by Mike Arnold
As this series draws to a close, I thought it would be appropriate to conclude by posting a list of clinical trials detailing Milk Thistle’s effectiveness as a liver protectant. As science continues to learn more about this herb, I believe its status as the premiere liver protectant will continue to grow. See below for clinical trials.
Detailed Clinical Trials
Liver-protective action of silymarin therapy in chronic alcoholic liver diseases.
Fehér J, Deák G, Müzes G, Láng I, Niederland V, Nékám K, Kárteszi M.
The effects of silymarin (Legalon) therapy on liver function tests, serum procollagen III peptide level and liver histology were studied in 36 patients with chronic alcoholic liver disease in a six month double blind clinical trial. During silymarin treatment serum bilirubin, aspartate aminotransferase and alanin-aminotransferase values have been normalized, while gamma-glutamyl transferase activity and procollagen III peptid level decreased. The changes were significant, and there was a significant difference between post-treatment values of the two groups, as well. In the placebo group only gamma-glutamyl transferase values decreased significantly but to a lesser extent than that in the silymarin group. The histological alterations showed an improvement in the silymarin group, while remained unchanged in the placebo group. These results indicate that silymarin exerts hepatoprotective activity and is able to improve liver functions in alcoholic patients.
Milk thistle in liver diseases: past, present, future.
Abenavoli L, Capasso R, Milic N, Capasso F.
Department of Experimental and Clinical Medicine, University Magna Graecia, Catanzaro, Italy.
Silybum marianum or milk thistle (MT) is the most well-researched plant in the treatment of liver disease. The active complex of MT is a lipophilic extract from the seeds of the plant and is composed of three isomer flavonolignans (silybin, silydianin, and silychristin) collectively known as silymarin. Silybin is a component with the greatest degree of biological activity and makes up 50% to 70% of silymarin. Silymarin is found in the entire plant but it is concentrated in the fruit and seeds. Silymarin acts as an antioxidant by reducing free radical production and lipid peroxidation, has antifibrotic activity and may act as a toxin blockade agent by inhibiting binding of toxins to the hepatocyte cell membrane receptors. In animals, silymarin reduces liver injury caused by acetaminophen, carbon tetrachloride, radiation, iron overload, phenylhydrazine, alcohol, cold ischaemia and Amanita phalloides. Silymarin has been used to treat alcoholic liver disease, acute and chronic viral hepatitis and toxin-induced liver diseases.
Hepatoprotective effects of silymarin in androgenic-anabolic steroid-induced liver damage.
Radovanović D, Jovanović D, Mihailović D, Ranković G, Stojiljković N, Dimitrov V.
The use and abuse of anabolic-androgenic steroids (AAS) commonly induces liver damage.
MATERIAL AND METHODS:
The study included 40 male Wistar rats, divided into 4 groups of 10 rats each. Animals in the first experimental group (M), were subjected to progressive systematic forced swimming test, 5 days a week, during 8 weeks. Animals in this group were treated with AAS methandienone, 2 mg/kg BW/day, per os, before swimming, 5 d/w for 8 weeks. After swimming, animals were given three times more food than the laboratory animals of the same age and kind. Animals in the second group (M+S), were subjected to progressive forced swimming test, 5 d/w 8 weeks. Animals in this group were treated with methandienone equally as the experimental group M and received the same amount of food. Apart from that, they received silymarin 20 mg/kg BW/day. Animals in the third group (K), represented the control group, which was neither subjected to swimming test, nor treated with
methandienone or silymarin. Animals in this group received the same amount of food as animals in groups M and M+S. Animals in the fourth group (C), also represented a control. This group was not exercised nor treated, and animals received a standard amount of food for laboratory animals of this kind and age. Quantitative analysis of obtained hemataxylin-eosin, periodic acid shift and enzymohistochemical preparations was processed using Digital Image Analysis System: Microimage 3.0.
It was established that processes in the nuclei of animals in groups M and K were significantly more intensive (p<0.001) in relation to groups M+S and C. The investigation of glycogen showed significantly higher density in the cells of groups M and M+S in comparison to groups K and C. Also, there was a significant difference between groups M+S and M. Density of enzyme activity of glutamate dehydrogenase in hepatocytes of animals in the group M+S was significantly higher in relation to the remaining three groups. A statistically significant difference was not found in enzyme activity of succinate dehydrogenase and lactate dehydrogenase.
In cell nuclei of animals in the experimental group M, in the absence of silymarin effect, methandienone causes damages which induce regenerative processes and in this way increase high intensity activity. Silymarin significantly increases the glycogen density in hepatocytes. Increased activities of GDH are attributed to cell vitality.
The present results show hepatoprotective effects of silymarin in androgenic-anabolic steroid induced liver damage.
Silymarin: a review of its clinical properties in the management of hepatic disorders.
Wellington K, Jarvis B.
Adis International Limited, Auckland, New Zealand. email@example.com
The mechanisms of action of silymarin involve different biochemical events, such as the stimulation of the synthetic rate of ribosomal RNA (rRNA) species through stimulation of polymerase I and rRNA transcription, protecting the cell membrane from radical-induced damage and blockage of the uptake of toxins such as alpha-amanitin. Studies in patients with liver disease have shown that silymarin increases superoxide dismutase (SOD) activity of lymphocytes and erythrocytes, as well as the expression of SOD in lymphocytes. Silymarin has also been shown to increase patient serum levels of glutathione and glutathione peroxidase. Silybin 20 to 48 mg/kg/day has shown promise as a clinical antidote to acute Amanita (deathcap mushroom) poisoning. Primary efficacy data from 3 trials which examined the therapeutic potential of silymarin in patients with cirrhosis, and included patient survival as an end-point, demonstrated that silymarin had no significant beneficial effect on patient mortality. However, upon subanalysis, silymarin 420 mg/day had a significantly beneficial effect on patient survival rate (compared with patients receiving placebo) in 1 randomized, double-blind trial in patients with alcoholic cirrhosis. Silymarin 420 mg/day was also shown to improve indices of liver function [AST, ALT, gamma-glutamyl transferase and bilirubin] in patients with liver disease of various aetiology, including those exposed to toxic levels of toluene or xylene; however, it was largely ineffective in patients with viral hepatitis. Reports of adverse events while receiving silymarin therapy are rare. However, there have been accounts of nausea, epigastric discomfort, arthralgia, pruritus, headache and urticaria. Silymarin has also been reported to have possibly caused a mild laxative effect.
The antioxidant properties of silymarin (a mixture of at least 4 closely related flavonolignans, 60 to 70% of which is a mixture of 2 diastereomers of silybin) have been demonstrated in vitro and in animal and human studies. However, studies evaluating relevant health outcomes associated with these properties are lacking. Although silymarin has low oral absorption, oral dosages of 420 mg/day have shown some therapeutic potential, with good tolerability, in the treatment of alcoholic cirrhosis. Moreover, silybin 20 to 48 mg/kg/day has shown promise as an antidote for acute mushroom poisoning by Amanita phalloides; however, further studies paying attention to the amount of ingested mushroom and time elapsed before administration of treatment are needed to clarify its role in this indication. Studies in patients with the early onset of liver disease may demonstrate the liver regeneration properties that silymarin is promoted as possessing.
Silymarin and hepatoprotection.
Burczynski FJ, Wang G, Nguyen D, Chen Y, Smith HJ, Gong Y.
University of Manitoba, Winnipeg Manitoba R3E OT5, Canada. firstname.lastname@example.org
To determine the hepatoprotective effect of silymarin with Chang cell cultures. Specifically, to investigate the antioxidant properties of silymarin and its protective function in reducing pro-apoptotic markers.
Intracellular free radical levels were assessed with dichlorofluorescein (DCF) fluorescence after exposing cells to an oxidative stress of 400 μmol/L H2O2 for 20 min. Levels of cellular ATP and bax expression were examined to evaluate the protective effects of silymarin.
Silymarin significantly reduced the DCF fluorescence signal. Cell viability, assessed by the MTT assay, showed that silymarin enhanced the cell growth. Drug treatment was also associated with enhanced ATP levels, and reduced Bax and protein mRNA levels.
Silymarin can function as a hepatoprotectant against free radical damage due to oxidative stress. The protective nature extends to reducing levels of pro-apoptotic Bax protein. Silymarin may be a useful adjuvant for the treatment of specific liver diseases.
Silibinin and acute poisoning with Amanita phalloides
[Article in Italian]
Carducci R, Armellino MF, Volpe C, Basile G, Caso N, Apicella A, Basile V.
Cattedra di Tossicologia Ospedale A. Cardarelli, Università degli Studi di Napoli Federico II.
The aim of the present study was to show the therapeutic effect of silibinin dihemisuccinate in a case of intoxication by mushrooms of Amanita gender. We report a clinical case of a 4-person family intoxicated by ingestion of mushrooms Amanita phalloides and admitted to the center for poisoning treatment of the Hospital “A. Cardarelli” in Naples. Although all were treated with standard therapy, there was a worsening of the clinical picture till the third day, when it was decided to add silibinin dihemisuccinate by the intravenous route to the therapy. After the beginning of silibinin administration the patients showed a favourable course with a rapid resolution of the clinical picture, although the prognosis appeared severe on the basis of hematochemical examination results. On day 9 silibinin dihemisuccinate was replaced with silibinin betacyclodextrine per os. All patients were discharged on day 10-13. After two months all hematological parameters are in the normal range also a hepatobiliopancreatic echography does not show any morphological alteration. As in the case of polytherapies and because of the lack of comparative studies, it seems difficult to establish which therapeutic component had the major role in the resolution of the clinical picture. However, on the basis of our experience, and of the literature data, we think that silibinin may play a significant role in protecting hepatic tissue not yet injured. However we believe that other studies are necessary to confirm our hypothesis.
Effects of silybum marianum on patients with chronic hepatitis C.
Kalantari H, Shahshahan Z, Hejazi SM, Ghafghazi T, Sebghatolahi V.
Associate Professor of Gastroenterology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Silymarin derived from silybum marianum (milk thistle), a flowering member of the daisy family, may benefit liver function in people infected with the hepatitis C virus. The aims of this pilot study were to assess the efficacy and safety of silymarin on serum hepatitis C virus (HCV) RNA, serum aminotransferases (ALT, AST) levels, liver fibrosis and well-being in patients with chronic hepatitis C (CHC).
This prospective self-controlled trial study was conducted from March to September 2006 at Department of Gastroenterology, Isfahan University of Medical Sciences, Isfahan, Iran. 55 patients with HCV (10 female and 45 male) with a mean age of 31.8 ± 6.4 years (10-67 years) were participated in the study. Patients received 24 weeks of silymarin (630 mg/day). Baseline virological biochemical, liver fibrosis (by a serum fibrosis markers, including YKL-40 and Hyaluronic acid), and SF-36 questionnaire were performed with biochemical tests repeated at the end of the treatment period.
There was statistically difference in mean of ALT (108.7 ± 86.6 vs 70.3 ± 57.7) before and after the treatment (p < 0.001). The means of AST were 99.4 ± 139.7 and 59.7 ± 64.32 before and after the treatment with statistically differences (p = 0.004). After the treatment, nine patients were found with negative HCV-RNA (p = 0.004) and statistically significant improvement in results of liver fibrosis markers were found only in fibrosis group (p = 0.015). Quality of life was improved significantly. CONCLUSIONS: This study indicated that in patients with CHC performing silymarin (650 mg/day) for 6 months, improved serum HCV-RNA titer, serum aminotransferases (ALT, AST), hepatic fibrosis and patient's quality of life. More future studies are warranted
The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial.
Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M.
Department of Pharmacology, Institute of Medicinal Plants, ACECR Tehran, Iran. email@example.com
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 valuable effect of antioxidant nutrients on the glycemic control of diabetic patients has been reported in experimental and clinical studies. The present study was designed to investigate the effects of the herbal medicine, Silybum marianum 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.
Advances in the use of milk thistle (Silybum marianum). Post-White J, Ladas EJ, Kelly KM.
University of Minnesota, Minneapolis, Minnesota 55403, USA. firstname.lastname@example.org
Milk thistle (Silybum marianum) is an herbal supplement used to treat liver and biliary disorders. Silymarin, a mixture of flavanoid complexes, is the active component that protects liver and kidney cells from toxic effects of drugs, including chemotherapy. Although milk thistle has not significantly altered the course of chronic liver disease, it has reduced liver enzyme levels and demonstrated anti-inflammatory and T cell-modulating effects. There is strong preclinical evidence for silymarin’s hepatoprotective and anticarcinogenic effects, including inhibition of cancer cell growth in human prostate, skin, breast, and cervical cells. Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. More clinical trials of rigorous methodology, using standardized and well-defined products and dosages, are needed to evaluate the potential of silymarin against liver toxicity, chronic liver disease, and human cancers.
Of all the herbal products sold today, none have amassed a more impressive body of evidence supporting their use in the treatment of such a wide range of liver disorders/conditions, as Milk Thistle. Its hepatoprotective/rejuvenating effects are well documented, especially when utilized in the treatment of drug-toxin (AAS) induced liver damage. Numerous clinical studies demonstrate improvements in liver function in conjunction with reductions in liver enzymes, including ALR, AST, Bilirubin, and others. Anecdotal evidence lends further credibility to these claims, solidifying its place as the #1 selling herbal liver protectant on the market. If you are looking for an OTC product backed by an extensive history of both clinical and anecdotal evidence, nothing surpasses Milk Thistle.
Clinical applications of Silybum marianum in oncology.
Greenlee H, Abascal K, Yarnell E, Ladas E.
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York 10032, USA.
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. This article provides an overview of the current clinical applications of milk thistle in the oncology setting, including guidelines on commonly used forms and doses.