Milk Thistle
May 14
Is There a Future for Milk Thistle In
HCV?
Feb 7 2013
Antioxidant and Anti-Hepatitis C Viral Activities of Commercial
Milk Thistle Food Supplements
Jan 1 2013
Milk thistle shows merit for liver health
Sept 23 2012
Silymarin Is Ineffective for Chronic Hepatitis C Virus Infection
July 2012
2012-Milk Thistle No Help in Tough Hepatitis C Cases
May 16 2012
Milk Thistle Does Not Alter Disease Activity in Hepatitis C Patients
ISSUE: MAY 2012 | VOLUME: 1
Source
by Christina Frangou
San Francisco—One of the first rigorous trials to test the popular herbal extract milk thistle (silymarin) has shown that this treatment does not relieve symptoms or slow disease progression in patients with hepatitis C who are nonresponsive to interferon (IFN).
Read More....
Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C
unsuccessfully treated with interferon therapy: a randomized controlled trial
Expert's Picks: Silymarin for NAFLD
Silymarin commonly known as milk thistle, was used in classical Greece to treat hepatic and gallbladder diseases and to protect the liver from toxins. Somewhat more recently, there has been renewed interest in its potential efficacy in
non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD), particularly given the role that oxidative stress is thought to play in the pathogenesis of NAFLD and the anti-oxidant properties of the herb
DDW- Georgetown doctors test milk thistle to counter amanitin toxins in the liver
Laurin’s team called the local Poison Control Center who in turn, put them in contact with a California physician who is the principal investigator for a study using the IV preparation of milk thistle seeds (silibinin) in the United States for amanitin poisoning. Arrangements were made to have the drug flown and then couriered to the hospital where it arrived within hours. The patient received silibinin that evening.
Summary Of The 47th European Association for the Study of the Liver EASL - 2012
Milk Thistle:
Trusted Support for Health & Healing in a Toxic World
ProHealth.com by Karen Lee Richards*
May 14, 2012
Although milk thistle was known to be beneficial for liver problems for many centuries, it wasn't until 1990 that scientists at a liver pathology institute in Clichy, France finally discovered exactly how milk thistle works to protect the liver.
AASLD
2011 - Herb Favored by Hep C Patients Has No Medical Benefit: Study
By Rob Goodier
NEW YORK (Reuters Health) Nov 10 - Milk thistle extract, an herbal supplement popular among patients with chronic liver disease, had no benefit for hepatitis C patients, a new study found.
In a randomized multicenter trial, milk thistle-the botanical compound silymarin-did not beat the placebo at improving liver function test results.
"The study was not able to document specific efficacy in hepatitis C virus," said Dr. Henry Bodenheimer, Jr., a hepatologist at the Beth Israel Medical Center in New York City who chaired the study's data safety monitoring committee.
"Milk thistle is also used in many other forms of liver disease, but has not often been systematically studied," Dr. Bodenheimer added in an email to Reuters Health.
Dr. Michael Fried, at the University of North Carolina at Chapel Hill, who led the study, presented the results November 8 at the American Association for the Study of Liver Diseases annual meeting in San Francisco.
Patients take silymarin as an alternative to, or to supplement, conventional HCV therapy, which can be toxic and have a limited effect, Dr. Bodenheimer said.
Accordingly, Dr. Fried's team restricted the study to 154 hepatitis C patients who had not responded to interferon therapies. The patients also had serum alanine aminotransferase (ALT) enzyme levels greater than 65 IU/L, with a median of 106 IU/L. A normal level is 45 IU/L, Dr. Fried's team writes.
The researchers randomly assigned the patients to one of three groups, two of which took high doses of a standardized form of silymarin at 420mg or 700mg three times daily. The third group took a placebo.
The silymarin doses in the study were 4.5-7.5 times higher than customary, the researchers said in their abstract for the meeting. The doses were chosen based on results of an earlier phase I study.
Of the 138 patients who completed the 24-week study, 90% were able to adhere to at least 80% of the pill regimen. In spite of the compliance, however, the mean drop in serum ALT was not significantly different between the three groups. And only two patients in each group met the primary endpoint, either normalization of ALT or a drop of at least 50% from baseline.
Silymarin is a polyphenolic flavenoid that, in vitro, is an antioxidant and anti-inflammatory. Its pharmacokinetics in this study, and its effect on hepatitis C virus RNA, have not yet been reported.
"In my experience, the use of this agent is patient driven rather than being prescribed by physicians," Dr. Bodenheimer said.
A Randomized, Placebo-Controlled Trial of Oral Silymarin (Milk Thistle) For Chronic Hepatitis C: Final Results of the SYNCH Multicenter Study
M. W. Fried 1; V. J. Navarro 2; N. H. Afdhal3; A. S. Wahed4; R. L. Hawke5; S. H. Belle4; E. Doo6; C. M. Meyers7; K. Reddy8
1. UNC Liver Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
2. Thomas Jefferson University, Philadelphia, PA, United States.
3. Beth Israel Deaconess Medical Center, Boston, MA, United States.
4. University of Pittsburgh, Pittsburgh, PA, United States.
5. Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, United States.
6. NIDDK, National Institutes of Health, Bethesda, MD, United States.
7. NCCAM, National Institutes of Health, Bethesda, MD, United States.
8. University of Pennsylvania, Philadelphia, PA, United States.
Background:
The botanical extract silymarin, commonly known as milk thistle, is a polyphenolic flavonoid with anti-oxidant, anti-inflammatory, and immunomodulatory properties in vitro and is used extensively by patients with chronic liver disease. This trial evaluated the effect of high doses of oral silymarin on disease activity in patients with chronic hepatitis C.
Methods:
Patients with chronic hepatitis C infection who were previously unsuccessfully treated with interferon-based therapies and with serum ALT activity > 65 IU/L were eligible.
Participants were randomly assigned to either placebo or one of two doses of a standardized silymarin preparation (Legalon® 140, Rottapharm Madaus) at 420 or 700 mg administered orally thrice daily for 24 weeks.
These doses, 4.5-7.5 times higher than customary, were chosen based on results of a phase I pharmacokinetic study. The prespecified primary endpoint, assessed at the end of therapy, was serum ALT < 45 IU/L (considered to be within the normal range) or ALT <65 IU/L (<1.5 x ULN), provided this was at least a 50% decline from baseline values.
Changes in serum ALT and HCV RNA during treatment, and the relationship of these to study medication adherence, measured by dose counts, and silymarin levels were also examined.
Results:
Four U.S. clinical centers enrolled 154 patients, of whom 138 (90%) completed the endpoint evaluation at week 24.
Baseline characteristics were well matched with the exception of a larger proportion of whites in the placebo group.
Most participants were male (71%) and the median age was 54 years. Median ALT was 106 IU/L.
The mean decline in serum ALT activity at the end of treatment did not differ significantly (p=0.75) across the 3 treatment groups.
Only 6 participants (2 in each treatment group, p =1.00) met the primary endpoint.
Based on dose cups returned, over 90% of participants met or exceeded an 80% adherence to study medications, despite the substantial pill burden (15 capsules per day).
Analysis of serum ALT activity performed by per protocol analysis (those with > 80% adherence) did not demonstrate significant changes in serum ALT activity among the treatment arms.
Silymarin treatment at both doses had an adverse event profile comparable to placebo. Pharmacokinetics of silymarin and HCV RNA results are pending.
Conclusion:
Although well tolerated, oral silymarin administered at higher than customary doses did not significantly alter biochemical markers of disease activity in patients with chronic hepatitis C who had failed prior treatment with interferon-based regimens. (Funded by National Institutes of Health, NCCAM and NIDDK).
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2011-2010 Related Articles
Milk Thistle Bolsters HCV Treatment
Nov 2011
With the addition of two medications recently approved to augment combination therapy, treatment for Hepatitis C has dramatically improved in the past year. Thankfully, the likelihood of beating the Hepatitis C virus has risen from around a 1 in 2 chance to a 3 in 4 chance by taking triple therapy with either Incivek or Victrelis. Even with these increased odds, most individuals with chronic Hepatitis C could benefit by simultaneously supporting and protecting their liver with milk thistle.
Researchers identify cancer blocking properties of thistle – Portugal
The thistle, a plant used in the manufacture of cheese, has potential anti-tumor properties that could prevent and treat two types of cancer, breast and liver cancer, two uncommon but often fatal forms of cancer, Portuguese researchers have claimed.
Silymarin (Milk Thistle) study showed significantly improved the serum liver enzymes
Hepatitis C is a major cause of liver -related morbidity and mortality.1,2 Ribavirin plus interferon combination therapy, is presently considered the optimal treatment for patients with chronic hepatitis C, but the recommended treatment regimen is associated with considerable expense, adverse effects and poor efficacy in some patients with hepatitis C. Therefore, many hepatitis C patients use the herb silymarin (milk thistle), an alternative therapy for hepatitis C, in addition to or instead of standard treatment for chronic hepatitis C virus infection.3
Although the popularity of silymarin has been increased in people with liver disease4,5 but a little evidences with controversial results exist in effect of silaymarin on chronic hepatitis C.....
Hepatitis C and CAM
March 2011
,
Hepatitis C, a liver disease caused by a virus, is usually chronic (long-lasting), with symptoms ranging from mild (or even none) to severe. Conventional medical treatments are available for hepatitis C; however, some people also try complementary and alternative medicine (CAM) therapies, especially herbal supplements. This issue summarizes the scientific research on the effectiveness and safety of selected supplements.
Read more about what the science says
Hepatitis C : Complete Text On Silymarin (Milk Thistle) use is associated with reduced progression to cirrhosis in Hep C
Questions and Answers About Milk Thistle/2010
What Does Milk Thistle Do ?
Milk Thistle/The Study 2010
Milk Thistle / HCV Advocate
HEALTHWISE: Milk Thistle
—Lucinda K. Porter, RN
People with chronic hepatitis C virus infection (HCV) who are interested in alternative medicine generally consider milk thistle (silybum marianum). This popular herb is a common ingredient in supplement blends that promote liver health. Researchers have investigated the efficacy of milk thistle and its components for a variety of conditions, including viral hepatitis, type II diabetes, cancer and toxin-removal from the liver.
The Basics
Milk thistle (Silybum marianum) is a plant from the aster family. Silymarin is the active ingredient in milk thistle that is likely responsible for its medicinal qualities. Silymarin is actually a group of flavanoids, with silybin (aka silibinin) being the most powerful. Typically, milk thistle is sold in standardized amounts of 70 to 80% silymarin.
The February 2008 issue of Hepatology looked at milk thistle use among 1145 participants in the HALT-C study, sponsored by the National Institute of Diabetes and Digestive and Kidney Disease, headed by Leonard Seeff. In this HCV study, 44% of the subjects had used herbs at some point, with 23% using them at the time of enrollment. Among all participants, milk thistle was used by 33%, 17% upon enrollment. Although milk thistle users showed similar ALT levels and HCV viral loads to non-users, they showed fewer liver-related symptoms and improved quality of life. Researchers observed that this aspect of the study was uncontrolled and that milk thistle use was self-motivated. They concluded that “a well-designed prospective study can determine whether silymarin provides benefit to persons with chronic hepatitis C.”1
Continue reading before you run out and buy milk thistle. All milk thistle is not alike and what is in the bottle may not match what is promised on the label. In a startling report published by ConsumerLab.com (CL), only one of 10 products passed the necessary tests in order to carry the CL seal of approval.
CL is an independent organization that provides information and testing of nutritional products. They have been around for about ten years. Some information is free, but product reports are available only to subscribers. A one year subscription is $30 and worth every penny. www.consumerlab.com
What caught my attention about the milk thistle testing is that most supplements win CL’s approval. It’s a voluntary program, so presumably manufacturers feel confident enough to submit to testing. The failure of nine out of ten products is extraordinary. One can only imagine the quality of products that don’t agree to testing.
The Results
Two of the ten milk thistle products were disqualified for failure to meet the Food and Drug Administration’s (FDA) labeling requirements. Additionally, one of these products had different dosing information from jar to jar, all from the same lot number.
Seven of the remaining eight products did not provide the standardized amount of silymarin although they all claimed to have 80%. Actual amounts were between 47 and 67%. The only product to pass was Jarrow Formulas Milk Thistle. Although the amount of silymarin was not specified on the label, the manufacturer declared that the milk thistle extract contained 80% flavonoids. The actual testing confirmed that Jarrow Formulas Milk Thistle met the minimum industry standard of 70% silymarin.
The HCV Advocate and I do not endorse particular products or treatments. However, it seemed cruel to reveal that only one in ten milk thistle products passed muster without mentioning the name of the product. However, before you run out and buy milk thistle, there are other issues.
First, why didn’t the products pass? ConsumerLabs suggested it was likely due to substandard milk thistle extract, often purchased from Chinese suppliers. Unfortunately, since herbs are not strictly regulated by the FDA, it is virtually impossible to know what is safe and effective.
Second, what is the scientific evidence for or against milk thistle?
Why take milk thistle?
Is it because you read about it in an article? Did you hear about a study, and if so, what do you know about the research? Or did you wander into your local health food store and ask a sales clerk to recommend something good for the liver.
Third, without specific product information, do you know how much milk thistle to take, what kind, when to take it and when you shouldn’t? Do you know if it interacts with other medications you may be taking? Are there any side effects? Apply the same common sense investigation to dietary supplements as you would to any medicine.
The Research
When it comes to research on dietary supplements and liver disease, milk thistle tops the list. There were 222 milk thistle listings on the U.S. Library of Medicine’s PubMed site dating back to 1952. Although this sounds like a lot of research, compare this to 122,853 listings back to 1957 for interferon. Although research has yet to prove the benefits of milk thistle, it has also not disproved it. This is largely due to inadequate testing or poor scientific methods.
Here are highlights of some current research:
The December 2009 issue of Gastroenterology published a French study headed by Ahmed-Belkacem, “Silibinin and Related Compounds Are Direct Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase.” They used a commercially available intravenous preparation of silibinin. This is an encouraging beginning to more research.
According to the U. S. Department of Health and Human Services’ Agency for Healthcare Research and Quality (AHRQ), there is evidence that milk thistle may protect the liver.2 However, the research is unreliable due to poor scientific method, so it’s difficult to sort out the facts.
A search of Germany’s independent, evidence-based Cochrane Library revealed similar observations. According to Rambaldi A, Jacobs BP, and Gluud C “[There is] no evidence supporting or refuting milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Low-quality trials suggested beneficial effects. High-quality randomized clinical trials on milk thistle versus placebo are needed.”3
Another problem is the test product. AHRQ’s website states, “The largest producer of milk thistle is Madaus (Germany), which makes an extract of concentrated silymarin. However, numerous other extracts exist, and more information is needed on comparability of formulations, standardization, and bioavailability for studies of mechanisms of action and clinical trials.”
If the issue isn’t already complicated, consider this – taken as a supplement, milk thistle is poorly absorbed. After digestion, very little is left for the liver. This is particularly true for older adults. As little as 10% of silymarin may be absorbed in the adult over age 60.
In an article in September 2009 Alternative Medicine Review, biomedical research Parris Kidd, University of California, Berkeley, notes how milk thistle’s most active flavonoid, silybin is poorly absorbed by the body. Kidd states, “silybin-phosphatidylcholine complexed as a phytosome provides significant liver protection and enhanced bioavailability over conventional silymarin.”4 Twenty years ago, an Italian research team reached the same conclusion based on a pharmacokinetic study of nine subjects.5
It all boils down to this – ignoring the lack of scientific research, and choosing to take milk thistle, what product does one buy? Although the Jarrow supplement has been tested by CL, it was not used in clinical research. The one that has been used in research is the Madaus, but it is not available in the U.S. Silybin-phosphatidylcholine, used in various U.S. studies, is available. However, research grade silybin-phosphatidylcholine is not necessarily identical to consumer products.
Cautions
Talk to your medical provider before taking milk thistle, particularly if you take other drugs or supplements. Milk thistle is usually well-tolerated. It may have a laxative effect along with other gastrointestinal side effects. Allergic reaction is always a possibility, no matter what you are taking. Theoretically, milk thistle could lower blood sugar levels, so use caution if taking blood sugar-lowering medications. Exacerbation of hemochromatosis has been associated with ingestion of milk thistle.
Milk thistle should not be used by pregnant or breast-feeding women. People with a history of hormone-related cancers, including breast and uterine cancer and prostate cancer, may need to avoid milk thistle.
Since milk thistle is metabolized by the liver, it may interact with other drugs. However, despite earlier warnings about this, evidence of this is flawed. One strategy is to take milk thistle alone rather than in combination with other drugs, particularly oral contraceptives and coumadin. Milk thistle has a short half-life (4 hours).
Dosing
The following adult doses are from Natural Standard and are based on clinical research levels:
Silymarin (Legalon®) 230-600 milligrams per day divided into two to three doses
Silipide® (IdB 1016) 160-480 milligrams per day in silybin equivalents
The Bottom Line
Talk to your medical provider before taking milk thistle.
There is no evidence that milk thistle will eliminate HCV.
Milk thistle may provide some benefit to the liver but research has not proved or disproved this.
Milk thistle varies between manufacturers. Do your research before you purchase.
Milk thistle is poorly absorbed by the body, so if you take it, choose a formulation and dose that is bioavailable.
Alcohol extracts should be avoided by anyone with alcohol-related liver disease.
References
Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. Seeff LB, Curto TM, Szabo G, Everson GT, Bonkovsky HL, Dienstag JL, Shiffman ML, Lindsay KL, Lok AS, Di Bisceglie AM, Lee WM, Ghany MG. Hepatology. 2008 Feb;47(2):605-12.
Agency for Healthcare Research and Quality. Milk Thistle: Effects on Liver Disease and Cirrhosis and Clinical Adverse Effects. Evidence Report/Technology Assessment no. 21. Rockville, MD: Agency for Healthcare Research and Quality; 2000. 01-E024.
Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Rambaldi A, Jacobs BP, Gluud C. Cochrane Database of Systematic Reviews 2007, Issue 4.
A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos). Kidd P, Head K. Alternative Medicine Review. 2009 Sep;14(3):226-46.
Pharmacokinetic studies on IdB 1016, a silybin-phosphatidylcholine complex, in healthy human subjects. Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E. European Journal of Drug Metabolism and Pharmacokinetics. 1990 Oct-Dec;15(4):333-8.
http://www.hcvadvocate.org/news/newsLetter/2010/advocate0210.html#2
Silymarin use and liver disease progression in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial
. Alimentary Pharmacology & Therapeutics
N. D. Freedman 1, T. M. Curto 2, C. Morishima 3, L. B. Seeff 4, Z. D. Goodman 5, E. C. Wright 6, R. Sinha 1, J. E. Everhart 7, the HALT-C Trial Group 1
Article first published online: 2 NOV 2010
DOI: 10.1111/j.1365-2036.2010.04503.x
Published 2010. This article is a US Government work and is in the public domain in the USA.
Author Information
1 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA.
2 New England Research Institutes, Watertown, MA, USA.
3 Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
4 Division of Digestive Diseases and Nutrition, and Liver Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
5 Division of Hepatic Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
6 Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
7 Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
* Correspondence: Dr N. D. Freedman, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS/320, MSC 7232, Rockville, MD 20852, USA. E-mail: freedmanne@mail.nih.gov
Abstract
* Note: The terms "milk thistle" and "silymarin" are often used interchangeably.
Background
Silymarin is the most commonly used herbal product for chronic liver disease; yet, whether silymarin protects against liver disease progression remains unclear.
Aim
To assess the effects of silymarin use on subsequent liver disease progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had failed prior peginterferon plus ribavirin treatment.
Methods
Patients recorded their use of silymarin at baseline and were followed up for liver disease progression (two point increase in Ishak fibrosis score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for clinical outcomes.
Results
At baseline, 34% of patients had used silymarin, half of whom were current users. Use of silymarin was associated (P more then 0.05) with male gender; oesophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among other features. Baseline users had less hepatic collagen content on study biopsies and had less histological progression (HR: 0.57, 95% CI: 0.33–1.00; P-trend for longer duration of use=0.026). No effect was seen for clinical outcomes.
Conclusions
Silymarin use among patients with advanced hepatitis C-related liver disease is associated with reduced progression from fibrosis to cirrhosis, but has no impact on clinical outcomes (Clinicaltrials.gov #NCT00006164).
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2010.04503.x/abstract
Effects of Milk Thistle Extract on the Hepatitis C Virus Lifecycle
,
A laboratory study suggests that silymarin—an extract from the milk thistle plant—has multiple effects against the lifecycle of the hepatitis C virus. Hepatitis C is a chronic (long lasting) disease that primarily affects the liver and is often difficult to cure. The laboratory study examined the antiviral properties and mechanisms of silymarin on cultured (grown in a lab) human liver cells infected with the virus. The study, funded in part by NCCAM, was published in the journal Hepatology. l.
The researchers grew human liver cells and infected them in vitro with the hepatitis C virus. The cells were then exposed to either standard hepatitis C drug treatment or to a diluted dose of silymarin. By analyzing the interactions between silymarin and the virus, the researchers observed that silymarin prevented the entry and fusion of the hepatitis C virus into the target liver cells. . They also found that silymarin inhibited the ability of the virus to produce RNA (a chemical that plays an important role in protein synthesis and other chemical activities of the cell), interfering with a portion of the virus's lifecycle. When measured against untreated cells, silymarin also significantly decreased viral load (the amount of virus in the cells), although to a lesser degree than treatment with interferon did. The researchers also found that silymarin prevented the cell-to-cell spread of the virus. .
These findings build on previous research of silymarin's antiviral and anti-inflammatory properties and provide more information about the potential mechanisms involved in silymarin's antiviral actions. Further research, particularly in clinical trials, is needed to determine if silymarin could be a safe and effective supplement for treating hepatitis C in humans.
Reference
Wagoner J, Negash A, Kane OJ, et al. Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology. 2010;51(6):1912–1921. . .
The Study / Hepatology.
2010 Jun;51(6):1912-21.
Multiple effects of silymarin on the hepatitis C virus lifecycle.
Wagoner J, Negash A, Kane OJ, Martinez LE, Nahmias Y, Bourne N, Owen DM, Grove J, Brimacombe C, McKeating JA, Pécheur EI, Graf TN, Oberlies NH, Lohmann V, Cao F, Tavis JE, Polyak SJ. .
Department of Laboratory Medicine, University of Washington, Seattle, WA 98104-2499, USA.
.
Abstract .
Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus HCV infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions. .. Silymarin had antiviral effects against hepatitis C virus cell culture (HCVcc) infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production. .
Silymarin did not block HCVcc binding to cells but inhibited the entry of several viral pseudoparticles
(pp), and fusion of HCVpp with liposomes. Silymarin but not silibinin inhibited genotype 2a NS5B RNA-dependent RNA polymerase (RdRp) activity at concentrations 5 to 10 times higher than required for anti-HCVcc effects. .
Furthermore, silymarin had inefficient activity on the genotype 1b BK and four 1b RDRPs derived from HCV-infected patients. ..
Moreover, silymarin did not inhibit HCV replication in five independent genotype 1a, 1b, and 2a replicon cell lines that did not produce infectious virus. . Silymarin inhibited microsomal triglyceride transfer protein activity, apolipoprotein B secretion, and infectious virion production into culture supernatants. Silymarin also blocked cell-to-cell spread of virus. . CONCLUSION: Although inhibition of in vitro NS5B polymerase activity is demonstrable, the mechanisms of silymarin's antiviral action appear to include blocking of virus entry and transmission, possibly by targeting the host cell. .
PMID: 20512985 [PubMed - indexed for MEDLINE]
Publication Types, MeSH Terms, Substances, Grant Support
Cases in CAM: Milk Thistle for the Liver -- Any Evidence?
Désirée Lie, MD, MSEd
Authors and Disclosures
Posted: 03/02/2010
Mr. Y is a 40-year-old divorced car dealer who admits to binge alcohol consumption over the weekend with his buddies, consisting of 5 to 12 bottles of beer each on Friday and Saturday nights. He reports that he is sometimes inebriated and awakes the following morning with a hangover and amnesia for some of the previous night’s events. His father died of alcoholic cirrhosis at age 54 years. He is on no medications other than acetaminophen for occasional headaches. At his annual physical he expresses a desire to control his alcohol intake because of a new relationship he has forged which he believes has long-term potential. His new girlfriend has urged him to seek medical advice to control his alcohol intake. He denies alcohol dependence manifested as withdrawal symptoms when he misses the 'weekend booze.' His girlfriend brought up milk thistle as a treatment and suggested that he ask the doctor if it can reduce his appetite for beer and/or counteract acute effects of liver damage from alcohol consumption. She was also wondering whether milk thistle could improve her own complexion and reduce wrinkles.
On examination, Mr. Y is healthy and normotensive with no physical signs of chronic liver disease. A metabolic panel including liver function tests (LFTs) is normal. His last alcohol binge was 5 days ago.
Milk thistle (also known as Silybum marianum or silymarin) has been used medicinally for over 2000 years,[1] primarily for the treatment of hepatic and biliary disorders.[2-5] A flavonoid complex called silymarin is believed to be its active component.[2,3] Silibinin (the most active component of silymarin) can inhibit the 5-lipoxygenase pathway (which is involved in the formation of free radicals), scavenge hydroxyl radicals, and inhibit tumor necrosis factor (TNF).[6] Animal models have supported milk thistle’s role as an antioxidant that reduces free radical generation and affects cell growth and apoptosis, thereby reducing inflammation and supporting the liver’s tolerance of oxidative stress, including damage induced by toxins such as carbon tetrachloride.[7-11] The German commission E approves milk thistle for use in the treatment of[12-14]:
Liver conditions including toxin-induced damage and hepatic cirrhosis; and
Dyspepsia.
Milk thistle is one of the most frequently sold herbal products in the United States, with retail sales reaching $8.9 million in 2000, a 14% increase over sales in 1999.[15] It is used in gastroenterology clinics to treat hepatitis and cirrhosis and in oncology settings as a hepatoprotectant to:
Clear toxins;
Assuage symptoms of cancer; and
Improve tolerance to chemotherapy.
The intravenous form of silymarin has also been used as supportive treatment for Amanita phalloides mushroom poisoning.[2,3] Preliminary studies suggest that milk thistle may be potentially beneficial in treating or preventing some cancers[16] for example, it may prove to play a role in any one of the following cancers:
Prostate;
Skin;
Squamous cell cancer of the tongue;
Bladder;
Breast;
Cervical;
Colon; and
Leukemia.
Of note, a recent dermatologic review examined the use of topical milk thistle as a protectant against ultraviolet (UV) radiation and concluded that it may fall into the category of a botanical cosmeceutical with antioxidant properties that might offset the effects of skin aging and skin cancer.[17]
Milk Thistle for Liver Disease: What Does the Data Support?
Four systematic reviews examined the efficacy of milk thistle for the treatment of liver diseases, in particular, alcoholic liver disease and hepatitis B and C.[18-21] In one review, overall mortality for all chronic liver diseases studied in 14 trials was not reduced and there were no improvements in liver function by histology or biochemical testing that were of clinical significance.[18] The investigators recommended more definitive trials to examine efficacy. In the other reviews, based on high-quality trials, milk thistle did not influence the course of alcoholic or hepatitis B or C disease by outcomes of mortality and histology, but it had the potential to affect liver injury, with improvements seen in liver function tests after acute injury.[19-21]
A recent randomized, placebo-controlled clinical trial assessing the effects of silymarin on acute hepatitis (defined as alanine amino transferase levels higher than 2.5 times normal), mostly due to acute viral hepatitis, used 140 milligrams (mg) of silymarin 3 times daily and reported quicker resolution of symptoms of biliary retention and reduction in indirect bilirubin, but not other LFTs, over 4 weeks.[22] Another recent study suggests that a mixture of Silybum marianum and Aloe vera was protective against carbon tetrachloride-induced acute hepatotoxicity and liver fibrosis.[23]
What to tell your patients. The National Institutes of Health’s National Center for Complementary and Alternative Medicine (NCCAM) provides patient information on the use of milk thistle for hepatitis C.[24] It emphasizes the lack of definitive evidence for its efficacy in treating hepatitis C and urges patients not to replace conventional medical therapy with milk thistle.
Preparations, Dosage, Side Effects, and Contraindications
Milk thistle capsules, tincture, and powder are standardized to contain 70% to 80% silymarin, but different preparations may vary in terms of bioavailability. Chromatographic methods have been used to identify its active ingredients to satisfy Good Manufacturing Practices.[2] It is considered safe at doses up to 1500 mg daily and for treatment durations of up to 41 months.[25] No significant interactions or contraindications have been reported for milk thistle use.[26] Adverse effects are uncommon, with the most commonly reported being mild gastrointestinal disturbance, including a laxative effect.[15]
There is insufficient data on its use in pregnancy and lactation; therefore, it is not recommended for women during these times.[2,3]
Suggested doses in standardized preparations for cirrhosis and acute toxin-induced hepatotoxicity range from 160 to 800 mg daily by mouth. For chronic hepatitis, suggested doses range from 160 to 480 mg daily in silybin equivalents and 420 mg daily in 3 divided doses for silymarin.[2] The preparations Legalon® (containing silymarin), Nature's Way® Thisilyn, and Standardized Milk Thistle Extract Maximum Absorption Formula 2X have been used in clinical trials. Silymarin is also found in some moisturizers for photoaging (for example, RosaCure+ and SkinCeuticals Antioxidant Lip Repair.[17]
In summary, there is ample evidence from animal models for the antioxidant, anti-inflammatory, and antitoxin action of milk thistle, but limited up-to-date clinical evidence from high-quality randomized trials that milk thistle and its components offer significant benefit in the treatment of liver diseases including acute hepatitis and cirrhosis. The clinical benefits that have been demonstrated are of limited magnitude and significance. There are no studies documenting its efficacy in protecting against acute effects of alcohol intoxication or any evidence to suggest that it can reduce one’s appetite for alcohol. A recent review of an integrative medicine strategy for alcohol abuse advocates a balanced holistic approach that includes[1]:
Nutritional counseling;
Healthy lifestyle;
Relaxation;
Judicious use of supplementation with B vitamins, probiotics, zinc, and carnitine, as well as botanical products such as milk thistle; and
Acupuncture and mind-body therapy.
Abstinence from alcohol is the key to success in any case of chronic alcohol abuse.
Case Response
Although Mr. Y showed no physical signs or biochemical evidence of alcoholic liver damage at the time of initial presentation, he is at risk for chronic liver disease if his drinking pattern persists or escalates. Because he is motivated to change his approach to drinking, this is an ideal opportunity to move him from 'contemplation' to 'action' on the Prochaska cycle of motivation.[27] His girlfriend could be involved in his future care, and the partnership will help provide the incentives to move him along in small steps to achieve his goal. Since adverse effects of milk thistle are minimal, he may choose it as a supplement to prevent acute alcoholic liver damage during follow-up. When advising Mr. Y, however, the clinician should stress that the evidence for milk thistle's benefits derive from studies on acute viral hepatitis and chronic cirrhosis, and not acute alcohol-induced hepatitis.
There is currently no evidence for a preventive role against liver damage for milk thistle, and using milk thistle is not a substitute for medical care. Follow-up of Mr. Y is essential to ensure progression to abstinence or control of alcohol intake.
The potential for protection against photoaging may be mentioned as a possible benefit of topical milk thistle, although the evidence is preliminary and based mainly on animal studies. Providing the source of evidence for a dermatologic role for milk thistle would be prudent.
A Warning about Milk Thistle and Drug Interactions
The seeds of the milk thistle plant are commonly used to protect the liver from damage caused by hepatitis viruses as well as alcohol and other substances. Compounds found in milk thistle - sylibin, sylimarin - act as antioxidants and also stimulate the repair of the liver. But now it appears that these and possibly other compounds in milk thistle can have other effects. ............click link below to continue reading
http://www.hcvadvocate.org/hepatitis/hepC/mthistle.html
Site Of The Day
http://www.hcvadvocate.org
http://www.hcvadvocate.org/hepatitis/factsheets_pdf/CAM_herbs_10.pdf
http://www.hcvadvocate.org/hepatitis/factsheets_pdf/HERBS_color.pdf