Discussion
Generally, ashwagandha has been thought to be well tolerated and possibly hepatoprotective.7-10 However, recent studies suggest potential for hepatotoxicity, though without clear guidance about which patients are most at risk.5,11,12 A study by Inagaki and colleagues suggests the potential for dose-dependent mechanism of liver injury, and this is supported by in vitro CYP450 inhibition with high doses of W Somnifera extract.11,13 We hypothesize that there may be a multihit process that makes some patients more susceptible to supplement harm, particularly those with repeated exposures and with ongoing exposure to hepatic toxins, such as AUD.14 Supplements should be used with more caution in these individuals.
Additionally, although there are no validated guidelines to confirm the diagnosis of drug-induced liver injury (DILI) from a manufactured medication or herbal remedy, the Council for International Organizations of Medical Sciences (CIOMS) developed RUCAM, a set of diagnostic criteria for DILI, which can be used to determine the probability of DILI based on pattern of injury.15 Although not widely used in clinical practice, RUCAM can help identify the possibility of DILI outside of expert consensus.16 It seems to have better discriminative ability than the Maria and Victorino scale, also used to identify DILI.16,17 While there is no replacement for clinical judgment, these scales may aid in identifying potential causes of DILI. The National Institutes of Health also has a LiverTox online tool that can assist health care professionals in identifying potentially hepatotoxic substances.6
Conclusions
We present a patient with AUD who developed cholestatic liver injury after ashwagandha use. Crucial to the diagnostic process is quantifying the amount ingested before presentation and the presence of contaminants, which is currently difficult to quantify given the lack of mechanisms to test supplements expediently in this manner in the clinical setting, which also requires the patient to bring in the supplements directly. There is also a lack of regulation and uniformity in these products. A clinician may be inclined to measure ashwagandha serum levels; however, such a test is not available to our knowledge. Nonetheless, using clinical tools such as RUCAM and utilizing databases, such as LiverTox, may help clinicians identify and remove potentially unsafe supplements. While there are many possible synergies between current medical practice and herbal remedies, practitioners must take care to first do no harm, as outlined in our Hippocratic Oath.