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Drugs and Health Products

Milk Thistle

This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLAs) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient.

Notes

  • Text in parentheses is additional optional information which can be included on the PLA and product label at the applicant's discretion.
  • The solidus (/) indicates that the terms and/or the statements are synonymous. Either term or statement may be selected by the applicant.

Date

June 19 2009

Proper name(s)

Silybum marianum (L.) Gaertn. (Asteraceae) (USDA 2001)

Common name(s)

  • Milk thistle (McGuffin et al. 2000)
  • Mary's thistle (McGuffin et al. 2000)

Source material(s)

  • Fruit (Barnes et al. 2007; Bradley 2006; Mills and Bone 2005; Blumenthal et al. 2000)
  • Seed (Barnes et al. 2007; Bradley 2006; Mills and Bone 2005; Blumenthal et al. 2000)

Route(s) of administration

Oral

Dosage form(s)

  • Those pharmaceutical dosage forms suited to oral administration, including but not limited to chewables (eg. gummies, tablets), caplets, capsules, strips, lozenges, powders or liquids where the dose is measured in drops, teaspoons or tablespoons, are acceptable. This monograph is not intended to include foods or food-like dosage forms such as bars, chewing gums or beverages.
  • Due to poor water solubility of silymarin, infusions and decoctions are not permitted for "hepatoprotectant/liver protectant and/or support of liver function" claims (Blumenthal 2003).

Use(s) or Purpose(s)

Statement(s) to the effect of:

  • (Traditionally used in Herbal Medicine as a) hepatoprotectant/ liver protectant (Bradley 2006; Hoffmann 2003; Blumenthal et al. 2000; Mills and Bone 2000; Ellingwood 1983 [1919]; Felter and Lloyd 1983 [1898]; Wren 1907).
  • (Used in Herbal Medicine to) help(s) to support liver function (Velussi et al. 1997; Fehér et al. 1989; Salmi and Sarna 1982; Magliulo et al. 1978).
  • Used in Herbal Medicine to help relieve digestive disturbances/dyspepsia (Blumenthal et al. 2000; Mills 1993).

Note: Claims for traditional use must include the term "Herbal Medicine".

Dose(s)

Dose(s)

  • Preparations equivalent to 3-14.5 g dried fruit/seed, per day; not to exceed 4 g per dose (Blumenthal et al. 2000; Mills and Bone 2000; Mills 1993)
  • Preparations equivalent to 140-600 mg silymarin (calculated as silibinin/silybin), per day; not to exceed 200 mg per dose (Williamson 2003; Blumenthal et al. 2000; Mills and Bone 2000; Velussi et al. 1997; Fehér et al. 1989; Salmi and Sarna 1982; Magliulo et al. 1978)

See Appendix 1 for examples of dosage preparations, frequencies of use and directions for use, according to cited references. The purpose of Appendix 1 is to provide guidance to industry.

Subpopulation(s)

Adults (≥ 18 years)

Duration(s) of use

Hepatoprotectant/liver protectant agent and/or support of liver function:
Use for a minimum of 3 weeks to see beneficial effects (Flora et al. 1998; Magliulo et al. 1978).

Digestive disturbances/dyspepsia:
No statement required.

Risk information

Statement(s) to the effect of:

Caution(s) and warning(s)

  • Consult a health care practitioner if symptoms persist or worsen.
  • Consult a health care practitioner prior to use if you are pregnant (Brinker 2008; Mills et al. 2006).

Contraindication(s)

No statement required.

Known adverse reaction(s)

Hypersensitivity, such as allergy, has been known to occur; in which case, discontinue use (Geier et al. 1990; Mironets et al. 1990).

Non-medicinal ingredients

Must be chosen from the current NNHPD Natural Health Products Ingredients Database and must meet the limitations outlined in the database.

Specifications

  • The finished product must comply with the minimum specifications outlined in the current NNHPD Compendium of Monographs.
  • The medicinal ingredient may comply with the specifications outlined in the pharmacopoeial monographs listed in Table 1 below.
Table 1: Milk thistle monographs published in the British Pharmacopoeia (BP), European Pharmacopoeia (Ph. Eur.) and US Pharmacopoeia (USP)
Pharmacopoeia Monograph
BP Milk-thistle Fruit
Ph. Eur. Milk-Thistle Fruit
Milk Thistle Dry Extract, Refined and Standardised
USP Milk Thistle
Powdered Milk Thistle
Powdered Milk Thistle Extract
Milk Thistle Capsules
Milk Thistle Tablets

References cited

  • Barnes J, Anderson LA, Philipson JD. 2007. Herbal Medicines, 3rd edition. London (UK): The Pharmaceutical Press.
  • Blumenthal M. 2003. ABC Clinical Guide to Herbs. New York (NY): Thieme.
  • Blumenthal M, Goldberg A, Brinkmann J, editors. 2000. Herbal Medicine: Expanded Commission E Monographs. Boston (MA): Integrative Medicine Communications.
  • BP 2008: British Pharmacopoeia Commission. 2007. British Pharmacopoeia 2008, Volume 2. London (UK): The Stationary Office.
  • Bradley PR, editor. 2006. British Herbal Compendium: A Handbook of Scientific Information on Widely Used Plant Drugs, Volume 2. Bournemouth (UK): British Herbal Medicine Association.
  • Brinker F. 2009. Next link will take you to another Web siteOnline Updates and Additions to Herb Contraindications and Drug Interactions, 3rd edition. Sandy (OR): Eclectic Medical Publications. [Accessed 2008 September 22]
  • Ellingwood F. 1983. American Materia Medica, Therapeutics and Pharmacognosy. Sandy (OR): Eclectic Medical Publications [Reprint of 1919 original].
  • Fehér J, Deak G, Muzes G, Lang I, Niederland V, Nekam K, Karteszi M. 1989. [Liver-protective action of silymarin therapy in chronic alcoholic liver diseases]. Silymarin kezelés májvédő hatása idült alkoholos májbetegségben. Orvosi Hetilap 130(51):2723-2737 (in Hungarian).
  • Felter HW, Lloyd JU. 1983. King's American Dispensatory, Volume 1, 18th edition. Sandy (OR): Eclectic Medical Publications [Reprint of 1922 original].
  • Flora K, Hahn M, Rosen H, Benner K. 1998. Milk thistle (Silybum marianum) for the therapy of liver disease. The American Journal of Gastroenterology 93(2):139-143.
  • Geier J, Fuchs Th, Wahl R. 1990. [Anaphylactic shock due to an extract of Silybum marianum in a patient with immediate-type allergy to Kiwi fruit]. Anaphylaktischer Schock durch einen Mariendistel-Extrakt bei Soforttyp-Allergie auf Kiwi. Allergologie 13(10):387?388 (in German).
  • Hoffmann D. 2003. Medical Herbalism: The Science and Practice of Herbal Medicine. Rochester (VT): Healing Arts Press.
  • Magliulo E, Gagliardi B, Fiori GP. 1978. [Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centres]. Zur Wirkung Von Silymarin bei der Behandlung der akuten Virushepatitis. Medizinische Klinik 73(28-29):1060-1065 (in German).
  • McGuffin M, Kartesz JT, Leung AY, Tucker AO, editors. 2000. Herbs of Commerce, 2nd edition. Silver Spring (MD): American Herbal Products Association.
  • Mills E, Dugoua J, Perri D, Koren G. 2006. Herbal Medicines in Pregnancy and Lactation : An Evidence-Based Approach. London (UK): Taylor and Francis Medical.
  • Mills S. 1993. The Essential Book of Herbal Medicine. Toronto (ON): Arkana.
  • Mills S, Bone K. 2005. The Essential Guide to Herbal Safety. St. Louis (MO): Elsevier Churchill Livingstone.
  • Mills S, Bone K. 2000. Principles and Practice of Phytotherapy. Toronto (ON): Churchill Livingstone.
  • Mironets VI, Krasovskaia EA, Polischuk II. 1990. [A case of urticaria during carsil treatment]. Vrachebnoe Delo (7):86-87 (in Russian).
  • Ph. Eur. 2008: European Pharmacopoeia Commission. 2007. European Pharmacopoeia, 6th edition, Volume 2. Strasbourg (FR): Directorate for the Quality of Medicines and HealthCare of the Council of Europe (EDQM).
  • Salmi HA, Sarna S. 1982. Effect of silymarin on chemical, functional, and morphological alterations of the liver. Scandinavian Journal of Gastroenterology 17(4):517-521.
  • USDA 2001: United States Department of Agriculture, Agricultural Research Service, National Genetic Resources Program. Next link will take you to another Web siteGermplasm Resources Information Network (GRIN) [online database]. 2001. Silybum marianum (L.) Gaertn. Beltsville (MD): National Germplasm Resources Laboratory. [Accessed 2008 September 22].
  • USP 32: United States Pharmacopeial Convention. 2009. United States Pharmacopeia and the National Formulary (USP 32 - NF 27). Rockville (MD): The United States Pharmacopeial Convention.
  • Velussi M, Cernigoi AM, De Monte A, Dapas F, Caffau C, Zilli M. 1997. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective in hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. Journal of Hepatology 26(4):871-879.
  • Williamson EM. 2003. Potter's Herbal Cyclopedia: The Authoritative Reference work on Plants with a Known Medical Use. Saffron Walden (UK): The C.W. Daniel Company Limited.
  • Wren RC. 1907. Potter's Cyclopedia of Botanical Drugs and Preparations. London (UK): Potter and Clark.

References reviewed

  • ADRAC 1999: Adverse Drug Reactions Advisory Committee. An adverse reaction to the herbal medication milk thistle (Silybum marianum). The Medical Journal of Australia 170(5):218-219.
  • Barnes J, Anderson LA, Philipson JD. 2002. Herbal Medicines : A Guide for Healthcare Professionals, 2nd edition. London (UK): The Pharmaceutical Press.
  • Bartram T. 1998. Bartram's Encyclopedia of Herbal Medicine. New York (NY): Marlowe and Company.
  • BHP 1996: British Herbal Medicine Association (BHMA) Scientific Committee. 1996. British Herbal Pharmacopoeia 1996. Bournemouth (UK): British Herbal Medicine Association.
  • Bradley PJ, Denneby C, Ramirez G, Sapp J, Lawrence VA. 2002. Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. The American Journal of Medicine 113(6):506-515.
  • Brinker F. 2001. Herb Contraindications and Drug Interactions, 3rd edition. Sandy (OR): Eclectic Medical Publications.
  • Bunout D, Hirsch S, Petermann M, de la Maza MP, Silva G, Kelly M, Ugarte G, Iturriaga H. [Controlled study of the effect of silymarin on alcoholic liver disease]. Estudio controlado sobre el efecto de la silimarina en la enfermedad hepatic alcoholica. Revista Médica de Chile 120(12):1370-1375 (abstract only; article in Spanish).
  • Chandler F, editor. 2000. Herbs: Everyday Reference for Health Professionals. Ottawa (ON): Canadian Pharmacists Association and the Canadian Medical Association.
  • EMEA 1999. European Medicines Agency. Summary Report on Next link will take you to another Web siteSilybum marianum. London (UK): EMEA Committee on Veterinary Medicinal Products, August 1999. [Accessed 2008 September 22].
  • Fehér J, Láng I, Nékám K, Gergely P, Mũzes G. 1990. In vivo effect of free radical scavenger hepatoprotective agents on superoxide dismutase (SOD) activity in patients. The Tokai Journal of Experimental and Clinical Medicine 15(2,3):129-134
  • Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Lochs H, Meryn S, Base W, Schneider B. 1989. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. Journal of Hepatology 9(1):105-113.
  • Fetrow CW, Avila JR. 2004. Professional's Handbook of Complementary and Alternative Medicines, 3rd edition. Philadelphia (PA): Lippincott Williams and Wilkins.
  • Grieve M. 1971. A Modern Herbal, Volume 2. New York (NY): Dover Publications [Reprint of 1931 Harcourt, Brace & Company publication].
  • Johnston DE. 1999. Special considerations in interpreting liver function tests. American Family Physician 59(8):1-11.
  • Lucena MI, Andrade RJ, de la Cruz JP, Rodriguez-Mendizabal M, Blanco E, Sanchez de la Cuesta F. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. International Journal of Clinical Pharmacology and Therapeutics 40(1):2-8.
  • McGuffin M, Hobbs C, Upton R, Goldberg A, editors. 1997. American Herbal Products Association's Botanical Safety Handbook. Boca Raton (FL): CRC Press.
  • Mills S. 1985. The Dictionary of Modern Herbalism. Wellingborough (UK): Thorsons Publishers Ltd.
  • Parés A, Planas R, Torres M, Caballeria J, Viver JM, Acero D, Panés J, Rigau J, Santos J, Rodés J. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. Journal of Hepatology 28(4):615-621.
  • Rambaldi A, Jacobs BP, Iaquinto G, Gluud C. 2007. Milk thistle for alcoholic and/or hepatitis B or C virus liver disease (review). Cochrane Database of Systematic Reviews Issue 4. Art. No.:CD003620. DOI: 10.1002/14651858.CD003620.pub3.
  • Somogyi A, Ecsedi GG, Blazovics A, Miskolczi K, Gergely P, Fehér J. 1989. Short term treatment of type II hyperlipoproteinaemia with silymarin. Acta Medica Hungarica 46(4):289-295.
  • Strickland GT, Tanamly MD, Tadros F, Labeeb S, Makld H, Nessim D, Mikhail N, Magder LS, Afdhal NH, Medhat A, Abdel-Hamid M. 2005. Two-year results of a randomised double-blinded trial evaluating silymarin for chronic hepatitis C. Digestive and Liver Disease 37(7):542-543.
  • Szilard S, Szentgyorgyi D, Demeter I. 1988. Protective effect of Legalon in workers exposed to organic solvents. Acta Medica Hungarica 45(2):249-256.
  • Tanamly MD, Tadros F, Labeed S, Makld H, Shehata M, Mikhail N, Abdel-Hamid M, Shehata M, Abu-Baki L, Madhat A, Magder LS, Afdhal NH, Strickland GT. 2004. Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results. Digestive and Liver Disease 36(11):752-759.
  • Tanasescu C, Petrea S, Baldescu R, Macarie E, Chiriloiu C, Purice S. 1988. Use of the Romanian product silimarina in the treatment of chronic liver diseases. Medecine Interne 26(4):311-322.
  • Tilgner S. 1999. Herbal Medicine from the Heart of the Earth. Creswell (OR): Wise Acre Press.
  • Torres M, Rodriguez-Serrano F, Rosario DJ, Rodriguez-Perez F, Toro DH. 2004. Does silybum marianum play a role in the treatment of chronic hepatitis C? Puerto Rico Health Sciences Journal 23(2 Supp):69-74.
  • Trinchet JC, Coste T, Levy VG, Vivet F, Duchatelle V, Legendre C, Gotheil C, Beaugrand M. 1989. [Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients]. Traitement de l'hépatite alcoolique par la silymarine. Une étude comparative en double insu chez 116 malades. Gastroentérologie Clinique et Biologique 13(2):120-124 (article in French).
  • Whittington C. 2007. Exacerbation of hemochromatosis by ingestion of milk thistle. Canadian Family Physician 53(10):1671-1673.
  • Wiersema J, Léon B. 1999. Canadian Medicinal Crops. Ottawa (ON): National Research Council of Canada Monograph Publishing Program, NRC Research Press.
  • Williamson EM, Evans FJ, Wren RC. 1988. Potter's New Cyclopedia of Botanical Drugs and Preparations. Saffron Walden (UK): The C.W. Daniel Company Limited.

Appendix 1: Examples of dosage preparations, frequencies of use and directions for use

Dried fruit/seed:

4-9 g, per day (Mills and Bone 2000)

Infusion:

  • 3.5 g dried fruit/seed, 3 to 4 times per day (Blumenthal et al. 2000)
  • Directions for use: Pour 150 ml of boiling water on dried fruit/seed and steep for 10 to 15 minutes. Drink one half-hour before meals (Blumenthal et al. 2000).

Decoction:

  • 3 g dried fruit/seed, 3-4 times per day (Blumenthal et al. 2000)
  • Directions for use: Place dried fruit/seed in 150 ml of cold water, bring to a boil and simmer for 20 to 30 minutes (Blumenthal et al. 2000).

Fluidextract:

4-9 g dried equivalent, per day (1:1, 4-9 ml) (Mills and Bone 2000)

Tincture:

2-4 g dried equivalent, 3 times per day (1:5, 25% alcohol, 10-20 ml) (Mills 1993)

Preparations providing the following quantities of silymarin (calculated as silibinin/silybin):

  • 420 mg, per day (Williamson 2003; Salmi and Sarna 1982)
  • 200-400 mg, per day (Blumenthal et al. 2000)
  • 140 mg, 1-2 times per day (Mills and Bone 2000)
  • 200 mg, 3 times per day (Velussi et al. 1997)
  • 140 mg, 3 times per day (Fehér et al. 1989; Magliulo et al. 1978)