Silymarin; Health Benefits, Uses, Dosage, Side Effects

Silymarin; Health Benefits, Uses, Dosage, Side Effects

Silymarin is a mixture of flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum. It consists primarily of silybin and its isomers, silicristin, and silidianin. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury and shows potential as an antihepatotoxic agent.[1]

It is the member of Carduus marianum family, is an ancient medicinal plant which has been used for centuries for the treatment of different diseases such as liver and gallbladder disorders, protecting the liver against snake bite and insect stings, mushroom poisoning and alcohol abuse (). This plant can be found in Kashmir, North America, Canada, and Mexico with large leaves and a reddish-purple flower that is all thorny and the medicinal part of the plant is either the seeds or fruits ().

In chronic liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver diseases, drug- and chemical-induced hepatic toxicity), antioxidant medicines such as silymarin can have a beneficial effect.[4] Liver cirrhosis, non-alcoholic fatty liver, and steatohepatitis are risk factors for hepatocellular carcinoma (HCC). Insulin resistance and oxidative stress are the major pathogenetic mechanisms leading the hepatic cell injury in these patients. The silymarin exerts membrane-stabilizing and antioxidant activity, it promotes hepatocyte regeneration; furthermore, it reduces the inflammatory reaction and inhibits the fibrogenesis in the liver. [4]

Ingredients or Composition of Silymarin

When looking at Milk Thistle itself (prior to any extraction), the fruits or thistles contain:

  • Silymarin at 1.5-3% of dry weight (to be elucidated later)
  • Silyhermin and both Neosilyhermin A and B
  • Protein and Mucilage (taking up 25-30% of the herb by dry weight)
  • Quercetin and the dihydro variant is known as Taxifolin[5]
  • Kaempferol, Dihydrokaempferol, and the 7-glucoside and 3-sulfate of Kaempferol
  • Apigenin (and 7-O-Glucoside, 4,7-Diglucoside, and 7-O-Glucuronide)
  • Eriodyctiol, Chrysoeriol, and Naringin
  • 5,7-Dihydroxychromone
  • Vitamin E at 0.038%
  • Sterols (cholesterol, campesterol, stigmasterol and sitosterol) at 0.63%
  • Luteolin and its 7-O-Glucoside
  • Triterpene acetate
  • Fumaric acid
  • 65-80% ‘Silymarin’ (concentrated from 1.5-3% of the plant)
  • 20-35% Fatty acids (Linoleic at 60%, Oleic at 30%, and Palmitic at 9%; roughly)

The Silymarin component specifically includes

  • Silibinin (a diastereoisomeric blend of Silybinin A and Silybinin B[6]) which comprises 50-70% of Silymarin (and by extension, 39-56% of ‘Milk Thistle Extract’)
  • Isosilibin (Isosilybin A and Isosilybin [7]) comprising about 5% of Silymarin
  • Silychristine and Isosilychristine at around 20% Silymarin
  • Silydianin at around 10% Silymarin
  • Taxifolin (Quercetin conjugate knew as Dihydroquercetin) usually in nearly undetectable levels

Uses and Health Benefits of Silymarin

  • Hepatoprotection – Liver is the key organ of metabolism and excretion is continuously and variedly exposed to xenobiotics because of its strategic placement in the body. Toxins absorb from the intestinal tract first enter the liver resulting in a variety of liver disorders. Thus, liver diseases remain one of the serious health problems. Liver damage ranges from acute hepatitis to hepatocellular carcinoma, being caused through apoptosis, necrosis, inflammation, immune response, fibrosis, ischemia, altered gene expression, and regeneration [ For many years, silymarin has been used as a “hepatoprotectant”. Although the mechanism of action is not completely demonstrated, silymarin has been reported to have antioxidant, immunomodulatory, antifibrotic, antiproliferative, and antiviral properties. Silymarin has a short half-life and quick conjugation in the liver and principal excretion in bile. In means of controlling hepatic inflammation in vivo, it should be used with high or repeated oral doses [.
  • Cure Diabetes The liver works with the pancreas to regulate blood sugar, and elevated blood sugar levels (characteristic of diabetes) may reflect the reduced function of both organs. Three studies of people with type 2 diabetes have found that silymarin supplements can help improve blood sugar and other markers of glucose intolerance. In one of the studies, 51 patients received 200 mg of silymarin daily for four months. The supplements led to a 15 percent decrease in blood sugar, a 25 percent drop in fasting insulin levels, and a 13 percent decrease in glycated hemoglobin levels. Glycated hemoglobin (HbA1c) reflects a six-week average blood sugar level. Another study found a 20 percent decrease in fasting blood sugar, a 37 percent decline in postprandial blood sugar, and a 16 percent decrease in HbA1c-plus an 8.5 percent reduction in weight. One other study found improvements in all markers of diabetes over the course of a year
  • Prevention and treatment of CancersEffects of silymarin or silibinin on breast cancer [, ovarian cancer, lung cancer, skin cancer, prostate cancer, cervical cancer, bladder cancer, liver carcinoma [, and colon cancer (35), have been reported [. Mechanism of cytoprotective activity of silybin related to antioxidative and radical-scavenging effects as well as the specific receptor interaction and modulation of a variety of cell-signaling pathways e.g. NF-kappa B, suppression of EGFR-MAPK/ERK1/2 signaling and IGF-receptor signaling [. In addition, Anti-apoptotic effect of silymarin against UV irradiation has been revealed by up-regulation of tumor-suppressor genes p53- and p21CIP1 [.
  • Renal protection – The effect of silymarin has been tested in alloxan-induced diabetes mellitus models in rats. Alloxan produces reactive oxygen species (H2O2, •O2, and •OH) [, which injure renal tissue [. Silymarin was administrated 20 days after 9 weeks treatment with alloxan and it was effective on the renal tissue injuries. It has antioxidant effects via increase of gene expression of antioxidant enzymes and a number of the most important protection mechanisms against free radicals damage containing superoxide dismutase, glutathione peroxidase, and catalase. Therefore, silymarin can be used as a drug for diabetic nephropathy therapy [. Oxidative stress (ROS) reduces glomerular filtration. Treatment with silymarin or vitamin E improved alteration in serum creatinine concentrations in the gentamicin-treated dogs [. In another study, cisplatin and ifosfamide-induced renal toxicity can be antagonized by silymarin without reducing the anti-tumor efficacy of these drugs [.
  • Neuronal effect – High oxygen utilization, huge amounts of polyunsaturated fatty acids, elevated levels of free iron ions and low antioxidants defenses all together make the brain tissue vulnerable to reactive oxygen species injuries [. Silymarin when administered at a dose of 200 mg/kg/day, strongly reduced the proteins oxidation in hippocampus and cortex of elderly rats in comparison to the young ones. Silymarin can be used as a choice compound against Alzheimer disease in which the protein oxidation is an important early occasion. According to previous studies, silymarin has antioxidant activities in the central nervous system, which enables it to enter the CNS via the blood-brain barrier (BBB) [. Results showed that ethanolic extract had no effect on the duration of mice immobility while the aqueous extract significantly diminished it, concluding that aqueous extract of silymarin has the antidepressant effect in animal models [.
  • Immunomodulation – Based on a splenocytes examination by flow cytometric method, silymarin significantly reduced the number of CD3+ T-lymphocytes and the CD4+ population with 10 mg/kg dose. In this study, mice were exposed to different doses of silymarin (0, 10, 50 or 250 mg/kg, intraperitoneally, once a day for 5 days). In the lowest dose group, there was an increase in proliferation of phytohemagglutinin-induced T-lymphocyte. Doses of 10 and 50 mg/kg of silymarin increased B-lymphocyte blastogenesis induced by LPS (lipopolysaccharide) and reduced the expression of IL-2 and IL-4. However, it increased expression of TNF-α, iNOS, IL-1β, and IL-6 mRNA dose-dependently. As a result, ‘in vivo’ exposure to low doses of silymarin suppresses the function of T-lymphocyte and stimulates the inflammatory pathways at higher doses [. In further studies, silymarin significantly decreased IL-2 and interferon gamma (IFN-γ) production and blocked nuclear translocation of transcription factor κB (NF-κB) which activates IL-2 transcription. It can be concluded that silymarin suppresses activation and proliferation of T cells, particularly by affecting pathways of NF-κB activation or translocation [.
  • The protective effect on pancreas – Silymarin can increase serum insulin, reduce serum glucose and the rise of antioxidant enzymes and glutathione. as well as recover endocrine function and pancreatic morphology in diabetic models [. In addition, silybin has a chemoprotectant effect and can improve pancreatic function after exposure to toxic agents leading to damages [
  • Preventing effect against hemolysis – Reactive oxygen species can damage the cell membrane structure and destruct protein functions, especially enzymes. The membrane of erythrocytes is sensitive to lipid peroxidation in patients with glucose-6-phosphate dehydrogenase deficiency, sickle cell anemia and β-thalassemia disease [. According to a study on model of chain oxidation of lipids and proteins induced red blood cells hemolysis by 2, 2’-azobis–(2-amidinopropane) (AAPH), a water-soluble radical generator, silymarin increased the lag time of hemolysis and stabilized the cell membrane by reducing the rate and the total content of glutathione loss in erythrocytes. It also decreased the concentration of peroxyl radicals derived from AAPH as a chain-breaking antioxidant and radical scavenger [ .
  • Antiosteoporotic and selective estrogen receptor modulator – In one study silymarin intake could increase the parathormone concentration in ovariectomized -induced bone loss that had led to trabecula thickness of the femur and had a positive effect on bone formation. Estrogenic effects of silymarin lead to increasing the uterine weight and endometrial height, in addition to hypertrophy of luminal epithelium. However, silymarin had no estrogenic effects on the hypothalamic/pituitary axis (no effects on serum LH and FSH levels). Uncontrolled silymarin dose could elevate the risk of endometrial hyperplasia [.
  • Protective effect against environmental toxin – In a study involving healthy volunteers, the cytotoxic effect of Benzo(a) pyrene on peripheral blood mononuclear cells was prevented by silymarin through stabilizing cell membranes, increasing the GSH/GSSG ratio, restoration of glutathione metabolizing enzymes, elimination agents produced from lipid peroxidation and protein oxidation and functional stimulation of the antioxidant enzymes such as catalase and superoxide dismutase [
  • Seasonal allergies – Some research shows that taking milk thistle extract by mouth along with the allergy medication cetirizine (Zyrtec) reduces seasonal allergies more than taking cetirizine alone.
  • Alzheimer’s disease – Early research shows that taking a combination supplement containing milk thistle extract improves mental function in people with Alzheimer’ s disease.
  • Amanita mushroom poisoning – Early research shows that giving silibinin, a chemical found in milk thistle, intravenously (by IV) and then by mouth may lessen the liver damage caused by Amanita phalloides mushroom (death cap) poisoning. However, it is hard to obtain silibinin in the US.
  • Enlarged prostate (benign prostatic hyperplasia) –  Early research shows that taking a specific combination of milk thistle extract and selenium for 6 months might improve symptoms of enlarged prostate in men.
  • Blood disorder called beta-thalassemia – Early research in people 12 years or older with the blood disorder beta-thalassemia shows that taking a specific milk thistle extract for 3 months, along with conventional medicine, does not improve symptoms. But another study found that it might provide some benefits when taken for 9 months.
  • Hand-foot syndrome – Early research shows that applying a gel containing milk thistle extract to the hands and feet beginning on the first day of chemotherapy and continuing for 9 weeks decreases the severity of a complication of chemotherapy called hand-foot syndrome.
  • Chemotherapy toxicity – Early research shows that taking a specific milk thistle product containing the chemical silibinin beginning at the start of chemotherapy treatment does not significantly reduce liver toxicity caused by chemotherapy.
  • Kidney damage caused by the chemotherapy drug cisplatin – Early research shows that taking milk thistle extract beginning 24-48 hours before starting therapy with cisplatin, and continuing until the end of the treatment course, does not prevent or decrease the rates of kidney injury.
  • Liver scarring (cirrhosis) – Early research shows that milk thistle extract might reduce the risk of death and improve liver function in people with cirrhosis. However, milk thistle extract does not seem to benefit all patients with liver disease.
  • Kidney disease in people with diabetes – Early research shows that taking milk thistle extract together with conventional treatment might help treat kidney disease in people with diabetes.
  • Hepatitis – Research on the effects of milk thistle in people with hepatitis is not consistent. Some research shows that taking milk thistle extract by mouth for 4 weeks reduces hepatitis symptoms, such as dark urine and jaundice, but does not improve liver function tests. But taking a product containing the milk thistle constituent silybin plus phosphatidylcholine by mouth for 2 weeks to 3 months might improve some liver function tests.
  • Hepatitis B – Research on the effects of milk thistle in people with hepatitis B is not consistent. Early research shows that taking milk thistle extract by mouth for up to one year, or taking a product containing the milk thistle constituent silybin plus phosphatidylcholine by mouth for 1 week, improves liver function tests. But other research shows no benefit.
  • Hepatitis C – Research on the effects of milk thistle in people with hepatitis C is inconsistent. Early research shows that taking milk thistle extract by mouth for up to one year, or taking a product containing the milk thistle constituent silybin plus phosphatidylcholine by mouth for 1 week, improves liver function tests. But other research shows no benefit.
  • High cholesterol Taking milk thistle along with tree turmeric seems to prevent cholesterol levels from increasing in people with high cholesterol who are taking statins but who require their statin dose to be lowered. Taking this product also seems to help lower cholesterol when used alone or along with low-dose statins or ezetimibe in people with high cholesterol who can’t tolerate high dose statin treatment. It’s unclear if these benefits are due to milk thistle, tree turmeric, or the combination.
  • High levels of fat particles (lipids) in the blood – Taking milk thistle doesn’t seem to lower lipid levels in the blood in people with high levels due to liver disease.
  • Infertility – Early research shows that taking milk thistle extract along with fertility hormones might provide some benefits for women undergoing in vitro fertilization due to male infertility.
  • Low milk production – Early research shows that taking milk thistle extract for 4 weeks does not increase milk production in mothers of premature infants.
  • Menopausal symptoms – Research shows that taking a specific combination product containing milk thistle and other ingredients by mouth for 3 months reduces hot flashes by 73% and night sweats by 69% in people with menopausal symptoms. Sleep quality also improves. It’ s not clear if these benefits are due to milk thistle or other ingredients.
  • Multiple sclerosis (MS) – Early research shows that taking a combination supplement containing milk thistle extract can improve mental function and increase disease stabilization in people with multiple sclerosis.
  • Liver disease not caused by alcohol (nonalcoholic fatty liver disease; NAFLD) – Taking milk thistle does not seem to improve symptoms of severe NAFLD. But it might reduce scarring of the liver in these people. Early research also shows that dieting and taking milk thistle with vitamin E helps lessen the severity of NAFLD. But dieting alone also seems to work about as well.
  • Obsessive-compulsive disorder (OCD) – Early research shows that taking milk thistle leaf extract by mouth three times daily for 8 weeks has a limited effect on OCD symptoms. It does not appear to more beneficial than conventional medication.
  • Parkinson’s disease – Early research shows that taking a combination supplement containing milk thistle extract improves mental function and increases disease stabilization in people with Parkinson’s disease.
  • Prostate cancer – Prostate-specific antigen (PSA) is a protein in the blood that can be measured to diagnose and monitor prostate cancer. Early research shows that taking a supplement containing milk thistle extract, soy isoflavones, lycopene, vitamins, minerals and antioxidants by mouth daily can delay the rise in PSA levels in men with a history of prostate cancer. The effects of milk thistle alone are not clear.
  • Skin toxicity caused by radiation – Early research shows that applying a specific product containing the milk thistle extract reduces the effect of radiation on the skin in women being treated for breast cancer.
  • Inflammation and ulcers (mucositis) caused by radiation – Early research shows that taking milk thistle extract starting on the first day of radiation and continuing for 6 weeks thereafter decreases the severity of ulcers caused by radiation.
  • Liver damage caused by chemicals – The effect of milk thistle on liver damage caused by chemicals is inconsistent. Taking milk thistle by mouth helps the liver to function in people who have been exposed to the chemicals toluene or xylene or those taking drugs for tuberculosis. But taking milk thistle extract by mouth does not seem to prevent liver damage associated with the drug tacrine (Cognex) in people with Alzheimer’s disease.
  • Inflammation of the digestive tract (ulcerative colitis) – Early research shows that taking milk thistle extract by mouth for 6 months, in addition to standard medications, decreases the symptoms of ulcerative colitis and helps maintain remission.
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Dosage of Silymarin

  • For diabetes: 200 mg of milk thistle extract has been taken once daily or three times daily for 4 months to one year. A specific product (Berberol, PharmExtracta) containing 210 mg of milk thistle extract and 1176 mg of tree turmeric extract has been taken daily for 3-12 months.
  • For upset stomach (dyspepsia): 1 mL of a specific combination product (Iberogast by Medical Futures, Inc.) containing milk thistle and several other herbs has been used three times daily for 4 weeks.
  • Consumption of the oral form of milk thistle (standardized to 70% to 80% silymarin) at 420 mg/day in divided doses is considered safe for up to 41 months based on clinical trial data. [49]

The available forms of Milk thistle are capsules, tablet, tincture, and intravenous solution. Adult dosage in terms of hepatoprotection is 420 mg/day of extract (standardized to 70-80% silymarin) three times a day for 6-8 weeks. Maintenance dose is 280 mg/day. The intravenous solution is used for cyclopeptide mushroom poison in a dose of 33 mg/kg/day for approximately 81.67 hr [.

References

Silymarin

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