1. APRIL AYERS JEFF GIBBERMAN MELISSA HSU EL-KAMARYA SS, SHARDELLA MD, ABDEL-HAMID M, ET AL. A RANDOMIZED CONTROLLED TRIAL TO ASSESS THE SAFETY AND EFFICACY OF SILYMARIN ON SYMPTOMS, SIGNS AND BIOMARKERS OF ACUTE HEPATITIS. PHYTOMEDICINE 2009: (16) 391–400 Journal Club: A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis

2. To determine if the bioactive extract of milk thistle, silymarin, reduces the signs, symptoms, and biomarkers of acute hepatitis. Purpose

3. Double blind, randomized, placebo-controlled study 105 patients from two hospitals in Egypt Criteria  Alanine aminotransferase (ALT) level of more than 2.5 times the upper limit of normal (>100 IU/L)  Jaundice/scleral icterus  At least three additional symptoms of acute hepatitis Methods

4. Two study groups:  Vitamin placebo  140 mg of silymarin Treatment: 3x/day for 4 weeks Data collected:  Demographic information  Signs and symptoms  Adverse events/side effects  Laboratory tests  Alanine aminotransferase (ALT)  Aspartate aminotransferase (AST)  Direct and total bilirubin Methods (continued)

5. Impaired biliary excretion - silymarin group had a significantly faster resolution of symptoms compared to the placebo group  Dark urine, jaundice, and scleral icterus - significant indicators  Clay-colored stool and direct bilirubin – not significant Hepatocellular damage and systemic effects of liver inflammation - no significant difference between the two treatment groups Results

6. Weakness:  Lack of improvement in objective biomarkers, such as ALT, AST, and indirect and direct bilirubin  Pill treatment compliance Strength:  Demonstrated the safety of silymarin supplementation for acute hepatitis patients  no serious adverse events were recorded  side effects were similar in frequency in both the silymarin and placebo groups  diarrhea was rare and not more frequent in the silymarin group Strength/Weakness

7. Standard recommended doses of silymarin are safe and may be potentially effective in improving the symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process Conclusion

8. Background Milk thistle has been used medicinally for over 2,000 years, mainly to treat hepatic and biliary disorders. Silymarin is a flavonoid complex that can be extracted from the seeds of milk thistle and is thought to be the biologically active component.

9. Database Overview The study we chose to review looked at various forms of viral hepatitis while the databases, with the exception of Natural Standard, focused more on hepatitis B and C.

10. The Natural Standard Database Gives silymarin an evidence grade of C for acute viral hepatitis. Many of the studies reviewed were seen as methodologically weak, including; heterogeneous patient populations, small sample sizes, large drop out rates, and concomitant alcohol abuse. Also effects were seen as small insignificant. Gathered information from 211 sources.

11. Natural Medicine Comprehensive Database Insufficient evidence to rate whether milk thistle is a beneficial treatment for hepatitis B and C. There is some report of patients feeling better, but objective measures show no improvement.

12. Cochran Database A meta analysis found a lack of high quality evidence to support milk thistle as an intervention for viral hepatitis.

13. Up to Date Database Small studies have yielded conflicting results in terms of milk thistle’s effectiveness in treating hepatitis C and chronic liver disease. Conflict may be due to lack of standardization in preparation. It is stated that herbal preparations are essentially unregulated in the United States. It should be noted that the reviewed study took place in Egypt.

14. Database Conclusions Overall the information from these databases is comparable to the reviewed study where improvements seen with milk thistle treatment were subjective and considered “soft”. There was no significant reduction in the relevant biomarkers. It is inconclusive whether milk thistle is an effective treatment for viral hepatitis.

15. References El-Kamarya SS, Shardella MD, Abdel-Hamid M, Ismail S, El-Ateek M, Metwally M, Mikhail N, Hashem M, Mousa A, Aboul-Fotouh A, El-Kassas M, Esmat G, Strickland GT. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Phytomedicine. 2009;16: 391–400. Natural Standard Database – The Authority on Integrative Medicine. Foods, Herbs & Supplements Database: Silymarin. http://www.naturalstandard.com/databases/herbssupplements/all/milkthistle.asp. Updated June 1, 2012. Accessed June 1, 2012.http://www.naturalstandard.com/databases/herbssupplements/all/milkthistle.asp Natural Medicine Comprehensive Database – Unbiased, Scientific Clinical Information on Cemplemetary, Alternative, and Integrative Therapies. Milk Thistle. http://naturaldatabase.therapeuticresearch.com.rj2hh4ra6g.useaccesscontrol.com/nd/Search.aspx?cs=CP&s =ND&pt=100&id=138&fs=ND&searchid=35084706. Updated June 1, 2010. Accessed June 2, 2012. http://naturaldatabase.therapeuticresearch.com.rj2hh4ra6g.useaccesscontrol.com/nd/Search.aspx?cs=CP&s =ND&pt=100&id=138&fs=ND&searchid=35084706 Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD003620. DOI: 10.1002/14651858.CD003620.pub3. UpToDate Database – an evidence based, peer reviewed information resource. Tai AW, Chung RT. Investigational therapies for hepatitis C virus infection. http://www.uptodate.com/contents/investigational- therapies-for-hepatitis-c-virus-infection?source=search_result&search=milk+thistle&selectedTitle=2~9. Updated April 17, 2012. Accessed June 2, 2012.http://www.uptodate.com/contents/investigational- therapies-for-hepatitis-c-virus-infection?source=search_result&search=milk+thistle&selectedTitle=2~9