Liver toxicity. Where we stand.
Unpredictable idiosyncratic types, and predictable intrinsic types
The longer one sticks around the various pages and forums on the internet, the more likely they are to run across user concerns related to liver toxicity. Generally, this is a concern of new users just beginning to venture into the kava world. These concerns are thought to stem entirely from the 2001–2002 FDA safety alert issued for kava. Interestingly, the pages from the National Institute of Mental Health currently lead to error pages when researching and following links for this information [1].
Between the late 1990s and early 2000s, just under 100 cases of adverse liver effects were reported to be associated with kava consumption, with most users consuming it as an anxiolytic agent. We will go ahead and highlight here how it is questionable that these issues only spring from a specific period in time. Since then, scientists have attempted to discover the cause of this issue. They have looked at several possible causes. These causes include pipermethystine, flavokavain B, yangonin, methysticin, kavain, ethanol, co-medicated drugs, and mold hepatotoxins. Currently, substantiated evidence is lacking in all of these [3]. Currently, research has separated liver injury from kava into two types.
Unpredictable, idiosyncratic, and predictable intrinsic types [2].
Idiosyncrasy:
A characteristic, habit, mannerism, or the like that is peculiar to an individual.
Physical constitution peculiar to an individual.
A peculiarity of the physical or mental constitution, especially susceptibility to drugs, food, etc.
The metabolic idiosyncratic type of hepatotoxicity appears to be related to an individual’s inability to process certain chemicals through enzymatic metabolism. In this respect, the person in question’s genes may not have been expressed in a way that allowed them to process kavalactones. This reaction is extremely rare. If all cases related to liver injury were indeed from kava, the estimated risk would still be less than .3 cases per 1 million doses daily [4]. This reaction would represent even far less than this.
Intrinsic:
belonging to a thing by its very nature
Predictable, intrinsic types of hepatotoxicity are toxicities that can be prevented through appropriate measures. Here we enter the realm of poor-quality kava products and mold hepatotoxins, flavokavain B, kava varieties, and past liver injury or issues. During this time, a few batches of poor-quality kava extracts may have been sufficient to cause a limited number of individuals with dose-dependent hepatotoxic reactions of this predictable intrinsic type (Teschke 2011). In other words, just a small amount of contaminated product could have triggered the whole issue of liver toxicity.
The reality is that we may actually never know what caused these liver issues in the early 2000s. Researchers missed the opportunity to analyze the kava products taken by patients with toxic liver disease reportedly connected to or had a high probability of being caused by kava. As such, we can only speculate about the culprits during this time. With this in mind, we should also consider recent studies on the individual constituents of kava. It is interesting that kava research has identified many compounds as possibly toxic in the kava plant; however, they require doses far greater than those taken by kava consumers to reach this level. Many of these studies were conducted in vitro, and compounds were added directly to cells or cell cultures. These conditions are not necessarily relevant to whole kava extracts commonly used in humans, and virtually any chemical compound used at untherapeutic amounts may produce cytotoxicity in a dose-dependent manner [3].
In conclusion, we are closer, but we are still far from understanding what happened 20 years ago. However, we can say that through these attempts at finding it, we have discovered that traditional kava presents an impressive safety profile tracing back thousands of years. As long as noble “beverage” grade kava is selected for daily consumption, only below-ground parts of the plant are used, and the rhizomes and roots are peeled, issues are extremely rare, being limited only to idiosyncratic reactions in healthy individuals.
[1] Kava. (n.d.). Retrieved January 26, 2021, from https://ods.od.nih.gov/HealthInformation/kava.aspx
[2] Teschke R, Qiu SX, Lebot V. Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits. Dig Liver Dis. 2011 Sep;43(9):676-81. doi: 10.1016/j.dld.2011.01.018. Epub 2011 Mar 4. PMID: 21377431. https://pubmed.ncbi.nlm.nih.gov/21377431/
[3] Teschke R, Sarris J, Lebot V. Contaminant hepatotoxins as culprits for kava hepatotoxicity--fact or fiction? Phytother Res. 2013 Mar;27(3):472-4. doi: 10.1002/ptr.4729. Epub 2012 May 14. PMID: 22585547. https://pubmed.ncbi.nlm.nih.gov/22585547/
[4] Bian T, Corral P, Wang Y, Botello J, Kingston R, Daniels T, Salloum RG, Johnston E, Huo Z, Lu J, Liu AC, Xing C. Kava as a Clinical Nutrient: Promises and Challenges. Nutrients. 2020 Oct 5;12(10):3044. doi: 10.3390/nu12103044. PMID: 33027883; PMCID: PMC7600512. https://pubmed.ncbi.nlm.nih.gov/33027883/