Milk Thistle

• Liver support in NAFLD/NASH: Research suggests standardized silymarin extracts may modestly lower ALT/AST and improve ultrasound/biomarker indicators of steatosis over 8–24+ weeks; effect sizes are small-to-moderate and heterogeneous (evidence: moderate; meta-analyses/systematic reviews). - Amanita phalloides (death-cap) mushroom poisoning: Hospital-use IV silibinin (a silymarin component) is associated with lower risk of acute liver failure and mortality when used early alongside standard care; this is not the same as oral OTC supplements (evidence: moderate; systematic reviews/observational cohorts). - Chronic viral hepatitis and alcoholic liver disease: Trials show mixed and generally low-quality evidence; some studies note enzyme improvements, but consistent effects on clinical outcomes (fibrosis progression, mortality) are unconfirmed (evidence: emerging/mixed; older RCTs, reviews). - Glycemic and lipid parameters in type 2 diabetes: Some RCTs report small improvements in fasting glucose, HbA1c, and lipids with adjunct silymarin; results vary and study quality is variable (evidence: emerging to moderate; meta-analyses of small RCTs). - Chemotherapy-associated hepatotoxicity (e.g., pediatric ALL): Small RCTs suggest reduced transaminase elevations with silymarin adjunct therapy; confirmation in larger trials is needed (evidence: emerging). - Antioxidant/anti-inflammatory actions: Demonstrated in preclinical and mechanistic human data; direct clinical outcome benefits remain to be established (evidence: emerging).

Generally well tolerated at typical supplemental doses. Common (1–10%): gastrointestinal upset (nausea, diarrhea, dyspepsia), bloating; headache. Uncommon: pruritus, rash, urticaria. Rare but serious: hypersensitivity reactions (including anaphylaxis) particularly in individuals allergic to Asteraceae (ragweed/daisy) family; potential hypoglycemia when combined with antidiabetic drugs. Dose-related GI effects may increase at higher intakes. Long-term safety data are limited but observational use suggests a favorable profile.

Commonly used ranges in studies (not prescriptive): - Standardized milk thistle extract (70–80% silymarin): 140 mg two to three times daily (total 280–420 mg/day) for 4–24+ weeks in liver-related studies. - Higher-dose regimens for NAFLD/NASH in some trials: 420–700 mg/day silymarin equivalents for 8–48 weeks. - Silybin–phosphatidylcholine (phytosome) complexes: often 80–160 mg two to three times daily (enhanced bioavailability; amounts are not directly equivalent to plain silymarin). - Type 2 diabetes trials have used roughly 200–600 mg/day for 8–16 weeks as adjunct to standard care. - Amanita phalloides poisoning is treated with IV silibinin in hospital settings; this is a prescription/clinical therapy, not an OTC supplement. Optimal dose varies by individual, product, and condition; consult a clinician for personalized guidance.

• Known allergy to Asteraceae/Compositae plants (e.g., ragweed, chrysanthemums, marigolds, daisies). - Pregnancy: Insufficient reliable human safety data; avoid unless advised by a clinician. - Breastfeeding: Traditionally used as a galactagogue, but robust safety/efficacy data are lacking; avoid unless supervised by a clinician. - Hormone-sensitive conditions (e.g., estrogen receptor–positive breast, uterine, or ovarian cancer; endometriosis; uterine fibroids): silymarin has weak phytoestrogen-like activity in vitro; use caution and consult oncology team. - Diabetes or risk of hypoglycemia: may enhance glucose-lowering; monitor closely if used. - Post-transplant or on narrow-therapeutic-index immunosuppressants (tacrolimus, cyclosporine, sirolimus): potential drug-level alterations; avoid unless managed by the transplant team. - Anticoagulation/antiplatelet therapy: potential interaction affecting coagulation or drug metabolism; monitor closely. - Pre-surgical: discontinue 1–2 weeks before elective procedures due to potential effects on blood glucose and coagulation/drug metabolism.