Kava discussion/fact of the day: Flavokavain-B (aka, what may have actually been one of the causes of the liver issues you see the warnings about )
Today I'm going to focus on one flavokavain, FKB. In this study they fed rats greater than 500mg/kg of pure kavalactones per day for 4 weeks and observed that KLs had no significant effects on liver cells. They also did the same thing with FKB at the amount of 25mg/kg for seven days and found varying levels of liver cell apoptosis.
FKB – Flavokavain (Flavokawain) B
In terms of toxicity, this chalcone has been identified as a potent GSH-Sensitive hepatoxin in vitro and in vivo. What this means is that FKB can cause oxidative stress and possibly cell death due to the consumption of glutathione and inhibition of IKK activity.
What Is GlutaTHIONE?
Glutathione is a tripeptide—i.e., a tiny protein—composed of three amino acids: cysteine, glycine, and glutamic acid (or glutamate). Often called the “master” antioxidant, glutathione boosts the utilization and recycling of other antioxidants, namely vitamins C and E, and alpha-lipoic acid and CoQ10.
There are two different forms of glutathione: reduced glutathione (GSH, or L-glutathione), which is the active form, and oxidized glutathione (GSSG), the inactive state. As GSH patrols the cellular environment and puts out oxidative “free radical” fires, it becomes oxidized and inactive, thus turning into GSSG.
Fortunately, inactive GSSG can be recycled back into the active GSH form, thanks to the glutathione reductase enzyme. When this enzyme is overwhelmed, and too much-oxidized GSSG accumulates (compared to the active GSH), your cells become susceptible to damage. [2]
In short, glutathione is an antioxidant that deactivates oxidative stress in living cells, and prevents premature cell apoptosis.
What is Apoptosis?
Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. The average adult human loses between 50 and 70 billion cells each day due to apoptosis.[3]
What is ROS (Reactive Oxygen Species)
A type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell. A buildup of reactive oxygen species in cells may cause damage to DNA, RNA, and proteins, and may cause cell death. Reactive oxygen species are free radicals. Also called oxygen radical.[4]
FKB depletes GSH. This reduces the cells ability to remove reactive oxygen species (ex peroxides). ROS (reactive oxygen species) are the chemicals in cells that are created in metabolic processes. When your cells produce energy, they also produce toxic byproducts. GSH deactivates these ROS molecules and prevents them from causing cell death.
What does this mean to the common kava drinker?
If your routine is making traditional kava by mixing powdered root (non-extract) with water and straining, very little. When making kava traditionally you are extracting an excess amount of glutathione along with any other phytochemicals found in kava. If, by chance, your kava has an excessive amount of FKs, a traditional preparation would keep the extraction of flavokavains to a minimum and additional glutathione would negate further action by FKB.
Where is the highest amount of FKB found?
Non-noble and wild kavas have the highest amounts of FKB.
Is there a kava product that may actually be affected by this?
Yes. Extracts. Specifically, ones made with organic solvents and non-noble varieties.
Modern extraction techniques using organic solvents (e.g., acetone, ethanol) yield significantly higher levels of kavalactones (~45-55%), and dramatically higher levels of lipophilic chalcones (FKs) in the extract (~160-fold for FKB)[1] This means any extract run on a non-noble or wild kava will have an abundance of FKs, and due to GSH’s low solubility in solvents will also not have that protecting addition of excess glutathione. The extraction of non-noble types of kava can lead to a product containing exceedingly high levels of FKs, depleting GSH leading to the possibilities of herb-drug interactions and cellular apoptosis or liver damage. This is what is thought to have caused the liver issues in Europe. Due to tudei type kavas having an excess of kavalactone %. Naturally phytopharmaceuticals targeted them for that reason. The companies even went as far as to request specific strains for farmers to grow due to the increased kavalactone content. The information about FKB was not known at the time. The strain requested was Palisi, a strong tudei kava. Organic solvents were run, and the product was packaged and sent to unassuming customers. The warning you see on the sides of kava containing products are a direct result.
There is another totally opposite side to FKB which we will get into quite soon. Studies are showing that although FKB can be seen as a hepatoxic molecule, it also has some really promising results against certain types of cancer as a chemotherapy agent.
Bula!
(PS, it takes me like 3 hours to write these things, lol. I’m going to keep doing them, as the more we know collectively, the stronger we are in terms of keeping our favorite root available to us who love it.)
[1]Zhou, Ping, et al. “Flavokawain B, the Hepatotoxic Constituent from Kava Root, Induces GSH-Sensitive Oxidative Stress through Modulation of IKK/NF-KappaB and MAPK Signaling Pathways.” FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, Federation of American Societies for Experimental Biology, Dec. 2010, www.ncbi.nlm.nih.gov/pmc/articles/PMC2992378/.
[2]https://coremedscience.com/blogs/wellness/glutathione-the-master-antioxidant
[3]https://en.wikipedia.org/wiki/Apoptosis
[4] https://www.cancer.gov/publications/dictionaries/cancer-terms/def/reactive-oxygen-species
Today I'm going to focus on one flavokavain, FKB. In this study they fed rats greater than 500mg/kg of pure kavalactones per day for 4 weeks and observed that KLs had no significant effects on liver cells. They also did the same thing with FKB at the amount of 25mg/kg for seven days and found varying levels of liver cell apoptosis.
FKB – Flavokavain (Flavokawain) B
In terms of toxicity, this chalcone has been identified as a potent GSH-Sensitive hepatoxin in vitro and in vivo. What this means is that FKB can cause oxidative stress and possibly cell death due to the consumption of glutathione and inhibition of IKK activity.
What Is GlutaTHIONE?
Glutathione is a tripeptide—i.e., a tiny protein—composed of three amino acids: cysteine, glycine, and glutamic acid (or glutamate). Often called the “master” antioxidant, glutathione boosts the utilization and recycling of other antioxidants, namely vitamins C and E, and alpha-lipoic acid and CoQ10.
There are two different forms of glutathione: reduced glutathione (GSH, or L-glutathione), which is the active form, and oxidized glutathione (GSSG), the inactive state. As GSH patrols the cellular environment and puts out oxidative “free radical” fires, it becomes oxidized and inactive, thus turning into GSSG.
Fortunately, inactive GSSG can be recycled back into the active GSH form, thanks to the glutathione reductase enzyme. When this enzyme is overwhelmed, and too much-oxidized GSSG accumulates (compared to the active GSH), your cells become susceptible to damage. [2]
In short, glutathione is an antioxidant that deactivates oxidative stress in living cells, and prevents premature cell apoptosis.
What is Apoptosis?
Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. The average adult human loses between 50 and 70 billion cells each day due to apoptosis.[3]
What is ROS (Reactive Oxygen Species)
A type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell. A buildup of reactive oxygen species in cells may cause damage to DNA, RNA, and proteins, and may cause cell death. Reactive oxygen species are free radicals. Also called oxygen radical.[4]
FKB depletes GSH. This reduces the cells ability to remove reactive oxygen species (ex peroxides). ROS (reactive oxygen species) are the chemicals in cells that are created in metabolic processes. When your cells produce energy, they also produce toxic byproducts. GSH deactivates these ROS molecules and prevents them from causing cell death.
What does this mean to the common kava drinker?
If your routine is making traditional kava by mixing powdered root (non-extract) with water and straining, very little. When making kava traditionally you are extracting an excess amount of glutathione along with any other phytochemicals found in kava. If, by chance, your kava has an excessive amount of FKs, a traditional preparation would keep the extraction of flavokavains to a minimum and additional glutathione would negate further action by FKB.
Where is the highest amount of FKB found?
Non-noble and wild kavas have the highest amounts of FKB.
Is there a kava product that may actually be affected by this?
Yes. Extracts. Specifically, ones made with organic solvents and non-noble varieties.
Modern extraction techniques using organic solvents (e.g., acetone, ethanol) yield significantly higher levels of kavalactones (~45-55%), and dramatically higher levels of lipophilic chalcones (FKs) in the extract (~160-fold for FKB)[1] This means any extract run on a non-noble or wild kava will have an abundance of FKs, and due to GSH’s low solubility in solvents will also not have that protecting addition of excess glutathione. The extraction of non-noble types of kava can lead to a product containing exceedingly high levels of FKs, depleting GSH leading to the possibilities of herb-drug interactions and cellular apoptosis or liver damage. This is what is thought to have caused the liver issues in Europe. Due to tudei type kavas having an excess of kavalactone %. Naturally phytopharmaceuticals targeted them for that reason. The companies even went as far as to request specific strains for farmers to grow due to the increased kavalactone content. The information about FKB was not known at the time. The strain requested was Palisi, a strong tudei kava. Organic solvents were run, and the product was packaged and sent to unassuming customers. The warning you see on the sides of kava containing products are a direct result.
There is another totally opposite side to FKB which we will get into quite soon. Studies are showing that although FKB can be seen as a hepatoxic molecule, it also has some really promising results against certain types of cancer as a chemotherapy agent.
Bula!
(PS, it takes me like 3 hours to write these things, lol. I’m going to keep doing them, as the more we know collectively, the stronger we are in terms of keeping our favorite root available to us who love it.)
[1]Zhou, Ping, et al. “Flavokawain B, the Hepatotoxic Constituent from Kava Root, Induces GSH-Sensitive Oxidative Stress through Modulation of IKK/NF-KappaB and MAPK Signaling Pathways.” FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, Federation of American Societies for Experimental Biology, Dec. 2010, www.ncbi.nlm.nih.gov/pmc/articles/PMC2992378/.
[2]https://coremedscience.com/blogs/wellness/glutathione-the-master-antioxidant
[3]https://en.wikipedia.org/wiki/Apoptosis
[4] https://www.cancer.gov/publications/dictionaries/cancer-terms/def/reactive-oxygen-species
