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Correcting Misinformation Google Link # 1 - WebMD's Article on Kava

The Kap'n

The Groggy Kaptain (40g)
KavaForums Founder
Hello kava lovers!

I took quite a bit of time today to dig into this. It's been a long running issue that when you type in "Kava" in google you get some dubious results on the first page. I'm taking it upon myself to list those here, and refute them where they have issues.


Search Results for "Kava" on google in incognito window.


Result 1: Webmd

  1. Overview
    • Point 1: “Kava is a beverage or extract that is made from Piper methysticum, a plant native to the western Pacific islands. The name "kava" comes from the Polynesian word "awa," which means bitter. In the South Pacific, kava is a popular social drink. It is consumed as a beverage in ceremonies to promote relaxation.”
      1. No issues with point one.
    • Point 2: “There have been some safety concerns about kava. Cases of liver damage and even some deaths have been traced to kava use. Because of these reports, kava was withdrawn from the market in Europe and Canada in the early 2000s. However, most countries have allowed kava to return to the market since that time. Kava has never been taken off the market in the U.S.”
      1. And my issues start here. “Cases of liver damage and even some deaths have been traced to kava use” is a hotly contested conclusion, and rather inflammatory when such paltry evidence exists to support it. The paragraph then goes on to state “However, most countries have allowed kava to return to the market since that time.” My issue here is; why are we not seeing these cases of liver failures and injury in countries where it’s freely available today, if it’s as liver toxic as it was said to be?
    • Point 3: “Kava is most commonly used for anxiety. Some people take kava for stress, restlessness, sleeping problems (insomnia), and many other conditions. But there is no good scientific evidence to support these uses.”
      1. “But there is no good scientific evidence to support these uses.” Hilariously they give quite good scientific evidence to support these uses directly in their references. Kava and kava extracts have been proven in double blind placebo controlled studies to reduce anxiety scores, and increase sleep duration/quality.
  2. How does it work?
    • Point 1: “Kava affects the brain and other parts of the central nervous system. The kavalactones in kava are believed to be responsible for its effects.”
      1. No issues with this. This has been demonstrated repeatedly in research.
  3. Possibly Effective for
    • Point 1: “Anxiety. Most research shows that taking kava extracts that contain 70% kavalactones can lower anxiety and might work as well as some prescription anti-anxiety medications. Most studies have used a specific kava extract (WS 1490, Dr. Willmar Schwabe Pharmaceuticals). It seems that kava supplements containing at least 200 mg kavalactones daily should be taken for at least 5 weeks for symptoms to improve.”
      1. Strangely, they just got finished saying there is no good scientific information on which to support these theories. Extra note: WS-1490 is an extract that has been embroiled in controversy. The extract is contested on the grounds that it was changed several times throughout the research periods from an ethanolic extract to an acetonic extract with no indication. You can see this by noting how the kavalactone percentage changes arbitrarily from 30% to 70%.
  4. Possibly Ineffective for
    • Point 1: “A type of persistent anxiety marked by exaggerated worry and tension (generalized anxiety disorder or GAD). Several early studies show that taking kava doesn't improve symptoms in people with GAD.”
      1. They conveniently don’t mark their sources in the article, but this one comes from Dr. Sarris in Australia in 2020. This research concluded that kava was more suitable for the reduction in stress and tension related to ‘situational’ anxiety, than it was for direct treatment of G.A.D.
  5. Insufficient Evidence for
    • Point 1 “Withdrawal from drugs called benzodiazepines. Early research suggests that slowly increasing the dose of kava extract over the course of one week while decreasing the dose of benzodiazepines over the course of two weeks can prevent withdrawal symptoms and reduce anxiety in people who have been taking benzodiazepines for a long period of time.”
      1. It can reduce anxiety, but the actual physical withdrawal is not treated by any action of the kavalactones themselves. It’s likely that the steady tapering of the BZP drug was what allowed these participants to cease their use with less acute withdrawal. Kava definitely helps, but it has different actions at the GABA-A receptor that are not similar to that of benzodiazepine drugs. Benzos target the BZP allosteric site on the GABA-A receptor where they exert their effect. Kava and flumazenil (a very potent anti-benzo or BZP antagonist) were administered at the same time in studies, and the effect of kava was not blocked.
    • Point 2 “Cancer. There is some early evidence that taking kava might help to prevent cancer.”
      1. I would say this “insufficient evidence” is actually an order of magnitude more studied and documented than the “liver damage” at the very beginning of this article. I’ve added additional citations below this papers citations, and I stopped citing at 12 research studies that show anti-cancer effects.
    • Point 3 “Insomnia. Research on the effectiveness of kava in people with sleeping problems is inconsistent. Some research shows that taking kava extract daily for 4 weeks reduces sleeping problems in people with anxiety disorders. But other research suggests that taking kava three times daily for 4 weeks does not reduce insomnia in people with anxiety.”
      1. The World Health organization monograph (2002) describes insomnia as a state supported by clinical data. This is generally accepted, however there were participants in studies on kava that dropped out due to insomnia complaints. While kava is overall a good fit for sleep issues, it likely won’t present that way to 100% of the people who drink it. We actually do see people complain about not being able to get to sleep after a strong kava. I say this to agree with the above paragraph where it states the research is inconsistent. It helps me with sleep, but that doesn’t mean it will be the same for everyone.
    • Point 4 “Symptoms of menopause. Early research shows that taking kava daily for 3 months might reduce depression, anxiety, and hot flashes.”
      1. While maybe insufficient, there is good evidence to support this. Two individual studies found improvement in mood, reduction in depression, and reduction in anxiety in perimenopausal individuals.
    • Point 5 “Stress. Early research suggests that taking a single dose of kava by mouth might reduce symptoms associated with mentally stressful tasks.”
      1. This is an odd one to say has insufficient evidence. A number of researchers including Münte, Sarris, Cropley, and Aporosa have found kava reduces symptoms associated with mentally stressful tasks.
    • Point 6 “Seizure disorder (epilepsy).”
      1. This is in line with reality. We only see glimpses into kava’s ability to modulate glutamate. Kavain was shown to inhibit veratridine-activated sodium channels. It’s possible that kava may help reduce seizures, but as said, there is insufficient evidence to say it precisely.
    • Point 7 “Muscle pain.”
      1. This I don’t agree with, and it’s a strange one to be saying there’s insufficient evidence for. Kava has marked antinociceptive (pain relieving) and muscle-relaxing properties. A good number of independent research studies have confirmed this.
    • Point 8 “Other conditions”
      1. I’m not really sure what to say here. I suppose it’s quite accurate to say that there is insufficient evidence for kava causing superhero-like powers to emerge.
  6. Side Effects
    • Paragraph 1 “When taken by mouth: Kava is POSSIBLY SAFE when taken for up to 6 months. Using kava can make you unable to drive or operate machinery safely. Do not take kava before you plan on driving. "Driving-under-the-influence" citations have been issued to people driving erratically after drinking large amounts of kava tea.”
      1. This is good, and goes pretty far based on the double blind placebo controlled studies. The one issue I have is the 6 month limit. There really isn’t any indication that taking kava beyond this time frame causes issues, it’s just when they cut the time limit of the study. Empirical evidence suggests kava, when consumed as a beverage, is safe indefinitely as shown by the South Pacific people who drink kava on a daily basis and have for generations. In regards to driving, I fully agree. If you’re consuming anything that makes you question your abilities with driving, call an uber/lyft.The risk is simply not worth it.
    • Paragraph 2 “People may have heard that use of kava can cause liver damage. The use of kava for as little as 1-3 months has resulted in the need for liver transplants and even death in some people. Early symptoms of liver damage include yellowed eyes and skin (jaundice), fatigue, and dark urine. But these cases appear to be relatively rare. Most people who have used kava have not experienced liver toxicity. Also, some experts believe that the liver toxicity seen in these cases cannot be directly linked to kava. Other factors may have contributed to these toxic effects. To be on the safe side, people who choose to use kava can get liver function tests.”
      1. That’s pretty honest, however the phrase “The use of kava for as little as 1-3 months has resulted in the need for liver transplants and even death in some people” really understates “some people”. The number of individuals allegedly harmed by kava is limited to less than 10. There has been no intrinsic (unable to be separated) toxicity seen in kava or any kava extracts, however idiosyncratic reactions of the immunologic type have occurred. This is extremely rare. I can’t say that enough. We’re talking on the scale of winning the lottery, being hit by lightning, and finding Jimmy Hoffa all at the same instant. If we turn our attention to things such as green tea extracts or acetaminophen we see intrinsic, predictable toxicity to the liver. This does not exist with kava.
  7. Special Precautions and Warnings
    • Point 1 “Pregnancy and breast-feeding: Don't use kava if you are pregnant or breast-feeding. Kava is POSSIBLY UNSAFE when taken by mouth. There is a concern that it might affect the uterus. Also, some of the dangerous chemicals in kava can pass into breast milk and might hurt a breast-fed infant.”
      1. They’re speaking about kavalactones, and they’re not “dangerous chemicals” however we don't fully understand the function of GABAergic substances on the developing brain. Kavalactones are known as lipophilic, meaning they tend to combine or dissolve in fats. This means they could likely also pass on through breastfeeding. There is no data confirming this suspicion, however with no experience available, kava is not recommended for use by pregnant or breast-feeding women. It’s much better to err on the side of caution. In regards to kava affecting the uterus, I’m afraid there is absolutely nothing confirming this. It’s an old myth from Fiji that kava stimulates the uterus, this doesn’t happen, and shouldn’t be listed as a precaution. Histopathology was performed on rats at 2.0g/kg of kavalactones and found no-effect level on the uterus. (2012. “Toxicology and Carcinogenesis Studies of Kava Kava Extract (CAS No. 9000-38-8) in F344/N Rats and B6C3F1 Mice (gavage Studies).” National Toxicology Program 571 (1): 1–186. https://ntp.niehs.nih.gov/publications/reports/tr/500s/tr571/index.html)
    • Point 2 “Liver disease: Kava might cause liver problems, even in healthy people. People who have a history of liver problems should avoid kava.”
      1. Well this sounds familiar. This will be the 3rd time this website has decided it was pertinent to warn us of liver damage. What they’ll throw at you sometimes is the instance of GGT elevation in metabolism tests seen in kava users in the late 80s and early 90s in Australia's Northern Territory. This is NOT indicative of liver damage. It indicates liver adaptation and is seen in kava drinkers that consume about a pound of dried kava per week. AST and ALT increases are not seen. I would even go as far to say here that kava is not even detrimental to those with liver problems. Kava is not intrinsically toxic to the liver in any way.
    • Point 3 “Parkinson disease: Kava might make Parkinson disease worse. Do not take kava if you have this condition.”
      1. This one is interesting. You have research on one side saying kava has no or very little activity at dopamine, then you have other research indicating that some kavalactones drop dopamine levels considerably. The one kavalactone in question here is Yangonin. Yangonin has shown in research to lower dopamine to below detectable levels. I personally believe that this is happening evidenced by the extrapyramidal movements seen in kava drinkers that went way overboard. They end up looking like they have parkinsons. If you are on medication such as levodopa that is specifically meant to increase free dopamine levels in the brain, kava can counteract this effect and cause the resurgence of parkinson's symptoms. So yes, I agree with this statement. If you have parkinsons it’s best to skip the kava.
    • Point 4 “Surgery: Kava affects the central nervous system. It might increase the effects of anesthesia and other medications used during and after surgery. Stop using kava at least 2 weeks before a scheduled surgery.”
      1. This is not talked about very much but should be taken into close consideration when approaching a surgery. Kava has many properties that haven’t been studied all that intensively. Kava has shown to have some mild antithrombotic actions. This means it may be able to prevent, to a degree, blood clotting. Give yourself at least a week if not two before any surgery to let your system flush out. Kava has also been shown to increase the sedation of anesthetic drugs. You’ll want to observe this just to be on the safe side.
  8. Major Interactions
    • Point 1 Alprazolam “Kava can cause drowsiness. Alprazolam (Xanax) can also cause drowsiness. Taking kava along with alprazolam (Xanax) may cause too much drowsiness. Avoid taking kava and alprazolam (Xanax) together.”
      1. Agreed
    • Point 2 “Kava might cause sleepiness and drowsiness. Medications that cause sleepiness are called sedatives. Taking kava along with sedative medications might cause too much sleepiness.Some sedative medications include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien), and others.
      1. Agreed as well. Sedation seems to be the pharmacodynamic interaction here.
  9. Moderate Interactions
    • Point 1 “Levodopa interacts with KAVA - Levodopa affects the brain by increasing a brain chemical called dopamine. Kava might decrease dopamine in the brain. Taking kava along with levodopa might decrease the effectiveness of levodopa.”
      1. I believe this to be correct. Levodopa is a medication meant to increase the levels of dopamine in the brain. Yangonin can decrease dopamine levels in the brain and counteract this medication.
    • Point 2 “Medications changed by the liver (Cytochrome P450 1A2 (CYP1A2) substrates) interact with KAVA - Some medications are changed and broken down by the liver.- Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are changed by the liver might increase the effects and side effects of some medications. Before taking kava talk to your healthcare provider if you take any medications that are changed by the liver. Some of these medications that are changed by the liver include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline, zileuton (Zyflo), zolmitriptan (Zomig), and others.
      1. This is also correct. CYP1A2 is the pathway of metabolization for caffeine. Kava causes inhibitory actions at this pathway and as such causes caffeine to appear in serum levels for much longer than without kava in the system. The individual effect of this combination may differ from person to person. CYP1A2 activity has a range of 40% between individuals. As such it’s quite difficult to make predictions of which drugs will do what when this pathway is inhibited.
    • Point 3 “Medications changed by the liver (Cytochrome P450 2C19 (CYP2C19) substrates) interact with KAVA - Some medications are changed and broken down by the liver Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are broken down by the liver can increase the effects and side effects of your medication. Before taking kava talk to your healthcare provider if you take any medications that are changed by the liver. Some of these medications changed by the liver include amitriptyline (Elavil), clomipramine (Anafranil), cyclophosphamide (Cytoxan), diazepam (Valium), lansoprazole (Prevacid), omeprazole (Prilosec), lansoprazole (Protonix), phenytoin (Dilantin), phenobarbital (Luminal), progesterone, and others.
      1. Correct as well; however, issues at this cytochrome with drugs that use this pathway are not heavily researched in regards to kava. They generally encompass the sedative effects and their increase when in combination with the drugs above. Caution should still be taken when combining these drugs with kava as it will likely make them stay in your system for considerably longer periods of time. DMY seems to be the most potent inhibitory kavalactone in this regard.
    • Point 4 “Medications changed by the liver (Cytochrome P450 2C9 (CYP2C9) substrates) interacts with KAVA - Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking kava talk to your healthcare provider if you take any medications that are changed by the liver. Some medications that are changed by the liver include amitriptyline (Elavil), diazepam (Valium), zileuton (Zyflo), celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), warfarin (Coumadin), and others.
      1. This inhibition was seen strongest with methysticin, the number 6 on chemotypes. The effect seen with methysticin was low, with only 1% of the strength of their positive control (Sulfaphenazole). I truly believe this would not have a strong impact on drugs that also use this pathway being kava/kavalactones have such a low affinity for it.
    • Point 5 “Medications changed by the liver (Cytochrome P450 2D6 (CYP2D6) substrates) interact with KAVA - Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are change by the liver can increase the effects and side effects of your medication. Before taking kava talk to your healthcare provider if you take any medications that are changed by the liver. Some medications that are changed by the liver include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), and others.
      1. This is incorrect. Kava has no inhibition property at this cytochrome even at absurdly high concentrations, and as such this is wrong.
    • Point 6 “Medications changed by the liver (Cytochrome P450 2E1 (CYP2E1) substrates) interact with KAVA - Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are change by the liver can increase the effects and side effects of your medication. Before taking kava talk to your healthcare provider if you take any medications that are changed by the liver.Some medications that are changed by the liver include acetaminophen, chlorzoxazone (Parafon Forte), ethanol, theophylline, and drugs used for anesthesia during surgery such as enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), and methoxyflurane (Penthrane).
      1. Again methysticin is the only kavalactone shown to interact with this cytochrome and it does it quite weakly. I wouldn’t suspect any immediate issues with drugs that use this pathway combined with kava.
    • Point 7 “Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates) interact with KAVA - Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking kava, talk to your healthcare provider if you are taking any medications that are changed by the liver. Some medications changed by the liver include lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra), triazolam (Halcion), and many others.
      1. This effect, if present, will be very light. Kava has shown very slight inhibitory properties at CYP3A4 with methysticin being the most potent inhibitor. Methysticin has shown to be about 1% the inhibitory properties of their positive control, Ketoconazole. I would not expect major interactions with pharmaceuticals along this pathway with kava.
    • Point 8 “Medications moved by pumps in cells (P-Glycoprotein Substrates) interacts with KAVA - Some medications are moved by pumps in cells. Kava might make these pumps less active and increase how much of some medications get absorbed by the body. This might increase the amount of some medications in the body, which could lead to more side effects. But there is not enough information to know if this is a big concern. Some medications that are moved by these pumps include etoposide, paclitaxel, vinblastine, vincristine, vindesine, ketoconazole, itraconazole, amprenavir, indinavir, nelfinavir, saquinavir, cimetidine, ranitidine, diltiazem, verapamil, corticosteroids, erythromycin, cisapride (Propulsid), fexofenadine (Allegra), cyclosporine, loperamide (Imodium), quinidine, and others.”
      1. A single dose of 800mg kavain gave a serum concentration level of 40ng/ml or .1um. This plasma level is unlikely to cause any significant inhibition of P-gp in vivo. Also, 800mg of kavain is quite unlikely to be consumed at once in a typical kava consuming session. The likelihood of inhibition here is very low. Results obtained in vitro vs in vivo were contradictory.
    • Point 9 “Medications that can harm the liver (Hepatotoxic drugs) interact with KAVA - Kava might harm the liver. Taking kava along with medication that might also harm the liver can increase the risk of liver damage. Do not take kava if you are taking a medication that can harm the liver. Some medications that can harm the liver include acetaminophen (Tylenol and others), amiodarone (Cordarone), carbamazepine (Tegretol), isoniazid (INH), methotrexate (Rheumatrex), methyldopa (Aldomet), fluconazole (Diflucan), itraconazole (Sporanox), erythromycin (Erythrocin, Ilosone, others), phenytoin (Dilantin), lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), and many others.”
      1. It should be obvious to limit the intake of liver toxic compounds, however some of them are rather ubiquitous. Acetaminophen, also known as APAP, Panadol, Paracetamol, and Tylenol is a potent hepatotoxic drug due to its metabolites. Kava likely does not interact with these drugs other than APAP. There is research leaning to indicate that the combination of APAP and kava should be avoided on the issue of glutathione degradation. IF kava does indeed reduce glutathione levels, mixing it with APAP would increase its toxicity.
  10. Dosing
    1. Paragraph 1 “By Mouth: For anxiety: 50-100 mg of a specific kava extract (WS 1490, Dr. Willmar Schwabe Pharmaceuticals), taken three times daily for up to 25 weeks, has been used. Also, 400 mg of another specific kava extract (LI 150, Lichtwer Pharma) taken daily for 8 weeks has been used. Five kava tablets each containing 50 mg of kavalactones have been taken in three divided doses daily for one week. One to two kava extract tablets has been taken twice daily for 6 weeks. Calcium supplements plus 100-200 mg of kava taken daily for 3 months have also been used.”
      1. This really doesn’t tell us anything to go by for our own personal dosing. In truth, there is no recommended dosage for powdered kava. These dosage recommendations come from several studies as well as the German Commission E. I take it that these numbers indicate the minimum amount of kavalactones it requires to see any effect without seeing intoxication. Seeing that many of us aim for intoxication these numbers are simply meaningless.






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Kapm's Citations:

[This is the citation for kava and cancer]
Bian, Tengfei, Pedro Corral, Yuzhi Wang, Jordy Botello, Rick Kingston, Tyler Daniels, Ramzi G. Salloum, et al. 2020. “Kava as a Clinical Nutrient: Promises and Challenges.” Nutrients 12 (10). https://doi.org/10.3390/nu12103044.

Botello, Jordy F., Pedro Corral, Tengfei Bian, and Chengguo Xing. 2020. “Kava and Its Kavalactones Inhibit Norepinephrine-Induced Intracellular Calcium Influx in Lung Cancer Cells.” Planta Med 86 (1): 26–31. https://doi.org/10.1055/a-1035-5183.

Celentano, Antonio, Andrew Tran, Claire Testa, Krishen Thayanantha, William Tan-Orders, Stephanie Tan, Mitali Syamal, Michael J. McCullough, and Tami Yap. 2019. “The Protective Effects of Kava (Piper Methysticum) Constituents in Cancers: A Systematic Review.” Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 48 (7): 510–29. https://doi.org/10.1111/jop.12900.

Celentano, Antonio, Callisthenis Yiannis, Rita Paolini, Pangzhen Zhang, Camile S. Farah, Nicola Cirillo, Tami Yap, and Michael McCullough. 2020. “Kava Constituents Exert Selective Anticancer Effects in Oral Squamous Cell Carcinoma Cells in Vitro.” Scientific Reports 10 (1): 1–11. https://doi.org/10.1038/s41598-020-73058-4.

Hua, Rong, Yaofei Pei, Haiyong Gu, Yifeng Sun, and Yi He. 2020. “Antitumor Effects of Flavokawain-B Flavonoid in Gemcitabine-Resistant Lung Cancer Cells Are Mediated via Mitochondrial-Mediated Apoptosis, ROS Production, Cell Migration and Cell Invasion Inhibition and Blocking of PI3K/AKT Signaling Pathway.” Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology 25: 262–67. https://www.jbuon.com/archive/25-1-262.pdf.

Li, Juan, Lei Zheng, Mi Yan, Jing Wu, Yongqing Liu, Xiaona Tian, Wen Jiang, Lu Zhang, and Rongmei Wang. 2020. “Activity and Mechanism of Flavokawain A in Inhibiting P-Glycoprotein Expression in Paclitaxel Resistance of Lung Cancer.” Oncology Letters 19 (1): 379–87. https://doi.org/10.3892/ol.2019.11069.

Li, Xuesen, Liankun Song, Shan Xu, Matthew Tippin, Shuan Meng, Jun Xie, Edward Uchio, and Xiaolin Zi. 2021. “Kava Root Extracts Hinder Prostate Cancer Development and Tumorigenesis by Involvement of Dual Inhibition of MAO-A and LSD1.” Journal of Translational Genetics and Genomics 5 (May): 163–72. https://doi.org/10.20517/jtgg.2021.22.

Liu, Zhongbo, U-Syn Ha, Ke Yu, Chunli Wu, Noriko Yokoyama, and Xiaolin Zi. 2017. “Kavalactone Yangonin Induces Autophagy and Sensitizes Bladder Cancer Cells to Flavokawain A and Docetaxel via Inhibition of the mTOR Pathway.” Journal of Biomedical Research 31 (5): 408–18. https://doi.org/10.7555/JBR.31.20160160.

Pan, Huayang, Fukai Liu, Jinge Wang, Ming Zhao, Dawei Wang, Chen Jia, Tong Wang, et al. 2020. “Dihydromethysticin, a Natural Molecule from Kava, Suppresses the Growth of Colorectal Cancer via the NLRC3/PI3K Pathway.” Molecular Carcinogenesis 59 (6): 575–89. https://doi.org/10.1002/mc.23182.

Wang, Yi, Sreekanth C. Narayanapillai, Katelyn M. Tessier, Lori G. Strayer, Pramod Upadhyaya, Qi Hu, Rick Kingston, et al. 2020. “The Impact of One-Week Dietary Supplementation with Kava on Biomarkers of Tobacco Use and Nitrosamine-Based Carcinogenesis Risk among Active Smokers.” Cancer Prevention Research 13 (5): 483–92. https://doi.org/10.1158/1940-6207.CAPR-19-0501.

Yiannis, Callisthenis, Kevin Huang, An Nhien Tran, Cathy Zeng, Emily Dao, Oliver Baselyous, Muaaz Adil Mithwani, et al. 2020. “Protective Effect of Kava Constituents in an in Vitro Model of Oral Mucositis.” Journal of Cancer Research and Clinical Oncology 146 (7): 1801–11. https://doi.org/10.1007/s00432-020-03253-3.

Zhang, Yidan, Yoav S. Zvi, Brian Batko, Nikolas Zaphiros, Edmond F. O’Donnell, Jichuan Wang, Kenji Sato, et al. 2018. “Down-Regulation of Skp2 Expression Inhibits Invasion and Lung Metastasis in Osteosarcoma.” Scientific Reports 8 (1): 14294. https://doi.org/10.1038/s41598-018-32428-9.
 

Alia

'Awa Grower/Collector
Hello kava lovers!

I took quite a bit of time today to dig into this. It's been a long running issue that when you type in "Kava" in google you get some dubious results on the first page. I'm taking it upon myself to list those here, and refute them where they have issues.


Search Results for "Kava" on google in incognito window.


Result 1: Webmd

  1. Overview
    • Point 1: “Kava is a beverage or extract that is made from Piper methysticum, a plant native to the western Pacific islands. The name "kava" comes from the Polynesian word "awa," which means bitter. In the South Pacific, kava is a popular social drink. It is consumed as a beverage in ceremonies to promote relaxation.”
      1. No issues with point one.
    • Point 2: “There have been some safety concerns about kava. Cases of liver damage and even some deaths have been traced to kava use. Because of these reports, kava was withdrawn from the market in Europe and Canada in the early 2000s. However, most countries have allowed kava to return to the market since that time. Kava has never been taken off the market in the U.S.”
      1. And my issues start here. “Cases of liver damage and even some deaths have been traced to kava use” is a hotly contested conclusion, and rather inflammatory when such paltry evidence exists to support it. The paragraph then goes on to state “However, most countries have allowed kava to return to the market since that time.” My issue here is; why are we not seeing these cases of liver failures and injury in countries where it’s freely available today, if it’s as liver toxic as it was said to be?
    • Point 3: “Kava is most commonly used for anxiety. Some people take kava for stress, restlessness, sleeping problems (insomnia), and many other conditions. But there is no good scientific evidence to support these uses.”
      1. “But there is no good scientific evidence to support these uses.” Hilariously they give quite good scientific evidence to support these uses directly in their references. Kava and kava extracts have been proven in double blind placebo controlled studies to reduce anxiety scores, and increase sleep duration/quality.
  2. How does it work?
    • Point 1: “Kava affects the brain and other parts of the central nervous system. The kavalactones in kava are believed to be responsible for its effects.”
      1. No issues with this. This has been demonstrated repeatedly in research.
  3. Possibly Effective for
    • Point 1: “Anxiety. Most research shows that taking kava extracts that contain 70% kavalactones can lower anxiety and might work as well as some prescription anti-anxiety medications. Most studies have used a specific kava extract (WS 1490, Dr. Willmar Schwabe Pharmaceuticals). It seems that kava supplements containing at least 200 mg kavalactones daily should be taken for at least 5 weeks for symptoms to improve.”
      1. Strangely, they just got finished saying there is no good scientific information on which to support these theories. Extra note: WS-1490 is an extract that has been embroiled in controversy. The extract is contested on the grounds that it was changed several times throughout the research periods from an ethanolic extract to an acetonic extract with no indication. You can see this by noting how the kavalactone percentage changes arbitrarily from 30% to 70%.
  4. Possibly Ineffective for
    • Point 1: “A type of persistent anxiety marked by exaggerated worry and tension (generalized anxiety disorder or GAD). Several early studies show that taking kava doesn't improve symptoms in people with GAD.”
      1. They conveniently don’t mark their sources in the article, but this one comes from Dr. Sarris in Australia in 2020. This research concluded that kava was more suitable for the reduction in stress and tension related to ‘situational’ anxiety, than it was for direct treatment of G.A.D.
  5. Insufficient Evidence for
    • Point 1 “Withdrawal from drugs called benzodiazepines. Early research suggests that slowly increasing the dose of kava extract over the course of one week while decreasing the dose of benzodiazepines over the course of two weeks can prevent withdrawal symptoms and reduce anxiety in people who have been taking benzodiazepines for a long period of time.”
      1. It can reduce anxiety, but the actual physical withdrawal is not treated by any action of the kavalactones themselves. It’s likely that the steady tapering of the BZP drug was what allowed these participants to cease their use with less acute withdrawal. Kava definitely helps, but it has different actions at the GABA-A receptor that are not similar to that of benzodiazepine drugs. Benzos target the BZP allosteric site on the GABA-A receptor where they exert their effect. Kava and flumazenil (a very potent anti-benzo or BZP antagonist) were administered at the same time in studies, and the effect of kava was not blocked.
    • Point 2 “Cancer. There is some early evidence that taking kava might help to prevent cancer.”
      1. I would say this “insufficient evidence” is actually an order of magnitude more studied and documented than the “liver damage” at the very beginning of this article. I’ve added additional citations below this papers citations, and I stopped citing at 12 research studies that show anti-cancer effects.
    • Point 3 “Insomnia. Research on the effectiveness of kava in people with sleeping problems is inconsistent. Some research shows that taking kava extract daily for 4 weeks reduces sleeping problems in people with anxiety disorders. But other research suggests that taking kava three times daily for 4 weeks does not reduce insomnia in people with anxiety.”
      1. The World Health organization monograph (2002) describes insomnia as a state supported by clinical data. This is generally accepted, however there were participants in studies on kava that dropped out due to insomnia complaints. While kava is overall a good fit for sleep issues, it likely won’t present that way to 100% of the people who drink it. We actually do see people complain about not being able to get to sleep after a strong kava. I say this to agree with the above paragraph where it states the research is inconsistent. It helps me with sleep, but that doesn’t mean it will be the same for everyone.
    • Point 4 “Symptoms of menopause. Early research shows that taking kava daily for 3 months might reduce depression, anxiety, and hot flashes.”
      1. While maybe insufficient, there is good evidence to support this. Two individual studies found improvement in mood, reduction in depression, and reduction in anxiety in perimenopausal individuals.
    • Point 5 “Stress. Early research suggests that taking a single dose of kava by mouth might reduce symptoms associated with mentally stressful tasks.”
      1. This is an odd one to say has insufficient evidence. A number of researchers including Münte, Sarris, Cropley, and Aporosa have found kava reduces symptoms associated with mentally stressful tasks.
    • Point 6 “Seizure disorder (epilepsy).”
      1. This is in line with reality. We only see glimpses into kava’s ability to modulate glutamate. Kavain was shown to inhibit veratridine-activated sodium channels. It’s possible that kava may help reduce seizures, but as said, there is insufficient evidence to say it precisely.
    • Point 7 “Muscle pain.”
      1. This I don’t agree with, and it’s a strange one to be saying there’s insufficient evidence for. Kava has marked antinociceptive (pain relieving) and muscle-relaxing properties. A good number of independent research studies have confirmed this.
    • Point 8 “Other conditions”
      1. I’m not really sure what to say here. I suppose it’s quite accurate to say that there is insufficient evidence for kava causing superhero-like powers to emerge.
  6. Side Effects
    • Paragraph 1 “When taken by mouth: Kava is POSSIBLY SAFE when taken for up to 6 months. Using kava can make you unable to drive or operate machinery safely. Do not take kava before you plan on driving. "Driving-under-the-influence" citations have been issued to people driving erratically after drinking large amounts of kava tea.”
      1. This is good, and goes pretty far based on the double blind placebo controlled studies. The one issue I have is the 6 month limit. There really isn’t any indication that taking kava beyond this time frame causes issues, it’s just when they cut the time limit of the study. Empirical evidence suggests kava, when consumed as a beverage, is safe indefinitely as shown by the South Pacific people who drink kava on a daily basis and have for generations. In regards to driving, I fully agree. If you’re consuming anything that makes you question your abilities with driving, call an uber/lyft.The risk is simply not worth it.
    • Paragraph 2 “People may have heard that use of kava can cause liver damage. The use of kava for as little as 1-3 months has resulted in the need for liver transplants and even death in some people. Early symptoms of liver damage include yellowed eyes and skin (jaundice), fatigue, and dark urine. But these cases appear to be relatively rare. Most people who have used kava have not experienced liver toxicity. Also, some experts believe that the liver toxicity seen in these cases cannot be directly linked to kava. Other factors may have contributed to these toxic effects. To be on the safe side, people who choose to use kava can get liver function tests.”
      1. That’s pretty honest, however the phrase “The use of kava for as little as 1-3 months has resulted in the need for liver transplants and even death in some people” really understates “some people”. The number of individuals allegedly harmed by kava is limited to less than 10. There has been no intrinsic (unable to be separated) toxicity seen in kava or any kava extracts, however idiosyncratic reactions of the immunologic type have occurred. This is extremely rare. I can’t say that enough. We’re talking on the scale of winning the lottery, being hit by lightning, and finding Jimmy Hoffa all at the same instant. If we turn our attention to things such as green tea extracts or acetaminophen we see intrinsic, predictable toxicity to the liver. This does not exist with kava.
  7. Special Precautions and Warnings
    • Point 1 “Pregnancy and breast-feeding: Don't use kava if you are pregnant or breast-feeding. Kava is POSSIBLY UNSAFE when taken by mouth. There is a concern that it might affect the uterus. Also, some of the dangerous chemicals in kava can pass into breast milk and might hurt a breast-fed infant.”
      1. They’re speaking about kavalactones, and they’re not “dangerous chemicals” however we don't fully understand the function of GABAergic substances on the developing brain. Kavalactones are known as lipophilic, meaning they tend to combine or dissolve in fats. This means they could likely also pass on through breastfeeding. There is no data confirming this suspicion, however with no experience available, kava is not recommended for use by pregnant or breast-feeding women. It’s much better to err on the side of caution. In regards to kava affecting the uterus, I’m afraid there is absolutely nothing confirming this. It’s an old myth from Fiji that kava stimulates the uterus, this doesn’t happen, and shouldn’t be listed as a precaution. Histopathology was performed on rats at 2.0g/kg of kavalactones and found no-effect level on the uterus. (2012. “Toxicology and Carcinogenesis Studies of Kava Kava Extract (CAS No. 9000-38-8) in F344/N Rats and B6C3F1 Mice (gavage Studies).” National Toxicology Program 571 (1): 1–186. https://ntp.niehs.nih.gov/publications/reports/tr/500s/tr571/index.html)
    • Point 2 “Liver disease: Kava might cause liver problems, even in healthy people. People who have a history of liver problems should avoid kava.”
      1. Well this sounds familiar. This will be the 3rd time this website has decided it was pertinent to warn us of liver damage. What they’ll throw at you sometimes is the instance of GGT elevation in metabolism tests seen in kava users in the late 80s and early 90s in Australia's Northern Territory. This is NOT indicative of liver damage. It indicates liver adaptation and is seen in kava drinkers that consume about a pound of dried kava per week. AST and ALT increases are not seen. I would even go as far to say here that kava is not even detrimental to those with liver problems. Kava is not intrinsically toxic to the liver in any way.
    • Point 3 “Parkinson disease: Kava might make Parkinson disease worse. Do not take kava if you have this condition.”
      1. This one is interesting. You have research on one side saying kava has no or very little activity at dopamine, then you have other research indicating that some kavalactones drop dopamine levels considerably. The one kavalactone in question here is Yangonin. Yangonin has shown in research to lower dopamine to below detectable levels. I personally believe that this is happening evidenced by the extrapyramidal movements seen in kava drinkers that went way overboard. They end up looking like they have parkinsons. If you are on medication such as levodopa that is specifically meant to increase free dopamine levels in the brain, kava can counteract this effect and cause the resurgence of parkinson's symptoms. So yes, I agree with this statement. If you have parkinsons it’s best to skip the kava.
    • Point 4 “Surgery: Kava affects the central nervous system. It might increase the effects of anesthesia and other medications used during and after surgery. Stop using kava at least 2 weeks before a scheduled surgery.”
      1. This is not talked about very much but should be taken into close consideration when approaching a surgery. Kava has many properties that haven’t been studied all that intensively. Kava has shown to have some mild antithrombotic actions. This means it may be able to prevent, to a degree, blood clotting. Give yourself at least a week if not two before any surgery to let your system flush out. Kava has also been shown to increase the sedation of anesthetic drugs. You’ll want to observe this just to be on the safe side.
  8. Major Interactions
    • Point 1 Alprazolam “Kava can cause drowsiness. Alprazolam (Xanax) can also cause drowsiness. Taking kava along with alprazolam (Xanax) may cause too much drowsiness. Avoid taking kava and alprazolam (Xanax) together.”
      1. Agreed
    • Point 2 “Kava might cause sleepiness and drowsiness. Medications that cause sleepiness are called sedatives. Taking kava along with sedative medications might cause too much sleepiness.Some sedative medications include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien), and others.
      1. Agreed as well. Sedation seems to be the pharmacodynamic interaction here.
  9. Moderate Interactions
    • Point 1 “Levodopa interacts with KAVA - Levodopa affects the brain by increasing a brain chemical called dopamine. Kava might decrease dopamine in the brain. Taking kava along with levodopa might decrease the effectiveness of levodopa.”
      1. I believe this to be correct. Levodopa is a medication meant to increase the levels of dopamine in the brain. Yangonin can decrease dopamine levels in the brain and counteract this medication.
    • Point 2 “Medications changed by the liver (Cytochrome P450 1A2 (CYP1A2) substrates) interact with KAVA - Some medications are changed and broken down by the liver.- Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are changed by the liver might increase the effects and side effects of some medications. Before taking kava talk to your healthcare provider if you take any medications that are changed by the liver. Some of these medications that are changed by the liver include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline, zileuton (Zyflo), zolmitriptan (Zomig), and others.
      1. This is also correct. CYP1A2 is the pathway of metabolization for caffeine. Kava causes inhibitory actions at this pathway and as such causes caffeine to appear in serum levels for much longer than without kava in the system. The individual effect of this combination may differ from person to person. CYP1A2 activity has a range of 40% between individuals. As such it’s quite difficult to make predictions of which drugs will do what when this pathway is inhibited.
    • Point 3 “Medications changed by the liver (Cytochrome P450 2C19 (CYP2C19) substrates) interact with KAVA - Some medications are changed and broken down by the liver Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are broken down by the liver can increase the effects and side effects of your medication. Before taking kava talk to your healthcare provider if you take any medications that are changed by the liver. Some of these medications changed by the liver include amitriptyline (Elavil), clomipramine (Anafranil), cyclophosphamide (Cytoxan), diazepam (Valium), lansoprazole (Prevacid), omeprazole (Prilosec), lansoprazole (Protonix), phenytoin (Dilantin), phenobarbital (Luminal), progesterone, and others.
      1. Correct as well; however, issues at this cytochrome with drugs that use this pathway are not heavily researched in regards to kava. They generally encompass the sedative effects and their increase when in combination with the drugs above. Caution should still be taken when combining these drugs with kava as it will likely make them stay in your system for considerably longer periods of time. DMY seems to be the most potent inhibitory kavalactone in this regard.
    • Point 4 “Medications changed by the liver (Cytochrome P450 2C9 (CYP2C9) substrates) interacts with KAVA - Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking kava talk to your healthcare provider if you take any medications that are changed by the liver. Some medications that are changed by the liver include amitriptyline (Elavil), diazepam (Valium), zileuton (Zyflo), celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), warfarin (Coumadin), and others.
      1. This inhibition was seen strongest with methysticin, the number 6 on chemotypes. The effect seen with methysticin was low, with only 1% of the strength of their positive control (Sulfaphenazole). I truly believe this would not have a strong impact on drugs that also use this pathway being kava/kavalactones have such a low affinity for it.
    • Point 5 “Medications changed by the liver (Cytochrome P450 2D6 (CYP2D6) substrates) interact with KAVA - Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are change by the liver can increase the effects and side effects of your medication. Before taking kava talk to your healthcare provider if you take any medications that are changed by the liver. Some medications that are changed by the liver include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), and others.
      1. This is incorrect. Kava has no inhibition property at this cytochrome even at absurdly high concentrations, and as such this is wrong.
    • Point 6 “Medications changed by the liver (Cytochrome P450 2E1 (CYP2E1) substrates) interact with KAVA - Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are change by the liver can increase the effects and side effects of your medication. Before taking kava talk to your healthcare provider if you take any medications that are changed by the liver.Some medications that are changed by the liver include acetaminophen, chlorzoxazone (Parafon Forte), ethanol, theophylline, and drugs used for anesthesia during surgery such as enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), and methoxyflurane (Penthrane).
      1. Again methysticin is the only kavalactone shown to interact with this cytochrome and it does it quite weakly. I wouldn’t suspect any immediate issues with drugs that use this pathway combined with kava.
    • Point 7 “Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates) interact with KAVA - Some medications are changed and broken down by the liver. Kava might decrease how quickly the liver breaks down some medications. Taking kava along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking kava, talk to your healthcare provider if you are taking any medications that are changed by the liver. Some medications changed by the liver include lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra), triazolam (Halcion), and many others.
      1. This effect, if present, will be very light. Kava has shown very slight inhibitory properties at CYP3A4 with methysticin being the most potent inhibitor. Methysticin has shown to be about 1% the inhibitory properties of their positive control, Ketoconazole. I would not expect major interactions with pharmaceuticals along this pathway with kava.
    • Point 8 “Medications moved by pumps in cells (P-Glycoprotein Substrates) interacts with KAVA - Some medications are moved by pumps in cells. Kava might make these pumps less active and increase how much of some medications get absorbed by the body. This might increase the amount of some medications in the body, which could lead to more side effects. But there is not enough information to know if this is a big concern. Some medications that are moved by these pumps include etoposide, paclitaxel, vinblastine, vincristine, vindesine, ketoconazole, itraconazole, amprenavir, indinavir, nelfinavir, saquinavir, cimetidine, ranitidine, diltiazem, verapamil, corticosteroids, erythromycin, cisapride (Propulsid), fexofenadine (Allegra), cyclosporine, loperamide (Imodium), quinidine, and others.”
      1. A single dose of 800mg kavain gave a serum concentration level of 40ng/ml or .1um. This plasma level is unlikely to cause any significant inhibition of P-gp in vivo. Also, 800mg of kavain is quite unlikely to be consumed at once in a typical kava consuming session. The likelihood of inhibition here is very low. Results obtained in vitro vs in vivo were contradictory.
    • Point 9 “Medications that can harm the liver (Hepatotoxic drugs) interact with KAVA - Kava might harm the liver. Taking kava along with medication that might also harm the liver can increase the risk of liver damage. Do not take kava if you are taking a medication that can harm the liver. Some medications that can harm the liver include acetaminophen (Tylenol and others), amiodarone (Cordarone), carbamazepine (Tegretol), isoniazid (INH), methotrexate (Rheumatrex), methyldopa (Aldomet), fluconazole (Diflucan), itraconazole (Sporanox), erythromycin (Erythrocin, Ilosone, others), phenytoin (Dilantin), lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), and many others.”
      1. It should be obvious to limit the intake of liver toxic compounds, however some of them are rather ubiquitous. Acetaminophen, also known as APAP, Panadol, Paracetamol, and Tylenol is a potent hepatotoxic drug due to its metabolites. Kava likely does not interact with these drugs other than APAP. There is research leaning to indicate that the combination of APAP and kava should be avoided on the issue of glutathione degradation. IF kava does indeed reduce glutathione levels, mixing it with APAP would increase its toxicity.
  10. Dosing
    1. Paragraph 1 “By Mouth: For anxiety: 50-100 mg of a specific kava extract (WS 1490, Dr. Willmar Schwabe Pharmaceuticals), taken three times daily for up to 25 weeks, has been used. Also, 400 mg of another specific kava extract (LI 150, Lichtwer Pharma) taken daily for 8 weeks has been used. Five kava tablets each containing 50 mg of kavalactones have been taken in three divided doses daily for one week. One to two kava extract tablets has been taken twice daily for 6 weeks. Calcium supplements plus 100-200 mg of kava taken daily for 3 months have also been used.”
      1. This really doesn’t tell us anything to go by for our own personal dosing. In truth, there is no recommended dosage for powdered kava. These dosage recommendations come from several studies as well as the German Commission E. I take it that these numbers indicate the minimum amount of kavalactones it requires to see any effect without seeing intoxication. Seeing that many of us aim for intoxication these numbers are simply meaningless.






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Kapm's Citations:

[This is the citation for kava and cancer]
Bian, Tengfei, Pedro Corral, Yuzhi Wang, Jordy Botello, Rick Kingston, Tyler Daniels, Ramzi G. Salloum, et al. 2020. “Kava as a Clinical Nutrient: Promises and Challenges.” Nutrients 12 (10). https://doi.org/10.3390/nu12103044.

Botello, Jordy F., Pedro Corral, Tengfei Bian, and Chengguo Xing. 2020. “Kava and Its Kavalactones Inhibit Norepinephrine-Induced Intracellular Calcium Influx in Lung Cancer Cells.” Planta Med 86 (1): 26–31. https://doi.org/10.1055/a-1035-5183.

Celentano, Antonio, Andrew Tran, Claire Testa, Krishen Thayanantha, William Tan-Orders, Stephanie Tan, Mitali Syamal, Michael J. McCullough, and Tami Yap. 2019. “The Protective Effects of Kava (Piper Methysticum) Constituents in Cancers: A Systematic Review.” Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 48 (7): 510–29. https://doi.org/10.1111/jop.12900.

Celentano, Antonio, Callisthenis Yiannis, Rita Paolini, Pangzhen Zhang, Camile S. Farah, Nicola Cirillo, Tami Yap, and Michael McCullough. 2020. “Kava Constituents Exert Selective Anticancer Effects in Oral Squamous Cell Carcinoma Cells in Vitro.” Scientific Reports 10 (1): 1–11. https://doi.org/10.1038/s41598-020-73058-4.

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You have done a tremendous amount of work here.
There are "Point"(s) which is them and your comments are listed as number. 1 etc.
I think that's how it is designed and it will take awhile to read.
Thanks for doing this.
 

avahZ

YAHWEH Shalom
good job!

I can agree with the muscle relaxing properties. Been using a daily low dose for years. Flexeril(sp) locks my bladder up. Yes and it is a bad as it sounds. Kava keeps my back muscles from cramping up. However, I am one of the unfortunate ones that if I take to close to bed time, it will not allow me to get into deep sleep. So, I take it in the morning with my coffee and eggs. On a rare occasion, I will break out the good stuff and let the ear ringing begin :)
 
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