Facts About Kava and the Liver
Kava Liver Factsheet:
Complied by Jimmy Price
Kava Hepatotoxicity is UNPROVEN
This means there is NO scientific evidence that can be firmly cited in which there can be a credible link shown to kava, its intrinsic properties, and liver toxicity. None. The only things that exist in the realm of kava hepatotoxicity are opinions, and tentative conclusions, not facts.
Some very microscopically small fraction of the population is possibly more sensitive to the inhibitory effects of flavokavains (FK), and higher FK products were more likely to elucidate these adverse reactions.
Kava in its original form was/is safe from its initial cultivation until today, or for almost 3000 years. Kava extracts were safe from at least the mid-1800s up until 1999 and then unsafe for certain individuals for a period between 1998-99 and 2004 but all forms went back to being safe again thereafter.
What does this tell us?
Does logic not dictate for us to look at the details of what happened during these specific years instead of labeling kava being intrinsically toxic to the liver, and closing the book?
“Lack of Evidence of Kava-Related Hepatotoxicity in Native Populations in Savaii, Samoa”
Newspaper Reference: Kava extract in Toledo Blade April 30 1896
The total scope of the issue: We’re talking about 5 actual accredited cases of liver toxicity that causality indicated probable to kava.
Kava has been used for decades as a medicinal product, and centuries to millennia of use in traditional kava drinking. Kava has always been known and described as an unusually safe commodity. Only a few and easily manageable adverse effects were known until 1999, with the most common side effects being a yellowing of the skin, excessive skin dryness, and scaling of the skin in cases of excessive consumption. Immunologic reactions were also seen in specific individuals who may be allergic to kava or some portion of kava, or allergens present in the kava roots.
The hypothesis of a liver toxicity of kava is still unproven to this day. In fact, there is evidence that the Swiss observations may have been the consequence of poor herbal starting material with one single product prepared with acetone as an extraction solvent, whereas all subsequent cases including those from Germany issuing from the use of ethanolic extracts were so poor in reporting quality that causality could not be established. To date it is unclear whether kava induced liver toxicity exists beyond the frequency of spontaneously occurring liver disease with no known cause, and in any case the incidence rate was confirmed as extremely low.
When and where were the first reports of liver injury?
End of 1999-2001
Switzerland
Germany
Different types of kava:
Noble
Daily drinking cultivars with low levels of flavokavains and low levels of dihydromethysticin. Richer in the kavalactone Kavain.
Tudei (Non-Noble)
Non-daily drinking cultivars which contain high proportions of flavokavains and dihydromethysticin.
‘Two-day’ kava is a designation of kava varieties with unpleasant effects, causing nausea, headaches, with such effects lasting for two days. As a consequence of the economic advantages of growing ‘two-day’ kava, Palisi is by now the most far-spread ‘two-day' variety in Vanuatu.
Wild
Piper wichmanii - The wild progenitor of kava. Only consumed in rare instances where no other kavas are to be found. Generally avoided.
What actually happened?
There are two distinct possibilities, both of which could be true. My personal opinion is #1.
Flavokavain B: In the second half of the 1990s, kava exports climbed sharply, and the supply of kava roots became a challenge. This situation led to the organization of a controlled cultivation project in Vanuatu, preceded by a screening of kava varieties. The variety selected for cultivation was the ‘two-day’ type Palisi, which for the contractor of the cultivation had the unique advantage of featuring high contents of kavalactones (the active constituents responsible for the relaxing effect), a high biomass upon harvesting of the roots, and the possibility of harvesting already after one year from plantation, whereas ‘noble’ kava varieties normally stay in the ground for at least two to three years. These non-noble varieties can contain up to 10 times more Flavokavain-B than noble varieties. (https://paperpile.com/app/p/3a3b8e48-318b-0c3e-9ce7-a216bc0e045f Page 1268 Table 4). This difference is what we speak of when we say “kava quality”. Flavokavain B has shown a possibility of being hepatotoxic in liver cells. A different solvent was used during this time and it was acetone. Acetone has been shown to extract Flavokavain B at rates 400% higher than water (Page 192).
Flavokavain B has been considered as a possible culprit for human kava hepatotoxicity. In vitro studies have shown that flavokavain B as a constituent of methanolic extracts derived from roots of the Two-Day kava cultivar Isa is cytotoxic to human hepatoma HepG2 cells, and it was explicitly mentioned that its in vivo hepatotoxicity effects are yet to be elucidated. Additional in vitro experiments revealed cytotoxicity not only in human HepG2 hepatoma cells but also in immortalized nontumor origin human liver cells, line L-02, following treatment with flavokavain B. This has been isolated and purified from ethanolic extracts of kava roots of a not further described kava cultivar that contained high amounts of flavokavain B as for instance the Two-Day cultivar Isa. When morphology of these L-02 cells exposed to flavokavain B was assessed, the cells showed loss of microvilli, cell rounding, and blebbing, suggesting that they were undergoing apoptosis. These cellular changes have been ascribed to GSH-sensitive oxidative stress through modulation of IKK/NF-[1]B and MAPK signaling pathways. It is obvious from these in vitro studies that kava cultivars have been used for assessment which are rich in flavokavain B and derived from problematic non-drink cultivars such as Palisi which does not belong to the favored group of noble cultivars. The timing of these events were such that at the same time as Palisi extracts hit the market, we began seeing adverse reports.
Seeing as the toxicity itself is idiosyncratic, it seems a very small fraction of the population may be more susceptible to the negative effects of Flavokavain-B. It would make sense that not much evidence has been uncovered for this due to the extraordinary rarity of the situation to begin with.
Mold / Aflatoxins due to improper processing/drying.
The major constraints occurring in the Pacific islands, where the weather is warm and humid, are the postharvest storage conditions of the kava plant parts. In Vanuatu and Pohnpei (Micronesia) where kava is always consumed fresh, the raw material has a shelf life of three to four weeks maximum. However, the storage conditions are partially so poor that molds may develop rapidly on the roots one week after harvest. In Pacific countries like Fiji, Tonga, and Samoa where the beverage is prepared from dried raw material, the parts can be stored for a longer period, but molds are also a problem. Finally, when the dried kava was exported in bags and containers to Europe, molds developed in the bags and, if proper inspection did not occur before grinding and extraction, it is likely that hepatotoxins, including aflatoxins, could be present. As an example, a moldy taste of the beverage served in local kava bars of Nouméa (New Caledonia) has been recognized as a problem (Lebot, personal field observation).
The reason I don’t feel confident with this, is that we would have seen this issue crop up independently, and still today if this were the issue, as some farmers use far from accepted processes to produce kava. We don’t see this today. We see food borne illnesses such as e.coli, but no liver related toxicities are reported. Also kava was tested for aflatoxins and it was found that kava powder contained less than the standard amount allowed in dried food products (<4ng/g) https://paperpile.com/app/p/a622a5e8-3c55-03ff-98df-302b62068b0d
But what about “improper plant parts”?
This is commonly posted when the issue arries in online forums. The old line of thinking was that farmers were grinding up entire plants for extraction, however after closer research, pipermethsyine, the alkaloid thought to possibly be a causative factor in liver toxicity, was totally absent when legacy samples of kava exports were analyzed. This was indicative that the proper parts of the plant were being used.
Pipermethystine isn’t as toxic as they initially thought. In vivo application of PM at high doses of 10mg/kg per day failed to result in any experimental liver injury. (https://paperpile.com/app/p/312ad35a-ca56-03eb-9b58-bb0127120777)
Report on Liver Toxicity by Dr. Waller - This is likely what has kept kava available in the United States.
If they bring up this link: https://www.ncbi.nlm.nih.gov/books/NBK548637/
(Also known as the “LiverTox” entry on kava)
This is a snapshot of kava from 2002-2003 and is not indicative of the intrinsic qualities of kava, only the toxicities that were unnaturally manufactured during that time.
Analogy to situation of today:
Do these warnings mean that all lettuce is intrinsically contaminated with listeria and e. coli no matter the source? No, similar to the livertox page, this is a snapshot of an issue with the product during a certain period of time. This does not infer intrinsic toxicity, as many have falsely concluded.
Answer to the question “Why do we see so many adverse reports during this time?”
Governing bodies sent out memos to report any and all adverse events in which kava was present. This doesn’t mean that they have to prove kava was the causative factor, they are simply reports, and as such can be riddled with errors and be all around lacking.
Inverse: Why do we see so FEW adverse reports today while kava remains freely available in all of its forms in the United States and abroad?
If they bring up websites like webmd, or other “review” type sites that pop up quickly when “kava” is searched, please remind them that they venture into the opinion realm. These website articles simply represent the limit of knowledge at the time of the author that wrote them.
Correcting Online Misinformation - Google Results for the word “Kava”:
Correcting Misinformation: Google Link #1 - WebMD
Kava fact of the day Part 2: Australian Alcohol & Drug Foundation
Correcting Misinformation: Google Link #3 National Institute of Health
Google Link #5 - Better Health Channel (Australian Government)
Any and all dedicated kava researchers have arrived at the same opinion. Kava is safe, its banning was unnecessary, and liver toxicity from kava is an artifact due to improper source selection and poor extract manufacturing, and not from kava itself.
Where we’re at now:
What this means is that all of the riff-raff from the early 2000s, all of the liver toxicity reports, all of the adverse events, everything, is no longer applicable to kava’s history. The very German regulatory agency that banned kava has overturned the ban and its reasoning for it. The only thing that keeps kava from being legitimate at this point in Germany (and consequently the rest of the world) is re-proving its anti-anxiety effects.
FDA Adverse Event Reports
2021 - Zero
2020 - One
2019 - One
None of the above included any liver toxicity, and this represents years that at least millions of doses of kava were consumed in the United States. If kava were liver toxic in some intrinsic way that number would be far far higher and at least reference some hepatic function issue.
(FDA Adverse Event Reporting System (FAERS) Public Dashboard)
**Important note about liver function**
We should remember that elevated liver test results can occur for an entire universe of reasons. Below is one of the most common reasons for temporary elevated liver function test results.
“Levels of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) may increase with strenuous exercise”
https://www.clinical-laboratory-diagnostics-2020.com/k51.html