Subject: Re: Blastomycosis - Histoplasmosis -- Please Help - Liver
Damage

HOWEDY Karen5572,

That'd be Jerry Howe, The Amazing Puppy Wizard <{) ; ~ )  >

Not really. The Amazing Puppy Wizard is NOT a veterinarian. HE
just IDENTIFIES EXXXPOSES and DISCREDITS incompetent
uncaring ill trained greedy cruel inept veterinary malpracticioners.

Those are caused by compromised auto immune systems.

To improve his condition reduce ALL stress in your
dog's life INCLUDING food bribes.

Here's HOWE:

                          <{#}: ~ } >8< { ~ :{@}>
                     <{#}: ~ } >           < { ~ :{@}>
               <{#}: ~ } >                         < { ~ :{@}>
    <{#}: ~ } > http://www.tinyurl.com/7bl5u  < { ~ :{@}>
               <{#}: ~ } >                         < { ~ :{@}>
                     <{#}: ~ } >           < { ~ :{@}>
                          <{#}: ~ } >8< { ~ :{@}>

You might want to consult The Amazing
Puppy Wizard's holistic veterinarian:

Dr. Roger L. DeHaan, DVM, MTS
105 Police Club Drive
Kings Mountain, NC 28086
Tel/Fax 704-734-0061

Here's some encouragement and information:

From: "Dr Ty" <T...@corecomm.net>
Subject: Re: Blastomycosis

Sorry to here that your dog has 'Blasto.' Several years ago, I was
involved
in treating a Rott with 'Blasto,' and after approx. an eight week stay
in
ICU. This was the worst case of 'Blasto' I've ever seen. She not only
showed
signs of blasto in her lungs, but also her eyes, lymph nodes,
intestinal
tract, & bone. She also had draining tracts in her skin. She had a
constant
fever; she didn't want to eat; and she also had her ups & downs (about
50:50). However, I am happy to say that she was CURED!! Everyone was
shocked
& very happy to finally see her go home.

So...if this dog could make it, there's got to be hope for yours.

As for the treatment, itraconazole is now the treatment of choice.
Treatment
is usually continued for at least 60-90 days (or at least 30 days after

all
the signs of disease have resolved). This drug (like many others) has
some
side effects.....dogs can lose their appetite due to a hepatic
toxicity.
Therefore, serum alanine aminotranferase (ALT), a liver enzyme, is
measured
regularly. The medication is then stopped until appetite resumes, and
then
started at a lower dose.  Some dogs may experience a vasculitis
(inflamed
lining of  the vessels) and cause edema of the limbs. This goes away
once
treatment is halted and started at a lower dose.

Treating 'Blasto' is a tough battle, but it can be beat. How long ago
was
"Beau" diagnosed? What lesions/signs does he have? What kind of 'downs'

is
he having? Primary cutaneous coccidioidomycosis and subsequent drug
eruption
to itraconazole in a dog AN Plotnick, EW Boshoven, and RA Rosychuk

Three weeks after traveling to Arizona, a 13-month-old, female Labrador

retriever
developed draining tracts in the right hind limb. Primary cutaneous
coccidioidomycosis
was diagnosed. Initial treatment with itraconazole resulted in
exacerbation of clinical
signs. Histopathology was suggestive of a cutaneous drug eruption.
Discontinuation of
the itraconazole caused resolution of the drug eruption. Successful
treatment of the
fungal infection was achieved using ketoconazole.

Treatment http://www.canismajor.com/dog/blstomyc.html

For many years, the standard therapy for blastomycosis has been
amphotericin B.
t is still the best choice for acute, life-threatening illness, and
treated dogs show
improvement in three to five days. Amphotericin must be given as an
intravenous
injection, either as a slow IV drip over several hours or as rapid IV
bolus injections,
one to three times weekly until a maximum cumulative dose is reached.

Rapid injections increase the potential for acute drug reactions, and
the drug has
a toxic effect on kidney function, which requires close monitoring. The

veterinarian
may temporarily delay therapy while the kidneys recover from the
injury.

Ketoconazole given orally twice a day has been effective against
blastomycosis.

Although it may take 10-14 days to see clinical improvement with this
drug, it may
be useful in a dog with poor kidney function and a mild form of the
disease. Given
alone, ketoconazole has a lower cure rate than amphotericin, but when
given together,
the two drugs work synergistically, allowing veterinarians to use lower

doses of
amphotericin and minimize the risk of kidney failure as well as
promoting a more rapid
and complete cure. The side effects of ketoconazole are related to
liver toxicity and include anorexia, nausea, and vomiting. It can be
harmful to pregnant dogs and may also affect
the fertility of male dogs.

Itraconazole is the newest drug used to treat blastomycosis. It is
given orally twice a
day at first, then once daily for 60-90 days. Like amphotericin, it
takes effect quickly,
and has the same cure rate as the amphotericin-ketoconazole
combination. The side
effects are related to liver toxicity, like ketoconazole, with the
addition of ulcerative skin
lesions and swelling of the legs at the higher dose.

The biggest drawback to itraconazole is the cost, about $10 per day for

a 40-pound
dog for the medication alone, about twice the cost of ketoconazole.
Because these
drugs are dosed on body weight, larger dogs will have comparably larger

drug costs.
Blood tests and other veterinary services must also be considered in
the cost of
treatment. Total fees of $1000 or more would not be unusual.

Blastomycosis is not generally considered a zoonotic disease, meaning
one that is
potentially contagious to people. If you have a pet with this
infection, it indicates that
you may be at risk for contracting the disease through a common
environmental source
such as contaminated soil near a waterway. Since it is the mold form
that releases
infective spores through the air, you cannot get blastomycosis from the

air around
your dog who is infected with the yeast form of the fungus.

Recent studies indicate some risk of exposure through penetrating
wounds with sharp contaminated objects such as a sharp stick or a dog
bite, so good safety and hygiene
precautions are indicated. Needless to say, persons with deficient
immune systems
should not be handling infected dogs.
--By Kathleen R. Hutton DVM--

(Dr. Hutton wrote this article after we received a request to report
about blastomycosis
from a reader who lost her Siberian Husky to this fungus disease. Dog
Owner's Guide
is always open to article submissions and suggestions from readers.
Medical articles
must be written by a veterinarian or other professional, but ideas are
always welcome.)

BLASTOMYCOSIS IN THE DOG

BLASTOMYCOSIS (Blasto) in the dog is a commonly misdiagnosed systemic
fungal
disease of dogs and humans and other mammals.  It is a great
masquerader and can
be mistaken for cancer, viral infections, Lyme Disease and other
systemic fungal
diseases such as Valley  Fever.  Many dogs Your ALT-Text here have been

euthanized
or had treatment delayed

because of an erroneous diagnosis of cancer being made. Blastomycosis
in the dog
causes weight loss, swollen lymph nodes, draining sores, coughing, poor

appetite,
fever, blindness, bone lesions, etc.  The reason there are so many
areas affected is
due to the widespread dissemination of the organisms throughout the
dog's body
from the original site which is usually the lungs.  In the environment
Blasto is present
mostly in the Mississippi, Wisconsin, and Ohio River systems.

Blasto grows in two ways.  One form, called the fungal form, occurs in
the environment
and the organism creates microscopically tiny spores that, once
airborne, are able to
pass far into the depths of the lungs.  These spores are released from
the fungus when
the soil is disturbed by the dog digging for gophers or simply by the
dog probing the
soils following the odor trails that they love so much.  Much less
common in cats (even
though cats do their share of digging in dusty soil when they eliminate

stool and urine)
than in dogs, Blasto is easily inhaled into the dog's lungs.  Infective

spores are more
likely to be present in organic soils such as are present along
streams, lakes, ponds
and even within the dried mud mortar of beaver lodges.  Landscaping
soil and even
potting soil can harbor Blastomycosis organisms and any cat or dog
digging up these
soils may be exposed to Blastomycosis.

When in the soil the fungal phase of Blastomycosis releases vast
numbers of extremely
tiny spores that are cast away into the Chest X-ray of a dog with
Blastomycosis dust and
dirt stirred up when the soil is disturbed.  Especially during dry
periods in the
environment, where the soil and spores may become more easily airborne,

the potential
for infection with Blastomycosis is greater.  The spores are so tiny
that the protective
mucous lining of the respiratory tract is unable to attract all of
them... and the
spores settle deep in the alveolar sacs at the end of the respiratory
tree.  Finding
themselves in a warm, moist and dark environment, rich in nutrients,
the spores become
infective yeast-like organisms and multiply in huge numbers.  While
inside the dog, the
body's normal defense mechanisms can simply eliminate these spores and
no disease
results.  However, if the load (numbers) of spores inhaled is very
great or the dog is
immune suppressed or stressed by other diseases or poor diet, the
organisms may begin to
reproduce rapidly and signs of disease occur.  Once the spores have
taken hold, they
grow as single celled yeast forms rather than the fungal form.  This is

why the Blasto
organism is called a biphasic organism... it can grow in the
environment as a fungus and
within a mammal as a yeast.  Click here to see a large image (it is
95Kb so it may take
a minute to load) of the chest radiograph above.

After inhalation of organisms the incubation period for Blasto can be
from a few days to
many weeks before any signs of disease show up.  Fever of 104 to 105
degrees, poor
appetite, low grade deep cough, loss of exercise tolerance, and
listlessness are
cardinal signs of Blastomycosis.  Similar to the other systemic fungal
infections,
Blastomycosis can spread throughout the body from the lungs and invade
lymph nodes,
joints, eye structures and skin.  Often the first evidence a
veterinarian has of
Blastomycosis is a small draining ulcer that looks like a small
abscess.  Sudden
blindness, lameness, and blood in the urine may be the first signs of
disease...
sometimes showing up before any coughing is noticed.

Blastomycosis can infect humans and dogs

       HUMAN CONTAGION:  It has happened quite often that a dog will
be
diagnosed
with Blasto and shortly thereafter the human resident of the dog's
household will display
malaise, fever, persistent cough and weight loss.  Hopefully the
physician will not be
fooled by this disease in disguise and will establish a diagnosis of
Blastomycosis and
begin treatment.  The natural question arises:  Did the human get the
disease from the
dog?  The answer 99% of the time is NO.  Both human and dog generally
acquire the
disease from the same environmental source in the soil.  Likewise the
dog rarely will
"get Blasto" from a human companion.  The exception occurs where there
is transmission
of yeast organisms directly from an open, draining lesion on the dog
into an open wound
or directly into the eye of a human.  The transmission of infective
yeast cells from dog
to human or human to dog can occur and result in a localized infected
lesion.
Fortunately this form of contagion is quite rare and usually responds
quickly to
treatment.

BLASTOMYCOSIS CASE PRESENTATION

A four year old Labrador Retriever mix was presented with signs of
weight loss, poor
appetite and lethargy.  The owners also noticed a few crusty sores on
the dog and said
that the dog was hacking and coughing.  Upon examination it was noted
that the lungs
sounded congested, there were swollen lymph nodes, the temperature was
104.5 degrees and
the dog appeared depressed and thin.  Since the dog lived in an area
endemic for
Blastomycosis, the veterinarian strongly suspected Blasto and obtained
a specimen for
microscopic evaluation.  By pressing a glass slide to a draining skin
lesion a sample of
the exudate was obtained, dried, stained and examined under the
microscope.

Usually New Methylene Blue stain works very well.  Hundreds of
organisms showed
up on the slide and a positive diagnosis was made for Blastomycosis
within a few
minutes of examining the patient.  Treatment was begun immediately.

Some cases can be much more challenging to diagnose if there are no
readily available
infected tissues to swab for examination.  In cases where Blasto is
suspected, a needle
aspirate of a swollen lymph node may be revealing.  Many cases need to
have needle
aspiration of the lungs or thorax performed in order to acquire
organisms for a positive
diagnosis.  To do a blood immune level exam, called a titer, may be
futile in that some
dogs with Blasto will show no evidence of an elevated titer!  Culturing

phlegm or other
exudative material can take weeks for a positive determination to be
made... and the dog
often will die long before those culture specimens are reported on.
There are times
when the veterinarian will determine that in the dog's best interest,
treatment for
Blasto should begin immediately... based upon circumstantial evidence
and without
positive identification of the organism.

Click on an image to see a full size presentation
Blastomycosis in the dog in ThePetCenter.com.

There were numerous skin lesions such as this one on the dog's skull.
This is how the lesion appears after gentle cleaning of the crusts
This is a close-up of the destructive effects of Blastomycosis
organisms

Another example from the dog's chest area.

Blastomycosis in the dog in ThePetCenter.com.

A close-up of a Blastomycosis skin lesion on the dog's leg
The microscope slide is pressed against the skin lesion

The specimen is stained with New Methylene

This is the high power view of the organisms which have a grape-like
appearance and are multiplying by budding NOTE!  Many dogs that travel
to an endemic area for Blastomycosis (or other systemic fungal
diseases)
and eventually start showing signs of the disease weeks or months later

when the dog is back home, are at greater risk for having a
mis-diagnosis
made for their sickness.  Always tell your veterinarian during the
history-
taking if the dog about any travel outside your home area.

If it just so happens that the dog spent time in an area endemic for
Blastomycosis and is displaying unusual or challenging signs of
sickness,
the veterinarian may benefit from your information.  For example, in
northern Wisconsin, an endemic Blasto area, every veterinarian has seen

dozens to hundreds of cases and can often zero in on a correct
diagnosis
in minutes.

 If a dog acquires the spores of Blastomycosis in Wisconsin on a
family
vacation and returns to central Iowa where Blasto is seldom seen, and
begins
to show signs of sickness two months later, the veterinarian will be
greatly
assisted by the knowledge that time was spent in an area endemic for
the disease.

Identification

Dr. Sheila McCullough of the University of Illinois College of
Veterinary
Medicine states, ?Fungal diseases often masquerade as other diseases.
The
affected pets present with lethargy, lameness, poor appetite, "not
doing
right" and may have a fever. Treatment may Examining the stained
specimen
for organisms. High power view of budding Blasto organisms.also be
delayed
because it is difficult to get a sample of the  organism from a lymph
node,
skin cytology or trans-tracheal wash.?  It is crucial that the
organisms be
identified under the microscope for establishing a positive diagnosis
of a
fungal disease such as Valley Fever or Blasto. Culturing infected
material
may take weeks and the patient simply cannot afford to wait even days
for
a diagnosis!

Blood tests are equivocal.  False positives and negatives are common.

The best and most direct method of establishing a definitive diagnosis
is
to gather tissue or fluid samples from infected areas such as a swollen

lymph node, draining skin lesion or material coughed up by the patient.

A needle biopsy of a lymph node is commonly done and can be performed
without anesthesia. During the office call the veterinarian will stain
the
specimen cells on a microscope slide and look for the infective
organisms.

If organisms are seen, BINGO!  Start treatment right now.  If they
aren?t
seen, special stains at a diagnostic lab are required.  The important
thing
to do is to BE PERSISTENT in striving to get a diagnosis for the
elusive
disease in disguise.

Treatment

In the past, Amphotericin-B was the only known medication useful
against
Blastomycosis and the other systemic fungal organisms.  Long term
medication
for fungal diseases may be necessary.It had to be given intravenously
and with
care to keep the dose from harming the kidneys.  This medication has
saved
thousands of canine (and human) lives.  Recently, though, researchers
have
provided us with oral medications just as effective in treating fungal
infections.

The most popular today are Itraconazole (Sporanox) and Fluconazole
(Diflucan).
These tablets are administered for three to six months (sometimes even
longer)
and your pharmacy bill will be substantial... but your formerly
infected dog out
in the yard playing fetch with the children wouldn?t be alive without
it.

Almost every dog that survives Blastomycosis will make a complete
recovery
and will run, play, hunt and live a completely normal life.  However,
the
success of treatment depends upon a number of factors such as location
of
lesions, the age of the dog, nutritional status, and stage of the
disease
when treatment has begun.  If Blastomycosis has spread to any bones, or

the
brain or spinal cord, treatment may not be rewarding.  It seems as well

that
the organism often affects the optic nerves and a sudden blindness in
an
otherwise apparently healthy dog should alert the veterinarian to the
possibility
of Blasto as the cause.  Once blinded by Blasto, the sight is never
regained.

Whenever your dog is sick be sure to provide your veterinarian with a
detailed patient history.  And you should be persistent in seeking a
definitive diagnosis.  Persistent detective work is your best weapon
for unmasking a disease such as Blastomycosis.

Prevention

What is the best way to insure that a dog does not fall under the spell

of Blastomycosis or other systemic fungal infections?  Dr. McCullough
has a suggestion based She'll be OK won't she Doctor?upon her
experiences
with systemic fungal infections.  ?Providing a thorough history is
very
important to obtain a full picture of what led up to the animal
becoming
ill,? says Dr. McCullough.  ?The client should inform the
veterinarian of
the patient's travel history within the past 6 months and what the
daily
environment is for the pet (i.e. camping, swimming, hunting, living
near
new construction or landscaping).  A thorough history is the key first
step toward figuring out the puzzle.  It is just as important to keep
an
ongoing dialogue with your veterinarian and to create a plan of action
if
the initial tests for an expected disease are negative.?

Dr. McCullough?s point should not be underestimated.  Knowledge of a
seemingly irrelevant environmental factor can be the key information
the doctor needs to proceed toward a proper diagnosis.  Something as
innocent as stating ?My dog loves to dig into gopher holes, Doctor?

or ?Two months ago we had soil carted in for landscaping? can turn
the doctor?s attention toward a fungal infection such as
Blastomycosis.

View another page about SYSTEMIC FUNGAL DISEASES including Valley
Fever,
Histoplasmosis, and Cryptococcosis.

Subject: Re: Blastomycosis - Histoplasmosis -- Please Help - Liver
Damage

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

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
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:

  1. Effects of milk thistle on liver disease of alcohol, viral,
toxin, cholestatic, and primary malignancy etiologies.
  2. 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.

Return to Contents
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.

Return to Contents
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.

Return to Contents
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.

Return to Contents
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.

Return to Contents
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 also online on the National Library of Medicine
Bookshelf.

Return to Contents

AHRQ Publication Number 01-E024
Current as of September 2000

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

Return EPC Evidence Reports
Clinical Information
AHRQ Home Page
Department of Health and Human Services