Hepatotoxicity Induced by “the 3Ks”: Kava, Kratom and Khat

Abstract

The 3Ks (kava, kratom and khat) are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, leading to deranged liver enzymes and also histopathological evidence of acute hepatocellular degeneration. Numerous reports of severe hepatotoxicity potentially induced by kava have also been highlighted, both in the USA and Europe. The aim of this review is to focus on the different patterns and the mechanisms of hepatotoxicity induced by “the 3Ks”, while trying to clarify the numerous aspects that still need to be addressed.

Khat chewing increases the risk for developing chronic liver disease: A hospital‐based case–control study

“…First, although there were no compelling features of an autoimmune process in the cases in the present study, previous case reports have documented low titers of autoantibodies and histological features reminiscent of an autoimmune hepatitis in patients suspected of having khat‐related liver injury . Second, the khat‐related alkaloids are metabolized extensively in the liver by the enzyme cytochrome P450 2D6 (CYP2D6) and have short half‐lives . The finding in one case series of very high concentrations of khat alkaloids in a sample of explanted liver many weeks after the last exposure to khat suggests that accumulation of khat and/or its metabolites may be important .…”

Kratom from Head to Toe—Case Reviews of Adverse Events and Toxicities

“…Their non-selectivity likely results in the beneficial multimodal effects of kratom especially for analgesia and mood elevation [20]. In vitro studies have exhibited cytotoxic effects on human neuronal, hepatic, and cardiac myocyte cell lines and have shown neuromuscular blocking effects [21][22][23][24]. Kratom was also reported to inhibit CYP 450 hepatic enzyme, particularly CYP 3A4, 2D6, and 1A2 [29,30].…”

Update on the Pharmacology and Legal Status of Kratom

“…Some of the reported effects include tachycardia, seizures, and liver damage. [44][45][46][47][48] In addition, there have been several deaths attributed to the use of purported kratom products. 8, 16,43,[49][50][51] From the foregoing summary, it is understandable why the DEA would be concerned about the safety of kratom.…”