S2939 Ashwagandha Toxicity: A Rare Case of Drug Induced Liver Injury (DILI)

Abstract

Introduction: The pursuance of natural and herbal remedies by many has brought with it further knowledge of the many causes of Drug Induced Liver Injury (DILI). Many of these "natural" over-the-counter (OTC) supplements may not be benign due to the lack of scientific analysis and unregulated production. Ashwagandha is a supplement used for memory enhancement, management of anxiety, and general increase in vitality. We present a case of Ashwagandha DILI in a healthy 36-year-old man. Case Description/Methods: A 36-year-old male presented to our institution with 1 week of fatigue, jaundice, nausea and subjective fevers. Upon presentation he was hemodynamically stable and afebrile. Physical exam was notable for jaundice without other stigmata of liver disease or mental status changes. He was found to have acute liver injury with lab chemistries remarkable for AST= 1482 U/L, ALT= 1375 U/L, Tbili= 22.3 mg/dL, alkaline phosphatase= 202 U/L and an INR of 1.6. He denied alcohol and drug use, recent travel or sick contacts. Medications list was notable for cetirizine, diphenhydramine (both taken as needed), OTC testosterone supplements, OTC apple cider vinegar gummies BID and OTC ashwagandha gummies BID. Workup was negative for autoimmune, infectious, metabolic, obstructive and vascular causes of liver injury. Acetaminophen level and urine drug screen were negative. Trans-jugular liver biopsy revealed evidence of acute portal and lobular hepatitis and cholestasis, suggestive of DILI. Patient's liver enzymes continued to downtrend (AST=929, ALT=765, Tbili=22.5) after withdrawal of his supplements and was discharged (Figure). Discussion: Ashwagandha causing DILI has been infrequently reported in the literature. One case series of 5 patients in Iceland and a single case in Japan reported that ashwagandha is an uncommon culprit linked to acute liver injury. None of the reported cases necessitated liver transplant. Average time to resolution and normalization of LFTs was 3.5 months and R values usually ranged in the mixed range (R value 2-5). The case series also revealed that ashwagandha's toxicity could be dose dependent, as higher peaks in LFT's were tied to recent increases in ashwagandha dosing. Although ashwagandha has been a rarely reported cause of DILI, a thorough history of medication and OTC supplements in patients with undifferentiated acute liver injury may yield more cases. Further study and reporting of DILI in the ever-growing supplement market appears to be required to minimize potential injury.Figure 1.: Tranjugular Liver Biopsy Findings.