The 18+ Benefits of Milk Thistle (Silybum marianum) and Mechanisms

Milk Thistle: More than Just a Liver Support

Milk thistle has been used for over 2000 years as a remedy for ailments of the liver, kidney and gallbladder. R 

It is still being studied in the medical field. Read more for the benefits and mechanisms of action.

 
 

Basics

Milk thistle is an annual or biennial plant of the Asteraceae family, native of souther Europe through to Asia. R

Germany is the largest producer of milk thistle using it for dyspeptic complaints and various amounts of liver conditions. R R

Milk thistle works primarily by silymarin, an active flavonoid, by protecting the liver as an antioxidant and as an anti-inflammatory. 

In publications, milk thistle is labeled as: R

  • Carduus marianus
  • Legalon
  • Mariendistel
  • Milk thistle
  • Silybin
  • Silybum marianum
  • Silybum
  • Silychristin
  • Silydianin
  • Silymarin
 
 

Benefits

1. Regrows The Liver and Protects the Biliary System 

 
 

The literature shows milk thistle may increase liver cell protein synthesis. R

It blocks toxins by stopping toxins from binding to hepatocyte (liver cell) membrane receptors. R

Milk thistle has anti-fibrogenic activity (reducing scar tissue from inflammation) while helping the liver regenerate cells. R R R

In a clinical trial with over 2000 patients with chronic liver diseases, administration of silymarin extract for 8 weeks resulted in a significant decrease in liver damage index in approximately 88% of the patients. R

In combination with vitamin E and phospholipids, milk thistle significantly improved steatosis, while improving liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis. R

Patients receiving the combination treatment of phosphatidylcholine and silybin showed improvements of liver enzymes, HOMA-IR and liver histology. R

Milk thistle protects liver health in patients after liver transplantation. R

In patients with alcoholic liver cirrhosis, glutathione production increased while lipid peroxidation decreased in blood with milk thistle supplementation. R

Liverubin™ (drug in the Indian market that contains silymarin) has shown to lower abnormally high liver biomarkers at 140-mg tid. R

Silymarin may help gallbladder toxicity in humans. R

It can ameliorate hepatic collagen accumulation even in advanced (biliary) fibrosis. R

It may protect the liver from damage during chemotherapy. R

In animals:

  • Silymarin reduced manganese-induced hepatic damage and apoptosis. R

  • Silybin and Vitamin C reversed the effect of alcohol (on increasing TBARS, SOD, GST, and reducing GSH content and catalase, GR and GPx). R

  • Silymarin minimized liver injury caused from alcohol, carbon tetrachloride, tylenol, radiation, cold ischaemia, Amanita phalloides and excess iron. R

2. Lowers Cholesterol and Controls Diabetes

 
 

Silybin significantly reduced fasting glucose levels and serum triglycerides, while lowering hemoglobin A1c levels. R R R

Silymarin over long term lowered levels of malondialdehyde (a marker for oxidative stress) in cirrhotic diabetic patients. R

In combination with selenium, milk thistle reduced LDL and total cholesterol in men after prostrate removal from prostate cancer. R

3. Provides Neuroprotection

 
 

Milk thistle increases TrkB, thus enhancing the production of the neurotrophic factors BDNF and NGF. R R

It delays activation of pro-inflammatory transcription factors STAT-1 and NF-kB and reduced NF-kB. R R

In animals:

  • Milk thistle protected against infection induced brain injury. R
  • It reduced memoary damage from LPS (lipoplysacharide) treatment. R
  • It increased ROS in the hippocampus (may not be the best thing though). R
  • Reduced amyloid protein aggregation via hormesis. R

4. Fights and Protects Against Cancer

 
 

Milk Thistle is most well known for its antioxidant and chemoprotective effects on the liver. R R R R R R R

Silymarin has been shown to inhibit various systems such as leukotriene synthesis, the effects of TNFα. R

In children with ALL (acute lymphoblastic leukemia), milk thistle is correlated to to reduction in liver toxicity. R

In combination with selenium, milk thistle reduced LDL and total cholesterol in men after prostrate removal from prostate cancer, which are associated with prostate cancer progression. R

In combination with omega-3 fatty acids, brain metastases patients had longer survival times and decreased percentage of tissue death from radiotherapy. R

Topical treatment of silymarin inhibited several tumor promoters and may be useful in sun protection. R

The protective effects of silymarin suggest a clinical application in cancer patients as an adjunct to established therapies, to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity. R

In patients with breast cancer, milk thistle (cream) may be an effective treatment for preventing skin lesions form radiotherapy. R

In human cancer cells, it inhibited the proliferation and promoted cell cycle arrest of the cells. R R

It inhibited osteosarcoma cells. R

It induced autophagy in kidney cancer. R

It induced destruction of laryngeal cancer cells. R

Isosilybin B may help with prostate cancer prevention and treatment by destroying prostate cancer cells. R R

In animals:

  • Milk-thistle compounds painted on the skin of mice exposed to ultraviolet radiation prevented the development of skin cancers. R
  • It inhibited prostate tumor growth, progression, invasion and spread. R R
  • It delayed the development of spontaneous breast tumors and tumor mass. R R
  • It prevented N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced bladder cancer. R

Although promising, there needs to be more clinical trials on milk thistle for cancer treatment . 

5. Has Antioxidant Properties

In type 2 diabetes patients, milk thistle significantly increased SOD (superoxide dismutase), GPX (glutathione peroxidase) activity and TAC (total antioxidant capacity). R

See more how in mechanism of action.

6. Has Anti-Inflammatory Properties

In type 2 diabetes patients, milk thistle reduced hs-CRP levels. R

It inhibited hydrogen peroxide release and TNFα production. R

In animals:

  • Milk thistle reduced inflammation-induced pre-term birth, while exerting anti-inflammatory activities by decreasing  LPS-stimulated expression of IL-6, IL-8, COX-2, prostaglandins (PGE2 and PGF2α) and MMP-9. R

7. Fights Infections

 
 

Milk thistle has been used as an emergency antidote for poisoning by death cap mushroom. After Amanita phalloides poisoning, milk thistle can prevent severe liver damage (up to 48 hours after poisoning). It is used as an antidote for acute liver toxicity from amatoaxin poisoning . The risk of a patient dying after treated with milk thistle is less than 10% from nearly 1500 documented cases in North America. R R R R

It does this by blocking cellular amatoxin re-uptake and thus interrupting circulation of the toxin from liver to the bile and thereby into the small intestine. R

Milk thistle in combination with oxacillin or ampicillin may be useful for controlling MRSA (Methicillin-resistant Staphylococcus aureus) infections. R

It showed promising potential, showing synergistic properties when combined with antibacterial drugs, against Escherichia coli. R

It inhibited RNA and protein synthesis in certain gram positive bacteria. R 

In animals:

  • Milk thistle inhibited gram-positive bacteria, while inhibiting biofilm activity in certain bacterial strains. R
  • It inhibited influenza A virus infection, while reducing virus replication and associated death. R
  • It helped with treatment of Schistosomal liver fibrosis in mice infected with Schistosoma mansoni. R

8. Reduces Acne

Acne vulgaris is associated with damaged lipids in the skin via free radicals in response to inflammation. R

In subjects taking 210mg of Silymarin a day showed a 53% reduction in total lesion counts. R

9. Supports Bone Health

 
 

Silibinin is a potential therapeutic agent for promoting bone-forming osteoblastogenesis and encumbering osteoclastic bone resorption. R

It does this possibly by sotpping tartrate-resistant acid phosphatase, Cathepsin K induction and MMP9 (matrix metalloproteinase-9) activiy. R

In animals:

  • Milk thistle supported bone healing of mice by improving BMD (bone mineral density), seum levels of ALP (bone alkaline phophatase) and osteocalcin. R

10. Helps the Heart

 
 

Human clinical studies have shown that milk thistle extract has significant cardioprotective effects. R

By regulating expresison of SIRT1 and Bcl-2 and restoring mitochondrial function, silibinin protects cardiac myocytes against isoproterenol-induced injury. R

In animals:

  • Milk thistle protected the heart from doxorubicin-induced toxicity. R
  • Heart muscle cells were protected against isoproterenol-induced injury. R

11. Stops Fat Cell Production

Milk thistle lowers adipogenesis (fat cell production) by upregulating insig-1 and insig-2. R

This allows milk thistle to decrease the expression of adipogenesis-related genes: R

  • CAAT/enhancer binding protein-alpha
  • fatty acid synthase
  • sterol response element binding protein 1c
  • adipocyte-specific lipid binding protein
  • peroxisome proliferator-activated receptor gamma
  • lipoprotein lipase

It increases expression of preadipocyte factor-1, a preadipocyte marker gene. R

Silybin and Dehydrosilybin (2,3-Dehydrosilybin Flavonolignans) ompetitively inhibit glucose for transporter into an adipocyte via GLUT4. R

In animals:

  • Silybin abolished the insulin-induced glucose uptake. R
  • Although in this study, the insulin-induce glucose uptake wasn't abolished. R

12. Enhances Milk Production

 
 

Milk thistle is a galactogogue that promotes lactation in new mothers. R

Using 1-3g of encapsulated crushed seeds or making tea drunk twice per day, helped as a galactogogue.  R R

420mg of micronized silymarin (BIO-C) increased milk production by 64%, without affecting milk quality. R

13. Reduces Lung Radiation Damage

In mice:

  • With lung tumors, milk thistle reduced the lung injury from radiation. R

It does this reducing by inflammation and fibrosis. R

14. Regulates Iron Absorption

In patients with β-thalassemia, the combination of desferrioxamine and milk thistle helps reduce iron overload. R

In patients with hereditary hemochromatosis, milk thistle had the potential to reduce iron absorption. R

15. Defends Against Toxins

 
 

Milk thistle protects against:

  • Amanita phalloides poisoning R
  • Microcystin toxicity in mice. R
  • Aflatoxins in chickens. R

16. Combats Drug-Induced Damage

Silymarin has been shown to be effective in combating against drug-induced hepatotoxicity in various animal models:

  • Rifampicin- and pyrogallol-induced hepatotoxicity R
  • Pyrogallol-induced hepatotoxicity R R

Hepatoprotective potential of silymarin is suggested to be due to its antioxidant, cell regeneration and cytoprotection activity. R

17. Helps with HIV and Hepatitis C

Milk thistle helps suppress viral infections, immune activation and inflammation and may be useful for HIV and Hepatitis C patients. R

For people with HIV and Hepatitis C, milk thistle may help liver health. R

Silymarin in combination with darunavir-ritonavir appears to be safe for HIV patients. R

My Experience

 
 

I use milk thistle 1-2 times a day to combat any negative effects any supplements may have on my liver. I alternate between SAT, milk thistle, and BH4/Liver Support.

I have noticed no negative effects.

Where to Get Milk Thistle and Dosage

 
 

The bioavailability of silybinin can also be enhanced by the complexation with phosphatidylcholine or β-cyclodextrin. R

Side Effects

Milk thistle appears to be safe for up to 41 months of use. R

Oral doses of Milk thistle (Silymarin) of up to 2.1 g per day were safe and well tolerated. R

Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. R

Regarding adverse effects, there is little evidence available regarding causality and available evidence suggests that milk thistle is only associated with a few/generally minor adverse effects. R

Adverse effects associated with oral ingestion of milk thistle include: R

  • 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

Mechanism of Action in the Body

 
 

Pharmacokinetics: R

  • Oral administration: About 20-50% of silymarin is absorbed and 80% is excreted in the bile, with 10% entering enterohepatic circulation.

Milk thistle has direct and indirect antioxidant properties. R

  • It scavenges free radicals and chelates free Fe and Cu in the gut.
  • It inhibits specific ROS-producing enzymes or improves the integrity of electron-transport chain of mitochondria in stress situations.
  • It activates a range of antioxidant enzymes and non-enzymatic antioxidants (mainly via NRF2 activation).
  • It decreases inflammatory responses in the gut by inhibiting NF-kB pathways. 
  • It activates vitagenes - responsible for synthesis of protective molecules (HSP, Trx, sirtuins, etc)
  • It affects microenvironment of gut.

Silybum marianum inhibits pancreatic lipase (PL) activities. R

In cancer:

  • Milk thistle induces growth arrest at g1 and g2 checkpoints. R
  • It leads to apoptosis through MAPK (mitogen activated protein kinase) / JNK (c-Jun-N-terminal kinase) pathway. R
  • It decreases PSA prostate specific antigen) expression. R
  • It controls the expression of Caspace-3 and PARP (Poly ADP ribose polymerase). R
  • It inhibits EGFR (Epidermal Growth Factor Receptor) signaling. R
  • It supresses CDK (cyclin dependent kinase) expression. R
  • It increases CDK-inhibitors p21(C1P1) and p27 (K1P1). R
  • It inhibits ERK1/2 (extracellular signal regulated kinases). R
  • It inhibits TGF-α. R 
  • It decreases cyclin B1 and cdc2. R
  • It increases p21 expression. R
  • It activates SIRT1 pathway. R

Composition of Milk Thistle

 
 

Prior to extraction, the fruit/thistles have:  R

  • Silybin
  • Silychristin
  • Silydianin
  • 3-Deoxyderivatives of silychristin and silydianin (silymonin)
  • Neosilyhermin A
  • Neosilyhermin B
  • 2,3-Dehydrosilybin
  • Taxifolin
  • Quercetin
  • Dihydrokaempferol
  • Kaempferol
  • Apigenin
  • Naringin
  • Eriodyctiol
  • Chrysoeriol
  • 5,7-Dihydroxy chromone
  • Dehydroconiferyl alcohol
  • Silyhermin
  • 20–30% fixed oil (∼60% linoleic acid; ∼30% oleic acid; ∼9% plamatic acid
  • 0.038% tocopherol
  • 0.63% sterols (cholesterol, campesterol, stigmasterol and sitosterol)
  • 25–30% protein, some mucilage
  • Flavonoids (apigenin and its 7-O-glucoside, 7-O-glucuronide; 4,7-diglucoside, kaempferol and its 7-glucoside and 3-sulphate)

The leaves have: R

  • Luteolin and its 7-glucoside
  • Sitosterol and its glucoside
  • Triterpene acetate
  • Fumaric acid
  • Polyacetylenes

More Research

  • Berberis aristata combined with Silybum marianum can be considered as addition to statins in patients in dyslipidemic patients intolerant to statins at high doses. R
  • Bacopa monniera extract; milk thistle extract, ashwagandha powder, green tea extract, Gotu kola powder, Ginko biloba leaf extract; Aloe vera powder; turmeric extract; and N-acetyl cysteine - in combination may reduce hs-CRP along with other anti-oxidant properties. R
  • Coadministration of silymarin with darunavir-ritonavir seems to be safe in HIV-infected patients; R
  • DCCD significantly increased the antibacterial activity of silybin in P. aeruginosa. R