Should a patient with alanine aminotransferase and aspartate aminotransferase levels above 400 IU/L stop or start chicory (cikori) and milk‑thistle (silymarin) supplementation?

Should Chicory and Milk Thistle Be Stopped or Started with ALT/AST >400 IU/L?

Stop both chicory and milk thistle immediately when ALT and AST exceed 400 IU/L, as this represents severe hepatocellular injury requiring urgent evaluation for acute liver failure, and herbal supplements—including milk thistle—can cause or worsen drug-induced liver injury. 1

Severity Classification and Urgent Management

• ALT and AST levels >400 IU/L represent severe hepatocellular injury (>10× upper limit of normal for women, >5× for men), requiring immediate evaluation rather than any supplementation 2
• This elevation pattern is highly correlated with acetaminophen poisoning and acute liver failure, warranting admission to an ICU with frequent monitoring and early contact with a transplant center 1
• All medications, supplements, and herbal products must be discontinued immediately when transaminases exceed 3× upper limit of normal, as continuing any hepatotoxic agent risks progression to acute liver failure 1, 2

Why Milk Thistle (Silymarin) Should Be Stopped

Limited Evidence in Severe Hepatocellular Injury

• Silymarin has no proven efficacy in reducing ALT or AST in severe hepatocellular injury—the only guideline-level recommendation for silymarin is in mushroom poisoning (Amanita phalloides), where it is used as an antidote despite lack of controlled trials proving efficacy 1
• In acute clinical hepatitis, silymarin showed no significant reduction in ALT or AST despite improving subjective symptoms like jaundice 3
• A 2025 Cochrane review found very low-certainty evidence that silymarin monotherapy may decrease ALT compared to placebo, but this was in metabolic dysfunction-associated steatotic liver disease (MASLD) with mild elevations, not severe acute injury 4

Risk of Drug-Induced Liver Injury

• Herbal supplements are a recognized cause of drug-induced liver injury, and medication-induced liver injury accounts for 8-11% of cases with elevated liver enzymes 2
• All prescription medications, over-the-counter drugs, and herbal supplements must be reviewed against the LiverTox® database for hepatotoxic potential when transaminases are elevated 2
• With ALT/AST >400 IU/L, any potentially hepatotoxic substance must be stopped immediately to prevent progression to acute liver failure 1, 2

Lack of Benefit in Acute Severe Injury

• The only context where silymarin is recommended in guidelines is mushroom poisoning with acute liver failure, where it is given intravenously as silibinin (not oral milk thistle) alongside penicillin G 1
• No guidelines recommend starting silymarin for unexplained severe transaminase elevations—the priority is identifying and removing the causative agent 1, 2

Why Chicory Should Be Stopped

• Chicory is not mentioned in any hepatology guidelines as a treatment for liver disease or elevated transaminases 1, 2
• As an herbal supplement, chicory carries the same risk as other botanical products of causing or contributing to drug-induced liver injury 2
• All non-essential supplements must be discontinued when investigating severe hepatocellular injury to eliminate potential hepatotoxins 1, 2

Immediate Diagnostic Priorities

Essential Workup

• Acetaminophen level must be drawn immediately in all patients with ALT/AST >400 IU/L, as acetaminophen is the leading cause of acute liver failure and levels exceeding 3,500 IU/L are highly correlated with acetaminophen poisoning 1
• Complete liver panel including total and direct bilirubin, albumin, prothrombin time/INR to assess synthetic function 2
• Viral hepatitis serologies (HBsAg, anti-HBc IgM, anti-HCV) as acute viral hepatitis typically shows elevations >400 IU/L 2
• Detailed medication and supplement history including all herbal products, with cross-reference to LiverTox® database 2

Urgent Referral Criteria

• ALT >5× ULN (>235 IU/L for males, >125 IU/L for females) requires hepatology referral, and levels >400 IU/L mandate urgent evaluation 2
• If bilirubin >2× ULN accompanies the transaminase elevation, this suggests potential for acute liver failure and requires immediate specialist involvement 1, 2
• Contact with a transplant center should be initiated early in patients with severe acute liver injury 1

Critical Pitfalls to Avoid

• Do not assume herbal supplements are safe or beneficial when transaminases are severely elevated—they must be treated as potential hepatotoxins until proven otherwise 2
• Do not delay stopping all supplements while awaiting diagnostic workup—immediate discontinuation is essential 1, 2
• Do not start any new supplements or medications (including "hepatoprotective" agents like milk thistle) until the cause of severe transaminase elevation is identified and synthetic liver function is confirmed to be preserved 1, 2
• Do not rely on silymarin to "protect" the liver while continuing other potentially hepatotoxic exposures—the only proven treatment for drug-induced liver injury is discontinuation of the offending agent 2

Monitoring After Discontinuation

• Repeat liver enzymes within 2-5 days to confirm direction of change 2
• If ALT/AST continue to rise or bilirubin increases, urgent hepatology consultation and consideration of ICU admission are warranted 1, 2
• Normalization of transaminases typically occurs within 2-8 weeks after discontinuation of the causative agent in medication-induced liver injury 2