Milk thistle (Luke Nguyen , University of Mississippi School of Pharmacy

MILK THISTLE

LUKE NGUYEN, STUDENT PHARMACIST, SPRING 2022

Other common names: Mary thistle, holy thistle, variegated thistle Scientific names: Silybum marianum, Carduus marianus

BACKGROUND BACKGROUND

Milk thistle is native to the

Mediterranean region and was brought to North America by early colonists. It is found in the eastern U.S., California, South America, Africa, Australia, and Asia. Silybum Marianum is a flowering herb related to the ragweed and daisy family. This herb grows up to 5 feet in height and flowers from June to September. The herb itself and its dried seeds are used in preparation to extract an active antioxidant ingredient called Silymarin. Milk thistle is marketed for its anti-inflammatory, antimicrobial, and CNS effects.

PHARMACOLOGY PHARMACOLOGY

Hepatoprotection in cirrhosis and chronic hepatitis Diabetes Indigestions (dyspepsia) Gallbladder disorders

Allergic rhinitis/asthma Dyslipidemia Amanita mushroom poisoning Cancer treatment–related adverse effects

https://woodlandessence.com/products /milk-thistle-seed-liquid-extract The possible antioxidant mechanisms of silymarin include: Prevention of free radical formation via inhibition of ROS‐producing enzymes Free radicals scavenger Ion chelation in the intestine Promotion of the synthesis of protective molecules, and activation of antioxidant enzymes. The active ingredient is called Silymarin It is composed of a complex of flavonolignans, fatty acids, proteins, and other compounds. Silymarin is poorly soluble in water. Capsule Caplet Tablet Tea bag Oral tincture IV solution

https://www.gnc.com/milk-thistle/GNCHerbal PlusMilkThistle1300MG.html

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TYPICAL DOSING TYPICAL DOSING

Daily dose: 420 mg/day orally in divided doses for up to 41 months Cirrhosis: 140 mg three times daily for 6-8 weeks, then a maintenance dose of 280 mg daily Mushroom poisoning, oral or IV infusion: 33 mg/kg/day Indigestion: 3.5 g of crushed milk thistle seed with 150 mL of boiling water three times a day before meals

In animal experiments, silymarin and silibinin are indicated to have protective effects on rat or mouse liver against ethanol intoxication and drug-induced © Thinkstock hepatotoxicity including cisplatin, acetaminophen, carbon tetrachloride, thioacetamide, D-galactosamine, and thallium Cisplatin and ifosfamide-induced renal toxicity can be antagonized by silymarin without reducing the anti-tumor efficacy of these drugs in animal models. A study has shown that concurrent treatment with alloxan and silymarin in alloxan-induced diabetic rats prevented high plasma glucose levels and damage in pancreatic cells within 3 days of the first dose of silymarin administration and 5 days later the mentioned changes were completely prevented.

SAFETY SAFETY

Milk thistle is contraindicated in patients with allergy to any plants in the daisy family In a retrospective clinical report of 205 patients with Amanita poisoning, no fatality observed after administration of intravenous silibinin to 16 individuals Generally safe in patients with acute or chronic liver diseases Little clinical data on the use of milk thistle during pregnancy or while breastfeeding Use with caution in diabetic patients Common adverse effects: GI disturbances (eg, bloating, abdominal pain, anorexia, changes in bowel habits, diarrhea, dyspepsia, flatulence, nausea Headache and pruritus Loss of appetite Rare/serious adverse effects: Anaphylaxis Hyperbilirubinemia and increases in ALT enzymes Muscle aches, joint pain, and sexual dysfunction

Avoid the use of the aboveground parts of the plant in women with hormonesensitive conditions Mild allergies were reported with dosages greater than 1,500 mg/day Acute oral toxicity of milk thistle in rats, dogs, and monkeys has been estimated at dosages greater than 5 g/kg

TOXICITIES TOXICITIES

Reduces efficacy of antivirals Decreases serum concentration of CYP2C9 substrates, Losartan, Metronidazole Increases serum concentration of deferiprone, fosphenytoin-Phenytoin, Raloxifene, Simeprevir, Sirolimus products, Vitamin K antagonists

P PR RO OFFE ES SS SIIO ON NA AL L O OP PIIN NIIO ON NS S

Based on current clinical data, I would recommend the use of Milk Thistle for its hepatoprotection effect in patients with cirrhosis and liver diseases. It does not have significant side effects or worsen other preexisting conditions. The uses of Milk Thistle in other diseases are still questionable due to the lack of evidence. ~ L. Nguyen

R RE EFFE ER RE EN NC CE ES S

Abenavoli, L., Izzo, A. A., Milić, N., Cicala, C., Santini, A., & Capasso, R. (2018). Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytotherapy research : PTR, 32(11), 2202–2213. https://doi.org/10.1002/ptr.6171 Beckerman J, ed. Milk thistle: Benefits and side effects. WebMD. https://www.webmd.com/digestive-disorders/milk-thistle-benefitsand-side-effects. Published June 9, 2021. Accessed March 2, 2022. Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. "Silymarin", a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci. 2011;14(4):308-317. Milk thistle. Mayo Clinic. https://www.mayoclinic.org/drugssupplements-milk-thistle/art-20362885. Published November 19, 2020. Accessed March 2, 2022. Milk thistle. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/milk-thistle. Published August 2020. Accessed March 2, 2022. Milk thistle. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed March 2, 2022. http://online.lexi.com Milk thistle. IBM Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Accessed August 24, 2016. http://www.micromedexsolutions.com. 102