Kava Dermopathy

What is it, and what causes it? A look into CYP Enzymes.

Kava dermopathy is characterized by dry, cracked, and scaly skin, particularly in the arms, legs, and face. This is not an acute reaction and develops over weeks and months when consuming larger amounts of kava regularly. This is not a rash. Reports of kava dermopathy can be seen as far back as the 1770s with the arrival of Captain Cook in Hawaii (Norton & Ruze 1994). The severity of dermopathy appears to be directly related to the dose and frequency of consumption (Singh 2004). It should also be noted that some people, even those who have been drinking kava heavily for decades, do not experience this reaction. 

Regular or daily consumption of kava interferes with cholesterol metabolism in skin cells known as keratinocytes. This interaction is thought to reduce the production of ceramides secreted by organelles within the cell known as “lamellar bodies”. Ceramides are a type of long-chain, omega-hydroxylated fatty acid that help maintain skin hydration, facilitate skin cell shedding, and protect the skin barrier. Decreased ceramide levels can lead to dry, scaly, and thickened skin. The condition can be reversed by reducing or ceasing kava consumption in kava dermopathy. (Uchida et al. 2008; Soares et al. 2022; Norton 1998).

The exact mechanism of this condition is debated; however, researchers suggest that enzyme inhibition over time is the culprit (Peterman et al. 2019). Kava inhibits some metabolizing enzymes known as CYPs in vitro (Zou et al. 2002). These CYP enzymes play a role in the metabolization of drugs, endogenous chemicals, fatty acids, and other compounds (Rendic 2002). Thus far, we have only seen this inhibition in humans at the locations of CYP1A2 and CYP2E1, with CYP1A2 being the strongest of the effects observed (Russmann et al. 2005). If CYP inhibition is the culprit, we may also observe inhibition at the enzyme location of CYP4F22. This enzyme is directly responsible for the conversion of long-chain fatty acids into omega hydroxylated acylceramide. A reduction in this metabolism would result in the same skin barrier effects seen in cases of ichthyosis (Akiyama 2021). This ichthyosis condition almost exactly mirrors that of kava dermopathy (Hannam et al. 2014). At present, we have no direct studies on this enzymatic location and kava, so we can only speculate. However, evidence is beginning to mount that this location could indeed be inhibited by kavalactone consumption (White 2018).

In short, daily heavy kava drinking over long periods may interfere with your skin’s ability to produce the compounds required to maintain the waterproof barrier. This allows moisture to escape the skin, accelerating the drying process, eventually interfering with desquamation, or flaking of dead skin, and finally leading to the condition known as “Kava dermopathy” or “Kava ichthyosis”.

Sources:

Akiyama, Masashi. 2021. “Acylceramide Is a Key Player in Skin Barrier Function: Insight into the Molecular Mechanisms of Skin Barrier Formation and Ichthyosis Pathogenesis.” The FEBS Journal 288 (7): 2119–30. https://doi.org/10.1111/febs.15497.

Hannam, Sarah, Michael Murray, Lucia Romani, Meciusela Tuicakau, and Margot J Whitfeld. 2014. “Kava Dermopathy in Fiji: An Acquired Ichthyosis?” International Journal of Dermatology 53 (12): 1490–94. https://doi.org/10.1111/ijd.12546.

Peterman, Kaeleigh, and Emily Reynolds. 2019. “Kava-Induced Ichthyosis.” Journal of the Dermatology Nurses’ Association 11 (6): 280. https://doi.org/10.1097/JDN.0000000000000503.

Norton, S. A., and P. Ruze. 1994. “Kava Dermopathy.” Journal of the American Academy of Dermatology 31 (1): 89–97. https://doi.org/10.1016/s0190-9622(94)70142-3.

Norton, S. A. 1998. “Herbal Medicines in Hawaii from Tradition to Convention.” Hawaii Medical Journal 57 (1): 382–86. https://www.ncbi.nlm.nih.gov/pubmed/9509742.

Rendic, Slobodan. 2002. “Summary of Information on Human CYP Enzymes: Human P450 Metabolism Data.” Drug Metabolism Reviews 34 (1-2): 83–448. https://doi.org/10.1081/DMR-120001392.

Russmann, Stefan, Bernhard H. Lauterburg, Yann Barguil, Erwan Choblet, Pierre Cabalion, Katharina Rentsch, and Markus Wenk. 2005. “Traditional Aqueous Kava Extracts Inhibit Cytochrome P450 1A2 in Humans: Protective Effect against Environmental Carcinogens?” Clinical Pharmacology and Therapeutics. https://doi.org/10.1016/j.clpt.2005.01.021.

Singh, Yadhu N. 2004. Kava: From Ethnology to Pharmacology (Medicinal and Aromatic Plants - Industrial Profiles). CRC Press.

Soares, Rita B., Ricardo Jorge Dinis-Oliveira, and Nuno G. Oliveira. 2022. “An Updated Review on the Psychoactive, Toxic and Anticancer Properties of Kava.” Journal of Clinical Medicine Research 11 (14). https://doi.org/10.3390/jcm11144039.

Uchida, Yoshikazu, and Walter M. Holleran. 2008. “Omega-O-Acylceramide, a Lipid Essential for Mammalian Survival.” Journal of Dermatological Science 51 (2): 77–87. https://doi.org/10.1016/j.jdermsci.2008.01.002.

White, C. Michael. 2018. “The Pharmacology, Pharmacokinetics, Efficacy, and Adverse Events Associated With Kava.” Journal of Clinical Pharmacology 58 (11): 1396–1405. https://doi.org/10.1002/jcph.1263.

Zou, L., M. R. Harkey, and G. L. Henderson. 2002. “Effects of Herbal Components on cDNA-Expressed Cytochrome P450 Enzyme Catalytic Activity.” Life Sciences 71 (13): 1579–89. https://doi.org/10.1016/s0024-3205(02)01913-6.