Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Apr 16;17(4):580.
doi: 10.3390/ijms17040580.

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

Flaminia Pantano  1 , Roberta Tittarelli  2 , Giulio Mannocchi  3 , Simona Zaami  4 , Serafino Ricci  5 , Raffaele Giorgetti  6 , Daniela Terranova  7 , Francesco P Busardò  8 , Enrico Marinelli  9
Affiliations
Review

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

Flaminia Pantano et al. Int J Mol Sci. .

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.

Keywords: hepatotoxicity; herb induced liver injury; herbals; kava; khat; kratom.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Kava leaves.
Figure 2
Figure 2
Leaves and flower of Mitragyna speciosa.
Figure 3
Figure 3
Khat leaves.
Figure 4
Figure 4
Chemical structures of kavalactones: yangonin, desmethoxyyangonin (DMY), methysticin (M), 7,8-dihydromethysticin (DHM), and kavain, 7,8-dihydrokavain.
Figure 5
Figure 5
Chemical structures of pipermethystine (PM), 3α,4α-epoxy-5β-pipermethystine and awaine.
Figure 6
Figure 6
Chemical structures of flavokawains (FK) A, B, and C.
Figure 7
Figure 7
Chemical structures of the most abundant indole alkaloids in M. speciosa.
Figure 8
Figure 8
Chemical structures of the most abundant alkaloids present in leaves of Catha edulis.
Figure 9
Figure 9
A dimer that is formed as a result of the decomposition of cathinone.
See this image and copyright information in PMC

References

    1. Teschke R., Frenzel C., Glass X., Schulze J., Eickhoff A. Herbal hepatotoxicity: A critical review. Br. J. Clin. Pharmacol. 2013;75:630–636. doi: 10.1097/MEG.0b013e3283603e89. - DOI - PMC - PubMed
    1. Teschke R., Frenzel C., Schulze J., Eickhoff A. Herbal hepatotoxicity: Challenges and pitfalls of causality assessment methods. World J. Gastroenterol. 2013;19:2864–2882. doi: 10.1097/MEG.0b013e3283603e89. - DOI - PMC - PubMed
    1. Teschke R., Wolff A. Kava hepatotoxicity: Regulatory data selection and causality assessment. Dig. Liver Dis. 2009;41:891–901. doi: 10.1016/j.dld.2009.04.003. - DOI - PubMed
    1. Danan G., Teschke R. RUCAM in drug and herb induced liver injury: The update. Int. J. Mol. Sci. 2015;17 doi: 10.3390/ijms17010014. - DOI - PMC - PubMed
    1. Teschke R., Genthner A., Wolff A., Frenzel C., Schulze J., Eickhoff A. Herbal hepatotoxicity: Analysis of cases with initially reported positive re-exposure tests. Dig. Liver Dis. 2014;46:264–269. doi: 10.1016/j.dld.2013.10.020. - DOI - PubMed

LinkOut - more resources