<div>Youngest reported case of liver injury related to Ashwagandha</div><div>Simran Waller MD MPH, Roseburg
Family Medicine Residency Program, swaller@umpquachc.org</div><div>Tsz Ho Wong MD, Roseburg Family Medicine Residency Program,
ewong@umpquachc.org</div><div>Robert Dannenhoffer MD MPH,
Roseburg Family Medicine Residency Faculty, rdannenhoffer@umpquachc.org</div><div>Funding statement: This research received no specific grant from any
funding agency in the public, commercial, or not-for-profit sectors.</div><div>Conflict of interest disclosure: The authors whose names are listed have
NO affiliations with or involvement in any organization or entity with
any financial interest, or non-financial interest in the subject matter
or materials discussed.
Ethics approval statement: This research did not involve any
human/animal subjects and thus did not require ethical approval from a
committee or Institutional Review Board.</div><div>Patient consent statement: Verbal and written consent was obtained from
the patient and legal guardian.</div><div>Material from other sources was not reproduced.</div><div>Ashwagandha, (Withania somnifera), is an herbal supplement in Ayurveda
treatment. In the United States, Ashwagandha is marketed for stress
reduction, brain boosting benefits, and treatment of depression. 
Although data on the effectiveness of this supplement is lacking, it is
widely available and generally thought to be safe. However, a recent
report noted 5 patients with liver injury related to Ashwagandha. Here
we present a case of a young man with acute liver injury associated with
its use.</div><div>A 20-year-old male with Hodgkin’s lymphoma in remission, anxiety, and
depression, presented to clinic with 2-weeks of generalized pruritus,
dark urine, and pale, greasy bowel movements.  He had associated chills,
fatigue, nausea, and decreased appetite with an 8 lb weight loss. He
denied abdominal pain, scleral icterus, vomiting, or swelling.
Medications included Alprazolam 0.5mg PRN, Clonazepam 1mg QHS,
Desvenlafaxine ER 150mg daily, Guanfacine 1.5mg daily, Lurasidone 160mg
daily, Omeprazole 20mg daily, and Risperidone 0.25mg PRN.</div><div>Upon further questioning, the patient disclosed that upon recommendation
from his psychiatric provider, his mother ordered the ”NOW” brand
”standardized extract” Ashwagandha supplement 450mg via the internet as
an adjuvant therapy for his anxiety. He had been taking the supplement
1-2 times daily for 4 weeks prior to the onset of symptoms.</div><div>Physical examination showed a young male in mild distress with visible
excoriations, no jaundice or organomegaly. The remainder of the exam was
unremarkable.  Lab work revealed normal complete blood count, ESR and
electrolytes. Total bilirubin was 1.5, AST 514, ALT 955 and bile acids
were elevated. A screening panel for EBV, Hepatitis A, B and C was
negative.</div><div>The recent report of Ashwagandha resulting in cholestatic liver disease
was noted and it was discontinued. Within two weeks, the pruritus and
additional symptoms had significantly improved, and the total bilirubin
and liver enzymes were down trending. One month after discontinuation,
the total bilirubin was 0.4, AST 36, ALT 64.</div><div>This is the youngest reported patient with the adverse effect of liver
injury related to Ashwagandha. It emphasizes the importance of obtaining
a complete history, especially herbal supplement use as their popularity
increases in the United States. It also highlights the value of case
series and reporting of rare side effects. Without the report in the
journal that so closely matched his symptoms, the search for an
alternative diagnosis may have resulted in the discontinuation of other
important medications or pursuit of a more extensive workup.</div><div>Key Clinical Message:</div><div>It is important to obtain a complete history especially in terms of
herbal supplement use as their popularity increases in the US. There are
many rare but potential serious side effects to be aware of.</div><div>Author Contribution:</div><div>Simran Waller, MD MPH – data collection, analysis, critical revision of
the article, final approval of the version
Tsz Ho Wong MD – data collection, analysis, drafting the article
Robert Dannenhoffer MD MPH – conception, final approval of the version</div><div>References:</div><div>Bjornsson, H., Bjornsson, E., et al. May 2020. Ashwagandha as a cause
for liver injury. <i>Liver International</i> . Volume 40, Issue 8.
Pages 2035-2036.</div>