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Milk Thistle

Milk Thistle is a herb that contains a few active ingredients collectively referred to as Silymarins. It is a nice liver therapeutic compound (to be taken after the insult to the liver) and most well known for that, similar in mechanism to TUDCA.

Our evidence-based analysis on milk thistle features 33 unique references to scientific papers.

Kamal Patel
Research analysis led by Kamal Patel.
All content reviewed by the Examine.com Team. Published:
Last Updated:

Things To Know & Note

Primary Function:

Also Known As

Marian thistle, Mary thistle, St Mary’s thistle, Our Lady’s thistle, Holy thistle, Sow thistle, Blessed Virgin thistle, Christ’s crown, Venue thistle, Heal thistle, Variegated Thistle, Wild Artichoke, Carduus Marianus, Silybum marianum

Do Not Confuse With

Artichoke Extract (despite Milk Thistle being known as 'Wild Artichoke'), Sphaeranthus Indicus (East Indian Thistle)

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects milk thistle has on your body, and how strong these effects are.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-d Acne Notable - See study
There is a significant decrease in total lesion counts in those who supplement Silymarin daily for at least eight weeks.

Scientific Research on Milk Thistle

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1Sources and Composition

1.1Sources

Milk Thistle (Silybum Marianum of the family Asteraceae) is a medicinal thistle that has been used in traditional medicines. It derives its name Silybum (sometimes also sillybon) from the greek physician Pedanius Dioscorides (used just to refer to being an edible thistle[1]) and Marianum appears to come from a legend that the white veins running through the plant’s leaves (the 'Milk' aspect of Milk Thistle) were caused by a drop of the Virgin Mary’s milk.[1] Due to the association with the Virgin Mary (Christianity), other names sometimes attributed to Milk Thistle include Marian thistle, Mary thistle, St Mary’s thistle, Our Lady’s thistle, Holy thistle, sow thistle, Blessed Virgin thistle, Christ’s crown, Venue thistle, heal thistle, and variegated thistle with other names not related to Mary being Wild Artichoke and Carduus marianus.[1]

It has a history of usage in the Middle East and Europe, and extends back to Roman and Greek usage (from where it was initially named); its most common recommendations if for a multitude of liver disorders including gallbladder disorders, including hepatitis, cirrhosis and jaundice, and to protect the liver against poisoning from chemical and environmental toxins, including snakebites, insect stings, mushroom poisoning and alcohol.[1] Its usage appears to have extended to Traditional Chinese Medicine and Ayurveda,[2] where it was recommended for the same reasons (liver 'tonic') but additionally for breast milk production, depression, and particularly for rehabilitation against the Amanita phalloides mushroom known as Death Cap; which tends to be lethal shortly after consumption due to the phallotoxins.[3]

Traditionally used in Greek and Roman medicine, spread to Europe as well as the East mainly for the purposes of liver health but also protection from environmental toxins such as Death Cap posioning or snake bites. Appears to have some historical records which tie it to Christianity and Motherhood

1.2Composition

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)[1]

  • Silyhermin and both Neosilyhermin A and B[1]

  • Protein and Mucilage (taking up 25-30% of the herb by dry weight)[1]

  • Quercetin and the dihydro varient known as Taxifolin[1]

  • Kaempferol, Dihydrokaempferol, and the 7-glucoside and 3-sulphate of Kaempferol[1]

  • Apigenin (and 7-O-Glucoside, 4,7-Diglucoside, and 7-O-Glucuronide)[1]

  • Eriodyctiol, Chrysoeriol, and Naringin[1]

  • 5,7-Dihydroxychromone[1]

  • Vitamin E at 0.038%[1]

  • Sterols (cholesterol, campesterol, stigmasterol and sitosterol) at 0.63%[1]

The leaves further contain:

  • Luteolin and its 7-O-Glucoside[1]

  • Triterpene acetate[1]

  • Fumaric acid[1]

When processed into an ethanolic extract and sold as Milk Thistle Extract (most common supplemental form), the composition tends to be:[4]

  • 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[1])

The Silymarin component specifically includes:

  • Silybinin (diastereoisomeric blend of Silybinin A and Silybinin B[5][4][6]) which comprises 50-70% of Silymarin[1] (and by extension, 39-56% of 'Milk Thistle Extract')

  • Isosilibin (Isosilybin A and Isosilybin [5][4][6]) comprising about 5% of Silymarin[1]

  • Silychristine and Isosilychristine[5] at around 20% Silymarin[1]

  • Silydianin[5] at around 10% Silymarin[1]

  • Taxifolin (Quercetin conjugate known as Dihydroquercetin)[5] usually in nearly undetectable levels[5]

The term 'Flavonolignans' is used to refer to seven compounds with the prefix of 'Sily-' or 'Isosily-'.[4] These compounds are pictured below, with changes at the α/β carbons confering the other isomers (A and B in the case of Silybinin and Isosilibin, Silychristine in the case of Isosilichristine; Silydianin nor Taxifolin have known isomers in the Silymarin mixture)

Milk Thistle as a herb contains a variety of compounds (if eating the thistle or buying Silybum Marianum seeds whole), but most studies use an ethanolic extract with a high Silymarin component; this Silymarin component is mostly just 7 flavonolignans that are seen as unique to Milk Thistle
Many studies assess 'Silymarin' collectively, which should be seen as a nondiscriminate mixture of the flavonolignans and possibly a Taxifolin content. Additionally, sometime studies refer to 'Silybinin' or 'Isosilybin' collectively; these studies assume the mixture and do not discriminate between A and B isomers

2Pharmacology

2.1Absorption

Phytosomes work for Milk Thistle supplementations for enhancing bioavailability, and are currently sold under the brand names IDB 1016 (Silipide or Siliphos);[7][8] Milk Thistle appears to be the first nutraceutical to use Phytosomes, which have extended to curcumin, green tea catechins, and grape seed extract.[8]

2.2Enzymatic Interactions

Silymarin (mixture) appears to inhibit the Xanthine Oxidase enzyme with an IC50 27.58+/-3.48mM and a Ki of 5.85mM in vitro via mixed (noncompetitive and uncompetitive) inhibition.[9] When assessing the Silibinin content (isomeric mixture), 50uM of Silybinin can reduce superoxide production by Xanthine Oxidase 20%, still confers mixed inhibition, and appeared to be of comparable potency to allopurinol in vitro yet conferred less inhibition than both Quercetin and Luteolin (all at the same concentrations).[10]

Appears to inhibit the Xanthine Oxidase enzyme in vitro with a fair bit of potency, similar to Allopurinol (research standard)

P-Glycoprotein (P-Gp) is an efflux protein expressed on cells and to a high degree in the intestines, where it may eject some compounds back into the intestinal lumen to reduce absorption rates. Compounds that are subject to P-Gp may have their bioavailability enhanced when this protein is inhibited secondary to less efflux.

Silymarin (mixture) at 50uM has been shown to accumulate daunomycin (substrate of P-Gp) in cells expressing P-Gp with no effect on cells without P-Gp, this study noted accumulation of 445+/-12%, which was similar to phloretin and slightly less than Morin (from Morus Alba) and Biochanin A.[11] Silmarin did not appear to influence protein content of P-Gp, did not interact with the ATPase activity of P-Gp, and inhibited Vermapril-induced ATPase activity on P-Gp; the inhibition at 100uM reaches 61.2+/-20.7% in vitro, comparable to Vinblastine.[11] This study noted enhancement of Doxorubicin cytotoxicity due to P-Gp inhibition, which has been noted in prostatic cells due to Silybinin[12] and noted elsewhere with Silybin[13] and the lack of changes to P-Gp protein content was replicated over 24 hours.[12][14]

This inhibition of P-Glycoprotein has been demonstrated in vivo to aid in the absorption of Berberine when Berberine is taken with 105mg Milk Thistle (60% Flavonolignans),[15] but another study using 300mg (80% Silymarin) thrice a day failed to find significant alterations to Digoxin kinetics.[16]

Can inhibit P-Glycoprotein and possibly enhance absorption of compounds that are subject to P-Glycoprotein, but may not be practically relevant in doing so

3Obesity and Fat Mass

3.1Adipogenesis

Silybinin (mixture) in predifferentiated 3T3-L1 adipocytes appears to concentration-dependently reduce differentiation and triglyceride accumulation with 5uM being significant (about 80% of control) and concentrations up to 30uM tested reducing triglyceride accumulation to about 40% of control;[17] a highly significant suppression of adipogenic markers was observed (PPARy, HSL, LPL, aP2, C/EBPα, and SREBP1c) which were thought to be downstream of an induction of insig-1 and insig-2 acutely (with no difference on the second day of incubation),[17] two proteins that regulate SREBP gene transcription and involved in adipogenesis.[18]

Limited evidence, but may have anti-obesity effects; potency unknown relative to other compounds or in a living system

One study in mouse adipocytes (MC3T3-G2/PA6) noted that Silybin did not inhibit insulin-induced phosphorylation of the receptor, nor the activation of Akt in response to insulin;[19][20] the insulin-induced glucose uptake, however, appears to be effectively abolished (not significantly different than medium without insulin) at 10uM concentration, with significance at 5uM[20] (although a later study using up to 40uM did not replicated the abolishment, but just noted concentration dependent reductions in glucose uptake.[19])

GLUT4 translocation does not appear to be impaired, nor does Hexokinase activity;[19] Silybin and Dehydrosilybin (a metabolite) appear to competitively inhibit glucose for transporter into an adipocyte via GLUT4.[19]

May reduce glucose uptake into cells via GLUT4, possibly by being taken up into cells via GLUT4 vesicles and competitively inhibiting transportation of glucose

4Interactions with the Liver

4.1Mechanisms

Milk Thistle is implicated in enhancing cellular protein synthesis, which may underlie therapeutic purposes of Milk Thistle in the liver. Injections of isolated Silybinin to rats has resulted in increase polymerase I activity and subsequent protein synthesis[21] and enhanced DNA synthesis has been observed in rats with a partial hepatectomy (missing parts of the liver) but failed to be observed in healthy controls or hepatoma/neoplastic cells.[3] The exact mechanism is unknown, but has been thought to be due to RNA polymerase I and ribosomal RNA activation somehow.[1]

May increase the rate of protein synthesis in liver cells and encourage subsequent repair after injury to the cells

4.2Steatohepatitis (Fatty Liver) and Lipotoxicity

In isolated HepG2 cells, the DNA fragmentation induced by excessive palmatate concentrations is concentration-dependently reduced by Silymarin and the LDH release (indicative of liver cell damage) also dose-dependently reduced.[22] This was not related to antioxidant properties (N-Acetylcysteine failed to mimic the protective effects) but Silymarin preserved activation of Akt (normally reduced during lipotoxicity, its preservation enhances cell survival).[22]

NF-kB may also be implicated, as a mouse model of Non-alcoholic fatty liver disease (NAFLD) noted abnormal expression of NF-kB and its subsets (p50, p65) activity which was normalized with 20mg/kg Silybinin injections.[23]

4.3Chemical Toxins and Alcohol

One of the traditional uses for Milk Thistle was rehabilitation against Amanita phalloides (Death Cap) poisoning, a highly lethal mushroom; the toxin in question, Amanitin, inhibits RNA polymerase II and inhibits protein synthesis (genomically, rather than just skeletal muscle protein synthesis; this prevents DNA from creating new proteins).[1] There are no controlled trials in humans on Death Cap Toxicity for ethical reasons, but a summary of case studies[24] using around 420-600mg (Total Silymarin) on average support traditional usage.

Has been used against Death Cap (Amanita phalloides) lethal mushroom poisoning and may be one of the few compounds to be used for this rehabilitative purpose, but has surprisingly little evidence to support this role

Some studies have looked at microcystin toxicity (found in most species of Blue-Green algae known as cyanobacteria except Spirulina) noted that 400mg/kg Silybin to mice (injections) an hour prior to microcystin injection noted that the expected increases of liver enzymes were reduced by 61% (ALT) and 12% (LDH) with the reduction in AST not being significant.[25] 200mg/kg Quercetin injections 3 hours prior to insult showed less protective effects and 400mg/kg Morin (from Morus Alba) given 3 hours prior to microcystin injections slightly augmented toxicity.[25]

May have protective effects against Microcystin toxicity if preloaded; limited evidence

4.4Environmental/Biological Toxins and Stressors

4.5Hepatocarcinoma

In mice (B6C3) given Hepatocellular Carcinoma (via injection of N-nitrosodiethylamine, allowing a few weeks for foci to form before testing[26]) Milk Thistle intervention appears to reduce the growth rate of tumors, an effect abolished by consumption of alcohol.[27] This study used 0.5% Silybinin for 9 weeks with alternate day ethanol administration (20% of drinking water), and noted that ethanol actually augmented tumor growth in male rats (no effects in female rats).[27]

Milk Thistle may attenuate the growth of hepatic carcinomas, which is abolished and potentially reversed with coingestion of alcohol (suggesting the trifecta of Alcohol, Milk Thistle, and preexisting carcinoma may augment growth according to one study)

5Interactions with Aesthetics

5.1Skin

Acne vulgaris is a chronic skin disease characterized by follicular hyperkeratinization,hormonally-mediated sebum overproduction, and chronic inflammation of the pilosebaceous unit.[28] It is believed that the damaging of lipids in the skin via free radicals is responsible for the inflammatory component of acne. Recent research has found that those who suffer from acne are unable to mitigate this damage efficiently because their antioxidant defense system is overwhelmed. [28]

Thus, based on this research, new studies have aimed to look at the effect of antioxidant supplementation on lesion counts.

A single-blind placebo controlled study that aimed to compare Silymarin, N-acetylcysteine, and Selenium to placebo in reducing lesion counts, found that after eight weeks of supplementation, there was a notable reduction in lesion count in all of the experimental groups, however, the reduction in lesion count was only statistically significant in the N-acetylcysteine and Silymarin groups. The Silymarin group supplemented 210 mg/day orally, for at least 8 weeks and saw a 53% reduction in total lesion counts. [29]

Milk Thistle may significantly reduce the total number of lesion counts in those who suffer from Acne Vulgaris after at least two months of supplementation.

6Possible Therapeutic Usages

6.1Galactogogue

Milk Thistle (as well as Fenugreek) appears to be one of the herbs recommended as a Galactogogue to promote lactation in new mothers.[30] According to two reviews,[31][32] the traditionally recommended method of ingestion for the purpose as a galactogogue is either 1-3g of the crushed seeds (encapsulated) or crushing the seeds and steeping them as a tea to be drunk thrice a day.

Currently only one trial exists using 420mg Micronized Silymarin where milk production at day 30 of supplementation increased 64% in the Milk Thistle group yet only 22% in placebo (numbers relative to baseline), with measurements at day 63 being increased to 86% and 32% respectively.[33] This study failed to report any Silymarin components in the breast milk when assessed, the composition of the breast milk did not appear to change, and the study did not appear to be funded by the producers of the supplement used (BIO-C).[33]

Limited evidence to support its usage as a milk production agent, but the only trial currently conducted appears to support it

Usage of Milk Thistle as a galactogogue may be related to the Christian legend of how the Virgin Mary could only seek refuge for the birth of Jesus via a shelter in a bower formed from the thorny leaves of the milk thistle,[1] which seems to have begun intertwining of Milk Thistle with motherhood in general.

References

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y Abenavoli L, et al. Milk thistle in liver diseases: past, present, future. Phytother Res. (2010)
  2. ^ Abenavoli L, et al. Complementary therapies for treating alcoholism First Annual meeting by Complementary Medicine Research Group of the Italian Society for Alcohol Studies-May 5, 2006, Florence, Italy. Fitoterapia. (2008)
  3. ^ a b Pradhan SC, Girish C. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J Med Res. (2006)
  4. ^ a b c d Kroll DJ, Shaw HS, Oberlies NH. Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integr Cancer Ther. (2007)
  5. ^ a b c d e f Kim NC, et al. Complete isolation and characterization of silybins and isosilybins from milk thistle (Silybum marianum). Org Biomol Chem. (2003)
  6. ^ a b Lee DY, Liu Y. Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J Nat Prod. (2003)
  7. ^ Membranes and the setting of energy demand.
  8. ^ a b Kidd PM. Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts. Altern Med Rev. (2009)
  9. ^ Sheu SY, Lai CH, Chiang HC. Inhibition of xanthine oxidase by purpurogallin and silymarin group. Anticancer Res. (1998)
  10. ^ Pauff JM, Hille R. Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod. (2009)
  11. ^ a b Zhang S, Morris ME. Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport. J Pharmacol Exp Ther. (2003)
  12. ^ a b Tyagi AK, et al. Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis. Clin Cancer Res. (2002)
  13. ^ Maitrejean M, et al. The flavanolignan silybin and its hemisynthetic derivatives, a novel series of potential modulators of P-glycoprotein. Bioorg Med Chem Lett. (2000)
  14. ^ Zhou S, Lim LY, Chowbay B. Herbal modulation of P-glycoprotein. Drug Metab Rev. (2004)
  15. ^ Di Pierro F, et al. Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control. Diabetes Metab Syndr Obes. (2012)
  16. ^ Gurley BJ, et al. Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos. (2006)
  17. ^ a b Ka SO, et al. Silibinin attenuates adipogenesis in 3T3-L1 preadipocytes through a potential upregulation of the insig pathway. Int J Mol Med. (2009)
  18. ^ Goldstein JL, DeBose-Boyd RA, Brown MS. Protein sensors for membrane sterols. Cell. (2006)
  19. ^ a b c d Zhan T, et al. Silybin and dehydrosilybin decrease glucose uptake by inhibiting GLUT proteins. J Cell Biochem. (2011)
  20. ^ a b Nomura M, et al. Inhibitory mechanisms of flavonoids on insulin-stimulated glucose uptake in MC3T3-G2/PA6 adipose cells. Biol Pharm Bull. (2008)
  21. ^ Sonnenbichler J, Zetl I. Biochemical effects of the flavonolignane silibinin on RNA, protein and DNA synthesis in rat livers. Prog Clin Biol Res. (1986)
  22. ^ a b Song Z, et al. Silymarin prevents palmitate-induced lipotoxicity in HepG2 cells: involvement of maintenance of Akt kinase activation. Basic Clin Pharmacol Toxicol. (2007)
  23. ^ Salamone F, et al. Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis. Transl Res. (2012)
  24. ^ Saller R, et al. An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch Komplementmed. (2008)
  25. ^ a b Jayaraj R, et al. Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in mice. Environ Toxicol. (2007)
  26. ^ Fausto N, Campbell JS. Mouse models of hepatocellular carcinoma. Semin Liver Dis. (2010)
  27. ^ a b Brandon-Warner E, et al. Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice. Cancer Lett. (2012)
  28. ^ a b Bowe WP, Patel N, Logan AC. Acne vulgaris: the role of oxidative stress and the potential therapeutic value of local and systemic antioxidants. J Drugs Dermatol. (2012)
  29. ^ Sahib A, et al. Effects of Oral Antioxidants on Lesion Counts Associated with Oxidative Stress and Inflammation in Patients with Papulopustular Acne. J Clin Exp Dermatol Res. (2012)
  30. ^ Forinash AB, et al. The use of galactogogues in the breastfeeding mother. Ann Pharmacother. (2012)
  31. ^ Low Dog T. The use of botanicals during pregnancy and lactation. Altern Ther Health Med. (2009)
  32. ^ Zapantis A, Steinberg JG, Schilit L. Use of herbals as galactagogues. J Pharm Pract. (2012)
  33. ^ a b Di Pierro F, et al. Clinical efficacy, safety and tolerability of BIO-C (micronized Silymarin) as a galactagogue. Acta Biomed. (2008)

This page is regularly updated, to include the most recently available clinical trial evidence.

Each member of our research team is required to have no conflicts of interest, including with supplement manufacturers, food companies, and industry funders. The team includes nutrition researchers, registered dietitians, physicians, and pharmacists. We have a strict editorial process.

This page features 33 references. All factual claims are followed by specifically-applicable references. Click here to see the full set of references for this page.

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