Can ashwagandha (Withania somnifera) cause fatty liver disease?

Ashwagandha Can Cause Liver Injury, Not Fatty Liver Disease

Ashwagandha does not cause fatty liver disease; instead, it causes acute drug-induced liver injury characterized by cholestatic or mixed hepatocellular-cholestatic patterns with jaundice, pruritus, and elevated liver enzymes. This is a fundamentally different pathophysiological process from the metabolic steatosis seen in nonalcoholic fatty liver disease (NAFLD).

Key Distinction: Acute Liver Injury vs. Fatty Liver Disease

• Ashwagandha causes acute hepatotoxicity, presenting with jaundice, severe pruritus, nausea, and marked elevations in liver enzymes after 2-12 weeks of use 1, 2, 3.
• Fatty liver disease (NAFLD) is a chronic metabolic condition characterized by hepatic steatosis (fat accumulation) related to obesity, diabetes, and metabolic syndrome, affecting 20-30% of the general population 4, 5.
• The injury pattern from ashwagandha is cholestatic or mixed (R-values 1.4-5.4), not steatotic 1, 2, 6.

Clinical Presentation of Ashwagandha-Induced Liver Injury

Ashwagandha hepatotoxicity presents with a distinct clinical phenotype:

• Latency period: Symptoms develop 30 hours to 12 weeks after starting ashwagandha 1, 6.
• Primary symptoms: Jaundice, severe pruritus (itching), nausea, lethargy, dark urine, and abdominal discomfort 1, 2, 3.
• Laboratory findings: Marked elevations in ALT (up to 315 IU/L), AST, alkaline phosphatase, and total bilirubin (up to 12.85 mg/dL), predominantly conjugated 1, 6, 7.
• Injury pattern: Hepatocellular or mixed cholestatic pattern, NOT fatty infiltration 2, 3.

Severity and Outcomes

The liver injury is typically self-limited but can be severe:

• Most cases resolve within 1-5 months after discontinuation, though pruritus and hyperbilirubinemia can persist for 5-20 weeks 1, 2.
• No hepatic failure occurred in the initial case series from Iceland and the US 1.
• Critical warning: In patients with pre-existing chronic liver disease, ashwagandha can precipitate acute-on-chronic liver failure with high mortality—all 3 such patients in the Indian series died 3.
• One case required liver transplantation in the global literature 2.
• One patient developed chronic HILI (herb-induced liver injury) 3.

Causality Assessment

The relationship between ashwagandha and liver injury is well-established:

• RUCAM (Roussel Uclaf Causality Assessment Method) scores consistently indicate "probable" causality (scores of 7) 2, 6.
• Chemical analysis of implicated supplements confirmed ashwagandha presence without toxic adulterants or contaminants 1, 3.
• Liver biopsy findings show acute cholestatic hepatitis with hepatocellular necrosis and lymphocyte/eosinophil-predominant portal inflammation 1, 3.

Critical Clinical Pitfalls

Avoid these common mistakes when evaluating patients taking ashwagandha:

• Do not confuse ashwagandha hepatotoxicity with NAFLD—the pathophysiology, presentation, and management are entirely different 4, 5, 1.
• Screen for pre-existing liver disease before patients start ashwagandha, as underlying chronic liver disease dramatically increases mortality risk 3.
• Obtain detailed supplement history in any patient presenting with cholestatic jaundice, as ashwagandha use is increasingly common 1, 2, 3.
• Do not assume herbal supplements are safe—ashwagandha is an emerging cause of drug-induced liver injury despite its widespread use in Ayurvedic medicine 2, 3.

Management Approach

When ashwagandha-induced liver injury is suspected:

• Immediately discontinue ashwagandha and all other herbal supplements 1, 2, 3.
• Exclude competing causes: Perform comprehensive workup for viral hepatitis (HAV, HBV, HCV, HEV), autoimmune hepatitis, Wilson disease, and other drug-induced liver injury 3, 6, 7.
• Supportive care: Ursodeoxycholic acid may provide symptomatic relief for pruritus and cholestasis 6.
• Monitor closely: Serial liver function tests until normalization, which typically occurs over 1-5 months 1, 2.
• Consider plasmapheresis in severe cases with marked hyperbilirubinemia 7.

Contrast with Actual Fatty Liver Disease

For context, true fatty liver disease has different characteristics:

• NAFLD is asymptomatic in most patients and discovered incidentally through abnormal liver enzymes or imaging 4.
• Ultrasound shows increased liver echogenicity from fat accumulation, not the acute inflammatory changes seen with ashwagandha 4.
• Management focuses on weight loss (3-10% body weight), Mediterranean diet, and metabolic risk factor control 8.
• Malnutrition can cause fatty liver but is fully reversible with refeeding and does not cause chronic liver disease 8.