MDA, whereas those who took placebo had declining MDA levels until the psychotropics were reinstated. There were no adverse effects associated with Milk Thistle treatment.

A 1981 double-blind study followed 106 Finnish soldiers with mild alcoholic liver disease. In the treated group, there was a significant improvement in liver function as measured by blood tests and biopsy. 19 Another study reported similar results.20 However, a study of 116 participants showed little to no benefit,21 as did another study of 72 people followed for 15 months.

Long-term treatment with silymarin significantly increased survival rates in a randomized, double-blind, placebo-controlled study of 105 people with cirrhosis. Subjects took either 420 mg of silymarin daily or placebo during the study, which lasted for approximately 41 months. Over a 4-year period, the mortality rate in the placebo group was twice that of the silymarin group. Silymarin showed the greatest benefit in those with alcohol-related cirrhosis. There appeared to be no difference in the results of liver function tests (transminases, bilirubin, SGGPT, and other liver enzymes) between the two groups. No side effects were reported.

Cirrhosis (Clinical Study): A homogeneous group of 60 patients with diabetes caused by liver cirrhosis who were being traded with insulin were randomly assigned to receive silymarin 600 mg/day or no silymarin for 6 months; all were receiving insulin therapy and had elevated endogenous insulin secretion suggestive on insulin resistance. Additional criteria for inclusion were; age between 45 and 70 year; insulin therapy stable for at least 2 years; negative markers for hepatitis A, B and C; alcohol abstinence for at least 2 years; liver cirrhosis determined on biopsy no earlier than 4 years previously; and class 2 according to the Child classification of cirrhosis. Ranges of measurements were conducted to assess metabolic control, serum lipid levels and liver function throughout the treatment period.

The baseline characteristics of the 2 groups were similar. Silymarin treatment produced a range of benefits in terms of diabetic control including significant reductions in daily and fasting blood glucose ¨C an effect mirrored in urine glucose measurements; significant improvement in glycosylated hemoglobin values; and a significant drop in insulin requirement and fasting insulinaemia. In contrast, the status of untreated patients declined during the trial, the outcome in silymarin recipients being significantly superior compared with the alternative group.
The benefits of measurements of blood malondialdehyde levels. These values decreased significantly in treated patients, from 2.2umol/dl at baseline to 1.6umo/dl after 6 months, whereas a slight increase was observed over the 6-months period in untreated patients. Compared with baseline, total cholesterol levels tended to increase in the treated patients, and to decrease in the untreated patients.After 6 months, all silymarin recipients chose to continue receiving their treatment.

The only difference between the patient groups in this study was silymarin treatment. The clinical benefits of silymarin observed probably involve restoration of the plasma membrane of liver cells and an increase in insulin receptor sensitivity, as a result of a reduction in lipoperoxidation of liver cell membranes. ¡°The results we obtained after 6 months of treatment indicate that we should administer silymarin for longer periods in order to identify the end point of the biochemical amelioration caused by the treatment.


arw Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metabolism and Disposition 2000;28(11):1270-1273.

arw Ladas EJ, Kelly KM. Milk thistle: is there a role for its use as an adjunct therapy in patients with cancer? J Altern Complement Med 2003;9(3):411-416.

arw Lawrence V, Jacobs B, Dennehy C, et al. Report on milk thistle: effects on liver disease and cirrhosis and clinical adverse effects. Evidence Report/Technology Assessment No. 21 (Contract 290-97-0012 to the San Antonio Evidence-based Practice Center, based at the University of Texas Health Science Center at San Antonio, and The Veterans Evidence-based Research, Dissemination, and Implementation Center, a Veterans Affairs Services Research and Development Center of Excellence). AHRQ Publication No. 01-E025. Rockville, MD: Agency for Healthcare Research and Quality. October 2000.

arw Lucena MI, Andrade RJ, de la Cruz JP, et al. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. Int J Clin Pharmacol Ther 2002;40(1):2-8.

arw Madisch A, Melderis H, Mayr G, et al. [A plant extract and its modified preparation in functional dyspepsia. Results of a double-blind placebo controlled comparative study]. Z Gastroenterol 2001;39(7):511-517.

arw McCord A. Milk thistle may help improve liver health in people with HIV and hepatitis C. Proj Inf Perspect. 2008 Sep;(46):18.

arw Melhem A, Stern M, Shibolet O, et al. Treatment of chronic hepatitis C virus infection via antioxidants: results of a phase I clinical trial. J Clin Gastroenterol 2005 Sep;39(8):737-42.

arw Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 1998;28(4):615-621.

arw Rambaldi A, Jacobs BP, Iaquinto G, et al. Milk thistle for alcoholic and/or hepatitis B or C liver diseases--a systematic cochrane hepato-biliary group review with meta-analyses of randomized clinical trials. Am J Gastroenterol 2005 Nov;100(11):2583-91.

arw Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003620. Update of Cochrane Database Syst Rev 2005;(2):CD003620.

arw Schroder FH, Roobol MJ, Boeve ER, et al. Randomized, double-blind, placebo-controlled crossover study in men with prostate cancer and rising PSA: effectiveness of a dietary supplement. Eur Urol 2005 Dec;48(6):922-30; discussion 930-1.

arw Tyagi AK, Singh RP, Agarwal C, et al. Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis. Clin Cancer Res 2002;8(11):3512-3519.

arw Velussi M, Cernigoi AM, Viezzoli L, et al. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin need in cirrhotic diabetic patients. Curr Ther Res 1993;53(5):533-545.

arw Velussi M, Cernigoi AM, De Monte A, et al. 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;26(4):871-879.

arw Whittington C. Exacerbation of hemochromatosis by ingestion of milk thistle. Can Fam Physician 2007 Oct;53(10):1671-3.

arw Zuber R, Modriansky M, Dvorak Z, et al. Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Phytother Res 2002;16(7):632-638.

arw Gaedeke J, Fels LM, Bokemeyer C, Mengs U, Stolte H, Lentzen H. Cisplatin nephrotoxicity and protection by silibinin.


arw Scambia G, De Vincenzo R, Ranelletti FO, Panici PB, Ferrandina G, D'Agostino G, Fattorossi A, Bombardelli E, Mancuso S.
Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin.


arw Invernizzi R, Bernuzzi S, Ciani D, Ascari E. Silymarine during maintenance therapy of acute promyelocytic leukemia.