Milk Thistle

[MonsterRugby]

Anybody, take this after dbol , or any test cycles.. or any cycles at all? If so how much and how often? Is it even that beneficial?

[monstercojones]

i take it ed... twice daily at 400 mgs.

[MonsterRugby]

and i am assuming it is beneficial to any test cycle yes? particularly dbol

[frank_frank]

u need it for dbol cuz its a 17AA steroid which is harsh on your liver

[Da Bull]

Milk Thistle

(Silybum Marianum)

Michelle Giesler and Kimberly Jones




General Description

Other names: Marian thistle, St. Mary's thistle, Our Lady's thistle
Family: Asteraceae
Distribution: Native to the Mediterranean region of Europe, but naturalized in California and the eastern US
Description of plant:

tall herb with prickly leaves and a milky sap
Small, hard fruits (achenes), a feathery tuft or pappus is removed
Milk white veins in the leaves (originated in the milk of the Virgin Mary which once fell upon the plant)
Parts used:

ripe fruit (not seeds), root, leaves, hull

Chemical composition

Silymarin- chemical mixture of antihepatotoxic principles; 1-4% conc. in fruit
Shown to consist of a large number of flavonolignans, including principally silybin accompanied by isosilybin, dehydrosilybin, silydianin, silychristin, etc.

History and folk use

Formerly frequently cultivated in gardens
The stalks may be eaten and are palatable and nutritious
Young leaves may be eaten as a salad, and were sometimes baked in pies
The heads were formerly boiled and eaten, treated like those of an Artichoke
Thought to be a great breeder of milk and proper diet for nursing women
Thought to have a healing property in those with snake bites
If worn around the neck it would protect you from snake bites
Fruit formerly thought to cure hydrophobia
Applied externally, said to have been proven beneficial in cases of cancer
The young, tender plant be boiled and eaten in the spring as a blood cleanser
Fruits have been used for many years for a variety of conditions, especially liver complaints. However, medicinal use of the plant, except as a simple bitter, was practically discontinued early in the twentieth century.

Primary effects in the body

Acts on cell membranes of liver cells to prevent the entry of toxic substances
Stimulates protein synthesis, accelerating regeneration process & production of liver cells
Acts as an antioxidant, with far greater free radical damage control than vitamin E
It may offer some protection against toxic side effects from acetaminophen

Clinical applications

Early treatment for chronic liver problems
Rehabilitation from alcohol, solvent or IV recreational abuse
Protects hepatocytes from heavy metal, chemical and alcohol injury
Limits fatty degeneration and speeds up hepatitis recovery, slowing or reversing cirrhosis
Supportive treatment for inflammatory liver conditions and cirrhosis

Toxicity

None reported

Drug and disease interactions

None reported

Dosage

Fruit (seeds): 2-3 capsules up to 3 x day
Tincture: 1:5, 60% alcohol, ½ to 1 teaspoon up to 4 x day (equal parts of root & seed with hull attached)
Silymarin is very poorly soluble in water so is not effective as a tea (< 10% plant activity)
Poor solubility and poor absorption from GI tract (20-50%) make active principles best administered parenterally
Oral use requires a concentrated product
Capsules containing 200mg of a concentrated extract representing 140mg of silymarin

Primary and Tertiary literature

Protection from Amanita phalloides intoxication Tox Appl Pharm 73 (1984)

Severe poisoning with mortality rate of 30%
Study in beagles
50 gm/kg silibinin 5 and 24 hrs post-intoxication
4 deaths in control group / 0 deaths with silibinin
Reduction in elevations of GPT, GOT, AP and bilirubin with silibinin; less decrease in PT
Mechanism of Action?
Modification or occupance of cell membrane receptor sites
Decrease phospholipid metabolism
Prevention of inhibition of RNA Polymerase and RNA synthesis by toxin

Increase of Glutathione Content in the Liver Planta Medica 55 (1989)

200 mg/kg silymarin single dose
Over 50% increase GSH in liver and intestine
Selectivity
accumulation principally in liver
entero-hepatic recirculation
An increase in GSH can increase conjugation/elimination of toxins and decrease lipid peroxidation
Mechanism of action?
Increase in membrane permeability of amino acids involved in GSH synthesis

Stimulation of DNA synthesis in malignant cell lines? Biochem Pharm 35(1986)

27 mg/kg silibinin prior to injection of radioactive thymidine
Silibinin increases ribosomal RNA synthesis
No influence on DNA synthesis in normal livers
Large increase in DNA synthesis in hepatectomized rats / 23-35% increase in thymidine incorporation
No influence on DNA synthesis in fast growing hepatoma cell cultures
Mechanism of action?
Hepatectomized rats
If the regulatory signal for replication initiation is given, increase in rRNA and protein synthesis also accelerates DNA synthesis
Hepatoma cells
The rate of proliferation is already maximal and cannot be further intensified

Effect of silibinin on biliary lipid composition Journal of Hepatology 12(1991)

The rats
100mg/kg or 50mg/kg silymarin for 7 days
measured biliary cholesterol, biliary phospholipid, total bile salt and bile flow
decrease in biliary cholesterol and phosolipid
no change in bile flow and total bile salts
The Humans
400mg/day silymarin in cholecystectomized and gallstone patients for 1 month
significant decrease in biliary cholesterol for both groups
Mechanism of Action?
Found a dose dependent decrease in HMG-CoA reductase in the liver with increasing silymarin concentration
A decrease in HMG-CoA reductase leads to a decrease in synthesis of cholesterol


____________________

[Da Bull]

Evidence Report/Technology Assessment: Number 21
Milk Thistle: Effects on Liver Disease and Cirrhosis and Clinical Adverse Effects
Summary

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Under its Evidence-based Practice Program, the Agency for Healthcare Research and Quality (AHRQ) is developing scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools. Contractor institutions review all relevant scientific literature on assigned clinical care topics and produce evidence reports and technology assessments, conduct research on methodologies and the effectiveness of their implementation, and participate in technical assistance activities.

Overview / Reporting the Evidence / Methodology / Findings / Future Research / Availability of Full Report


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Overview
This evidence report details a systematic review summarizing clinical studies of milk thistle in humans. The scientific name for milk thistle is Silybum marianum. It is a member of the aster or daisy family and has been used by ancient physicians and herbalists to treat a range of liver and gallbladder diseases and to protect the liver against a variety of poisons.

Two areas are addressed in the report:

Effects of milk thistle on liver disease of alcohol, viral, toxin, cholestatic, and primary malignancy etiologies.
Clinical adverse effects associated with milk thistle ingestion or contact.
The report was requested by the National Center for Complementary and Alternative Medicine, a component of the National Institutes of Health, and sponsored by the Agency for Healthcare Research and Quality.

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Reporting the Evidence
Specifically, the report addresses 10 questions regarding whether milk thistle supplements (when compared with no supplement, placebo, other oral supplements, or drugs):

Alter the physiologic markers of liver function.
Reduce mortality or morbidity, or improve the quality of life in adults with alcohol-related, toxin-induced, or drug-induced liver disease, viral hepatitis, cholestasis, or primary hepatic malignancy.
One question addresses the constituents of commonly available milk thistle preparations, and three questions address the common and uncommon symptomatic adverse effects of milk thistle.

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Methodology
Search Strategy
Eleven electronic databases, including AMED, CISCOM, the Cochrane Library (including DARE and the Cochrane Controlled Trials Registry), EMBASE, MEDLINE, and NAPRALERT, were searched through July 1999 using the following terms:

Carduus marianus.
Legalon.
Mariendistel.
Milk thistle.
Silybin.
Silybum marianum.
Silybum.
Silychristin.
Silydianin.
Silymarin.
An update search limited to PubMed was conducted in December 1999. English and non-English citations were identified from these electronic databases, references in pertinent articles and reviews, drug manufacturers, and technical experts.

Selection Criteria
Preliminary selection criteria regarding efficacy were reports on liver disease and clinical and physiologic outcomes from randomized controlled trials (RCTs) in humans comparing milk thistle with placebo, no milk thistle, or another active agent. Several of these randomized trials had dissimilar numbers of subjects in study arms, raising the question that these were not actually RCTs but cohort studies. In addition, among studies using nonplacebo controls, the type of control varied widely. Therefore, qualitative and quantitative syntheses of data on effectiveness were limited to placebo-controlled studies. For adverse effects, all types of studies in humans were used to assess adverse clinical effects.

Data Collection and Analysis
Abstractors (physicians, methodologists, pharmacists, and a nurse) independently abstracted data from trials; a nurse and physician abstracted data about adverse effects. Data were synthesized descriptively, emphasizing methodologic characteristics of the studies, such as populations enrolled, definitions of selection and outcome criteria, sample sizes, adequacy of randomization process, interventions and comparisons, cointerventions, biases in outcome assessment, and study designs. Evidence tables and graphic summaries, such as funnel plots, Galbraith plots, and forest plots, were used to examine relationships between clinical outcomes, participant characteristics, and methodologic characteristics. Trial outcomes were examined quantitatively in exploratory meta-analyses that used standardized mean differences between mean change scores as the effect size measure.

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Findings
Mechanisms of Action
Evidence exists that milk thistle may be hepatoprotective through a number of mechanisms: antioxidant activity, toxin blockade at the membrane level, enhanced protein synthesis, antifibriotic activity, and possible anti-inflammatory or immunomodulating effects.

Preparations of Milk Thistle
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.

Benefit of Milk Thistle for Liver Disease
Sixteen prospective trials were identified. Fourteen were randomized, blinded, placebo-controlled studies of milk thistle's effectiveness in a variety of liver diseases. In one additional placebo-controlled trial, blinding or randomization was not clear, and one placebo-controlled study was a cohort study with a placebo comparison group.
Seventeen additional trials used nonplacebo controls; two other trials studied milk thistle as prophylaxis in patients with no known liver disease who were starting potentially hepatotoxic drugs. The identified studies addressed alcohol-related liver disease, toxin-induced liver disease, and viral liver disease. No studies were found that evaluated milk thistle for cholestatic liver disease or primary hepatic malignancy (hepatocellular carcinoma, cholangiocarcinoma).
There were problems in assessing the evidence because of incomplete information about multiple methodologic issues, including etiology and severity of liver disease, study design, subject characteristics, and potential confounders. It is difficult to say if the lack of information reflects poor scientific quality of study methods or poor reporting quality or both.
Detailed data evaluation and syntheses were limited to the 16 placebo-controlled studies. Distribution of durations of therapy across trials was wide (7 days to 2 years), inconsistent, and sometimes not given. Eleven studies used Legalon®, and eight of those used the same dose. Outcome measures varied among studies, as did duration of therapy and the followup for which outcome measures were reported.
Among six studies of milk thistle and chronic alcoholic liver disease, four reported significant improvement in at least one measurement of liver function (i.e., aminotransferases, albumin, and/or malondialdehyde) or histologic findings with milk thistle compared with placebo, but also reported no difference between groups for other outcome measures.
Available data were insufficient to sort six studies into specific etiologic categories; these were grouped as chronic liver disease of mixed etiologies. In three of the six studies that reported multiple outcome measures, at least one outcome measure improved significantly with milk thistle compared with placebo, but there were no differences between milk thistle and placebo for one or more of the other outcome measures in each study. Two studies indicated a possible survival benefit.
Three placebo-controlled studies evaluated milk thistle for viral hepatitis. The one acute viral hepatitis study reported latest outcome measures at 28 days and showed significant improvement in aspartate aminotransferase and bilirubin. The two studies of chronic viral hepatitis differed markedly in duration of therapy (7 days and 1 year). The shorter study showed improvement in aminotransferases for milk thistle compared with placebo but not other laboratory measures. In the longer study, milk thistle was associated with a nonsignificant trend toward histologic improvement, the only outcome measure reported.
Two trials included patients with alcoholic or nonalcoholic cirrhosis. The milk thistle arms showed a trend toward improved survival in one trial and significantly improved survival for subgroups with alcoholic cirrhosis or Child's Group A severity. The second study reported no significant improvement in laboratory measures and survival for other clinical subgroups, but no data were given.
Two trials specifically studied patients with alcoholic cirrhosis. Duration of therapy was unclear in the first, which reported no improvement in laboratory measures of liver function, hepatomegaly, jaundice, ascites, or survival. However, there were nonsignificant trends favoring milk thistle in incidence of encephalopathy and gastrointestinal bleeding and in survival for subjects with concomitant hepatitis C. The second study, after treatment for 30 days, reported significant improvements in aminotransferases but not bilirubin for milk thistle compared with placebo.
Three trials evaluated milk thistle in the setting of hepatotoxic drugs: one for therapeutic use and two for prophylaxis with milk thistle. Results were mixed among the three trials.
Exploratory meta-analyses generally showed positive but small and nonsignificant effect sizes and a sprinkling of significant positive effects.
No studies were identified regarding milk thistle and cholestatic liver disease or primary hepatic malignancy.
Available evidence does not establish whether effectiveness of milk thistle varies across preparations. One Phase II trial suggested that effectiveness may vary with dose of milk thistle.
Adverse Effects
Adverse effects associated with oral ingestion of milk thistle include:

Gastrointestinal problems (e.g., nausea, diarrhea, dyspepsia, flatulence, abdominal bloating, abdominal fullness or pain, anorexia, and changes in bowel habits).
Headache.
Skin reactions (pruritus, rash, urticaria, and eczema).
Neuropsychological events (e.g., asthenia, malaise, and insomnia).
Arthralgia.
Rhinoconjunctivitis.
Impotence.
Anaphylaxis.
However, causality is rarely addressed in available reports. For randomized trials reporting adverse effects, incidence was approximately equal in milk thistle and control groups.

Conclusions
Clinical efficacy of milk thistle is not clearly established. Interpretation of the evidence is hampered by poor study methods and/or poor quality of reporting in publications. Problems in study design include heterogeneity in etiology and extent of liver disease, small sample sizes, and variation in formulation, dosing, and duration of milk thistle therapy. Possible benefit has been shown most frequently, but not consistently, for improvement in aminotransferases and liver function tests are overwhelmingly the most common outcome measure studied. Survival and other clinical outcome measures have been studied least often, with both positive and negative findings. Available evidence is not sufficient to suggest whether milk thistle may be more effective for some liver diseases than others or if effectiveness might be related to duration of therapy or chronicity and severity of liver disease. Regarding adverse effects, little evidence is available regarding causality, but available evidence does suggest that milk thistle is associated with few, and generally minor, adverse effects.

Despite substantial in vitro and animal research, the mechanism of action of milk thistle is not fully defined and may be multifactorial. A systematic review of this evidence to clarify what is known and identify gaps in knowledge would be important to guide design of future studies of the mechanisms of milk thistle and clinical trials.

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Future Research
The type, frequency, and severity of adverse effects related to milk thistle preparations should be quantified. Whether adverse effects are specific to dose, particular preparations, or additional herbal ingredients needs elucidation, especially in light of equivalent frequencies of adverse effects in available randomized trials. When adverse effects are reported, concomitant use of other medications and product content analysis should also be reported so that other drugs, excipients, or contaminants may be scrutinized as potential causal factors.

Characteristics of future studies in humans should include:

Longer and larger randomized trials.
Clinical as well as physiologic outcome measures.
Histologic outcomes.
Adequate blinding.
Detailed data about compliance and dropouts.
Systematic standardized surveillance for adverse effects.
Attention to specific study populations (e.g., patients with hepatitis B virus [HBV], or hepatitis C virus [HCV], or mixed infection or coinfection with human immunodeficiency virus [HIV]), comorbidities, alcohol consumption, and potential confounders.
There also should be detailed attention to preparation, standardization, and bioavailability of different formulations of milk thistle (e.g., standardized silymarin extract and silybin-phosphatidylcholine complex).

Precise mechanisms of action specific to different etiologies and stages of liver disease need explication. Further mechanistic investigations are needed and should be considered before, or in concert with, studies of clinical effectiveness. More information is needed about effectiveness of milk thistle for severe acute ingestion of hepatotoxins, such as occupational exposures, acetaminophen overdose, and amanita poisoning.

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Availability of Full Report
The full evidence report from which this summary was derived was prepared by 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 (VERDICT), a Veterans Affairs Health Services Research and Development Center of Excellence under contract No. 290-97-0012. Printed copies may be obtained free of charge from the AHRQ Publications Clearinghouse by calling 800-358-9295. Requesters should ask for Evidence Report/Technology Assessment Number 21, Milk Thistle: Effects on Liver Disease and Cirrhosis and Clinical Adverse Effects (AHRQ Publication No. 01-E025).

The Evidence Report is available online at http://hstat.nlm.nih.gov/hq/Hquest/...tAccess/db/3146 or can be downloaded as a zipped file at: http://www.ahrq.gov/clinic/evrptfiles.htm#thistle.

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AHRQ Publication Number 01-E024
Current as of September 2000


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Internet Citation:

Milk Thistle: Effects on Liver Disease and Cirrhosis and Clinical Adverse Effects. Summary, Evidence Report/Technology Assessment: Number 21, September 2000. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/epcsums/milktsum.htm


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AHRQ Home Page
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[Rhino58]

People like Bull make this site great, Thanks bro.

[SportsMedVIP]

Best thing about Milk Thistle (other than the obvious) is that you can see the results. A nice deep dark amber stream of results.

[OTSS1]

Yeah it is definetely helpful if you are on 17-AA's. It's cheap and can't hurt you. Why not?

[Spoon]

great post Da bull!!! very useful, i just ordered some

[TheSevnthWarrior]

DB you're just the walking encyclopedia lately huh Bro....

I take 1000mg of Milk Thistle, and 6 Liv-52 tabs ED, if I let up for more than a week with these, while on Orals, I get intense Muscle Cramps.
TSW

[Animal Cracker]

I take M.Thistle and Cran-x on every cycle.

[map200uk]

Milk Thistle/ALA / Cranberry is good for when using

[map200uk]

1000mg of milk thistle you do that everyday for the whole cycle or only when using orals?

[bjayg]

People like Bull make this site great, Thanks bro.

I 2nd that, great read Bull.

[frankthetank41778]

da bull great post. was gettig ready to ask a few questions and once again you have answered it for me. thank for sharing the knowledge

[frankthetank41778]

i just started taking thistle the other day after mixing oral winny and clen at the same time. by the way dont do that, your liver will wake up next to you crying in the morning. two orals with 17-Aa is not recomended by me. i fell better already. this stuff really works great. it probably isn't a bad idea to take some fro time to time for any one. my uncle is on the liver transplant list and that has really got me spooked so i thenk that im going to clean out from time to time.

[hung-solo]

i just started taking thistle the other day after mixing oral winny and clen at the same time. by the way dont do that, your liver will wake up next to you crying in the morning. two orals with 17-Aa is not recomended by me. i fell better already. this stuff really works great. it probably isn't a bad idea to take some fro time to time for any one. my uncle is on the liver transplant list and that has really got me spooked so i thenk that im going to clean out from time to time.

um clen is not harmful to your liver, but the winny is!