INTRODUCTION
Milk thistle has a long history of human and animal consumption. For centuries, nearly every part of the plant has been utilized. The flower heads can be enjoyed similar to artichokes, while the raw stalks and leaves add a unique touch to salads. Some historical recipes even included baked milk thistle in pies. The roots, comparable to salsify, were also consumed. Furthermore, milk thistle has served as a valuable source of animal feed, with records of its extensive use for cattle and horses in Scotland.
Beyond its culinary applications, milk thistle boasts a rich medicinal tradition. considered its potential health benefits. Popularity surged in the 19th century, particularly in the United States, where it was used to address various ailments including varicose veins, menstrual difficulties, and congestion of the liver, spleen, and kidneys.
HISTORICAL USES OF MILK THISTLE
Milk thistle has been widely marketed as a powerful liver protectant. Supporters claim it can even regenerate liver cells in various liver diseases like cirrhosis, jaundice, hepatitis, and cholangitis (inflamed bile ducts).
Proponents also tout milk thistle as a preventative measure. They believe it shields liver cells from incoming toxins and stimulates the liver's natural detoxification process, helping it eliminate harmful substances like alcohol, drugs, medications, mercury, and heavy metals. Additionally, milk thistle is promoted as a cleanser for overburdened livers, strengthening and invigorating weak ones.
However, there is limited scientific evidence to support these extensive claims. The following section will explore what science has revealed about milk thistle's benefits and side effects.
ACTIVE INGREDIENTS IN MILK THISTLE
Milk thistle extracts are standardized to a concentration of 70-80% of flavone lignans including isosilybinin, silybinin, silychristin, and silydianin, which are collectively called silymarin. Silymarin may play a role in displacing toxins binding to the liver and causing the liver cells to regenerate at a faster rate.
Milk thistle is a flowering herb. Silymarin can be extracted from the seeds (fruit). The seeds are used to prepare capsules containing powdered herb or seed; extracts; and infusions (strong teas). [NCCAM]
BIOAVAILABILITY OF MILK THISTLE
According to Sloan-Kettering Institute [SK], milk thistle is poorly absorbed from the gastrointestinal tract with a bioavailability of approximately 23-47%. Peak plasma concentrations (T max) occur within 2-4 hours after dosing and the elimination half-life of milk thistle is about 4 hours.
Certain formulations have been used for improving the absorption of milk thistle's active ingredients. Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle, is used clinically as a hepatoprotector to treat liver injuries and chronic hepatitis. However, it is poor oral bioavailability due to the poor solubility and low permeability across intestinal epithelium. It was found that silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) improved the oral bioavailability of silymarin in dogs. Pharmacokinetic study in beagle dogs showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.46-fold increase in oral bioavailability as compared with Legalon®, a commercial product. [aa4]
MILK THISTLE EXTRACT HEALTH BENEFITS
Milk thistle's protective effects on liver are well-known, milk thistle actually may have many other health benefits. Test-tube studies show that milk thistle may possibly be a potent anti-cancer agent. Further, milk thistle ingredients were found to have anti-inflammatory, cytoprotective, and anticarcinogenic effects and these beneficial effects are probably related to inhibition of activation of NF-kappa B and the kinases. [7] Here, we are going to review milk thistle benefits on different conditions:
Anti-microbial effects
Milk thistle ingredient, silybin, inhibited RNA and protein synthesis on gram-positive bacteria. [8]
Anti-oxidative effects
Silymarin reduced NO production at less than 300 ppm. [9]
Cardiovascular issues
Milk thistle may benefit people at risk of cardiovascular conditions. Milk thistle and lecithin have found to have anti-atherosclerotic activity in rabbits. Milk thistle-phospholipid complex showed a strong anti-atherosclerotic activity. [10]
Cancers
Milk thistle may benefit people at risk of various type of cancers. Silymarin, the milk thistle ingredient, exerts chemopreventive effects against tumorigenicity by inhibiting endogenous tumor promoter TNF alpha. [11] Silibinin and silymarin, have shown the anticancer effects in different cancer cells in multiple studies:
BLADDER CANCER Silibinin modulates cyclin-dependent kinase inhibitors - cyclin-dependent kinases -cyclin cascade and activates caspase 3 causing growth inhibition and apoptotic death of human bladder transitional cell carcinoma cells. [12] In another study, silibinin decreased survivin levels and caspases-PARP cleavages, in accord with a strong apoptotic death and growth inhibition of Human bladder transitional-cell papilloma cells. [13] And, silymarin was found to be effective in preventing OH-BBN-induced bladder carcinogenesis in mice. [14]
BREAST CANCER An in vitro study has suggested a possible synergism between silibinin and conventional cytotoxic agents for breast cancer treatment. [15] Milk thistle extract may exert a strong anticarcinogenic effect against breast cancer involving inhibition the threshold kinase activities of cyclin-dependent kinases and associated cyclins, leading to a G1 arrest in cell cycle progression. [16].
COLON CANCER A study showed the chemopreventive ability of silymarin against chemically induced colon tumorigenesis.[17]
ENDOTHELIAL CELLS CANCER Silibinin can be a anti-cancer agent as it has the ability inhibit angiogenesis through induction of endothelial apoptosis via modulation of NF-kappaB, Bcl-2 family and caspases. [18] Silibinin toxicity to cancer cells is also found to involve the epidermal growth factor receptor signaling pathway. [19]
GLIOBLASTOMA CANCER Glioblastoma multiforme is a deadly form of brain tumor. Sara Zarei Shandiz and colleagues showed that silymarin may exert its cytotoxic and anticancer effects by enhancing Nrf2/HO-1 pathway through antioxidant mechanisms in U-87 MG cells. [b1]
LUNG CANCER Milk thistle extracts containing Silibinin exerted a dose-dependent inhibitory effect on the invasion and motility of human lung cancer cells.[20]
LIVER CANCER Milk thistle may be useful in the prevention or treatment of liver dysfunction in patients undergoing anticancer therapy.[21]
PROSTATE CANCER In prostate cancer, silibinin exerts its anti-cancer effect probably via epidermal growth factor receptor, insulin-like growth factor receptor type I and nuclear factor kappa B signaling [23] Milk thistle extracts possess anticancer activities on human prostate carcinoma. Isosilybin A and B might be the most effective suppressors of prostate-specific antigen secretion by androgen-dependent LNCaP cells. Researchers suggested that milk thistle extracts enriched for isosilybin A or B might possess improved potency in prostate cancer prevention and treatment. [22] Finally, milk thistle silibinin was found to able to down regulate 5alpha-dihydrotestosterone, thus, milk thistle may be beneficial to prostate health. [23] There are a few more studies showing milk thistle benefits on prostate [24-32].
SKIN CANCER In studies of rats, milk thistle extracts provided substantial protection against different stages of UVB-induced carcinogenesis, possibly via its strong antioxidant properties. [33] In another study, topical treatment of silymarin inhibited 7,12-dimethylbenz(a)anthracene-initiated and several tumor promoters in mouse models. [34] There are two more studies showing the anti-tumor effects of milk thistle extracts on skin cancer: [35]
TONGUE CANCER Feeding of silymarin (500 p.p.m.) during the promotion phase of 4-NQO-induced rat tumorigenesis exerts chemopreventive ability against tongue squamous cell carcinoma through modification of phase II enzymes activity, cell proliferation, and/or PGE(2) content. [36]
Cholestasis
Milk thistle may benefit animals with cholestasis. Milk thistle prevents cholestasis induced by estrogens and taurolithocholate via inhibiting cAMP-phosphodiesterase. [38] In 1985, Koch HP reported that milk thistle was a very potent inhibitor of cyclic AMP phosphodiesterase. Milk thistle's constituents, silybin, silydianin and silychristin, are 12.66 to 52.06 times more active than theophylline. [37]
Diabetes
Milk thistle showed its health benefits on diabetic animals. Milk thistle extracts may be useful in treatment of non-insulin-dependent diabetes mellitus, as silibinin inhibits glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo. [39] Aqueous extracts of milk thistle exhibit potent hypoglycaemic and anti-hyperglycaemic activities in normal and streptozotocin diabetic rats without affecting insulin secretion.
[40] In a study, researchers treated diabetics with 200 mg of silymarin three times a day. After four months, patients had reductions in blood glucose levels. The results are very encouraging and the researchers planned to do further large multi-centre studies. [b2]
A group conducted literature review up to February 2011. They identified 9 trials (n=487). They found, silybum marianum (milk thistle) significantly improved glycemic control, whereas Cinnamomum cassia did not. [aa2] Another group reported a literature review in 2024, they concluded that silybin may improve diabetic conditions through multiple mechanisms, including reducing insulin resistance, lowering reactive oxygen species (ROS) levels, and affecting glycolysis, gluconeogenesis, and glycolysis. In various cellular and animal models of diabetes, silibinin treatment reduced blood glucose levels, oxidative stress markers, and inflammatory cytokines, while increasing glycated hemoglobin (HbA1C) and antioxidant marker levels. It also improves triglycerides, cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein levels. [b3]
HEART
Milk thistle extract, silymarin, protects cardiomyocytes against doxorubicin-induced oxidative stress via cell membrane stabilization effect, radical scavenging and iron chelating potency. {41]
Immune Modulation
A study of mice showed milk thistle silymarin could prevent UVB-induced immuno-suppression and oxidative stress probably by inhibiting the infiltration of leukocytes, and myeloperoxidase activity. [42]
A study demonstrated that milk thistle was immunostimulatory in vitro. Milk thistle increased lymphocyte proliferation in both mitogen and MLC assays. These effects of Milk Thistle were associated with an increase in interferon gamma, interleukin (IL)-4 and IL-10 cytokines in the MLC (table). This immunostimulatory effect increased in response to increasing doses of Milk Thistle. [43]
Osteoporosis
Bone-remodeling imbalance induced by decreased osteoblastogenesis and increased bone resorption is known to cause skeletal diseases such as osteoporosis. Silibinin is the major active ingredient of milk thistle. Studies suggest that silibinin is a powerful antioxidant and has anti-hepatotoxic properties and anti-cancer effects against carcinoma cells. A recent study shows that silibinin had bone-forming and osteoprotective effects in in vitro cell systems of murine osteoblastic MC3T3-E1 cells and RAW 264.7 murine macrophages. Silibinin accelerated cell proliferation and promoted matrix mineralization by enhancing bone nodule formation by calcium deposits. [aa3]
Liver Diseases
Milk thistle may benefit people at risk of liver diseases. CIRRHOSIS A double blind study of 170 patients with cirrhosis demonstrated that silymarin treatment was effective in patients with alcoholic cirrhosis. [44] A study has suggested that milk thistle and S-adenosylmethionine may be effective in alcoholic cirrhosis. [45] FIBROSIS Silymarin retarded the development of alcohol-induced hepatic fibrosis in 12 baboons, consistent with several positive clinical trials. [46] INJURY The hepatoprotective properties of milk thistle extracts in acute and chronic liver injury is probably related to inhibition of leukotriene B (4) formation by silibinin. [47] The protective effects of milk thistle on liver injury may be related to the recovery of the membrane fluidities of liver microsome and mitochondria [48] HEPATITIS C A double-blinded trial of 141 subjects demonstrated that milk thistle extract, silymarin, could improve symptoms and general well-being of patients suffered from hepatitis C. [49] However, some researchers found that milk thistle extracts had no benefits on liver health. For instance, milk thistle extract was found to have no hepatoprotective effect on dairy cows. [50]
Neural Issues
Milk thistle may have protective effects on neural system. In a cell study, silymarin significantly inhibited the LPS-induced activation of microglia and the production of inflammatory mediators, such as tumour necrosis factor-alpha and nitric oxide (NO), and reduced the damage to dopaminergic neurons.[51] Milk thistle extract also protected cultured rat hippocampal neurons against oxidative stress-induced cell death. [52]
Cerebral stroke is the third largest cause of death and the severe leading cause of disability, thus have astronomical financial and social burden worldwide. Accumulated evidence suggests that ROS can be scavenged through utilizing natural antioxidant compounds present in foods and medicinal plants. In a study, male Wistar rats were pre-treated with silymarin (200mg/kg body weight, dissolved in 0.3 % sodium carboxymethyl cellulose, once orally) for 15 days. On day 16, they underwent a transient 2h suture-occlusion of the middle cerebral artery followed by 22 h of reperfusion. Rats were tested for neurobehavioral activity after 22 h reperfusion. [aa1]
Silymarin was found to be successful in upregulating the antioxidant status and lowering the apoptotic responses, and functional recovery returned close to the baseline. This study revealed that silymarin may be helpful in slowing down the progression of neurodegeneration in focal cerebral ischemia. [aa1]
Please, note that most of these studies are done with animals or in test-tubes, clinical studies are needed to support the health claims.
MILK THISTLE SAFETY ISSUES
Milk thistle side effects
Milk thistle appears to be safe and accepted by patients. Side effects are usually mild and may involve stomach upset and diarrhea. Rash may be a result from touching milk thistle plants. Only a few cases of milk thistle side effect have been reported. Silymarin exposure did not produce any signs of overt toxicity or any changes in relative organ weights. [55-60] However, high dose of milk thistle may stimulate inflammatory process (from a mice study). [61] Milk thistle can also produce allergic reactions, which tend to be more common among people who are allergic to plants in the same family (e.g. ragweed, chrysanthemium, marigold, and daisy}.
Milk Thistle Drug Interaction
University of Maryland suggest not to use milk thistle if you are taking: antipsychotics, phenytoin(Dilantin), halothane, and birth control pills or hormone replacement therapy. Milk thistle may interact with allergy drugs -- such as fexofenadine (Allegra), statins, anti-anxiety drugs, anti-platelets, anti-coagulants, some cancer drugs and drugs borken down by liver. [UM]
Further, it has been reported that milk thistle decreased the trough concentrations of indinavir in humans. [53] But, another study showed milk thistle had no apparent effect on indinavir plasma concentrations. [54] This conflicting data might be due to different milk thistle product preparation, extraction method, product composition, experimental design or even the purity of milk thistle.
CONCLUSION
Milk thistle has been known for its protective effects on liver, while milk thistle may also be a potent anti-cancer agent. Milk thistle side effects are limited, but it may interact certain drug products. Users must discuss with their doctors before taking milk thistle.
Milk Thistle Classification:
Silybum Adans.
Click on a scientific name below to expand it in the PLANTS Classification Report.
Kingdom Plantae – Plants
Subkingdom Tracheobionta – Vascular plants
Superdivision Spermatophyta – Seed plants
Division Magnoliophyta – Flowering plants
Class Magnoliopsida – Dicotyledons
Subclass Asteridae
Order Asterales
Family Asteraceae – Aster family
Genus Silybum Adans. – milkthistle
REFERENCES
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[b1] Sara Zarei Shandiz et al, Protective effects of silymarin in glioblastoma cancer cells through redox system regulation, Mol Biol Rep. 2024 Jun 4;51(1):723. [b2] Milk thistle may help diabetics -study, Reuters, October 30, 2006. [b3] Parisa Zare Mehrjerdi, Silibinin as a major component of milk thistle seed provides promising influences against diabetes and its complications: a systematic review, Naunyn Schmiedebergs Arch Pharmacol . 2024 May 27.