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Milk thistle key ingredients
Milk thistle extracts are standardized to a concentration of 70-80% of flavone lignans including isosilybinin, silybinin, silychristin, and silydianin, which
are
collectively called silymarin. Silymarin may play a role in displacing toxins binding to the liver and causing the liver cells to regenerate at a
faster rate.

Milk thistle is a flowering herb. Silymarin can be extracted from the seeds (fruit). The seeds are used to prepare capsules containing powdered herb
or seed; extracts; and infusions (strong teas). [NCCAM]

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Milk Thistle Bioavailability
According to Sloan-Kettering Institute [SK], milk thistle is poorly absorbed from the gastrointestinal tract with a bioavailability of approximately
23-47%. Peak plasma concentrations (T max) occur within 2-4 hours after dosing and the elimination half-life of milk thistle is about 4 hours.

Formulation for improving absorption
Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle, is used clinically as a hepatoprotector to treat liver injuries and chronic
hepatitis. However, it is poor oral bioavailability due to the poor solubility and low permeability across intestinal epithelium. It was found that silymarin
glyceryl monooleate/poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) improved the oral bioavailability of silymarin in dogs.
Pharmacokinetic study in beagle dogs showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a
3.46-fold increase in oral bioavailability as compared with Legalon®, a commercial product. [aa4]
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MILK THISTLE EXTRACT HEALTH BENEFITS
Milk thistle's protective effects on liver are well-known, milk thistle actually may have many other health benefits. Test-tube studies show that milk
thistle may possibly be a potent anti-cancer agent. Further, milk thistle ingredients were found to have anti-inflammatory, cytoprotective, and
anticarcinogenic effects and these beneficial effects are probably related to inhibition of activation of NF-kappa B and the kinases. [7] Here, we are
going to review milk thistle benefits on different conditions:

Anti-microbial effects
Milk thistle ingredient, silybin, inhibited RNA and protein synthesis on gram-positive bacteria. [8]

Anti-oxidative effects
Silymarin reduced NO production at less than 300 ppm. [9]

Cardiovascular issues
Milk thistle may benefit people at risk of cardiovascular conditions. Milk thistle and lecithin have found to have anti-atherosclerotic activity in rabbits.
Milk thistle-phospholipid complex showed a strong anti-atherosclerotic activity. [10]

Cancers
Milk thistle may benefit people at risk of various type of cancers. Silymarin, the milk thistle ingredient, exerts chemopreventive effects against
tumorigenicity by inhibiting endogenous tumor promoter TNF alpha. [11] Silibinin and silymarin, have shown the anticancer effects in different
cancer cells in multiple studies:

BLADDER CANCER Silibinin modulates cyclin-dependent kinase inhibitors - cyclin-dependent kinases -cyclin cascade and activates caspase 3
causing growth inhibition and apoptotic death of human bladder transitional cell carcinoma cells. [12] In another study, silibinin decreased survivin
levels and caspases-PARP cleavages, in accord with a strong apoptotic death and growth inhibition of Human bladder transitional-cell papilloma
cells. [13] And, silymarin was found to be effective in preventing OH-BBN-induced bladder carcinogenesis in mice. [14]

BREAST CANCER An in vitro study has suggested a possible synergism between silibinin and conventional cytotoxic agents for breast cancer
treatment. [15] Milk thistle extract may exert a strong anticarcinogenic effect against breast cancer involving inhibition the threshold kinase activities
of cyclin-dependent kinases and associated cyclins, leading to a G1 arrest in cell cycle progression. [16].

COLON CANCER A study showed the chemopreventive ability of silymarin against chemically induced colon tumorigenesis.[17]

ENDOTHELIAL CELLS CANCER Silibinin can be a anti-cancer agent as it has the ability inhibit angiogenesis through induction of endothelial
apoptosis via modulation of NF-kappaB, Bcl-2 family and caspases. [18] Silibinin toxicity to cancer cells is also found to involve the epidermal growth
factor receptor signaling pathway. [19]

LUNG CANCER Milk thistle extracts containing Silibinin exerted a dose-dependent inhibitory effect on the invasion and motility of human lung cancer
cells.[20]

LIVER CANCER Milk thistle may be useful in the prevention or treatment of liver dysfunction in patients undergoing anticancer therapy.[21]

PROSTATE CANCER In prostate cancer, silibinin exerts its anti-cancer effect probably via epidermal growth factor receptor, insulin-like growth
factor receptor type I and nuclear factor kappa B signaling [23] Milk thistle extracts possess anticancer activities on human prostate carcinoma.
Isosilybin A and B might be the most effective suppressors of prostate-specific antigen secretion by androgen-dependent LNCaP cells. Researchers
suggested that milk thistle extracts enriched for isosilybin A or B might possess improved potency in prostate cancer prevention and treatment. [22]
Finally, milk thistle silibinin was found to able to down regulate 5alpha-dihydrotestosterone, thus, milk thistle may be beneficial to prostate health.
[23] There are a few more studies showing milk thistle benefits on prostate [24-32].

SKIN CANCER In studies of rats, milk thistle extracts provided substantial protection against different stages of UVB-induced carcinogenesis,
possibly via its strong antioxidant properties. [33] In another study, topical treatment of silymarin inhibited 7,12-dimethylbenz(a)anthracene-initiated
and several tumor promoters in mouse models. [34] There are two more studies showing the anti-tumor effects of milk thistle extracts on skin
cancer: [35]

TONGUE CANCER Feeding of silymarin (500 p.p.m.) during the promotion phase of 4-NQO-induced rat tumorigenesis exerts chemopreventive
ability against tongue squamous cell carcinoma through modification of phase II enzymes activity, cell proliferation, and/or PGE(2) content. [36]

Cholestasis
Milk thistle may benefit animals with cholestasis. Milk thistle prevents cholestasis induced by estrogens and taurolithocholate via inhibiting
cAMP-phosphodiesterase.  [38] In 1985, Koch HP reported that milk thistle was a very potent inhibitor of cyclic AMP phosphodiesterase. Milk thistle's
constituents, silybin, silydianin and silychristin, are 12.66 to 52.06 times more active than theophylline. [37]

Diabetes
Milk thistle showed its health benefits on diabetic animals. Milk thistle extracts may be useful in treatment of non-insulin-dependent diabetes mellitus,
as silibinin inhibits glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo. [39] Aqueous extracts of milk
thistle exhibit potent hypoglycaemic and anti-hyperglycaemic activities in normal and streptozotocin diabetic rats without affecting insulin secretion.
[40]  In a study, researchers treated  diabetics with 200 mg of silymarin three times a day. After four months, patients had reductions in blood
glucose levels. The results are very encouraging and the researchers planned to do further large multi-centre studies. [Milk thistle may help
diabetics -study, Reuters, October 30, 2006.]

Randomized controlled trials were identified through electronic searches (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials)
up until February 2011. Nine randomized, placebo-controlled trials (n=487 patients) were identified. Ipomoea batatas, Silybum marianum (milk
thistle) and Trigonella foenum-graecum significantly improved glycemic control, whereas Cinnamomum cassia did not. [aa2]

HEART
Milk thistle extract, silymarin, protects cardiomyocytes against doxorubicin-induced oxidative stress via cell membrane stabilization effect, radical
scavenging and iron chelating potency. {41]

Immune Modulation
A study of mice showed milk thistle silymarin could prevent UVB-induced immuno-suppression and oxidative stress probably by inhibiting the
infiltration of leukocytes, and myeloperoxidase activity. [42]

A study demonstrated that milk thistle was immunostimulatory in vitro. Milk thistle increased lymphocyte proliferation in both mitogen and MLC
assays. These effects of Milk Thistle were associated with an increase in interferon gamma, interleukin (IL)-4 and IL-10 cytokines in the MLC (table).
This immunostimulatory effect increased in response to increasing doses of Milk Thistle.  [43]

Osteoporosis
Bone-remodeling imbalance induced by decreased osteoblastogenesis and increased bone resorption is known to cause skeletal diseases such as
osteoporosis. Silibinin is the major active ingredient of milk thistle. Studies suggest that silibinin is a powerful antioxidant and has anti-hepatotoxic
properties and anti-cancer effects against carcinoma cells. A recent study shows that silibinin had bone-forming and osteoprotective effects in in
vitro cell systems of murine osteoblastic MC3T3-E1 cells and RAW 264.7 murine macrophages. Silibinin accelerated cell proliferation and promoted
matrix mineralization by enhancing bone nodule formation by calcium deposits. [aa3]

Liver Diseases
Milk thistle may benefit people at risk of liver diseases. CIRRHOSIS A double blind study of 170 patients with cirrhosis demonstrated that silymarin
treatment was effective in patients with alcoholic cirrhosis. [44]  A study has suggested that milk thistle and
S-adenosylmethionine may be effective
in alcoholic cirrhosis. [45]
FIBROSIS Silymarin retarded the development of alcohol-induced hepatic fibrosis in 12 baboons, consistent with several
positive clinical trials. [46]
INJURY The hepatoprotective properties of milk thistle extracts in acute and chronic liver injury is probably related to
inhibition of leukotriene B (4) formation by silibinin. [47] The protective effects of milk thistle on liver injury may be related to the recovery of the
membrane fluidities of liver microsome and mitochondria [48]
HEPATITIS C A double-blinded trial of 141 subjects demonstrated that milk thistle
extract, silymarin, could improve symptoms and general well-being of patients suffered from hepatitis C. [49] However, some researchers found that
milk thistle extracts had no benefits on liver health. For instance, milk thistle extract was found to have no hepatoprotective effect on dairy cows. [50]

Neural Issues
Milk thistle may have protective effects on neural system. In a cell study, silymarin significantly inhibited the LPS-induced activation of microglia and
the production of inflammatory mediators, such as tumour necrosis factor-alpha and nitric oxide (NO), and reduced the damage to dopaminergic
neurons.[51] Milk thistle extract also protected cultured rat hippocampal neurons against oxidative stress-induced cell death. [52]

Cerebral stroke is the third largest cause of death and the severe leading cause of disability, thus have astronomical financial and social burden
worldwide. Accumulated evidence suggests that ROS can be scavenged through utilizing natural antioxidant compounds present in foods and
medicinal plants. In a study, male Wistar rats were pre-treated with silymarin (200mg/kg body weight, dissolved in 0.3 % sodium carboxymethyl
cellulose, once orally) for 15 days. On day 16, they underwent a transient 2h suture-occlusion of the middle cerebral artery followed by 22 h of
reperfusion. Rats were tested for neurobehavioral activity after 22 h reperfusion. [aa1]

Silymarin was found to be successful in upregulating the antioxidant status and lowering the apoptotic responses, and functional recovery returned
close to the baseline. This study revealed that silymarin may be helpful in slowing down the progression of neurodegeneration in focal cerebral
ischemia. [aa1]

Please, note that most of these studies are done with animals or in test-tubes, clinical studies are needed to support the health claims.
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MILK THISTLE SAFETY ISSUES

Milk thistle side effects
Milk thistle appears to be safe and accepted by patients. Side effects are usually mild and may involve stomach upset and diarrhea. Rash may be a
result from touching milk thistle plants. Only a few cases of milk thistle side effect have been reported. Silymarin exposure did not produce any signs
of overt toxicity or any changes in relative organ weights. [55-60] However, high dose of milk thistle may stimulate inflammatory process (from a mice
study). [61] Milk thistle can also produce allergic reactions, which tend to be more common among people who are allergic to plants in the same
family (e.g. ragweed, chrysanthemium, marigold, and daisy}.

Milk Thistle Drug Interaction
University of Maryland suggest not to use milk thistle if you are taking: antipsychotics, phenytoin(Dilantin), halothane, and birth control pills or
hormone replacement therapy. Milk thistle may interact with allergy drugs -- such as fexofenadine (Allegra), statins, anti-anxiety drugs, anti-platelets,
anti-coagulants, some cancer drugs and drugs borken down by liver. [
UM]

Further, it has been reported that milk thistle decreased the trough concentrations of indinavir in humans. [53] But, another study showed milk
thistle had no apparent effect on indinavir plasma concentrations. [54]  This conflicting data might be due to different milk thistle product
preparation, extraction method, product composition, experimental design or even the purity of milk thistle.
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CONCLUSION
Milk thistle has been known for its protective effects on liver, while milk thistle may also be a potent anti-cancer agent. Milk thistle side effects are
limited, but it may interact certain drug products. Users must discuss with their doctors before taking milk thistle.

                                                           
Reference
Milk Thistle
October 18, 2011
There are always new information. Please, send me an email (zhion@zhion.com) to correct my mistake(s).
Reasonable care has been taken in preparing this document and the information provided herein is
believed to be accurate. The information is not intended to be a substitute for professional medical advice.
It is important to seek the advice of a physician about any medical condition or symptom or the benefits and
side effects of Milk Thistle. Finally, please, do not transfer the article to other website. Thank you. ALL
RIGHTS RESERVED.
For centuries, nearly every part of milk thistle-from root to hull-has been used in some way. Milk thistle can be
eaten, including the heads like an artichoke, raw stalks, and the leaves as a salad. Milk thistles were sometimes
baked in pies. The roots may be eaten like those of Salsify. Milk thistle has also historically been used for animal
feed. In Scotland, the leaves were used extensively as food for cattle and horses.Milk thistle has been popularly
used as a medicinal plant for many years. In 19th century, milk thistle became popular in the United States. At that
time, milk thistle was used for varicose veins, menstrual difficulty, and congestion of the liver, spleen, and kidneys.

Milk Thistle Classification:
Silybum Adans.
Click on a scientific name below to expand it in the PLANTS Classification Report.

Kingdom Plantae – Plants
Subkingdom Tracheobionta – Vascular plants
Superdivision Spermatophyta – Seed plants
Division Magnoliophyta – Flowering plants
Class Magnoliopsida – Dicotyledons
Subclass Asteridae
Order Asterales
Family Asteraceae – Aster family

Genus Silybum Adans. – milkthistle
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Milk Thistle in Market
Milk Thistle has been marketed as a herbal supplement having a  protecting benefits on the liver, they claim milk
thistle can even regenerate the liver cells in most liver diseases such as cirrhosis (hardening of the liver), jaundice
and hepatitis (inflammation of the liver), cholangitis (inflammation of bile ducts resulting in decreased bile flow).

Milk Thistle is also marketed as a preventative medicine to protect each cell of the liver from incoming toxins and
encourage the liver to cleanse itself of damaging substances, such as alcohol, drugs, medications, mercury and
heavy metals. Milk thistle is also promoted as an agent which can cleanse and detoxify  overburdened and
stagnant livers, strengthen and tonify weak livers.


Milk thistle is also suggested to be used as a gentle and mild laxative, as it may be able to increase bile secretion
and flow in the intestinal tract. This herb is also claimed to be able to lubricate and soften the stools to a mild
laxative effect- a balance between constipation and diarrhea.  However, scientific supports to these claims are
limited. In the following section, we review what scientists found about milk thistle - benefits and side effects.