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Milk thistle (Silybum marianum)
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Milk thistle/Drug Interactions:- Alcohol (ethanol)Alcohol (ethanol): Positive Interaction: Milk thistle may reduce hepatotoxicity associated with ethanol ingestion. In rats, the flavonolignans, silybin (silibinin), silydianin, and silychristin have been found to exert hepatocyte membrane-stabilizing and antioxidant effects (81).
- AmiodaroneAmiodarone: Milk thistle ingredients have been shown to prevent amiodarone toxicity in studies done in animals, but before this herb is used for this indication, further studies in humans must be done.
- Antidiabetic agentsAntidiabetic agents: Silymarin has been reported to decrease fasting plasma glucose, hemoglobin A1c (HbA1c), and fasting insulin levels in patients with insulin-dependent diabetes associated with cirrhosis (29). Concomitant use with other hypoglycemic agents may require dose adjustments.
- Antineoplastic agents (platinums, anthracyclines)Antineoplastic agents (platinums, anthracyclines): Positive interaction: There is pre-clinical data that silibinin may increase the efficacy of platinum compounds (cisplatin, carboplatin) on human PCA cells (82); doxorubicin effects may also be increased (83).
- Antilipemic agentsAntilipemic agents: Early animal experimentation with silybin demonstrated decreased cholesterol synthesis (84), and reduced biliary excretion of cholesterol salts by 60-70%, while leaving biliary flow rates unchanged (59). In perfused livers from rats fed a high cholesterol diet, silymarin normalized the clearance of low-density lipoproteins (85), providing significant protection against dietary-induced hypercholesterolemia (85). Thus, milk thistle may have additive effects with hypocholesterolemic agents.
- Antiretroviral agentsAntiretroviral agents: Animal and laboratory studies have suggested that milk thistle has an inhibitory effect on the CYP system (particularly CYP2D6. 2C9, 3A4), which is responsible for metabolism of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (30; 31; 31; 30). Theoretically, concurrent use may increase levels of antiretroviral agents. However, in human study, milk thistle did not affect the metabolism of indinavir in healthy volunteers (86).
- Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: There is equivocal data from animal studies, in vivo, and in vitro studies to suggest inhibition of the cytochrome P450 system by milk thistle, and effects in humans are unknown. There is recent evidence of inhibition of CYP 3A4, CYP 2C9, and 2D6 (30; 31; 31; 30). Therefore, increased concentrations of concomitant medications (substrates) may occur. However, some reports disagree, stating that milk thistle and black cohosh appear to have no clinically relevant effect on CYP3A activity in vivo (87).
- Glucuronidated agentsGlucuronidated agents: Silymarin may inhibit beta-glucurondase (88), and theoretically may decrease the clearance of glucuronidated agents, such as lorazepam (Ativan®), lamotrigine (Lamictal®), and entacapone (Comtan®) (31).
- Hormonal agentsHormonal agents: Milk thistle may interact with hormonal agents. In theory, silymarin might increase the clearance of estrogen by inhibiting beta-glucuronidase (89).
- Phenytoin (Dilantin®)Phenytoin (Dilantin®): Milk thistle may inhibit P-glycoprotein (90), and theoretically increase concentrations and risk of adverse effects associated with phenytoin.
- P-glycoprotein modulatorsP-glycoprotein modulators: The resulting isoprenoid dehydrosilybins from the flavonolignan silybin has been shown to display high in vitro affinity for direct binding to P-glycoprotein (91; 90).
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Milk thistle/Herb/Supplement Interactions:- AntilipemicsAntilipemics: Early animal experimentation with silybin demonstrated decreased cholesterol synthesis (84), and reduced biliary excretion of cholesterol salts by 60-70%, while leaving biliary flow rates unchanged (59). In perfused livers from rats fed a high cholesterol diet, silymarin normalized the clearance of low-density lipoproteins (85), providing significant protection against dietary-induced hypercholesterolemia (85). Thus, milk thistle may have additive effects with hypocholesterolemic agents.
- AntineoplasticsAntineoplastics: Based on animal and laboratory study, silymarin has demonstrated possible anti-carcinogenic effects (92; 93; 6; 7; 94; 95; 88; 96; 97; 98; 99; 100; 101; 83; 102). Reports in humans are lacking.
- AntioxidantsAntioxidants: Flavonoids present in milk thistle, such as silymarin and silybin, have been shown to act as antioxidants and free radical scavengers (103; 104; 105; 106; 107; 108; 109; 110; 111; 112). In animal studies, silymarin demonstrated strong antioxidant properties (22; 113).
- CalciumCalcium: Studies suggest that silymarin and silybin protect against genomic injury, increase hepatocyte protein synthesis, decrease the activity of tumor promoters, stabilize mast cells, chelate iron, and slow calcium metabolism (23).
- Cytochrome P450 metabolized herbs and supplementsCytochrome P450 metabolized herbs and supplements: There is equivocal data from animal studies, in vivo, and in vitro studies to suggest inhibition of the cytochrome P450 system by milk thistle, and effects in humans are unknown. There is recent evidence of inhibition of CYP 3A4, CYP 2C9, and 2D6 (30; 31; 31; 30). Therefore, increased concentrations of concomitant medications (substrates) may occur. However, some reports disagree, stating that milk thistle and black cohosh appear to have no clinically relevant effect on CYP3A activity in vivo (87).
- Hormonal herbs and supplementsHormonal herbs and supplements: Milk thistle may interact with hormonal agents. In theory, silymarin might increase the clearance of estrogen by inhibiting beta-glucuronidase (89).
- HypoglycemicsHypoglycemics: Silymarin has been reported to decrease fasting plasma glucose, hemoglobin A1c (HbA1c), and fasting insulin levels in patients with insulin-dependent diabetes associated with cirrhosis (29). Concomitant use with other hypoglycemic agents may require dose adjustments.
- IronIron: Studies suggest that milk thistle may protect against genomic injury, increase hepatocyte protein synthesis, decrease the activity of tumor promoters, stabilize mast cells, chelate iron, and slow calcium metabolism (23). Treatment with a standardized silybin and soy phosphatidylcholine complex (IdB 1016) is associated with reduced body iron stores among patients with advanced Batts-Ludwig fibrosis and hepatitis C; serum iron or transferrin-iron saturation do not appear affected (114).
- P-glycoprotein modulatorsP-glycoprotein modulators: The resulting isoprenoid dehydrosilybins from the flavonolignan silybin has been shown to display high in vitro affinity for direct binding to P-glycoprotein (91).
- Vitamin EVitamin E: Positive interaction: Silymarin and vitamin E have been reported to prevent amiodarone toxicity in animal studies. Silymarin and its active constituent, silybin, have been reported to work as antioxidants, scavenging free radicals and inhibiting lipid peroxidation (23).
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Milk thistle/Food Interactions:- Insufficient available evidence.
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Milk thistle/Lab Interactions:- Blood glucoseBlood glucose: Silymarin has been reported to decrease fasting plasma glucose, hemoglobin A1c (HbA1c), and fasting insulin levels in patients with insulin-dependent diabetes associated with cirrhosis (29).
- IronIron: Studies suggested that milk thistle may chelate iron (23). Treatment with a standardized silybin and soy phosphatidylcholine complex (IdB 1016) was associated with reduced body iron stores among patients with advanced Batts-Ludwig fibrosis and hepatitis C; serum iron or transferrin-iron saturation did not appear affected (114)
- Lipid profileLipid profile: Early animal experimentation with silybin demonstrated decreased cholesterol synthesis (84), and reduced biliary excretion of cholesterol salts by 60-70%, while leaving biliary flow rates unchanged (59). In perfused livers from rats fed a high cholesterol diet, silymarin normalized the clearance of low-density lipoproteins (85), providing significant protection against dietary-induced hypercholesterolemia (85). Thus, milk thistle may decrease blood cholesterol.
- Liver function testsLiver function tests: In one study, the most prominent adverse event was hyperbilirubinemia, with grade 1-2 bilirubin elevations in nine of the 13 patients (34). The only grade 3 toxicity observed was elevation of alanine aminotransferase (ALT) in one patient; no grade 4 toxicity was noted. Silymarin in CCl4-induced liver-damaged rats decreased the elevation of aspartate aminotransferase (AST), ALT, and alkaline phosphatase in serum, and also reversed the altered expressions of alpha-smooth muscle actin in liver tissue (115). Silymarin also reduced the AST levels in humans co-infected with HIV and hepatitis C (116).
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Copyright © 2011 Natural Standard (www.naturalstandard.com)
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The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
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