kalmia_latifolia
Dad, scientist, gardener, living in the SE USA
Hey everyone,
I’m relatively new to kava, but like many out there I’m looking for something that relaxes without blurring my mind, as alcohol does. I’m a tenure-track research professor in biological sciences at a major US university where I run a research lab. I don’t know much about chemistry or medicine, but I know how to read papers and evaluate scientific evidence. Before embarking on the Kava journey, I, like many others, wanted to figure out if it is safe. I found many reassurances on the forums (you folks are awesome!), but I’m, at heart, a scientist, and I wasn’t satisfied until I’d gone through the peer reviewed literature with a fine-toothed comb. Rather than keep this information to myself, I decided to take the time to write up my scientific journey for those of you that are interested. Important disclaimer: I am not a medical doctor and I am not qualified to give medical advice, so nothing here should be construed as medical advice. This is just my personal analysis of kava's safety after reading dozens of scientific papers on the topic. Of course you’re going to want to consult your doctor before making any medical decisions.
My top line takeaway is that aqueous extracts of high quality kava (noble cultivars, peeled rhizome and root only, free from contamination by microbes, pesticides, and heavy metals) should be reasonably safe for healthy adults when used in moderation without other drugs or alcohol. If this sounds familiar, it is because it is also the position held by many on this board- but I wanted to know how the scientific community reached this result. So, if you’re interested in how I got to that conclusion, read on. My review focuses only on the hepatotoxic (liver injury) effects of kava- while there are other side effects (e.g., rashes, dehydration, headaches, etc.), they are considered minor and typically resolve quickly after the cessation of kava consumption.
As we’re all aware, kava has been linked to severe hepatotoxic reactions in a small number of people about 20 years ago (less than 70 people, more than 10- the numbers vary depending on if you exclude people for things like the use of alcohol or concomitant medication). However, fairly strong evidence exists that liver injury occurred in people with all forms of consumption, mainly with organic extracts but a couple with aqueous extract. This is understandably worrying.
Yet the statistics on use are reassuring: in Europe, 14 cases of liver injury were deemed to be have had kava as a ‘probable’ cause. For context, this is after the use of 60–125 million doses (Ernst, 2007). Monitoring studies following 7078 patients taking daily doses of 120-150mg of organically extracted Kava for a few months showed no signs of hepatotoxicity. Note, however, that this does not mean that rare severe reactions can’t occur, one would need a much larger dataset to make inference about rare events. As far as I’m aware, the cases of severe hepatotoxicity occurred in the late 1990s / early 2000s, and haven’t continued, despite hundreds of thousands of people using kava daily (if I’m wrong here, please let me know). All of the case reports I could find reference to in the literature are from about 20 years ago, but that could be due to the fact that these cases spurred regulatory action in Europe which provided the motivation for the scientific community to study kava. Ethnographic data suggests that Kava does not cause liver damage in the descendants of the indigenous people who domesticated kava, and contemporary populations of heavy kava drinkers (some of whom are estimated to consume 100,000 bowls of kava in their lifetimes, and often consume more than 2.5g of kavalactones in one night) in the south pacific do not seem to have an elevated rate of liver damage. Oh, and there are also rodent studies: Singh and Devkota (2003) fed rats super high doses of aqueous kava extract (500 mg kavalactones / kg of body weight per day- that would be 35g of kavalactones for an average adult male human per day!), which didn’t cause liver injury after short-term use (2-4 weeks). Rats fed lower doses of organically extracted kava for a longer time period (3 months) had no liver issues (DiSilvestro et al, 2007). Both of these studies had relatively small numbers of animals, and in general these rodents come from highly inbred lines, so we can’t assess whether between-animal genetic differences might contribute to rare adverse reactions. Still, this is all strong evidence that kava is reasonably safe.
Should we be scared of organic extracts? Possibly- I’m avoiding them out of an abundance of caution. Kavalactones aren’t very soluble in water, so lot of companies extract them with organic solvents, primarily ethanol and acetone. These extracts are super popular and millions of people have taken them without issue. However, I think they may be a risk factor for liver injury, but we just don’t have enough data yet to know. There are two things I worry about with extracts:
1) You don’t know what the source material was, and it seems to me that market forces would favor the use of cheap, low quality kava for extracts that cannot be sold as the more expensive ground root.
2) Organic extracts pull out some chemicals much more efficiently than water. The main focus here been on flavokavains. To review, flavokavains are a class of chalcones which naturally exist in kava roots. Kava contains 3 different flavokavains (called flavokavain A, B and C); B is the one most people worry about since it’s the most abundant and cytotoxic. Cells grown in tissue culture (so in test tubes, not in animals) are very sensitive to flavokavain B, where it causes cell death by triggering cellular suicide (Zhou et al, 2010). These researchers also found that mice given a really large dose of flavokavain B (25 mg / kg) for a week had acute liver damage. While scary, this is not a realistic dose for human consumption. According to Lebot (2011), 25 mg/kg represents a minimum of 250 times more than humans would consume, assuming a ‘worst case scenario’ in which they consumed 120mg of kavalactones derived from an ethanolic extract of a tudei variety with a lot of flavokavain B. Of course, many people take much more than 120mg kavalactones, but we’re usually not drinking organic extracts of tudei varieties, so I think this ballpark number is reasonable. Unfortunately, Zhou et al, 2010 didn’t test lower doses of flavokavain B in mice, so we don’t know what the threshold concentration for liver toxicity is in living animals.
I personally don’t want to mess with flavokavains, and they’re greatly enriched in organic extracts relative to water. Here’s a nice graph showing differences between water and ethanol extraction, from Martin et al, 2014. Note that organic extraction of flavokavain B is much higher than aqueous (bottom subfigure). Similarly, Zhou et al (2010) estimate that 95% ethanol and 100% acetone are ~160-times better at extracting flavokavain B than water. One thing that makes me somewhat reassured that flavokavain B isn’t very scary at typical rates of intake is the fact that that acute liver toxicity is a very rare issue, even with organic kava extracts. If typical organic extracts of kava had enough flavokavain B to cause acute liver injury, we’d expect to see it more often with those taking organic extracts.
So, what caused people to have acute liver failure after taking kava? We currently don’t know. The number of cases is low, and we didn’t have Dr. House go and test their exact batch of kava to see if it was contaminated with mold aflatoxins, etc. It’s likely one of three explanations: 1) An idiosyncratic allergic reaction. 2) Bad kava, contaminated with either toxic mold, aerial plant parts which can contain a toxic alkaloid not found in the roots, or even other plant species entirely. 3) Use by people with pre-existing liver issues or stress placed on the liver via concomitant use with other drugs or alcohol.
Fortunately, you have control over many of these factors. You can source good kava root from one of the main, trusted vendors out there that have a reputation for knowing their farmers (or growing it themselves) and getting high quality root. This should greatly reduce your chances of getting contaminated or mislabeled kava. I’d avoid organic extracts for the reasons outlined above. You can be sure you have a healthy liver prior to taking kava, and avoid taking kava with alcohol or other drugs. And you can go easy, giving your body plenty of time to recover from any stress caused by kava (this is probably good advice for all intoxicants, by the way!). Unfortunately, there’s a bit of a stochiastic element in all this that you may not have much control over: if a very low proportion of people have an allergic reaction to kava that causes acute liver failure, and there’s no way of predicting this ahead of time (note that this is just a hypothesis right now, we don’t know if this is true), that’s legitimately scary. For me, I’ve decided to go light on kava in my first month of use, seeing if it has any negative physical side-effects. If it does, I will go get my liver function tested by my doctor before continuing use. Better safe than sorry.
One thing I’d love to hear from the community is whether acute hepatotoxic reactions continue to occur every year, or whether they occurred 20 years ago and haven’t occurred again since then. After all, hundreds of thousands of people take kava every day, and thus we can make a pretty powerful statistical inference from the long-term incidence rate (I mean, this is epidemiology 101). If contemporary hepatotoxic reactions are virtually nonexistent, then I think this provides pretty strong inferential evidence that the cases which occurred 20 years ago were caused by something other than kava itself (e.g., toxins other those naturally found in kava that got introduced into the supply chain through poor quality control).
Anyway, I hope this is helpful to some of you who want a bit more data to go with your reassurances that kava is safe for human use when basic precautions are taken. Also, big thanks to Mike at @Kalm with Kava for the great kava, for answering my questions, and for encouraging me to write this up for the boards.
I’m relatively new to kava, but like many out there I’m looking for something that relaxes without blurring my mind, as alcohol does. I’m a tenure-track research professor in biological sciences at a major US university where I run a research lab. I don’t know much about chemistry or medicine, but I know how to read papers and evaluate scientific evidence. Before embarking on the Kava journey, I, like many others, wanted to figure out if it is safe. I found many reassurances on the forums (you folks are awesome!), but I’m, at heart, a scientist, and I wasn’t satisfied until I’d gone through the peer reviewed literature with a fine-toothed comb. Rather than keep this information to myself, I decided to take the time to write up my scientific journey for those of you that are interested. Important disclaimer: I am not a medical doctor and I am not qualified to give medical advice, so nothing here should be construed as medical advice. This is just my personal analysis of kava's safety after reading dozens of scientific papers on the topic. Of course you’re going to want to consult your doctor before making any medical decisions.
My top line takeaway is that aqueous extracts of high quality kava (noble cultivars, peeled rhizome and root only, free from contamination by microbes, pesticides, and heavy metals) should be reasonably safe for healthy adults when used in moderation without other drugs or alcohol. If this sounds familiar, it is because it is also the position held by many on this board- but I wanted to know how the scientific community reached this result. So, if you’re interested in how I got to that conclusion, read on. My review focuses only on the hepatotoxic (liver injury) effects of kava- while there are other side effects (e.g., rashes, dehydration, headaches, etc.), they are considered minor and typically resolve quickly after the cessation of kava consumption.
As we’re all aware, kava has been linked to severe hepatotoxic reactions in a small number of people about 20 years ago (less than 70 people, more than 10- the numbers vary depending on if you exclude people for things like the use of alcohol or concomitant medication). However, fairly strong evidence exists that liver injury occurred in people with all forms of consumption, mainly with organic extracts but a couple with aqueous extract. This is understandably worrying.
Yet the statistics on use are reassuring: in Europe, 14 cases of liver injury were deemed to be have had kava as a ‘probable’ cause. For context, this is after the use of 60–125 million doses (Ernst, 2007). Monitoring studies following 7078 patients taking daily doses of 120-150mg of organically extracted Kava for a few months showed no signs of hepatotoxicity. Note, however, that this does not mean that rare severe reactions can’t occur, one would need a much larger dataset to make inference about rare events. As far as I’m aware, the cases of severe hepatotoxicity occurred in the late 1990s / early 2000s, and haven’t continued, despite hundreds of thousands of people using kava daily (if I’m wrong here, please let me know). All of the case reports I could find reference to in the literature are from about 20 years ago, but that could be due to the fact that these cases spurred regulatory action in Europe which provided the motivation for the scientific community to study kava. Ethnographic data suggests that Kava does not cause liver damage in the descendants of the indigenous people who domesticated kava, and contemporary populations of heavy kava drinkers (some of whom are estimated to consume 100,000 bowls of kava in their lifetimes, and often consume more than 2.5g of kavalactones in one night) in the south pacific do not seem to have an elevated rate of liver damage. Oh, and there are also rodent studies: Singh and Devkota (2003) fed rats super high doses of aqueous kava extract (500 mg kavalactones / kg of body weight per day- that would be 35g of kavalactones for an average adult male human per day!), which didn’t cause liver injury after short-term use (2-4 weeks). Rats fed lower doses of organically extracted kava for a longer time period (3 months) had no liver issues (DiSilvestro et al, 2007). Both of these studies had relatively small numbers of animals, and in general these rodents come from highly inbred lines, so we can’t assess whether between-animal genetic differences might contribute to rare adverse reactions. Still, this is all strong evidence that kava is reasonably safe.
Should we be scared of organic extracts? Possibly- I’m avoiding them out of an abundance of caution. Kavalactones aren’t very soluble in water, so lot of companies extract them with organic solvents, primarily ethanol and acetone. These extracts are super popular and millions of people have taken them without issue. However, I think they may be a risk factor for liver injury, but we just don’t have enough data yet to know. There are two things I worry about with extracts:
1) You don’t know what the source material was, and it seems to me that market forces would favor the use of cheap, low quality kava for extracts that cannot be sold as the more expensive ground root.
2) Organic extracts pull out some chemicals much more efficiently than water. The main focus here been on flavokavains. To review, flavokavains are a class of chalcones which naturally exist in kava roots. Kava contains 3 different flavokavains (called flavokavain A, B and C); B is the one most people worry about since it’s the most abundant and cytotoxic. Cells grown in tissue culture (so in test tubes, not in animals) are very sensitive to flavokavain B, where it causes cell death by triggering cellular suicide (Zhou et al, 2010). These researchers also found that mice given a really large dose of flavokavain B (25 mg / kg) for a week had acute liver damage. While scary, this is not a realistic dose for human consumption. According to Lebot (2011), 25 mg/kg represents a minimum of 250 times more than humans would consume, assuming a ‘worst case scenario’ in which they consumed 120mg of kavalactones derived from an ethanolic extract of a tudei variety with a lot of flavokavain B. Of course, many people take much more than 120mg kavalactones, but we’re usually not drinking organic extracts of tudei varieties, so I think this ballpark number is reasonable. Unfortunately, Zhou et al, 2010 didn’t test lower doses of flavokavain B in mice, so we don’t know what the threshold concentration for liver toxicity is in living animals.
I personally don’t want to mess with flavokavains, and they’re greatly enriched in organic extracts relative to water. Here’s a nice graph showing differences between water and ethanol extraction, from Martin et al, 2014. Note that organic extraction of flavokavain B is much higher than aqueous (bottom subfigure). Similarly, Zhou et al (2010) estimate that 95% ethanol and 100% acetone are ~160-times better at extracting flavokavain B than water. One thing that makes me somewhat reassured that flavokavain B isn’t very scary at typical rates of intake is the fact that that acute liver toxicity is a very rare issue, even with organic kava extracts. If typical organic extracts of kava had enough flavokavain B to cause acute liver injury, we’d expect to see it more often with those taking organic extracts.
So, what caused people to have acute liver failure after taking kava? We currently don’t know. The number of cases is low, and we didn’t have Dr. House go and test their exact batch of kava to see if it was contaminated with mold aflatoxins, etc. It’s likely one of three explanations: 1) An idiosyncratic allergic reaction. 2) Bad kava, contaminated with either toxic mold, aerial plant parts which can contain a toxic alkaloid not found in the roots, or even other plant species entirely. 3) Use by people with pre-existing liver issues or stress placed on the liver via concomitant use with other drugs or alcohol.
Fortunately, you have control over many of these factors. You can source good kava root from one of the main, trusted vendors out there that have a reputation for knowing their farmers (or growing it themselves) and getting high quality root. This should greatly reduce your chances of getting contaminated or mislabeled kava. I’d avoid organic extracts for the reasons outlined above. You can be sure you have a healthy liver prior to taking kava, and avoid taking kava with alcohol or other drugs. And you can go easy, giving your body plenty of time to recover from any stress caused by kava (this is probably good advice for all intoxicants, by the way!). Unfortunately, there’s a bit of a stochiastic element in all this that you may not have much control over: if a very low proportion of people have an allergic reaction to kava that causes acute liver failure, and there’s no way of predicting this ahead of time (note that this is just a hypothesis right now, we don’t know if this is true), that’s legitimately scary. For me, I’ve decided to go light on kava in my first month of use, seeing if it has any negative physical side-effects. If it does, I will go get my liver function tested by my doctor before continuing use. Better safe than sorry.
One thing I’d love to hear from the community is whether acute hepatotoxic reactions continue to occur every year, or whether they occurred 20 years ago and haven’t occurred again since then. After all, hundreds of thousands of people take kava every day, and thus we can make a pretty powerful statistical inference from the long-term incidence rate (I mean, this is epidemiology 101). If contemporary hepatotoxic reactions are virtually nonexistent, then I think this provides pretty strong inferential evidence that the cases which occurred 20 years ago were caused by something other than kava itself (e.g., toxins other those naturally found in kava that got introduced into the supply chain through poor quality control).
Anyway, I hope this is helpful to some of you who want a bit more data to go with your reassurances that kava is safe for human use when basic precautions are taken. Also, big thanks to Mike at @Kalm with Kava for the great kava, for answering my questions, and for encouraging me to write this up for the boards.
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