Liver Injury Associated With Kratom ( Mitragyna speciosa ): A Systematic Review

Kratom ( Mitragyna speciosa ) is a psychoactive herbal product increasingly used for pain, anxiety, and opioid withdrawal. Although marketed as a natural dietary product, concerns have emerged regarding adverse effects like cardiotoxicity, seizures, opioid-like physical dependence, and, particularly, liver toxicity.

We conducted a systematic review following PRISMA 2020 guidelines of all studies on kratom use and liver toxicity.

Thirty-one studies were included, comprising 32 cases of kratom-associated liver injury. Most reports originated from the United States and were single-patient case reports. Most patients were adult males, with frequent co-occurrence of polysubstance use and comorbid conditions. Concomitant exposures were commonly reported but variably characterized across studies. Baseline liver disease was present in 3 patients (9%). Kratom dose, form, frequency, and duration were inconsistently reported. Only 7 cases (22%) provided complete exposure details, whereas the remainder lacked one or more elements. Kratom use was temporally associated with the onset of liver injury, commonly presenting with jaundice and elevations in liver enzymes. The patterns of injury were predominantly cholestatic. In most cases, liver enzymes and function improved after cessation of kratom use. In 4 cases, the patient's liver function did not improve and progressed to liver transplantation. Although formal causality assessments were inconsistently reported, many reports supported an association based on exclusion of alternative etiologies and, in some cases, rechallenge episodes.

Further research is needed to better characterize kratom's mechanisms of liver injury and to inform clinical decision-making and public health policy.