Kava Information - Scientific Studies

Several hundred worldwide studies of Kava and it's effects on humans are available online.  We have cataloged several showing scientific conclusions regarding the safety and uses of the Piper Methysticum plant we call Kava.

KAVAPLEX is a unique, full spectrum Kava oil that captures the full stress relieving properties of traditional Kava in a shelf stable, ready to use product. KAVAPLEX was developed by and is distributed by Sovereign Shield, LLC and marketed through its’ trademarked brand, Noble Roots Premium Kava.

KAVAPLEX supports:

  • A calm, positive mood [1,2,8-27]
  • Enhanced sociability [1,15,18,23]
  • Better memory and focus [23,24]
  • Deeper restorative sleep [1,2,12,13,20,22,26]
  • Neuroprotective pathways [25-33]
  • A healthy inflammatory response [34,35]
  • The body’s removal of senescent cells [36-57]

Ingredients:

  • Kava root oil (Piper Methysticum)- is almost identical in chemical composition to the traditional Kava drink, Which is considered the gold standard in terms of its therapeutic effects.
  • Sunflower oil (cold pressed)- Used as a carrier to increase absorption of the Kava oil because of its high lecithin content.

 

What is Traditional Kava

Traditional Kava is a drink prepared from the roots of Piper Methysticum, a plant native to islands in the south pacific, where it is used for its natural relaxing and social enhancing qualities. It also has traditionally been used as a medicine for nervous system conditions and other ailments. The effects are much like alcohol, but without the “drunkenness” that can impair fine motor skills. Kava is well known to be totally non-addictive and non-toxic when quality product is used.1,2 There are over 100 different varieties of Kava, all with varying effects due to slight differences in chemical properties. Of all of these different varieties, a specific class referred to as “Noble varieties” are the absolute highest quality of all Kava cultivars. In fact, these are the only varieties that the islanders will consume daily due to their safety and lack of side effects.3

The Science

The therapeutic effects of kava are due to a combination of the main active ingredients in the plant, (known as Kavalactones), not to any single substance or compound. There are a total of 18 different Kavalactones and many other supportive constituents. It is the presence of all of these compounds combined that gives traditional Kava its full effects.4,5,6 There is a large body of scientific literature on Kava and its many mechanisms of action in the body.7 In fact, Kava has been more thoroughly studied than almost any herb in the world. Some of the clinical applications that Kava has been studied for include:

Anxiety and Insomnia

Anxiety relief is the most common usage of Kava, and tends to be seen as a completely safe and effective anxiety-reducing alternative to anti-anxiety Benzodiazepine drugs without the addiction factor.8 At least one study has introduced Kava at 50mg (WS 1490 extract) when current Benzodiazepine dosage is reduced by 50%, to later replace the benzodiazepines with 300mg WS 1490 extract daily.9 This substitution appeared to be effective, and Kava does not appear to be significantly more or less effective than some standard drugs used to treat anxiety.10 As assessed by animal studies using injections, the anti-anxiety effects of Kava and its Kavalactones can be very rapid and occur as soon as it hits the brain.11

Many scientific studies have shown that Kavalactones significantly increase GABA (Gamma amino butyric acid) activity in the brain, which is the body’s main chemical for shutting down excitability and inducing relaxation. They bind to a specific site in the brain called the GABA(A) receptor, which is a key target for most anti-anxiety drugs and is known as one of the master regulators of stress and sleep in the body.12,13,14

Depression

Kava has also been thoroughly looked at as a possible therapeutic agent for depression and other mood disorders. One randomized placebo controlled trial looked at 60 adult participants over a 3 week period of time and found that Kava produced significant antidepressant activity compared to placebo.15 This ability of Kava to enhance mood and sociability is believed to come primarily from its effects on Dopamine, which is the body’s main pleasure chemical.

Several Kavalactones have been shown to be very strong inhibitors of an enzyme in the body called MAO-B (Monoamine oxidase-B).16 This enzyme is responsible for breaking down Dopamine and other neurotransmitters, so inhibiting it’s activity leads to much higher Dopamine levels.17 Kava at 20, 120, and 220mg/kg bodyweight and injected into rats caused extracellular dopamine in the brain to increase and fluctuate around 125-150% of the levels of the control group for up to 8 hours after administration.18

Substance abuse disorders

Kava has also been seriously looked at in substance abuse disorders due to its non-addictive and mood lifting properties. Kava has been shown to be an excellent anti craving agent for those suffering from drug addiction and dependency.19 It is also well known for its ability to significantly reduce withdrawal symptoms when coming off of alcohol, Benzodiazepines, and other illicit substances. This is due to the fact that Kavalactones  bind to the same receptors in the brain as many of these substances, but modulates them in a way that doesn’t create tolerance and dependency.20,21 In fact, it is well known by long term Kava users that it can produce what is called “reverse tolerance”. This refers to instances where the more an individual uses Kava, the less they need to receive the same effects overtime. The exact mechanisms and reasons for why this occurs are not yet completely understood. However it has been hypothesized that consistent Kava use might actually increase ones natural GABA activity overtime by increasing the number of functional GABA receptors in the brain.22 This would mean that it could possibly assist in permanent rehabilitation of this system that may be impaired in many anxiety and mood disorders or damaged by long term substance abuse.

Cognitive dysfunction

Kava is also well known for its cognitive enhancing properties. In fact, is becoming very popular as a nootropic for studying, working or to enhance creativity. Many scientific studies have demonstrated positive effects on cognitive function. In one study on 20 healthy individuals (split gender), 300mg of Kava that was standardized to 90mg of Kavalactones was able to improve reaction time as assessed by Sternberg item recognition task, reducing reaction time from 2090.5+/-141.81 milliseconds to 1265.29+/-72.05 milliseconds (60% of baseline) with a slight increase in the amount of correct recognitions. Correct recognitions as assessed by the Sperling partial report test were also significantly increased while incorrect assessments were decreased, with no effect on omissions.23 In a separate study testing word recollection, the WS 1490 extract of Kava has shown efficacy in improving performance and acute recollection more than placebo.24

Neuroprotective effects

Kava has been consistently shown to be a powerful neuroprotective agent. This simply means that it has demonstrated the ability to protect the brain and nervous system from the damaging effects of stress, trauma and toxicity. It has been shown to illicit these protective effects through multiple mechanisms. Many studies have shown that Kavalactones exhibit actions very similar to common antiepileptic drugs that protect the brain from seizure induced damage.25 This occurs through increased GABA signaling26, but also through blocking what are called voltage gated calcium channels.27 The blocking of these channels lowers excitability in the brain as well and prevents the formation of something called hydroxyl free radicals, which are a byproduct of this over excitation that can cause significant damage to the cells.28 Over activation of these channels is also the primary mechanism by which many environmental stressors such as electromagnetic frequencies (EMFs) can induce cellular damage as well.29 This suggests that Kava could possibly be an important tool for protecting the brain cells from potential damage caused by EMFs. Kavalactones are also known to be activators of an adaptive pathway called Nrf2, which upregulates the body’s own antioxidant and detoxification systems and helps protect it from damage caused by environmental toxins.30,31 One study showed that Kavalactones were able to slow the progression of Alzheimer’s disease by protecting the neurons against beta amyloid plaque induced neurotoxicity through this Nrf2 activation.32

 Two kavalactones, dihydromethysticin and methysticin, have also demonstrated protective effects against ischemia (stroke induced damage) similar in potency to the pharmaceutical Memantine, with the former requiring 150% the dose and the latter 50% the dose of memantine.33 This was also seen with whole Kava extract, and was attributed to those two components as other Kavalactones showed no protective effects.

Anti-inflammatory effects

In recent years, Kava has also started gaining attention for its effects on pain and inflammation. Studies have shown that has action very similar to over the counter NSAIDS like Aspirin, Ibuprofen, and acetaminophen, which all act as what are called COX (cyclooxygenase) inhibitors. Kava has been shown to inhibit both COX1 and COX2 which in turn reduces the production of prostaglandins, chemicals that promote inflammation, pain, and fever.34,35

Cancer and metabolic disorders

Perhaps one of the most exciting areas of research currently being done on Kava is on its potential application in the field of Cancer and metabolic conditions. The interest of the scientific community was originally peaked back in 2000 when an epidemiological study showed a close inverse relationship between Cancer incidence and Kava consumption in a large number of different islands in the south pacific.36 The data indicated that the more Kava was consumed by a population, the lower the Cancer incidence for that population. This correlation was totally consistent across all 8 countries studied. Since then, the body of accumulating scientific data on Kava’s potential application for Cancer treatment and prevention has grown immensely. There are now a large number of studies that demonstrate multiple mechanisms of Kava’s anti mutagenic action.37 One Kavalactone in particular called Yangonin was shown to significantly increase cellular autophagy, a bodily process that involves breaking down and recycling old damaged cells (including cancerous cells) and their components into usable energy as fuel.38 This occurred partly through the suppression of a pathway called mTOR, which is one of the primary pathways that drives Cancer growth.39 Other compounds in Kava known as Flavokawains have been shown in numerous studies to be directly toxic to Cancer cells, stimulating what is called apoptosis (cell death) in these cells.40 These effects have been scientifically demonstrated in a vast array of different forms of Cancer including breast,41,42 bone,43 brain,44 gastric,45 oral,46,47 synovial,48 thyroid,49 lung,50,51 prostate,52 bladder,53,54 ovarian,55 Melanoma56 and Leukemia.57 More research needs to be done so this topic can be fully explored but so far the data is very promising.

 

Current forms of Kava on the market

Kava is traditionally prepared by placing the ground root powder into a strainer bag and kneading it in a bowl of cold water, in which the root’s Kavalactones are released and the water is then consumed. However, even though traditional Kava has always been the only form that provides the full therapeutic effects, it is very tedious and time consuming to prepare. It also has a very earthy taste that can be quite unpleasant and hard for people to consume, especially on a regular basis. For all of these reasons, the traditional Kava preparation has not been practical for large scale commercial use and thus is only used by a small percentage connoisseurs that are willing to deal with the inconvenience.

Most if not all of the Kava products available today in health food stores or on the internet come in the form of capsules, liquids, pastes or tea bags. These crude extracts are far inferior to traditional Kava in terms of their effects. This is because most of these companies perform their extractions using aggressive solvents and high temperatures that denature the Kava and only pull out a few of the active compounds that are found in the traditional drink. This leads to products that contain little to none of the effects that the traditional Kava preparation is so prized for in the islands. Many of these products are also adulterated with mold, mycotoxins, industrial chemicals, low grade kava varieties, and non-root aerial plant parts that are not safe for human consumption.58,59,60,61

 

 

KAVAPLEX… Noble Roots difference

At Noble Roots Kava we are committed to providing the absolute safest, highest quality kava products available anywhere on the market. Our oils are made only from the roots of certified Noble Kava varieties. All of our Kava is grown and processed to the absolute highest standard on south pacific farms;62 with each strain being carefully selected and allowed to fully mature for at least 5 years before being harvested. Absolutely no pesticides or industrial chemicals are used at any step of our process. Each batch of Kava root we receive is independent lab tested to ensure that it meets our strict quality standards.63

With our breakthrough proprietary extraction method we are able to extract using high pressure at very low temperatures, capturing the root’s full Kavalactone complex. This gives us a final product that is virtually indistinguishable from traditional kava in terms of its composition and effects. The end result is KAVAPLEX, our ready to use full spectrum Kava oil.

  • Made with 100% Noble Kava varieties
  • Free of Heavy metals, pesticides, and mycotoxins
  • Solvent free, low temperature extraction
  • Full spectrum Kavalactone profile
  • No tedious preparation or unpleasant taste

 

 

 

 

 

 

 

References

  1. Kava: an overview. J Ethnopharmacol. 1992 Aug;37(1):13-45.

Singh YN1.

  1. Kava-kava and anxiety: growing knowledge about the efficacy and safety. Life Sci. 2002 Apr 19;70(22):2581-97.

Bilia AR1, Gallon S, Vincieri FF.

  1. Kava hepatotoxicity solution: A six-point plan for new kava standardization. 2011 Jan 15;18(2-3):96-103. doi: 10.1016/j.phymed.2010.10.002.  Epub 2010 Nov 26.

Teschke R1, Sarris J, Lebot V.

  1. Safety review of kava (Piper methysticum) by the Natural Standard Research Collaboration. Expert Opin Drug Saf. 2005 Jul;4(4):779-94.

Ulbricht C1, Basch E, Boon H, Ernst E, Hammerness P, Sollars D, Tsourounis C, Woods J, Bent S.

  1. Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug Metab Dispos. 2005 Nov;33(11):1580-3. Epub 2005 Jul 28.  Weiss J1, Sauer A, Frank A, Unger M.
  2. Electrospray high performance liquid chromatography-mass spectrometry in phytochemical analysis of kava (Piper methysticum) extract. Planta Med. 1997 Feb;63(1):70-4.  He XG1, Lin LZ, Lian LZ.
  3. Kava extract for treating anxiety. Cochrane Database Syst Rev. 2003;(1):CD003383.  Pittler MH1, Ernst E.
  4. Kava-kava extract in anxiety disorders: an outpatient observational study. Adv Ther. 1998 Jul-Aug;15(4):261-9. Scherer J1.
  5. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Psychopharmacology (Berl). 2001 Sep;157(3):277-83.  Malsch U1, Kieser M.
  6. Kava-Kava extract LI 150 is as effective as Opipramol and Buspirone in Generalised Anxiety Disorder--an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patients. 2003;10 Suppl 4:38-49.  Boerner RJ1, Sommer H, Berger W, Kuhn U, Schmidt U, Mannel M.
  7. Extracts of kava (Piper methysticum) induce acute anxiolytic-like behavioral changes in mice. Psychopharmacology (Berl). 2003 Oct;170(1):33-41. Epub 2003 Jul 4.  Garrett KM1, Basmadjian G, Khan IA, Schaneberg BT, Seale TW.
  8. Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism. PLoS One. 2016 Jun 22;11(6):e0157700. doi: 10.1371/journal.pone.0157700. eCollection 2016. Chua HC1, Christensen ET1,2, Hoestgaard-Jensen K2, Hartiadi LY1, Ramzan I1, Jensen AA2, Absalom NL1, Chebib M1.
  9. GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence. Phytother Res. 2018 Jan;32(1):3-18. doi: 10.1002/ptr.5940. Epub 2017 Nov 23.  Savage K1,2, Firth J3,4, Stough C2, Sarris J1,4.
  10. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2013 Oct;33(5):643-8. doi: 10.1097/JCP.0b013e318291be67.  Sarris J1, Stough C, Bousman CA, Wahid ZT, Murray G, Teschke R, Savage KM, Dowell A, Ng C, Schweitzer I.
  11. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology (Berl). 2009 Aug;205(3):399-407. doi: 10.1007/s00213-009-1549-9. Epub 2009 May 9.  Sarris J1, Kavanagh DJ, Byrne G, Bone KM, Adams J, Deed G
  12. Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava). 1998 Sep;31(5):187-92.  Uebelhack R1, Franke L, Schewe HJ.
  13. Reversible and irreversible small molecule inhibitors of monoamine oxidase B (MAO-B) investigated by biophysical techniques. Bioorg Med Chem. 2015 Feb 15;23(4):770-8. doi: 10.1016/j.bmc.2014.12.063. Epub 2015 Jan 3.Rojas RJ1, Edmondson DE2, Almos T3, Scott R3, Massari ME3.
  14. Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Prog Neuropsychopharmacol Biol Psychiatry. 1998 Oct;22(7):1105-20.  Baum SS1, Hill R, Rommelspacher H.
  15. Kava as an anticraving agent: preliminary data. Pac Health Dialog. 2001 Sep;8(2):335-9.  Steiner GG1.
  16. Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism. PLoS One. 2016 Jun 22;11(6):e0157700. doi: 10.1371/journal.pone.0157700. eCollection 2016. Chua HC1, Christensen ET1,2, Hoestgaard-Jensen K2, Hartiadi LY1, Ramzan I1, Jensen AA2, Absalom NL1, Chebib M1.
  17. Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Prog Neuropsychopharmacol Biol Psychiatry. 1998 Oct;22(7):1105-20.  Baum SS1, Hill R, Rommelspacher H.
  18. Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain. Psychopharmacology (Berl). 1994 Dec;116(4):469-74.  Jussofie A1, Schmiz A, Hiemke C.
  19. Enhanced cognitive performance and cheerful mood by standardized extracts of Piper methysticum (Kava-kava). Hum Psychopharmacol. 2004 Jun;19(4):243-50.  Thompson R1, Ruch W, Hasenöhrl RU.
  20. Effects of oxazepam and an extract of kava roots (Piper methysticum) on event-related potentials in a word recognition task. 1993;27(1):46-53.  Münte TF1, Heinze HJ, Matzke M, Steitz J.
  21. Kava pyrones exert effects on neuronal transmission and transmembraneous cation currents similar to established mood stabilizers--a review. Prog Neuropsychopharmacol Biol Psychiatry. 2001 Nov;25(8):1555-70.  Grunze H1, Langosch J, Schirrmacher K, Bingmann D, Von Wegerer J, Walden J.
  22. Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism. PLoS One. 2016 Jun 22;11(6):e0157700. doi: 10.1371/journal.pone.0157700. eCollection 2016.  Chua HC1, Christensen ET1,2, Hoestgaard-Jensen K2, Hartiadi LY1, Ramzan I1, Jensen AA2, Absalom NL1, Chebib M1.
  23. Kava pyrones exert effects on neuronal transmission and transmembraneous cation currents similar to established mood stabilizers--a review. Prog Neuropsychopharmacol Biol Psychiatry. 2001 Nov;25(8):1555-70.  Grunze H1, Langosch J, Schirrmacher K, Bingmann D, Von Wegerer J, Walden J.
  24. Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects. J Cell Mol Med. 2013 Aug;17(8):958-65. doi: 10.1111/jcmm.12088. Epub 2013 Jun 26. 

Pall ML1.

  1. Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects. J Cell Mol Med. 2013 Aug;17(8):958-65. doi: 10.1111/jcmm.12088. Epub 2013 Jun 26. 

Pall ML1.

  1. A kavalactone derivative inhibits lipopolysaccharide-stimulated iNOS induction and NO production through activation of Nrf2 signaling in BV2 microglial cells. Pharmacol Res. 2013 May;71:34-43. doi: 10.1016/j.phrs.2013.02.002. Epub 2013 Feb 16.  Terazawa R1, Akimoto N, Kato T, Itoh T, Fujita Y, Hamada N, Deguchi T, Iinuma M, Noda M, Nozawa Y, Ito M.
  2. A novel kavalactone derivative protects against H2O2-induced PC12 cell death via Nrf2/ARE activation. Bioorg Med Chem. 2010 May 1;18(9):3133-9. doi: 10.1016/j.bmc.2010.03.034. Epub 2010 Mar 20.  Tanaka A1, Hamada N, Fujita Y, Itoh T, Nozawa Y, Iinuma M, Ito M.
  3. Kavalactones protect neural cells against amyloid beta peptide-induced neurotoxicity via extracellular signal-regulated kinase 1/2-dependent nuclear factor erythroid 2-related factor 2 activation. Mol Pharmacol. 2008 Jun;73(6):1785-95. doi: 10.1124/mol.107.042499. Epub 2008 Mar 11.  Wruck CJ1, Götz ME, Herdegen T, Varoga D, Brandenburg LO, Pufe T.
  4. Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents. Eur J Pharmacol. 1992 May 14;215(2-3):265-9.  Backhauss C1, Krieglstein J.
  5. Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots. 2002 Jan;9(1):41-7.  Wu D1, Yu L, Nair MG, DeWitt DL, Ramsewak RS.
  6. Novel compounds from Piper methysticum Forst (Kava Kava) roots and their effect on cyclooxygenase enzyme. J Agric Food Chem. 2002 Feb 13;50(4):701-5.  Wu D1, Nair MG, DeWitt DL.
  7. The correlation between cancer incidence and kava consumption.

Hawaii Med J. 2000 Nov;59(11):420-2.  Steiner GG.

  1. Anticancer activities of constituents of kava (Piper methysticum)

The South Pacific Journal of Natural Science  2005 vol 23:26-29

  1. N. Tabudravu, Marcel Jaspars
  2. Kavalactone yangonin induces autophagy and sensitizes bladder cancer cells to flavokawain A and docetaxel via inhibition of the mTOR pathway.

J Biomed Res. 2017 Sep 26;31(5):408-418. doi: 10.7555/JBR.31.20160160.

Liu Z1, Ha US1, Yu K1, Wu C1, Yokoyama N1, Zi X2.

  1. Kavalactone yangonin induces autophagy and sensitizes bladder cancer cells to flavokawain A and docetaxel via inhibition of the mTOR pathway.

J Biomed Res. 2017 Sep 26;31(5):408-418. doi: 10.7555/JBR.31.20160160.

Liu Z1, Ha US1, Yu K1, Wu C1, Yokoyama N1, Zi X2.

  1. The flavokawains: uprising medicinal chalcones.

Cancer Cell Int. 2013 Oct 22;13(1):102. doi: 10.1186/1475-2867-13-102.

Abu N, Ho WY, Yeap SK, Akhtar MN, Abdullah MP, Omar AR, Alitheen NB1.

  1. Flavokawain B induced cytotoxicity in two breast cancer cell lines, MCF-7 and MDA-MB231 and inhibited the metastatic potential of MDA-MB231 via the regulation of several tyrosine kinases In vitro. BMC Complement Altern Med. 2016 Feb 27;16:86. doi: 10.1186/s12906-016-1046-8.

Abu N1,2, Akhtar MN3, Yeap SK4, Lim KL5, Ho WY6, Abdullah MP7, Ho CL8, Omar AR9, Ismail J10, Alitheen NB11.

  1. In Vivo Anti-Tumor Effects of Flavokawain A in 4T1 Breast Cancer Cell-Challenged Mice. Anticancer Agents Med Chem. 2015;15(7):905-15.

Abu N, Mohamed NE, Yeap SK, Lim KL, Akhtar MN, Zulfadli AJ, Kee BB, Abdullah MP, Omar AR, Alitheen NB1.

  1. Flavokawain B, a kava chalcone, inhibits growth of human osteosarcoma cells through G2/M cell cycle arrest and apoptosis. Mol Cancer. 2013 Jun 10;12:55. doi: 10.1186/1476-4598-12-55.  Ji T1, Lin C, Krill LS, Eskander R, Guo Y, Zi X, Hoang BH.
  2. Inhibition of glioma growth by flavokawain B is mediated through endoplasmic reticulum stress induced autophagy. 2018;14(11):2007-2022. doi: 10.1080/15548627.2018.1501133. Epub 2018 Aug 17.  Wang J1, Qi Q1, Zhou W1, Feng Z1, Huang B1, Chen A1, Zhang D1, Li W1, Zhang Q1, Jiang Z1, Bjerkvig R2, Prestegarden L2, Thorsen F2,3, Wang X1, Li X1, Wang J1,2.
  3. Chalcone flavokawain B induces autophagic-cell death via reactive oxygen species-mediated signaling pathways in human gastric carcinoma and suppresses tumor growth in nude mice. Arch Toxicol. 2017 Oct;91(10):3341-3364. doi: 10.1007/s00204-017-1967-0. Epub 2017 Apr 3.  Chang CT1, Hseu YC2,3, Thiyagarajan V4, Lin KY5, Way TD6, Korivi M1, Liao JW7, Yang HL8.
  4. Flavokawain B induces apoptosis of human oral adenoid cystic cancer ACC-2 cells via up-regulation of Bim and down-regulation of Bcl-2 expression. Can J Physiol Pharmacol. 2011 Dec;89(12):875-83. doi: 10.1139/y11-088. Epub 2011 Nov 24.  Zhao X1, Chao YL, Wan QB, Chen XM, Su P, Sun J, Tang Y.
  5. The chalcone flavokawain B induces G2/M cell-cycle arrest and apoptosis in human oral carcinoma HSC-3 cells through the intracellular ROS generation and downregulation of the Akt/p38 MAPK signaling pathway.

J Agric Food Chem. 2012 Mar 7;60(9):2385-97. doi: 10.1021/jf205053r. Epub 2012 Feb 27.  Hseu YC1, Lee MS, Wu CR, Cho HJ, Lin KY, Lai GH, Wang SY, Kuo YH, Kumar KJ, Yang HL.

  1. Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines. J Orthop Res. 2012 Jul;30(7):1045-50. doi: 10.1002/jor.22050. Epub 2011 Dec 29.  Sakai T1, Eskander RN, Guo Y, Kim KJ, Mefford J, Hopkins J, Bhatia NN, Zi X, Hoang BH.
  2. Adenosine 5'-monophosphate-activated protein kinase-dependent mTOR pathway is involved in flavokawain B-induced autophagy in thyroid cancer ce Cancer Sci. 2018 Aug;109(8):2576-2589. doi: 10.1111/cas.13699. Epub 2018 Jul 20.  He Q1,2,3, Liu W1,2,3, Sha S1,2,3, Fan S4, Yu Y1,2,3, Chen L1,2,3, Dong M1,2,3.
  3. Lung tumorigenesis suppressing effects of a commercial kava extract and its selected compounds in A/J mice. Am J Chin Med. 2011;39(4):727-42.

Johnson TE1, Hermanson D, Wang L, Kassie F, Upadhyaya P, O'Sullivan MG, Hecht SS, Lu J, Xing C.

  1. Flavokawain B induces apoptosis of non-small cell lung cancer H460 cells via Bax-initiated mitochondrial and JNK pathway. Biotechnol Lett. 2012 Oct;34(10):1781-8. doi: 10.1007/s10529-012-0976-6. Epub 2012 Jun 23.

An J1, Gao Y, Wang J, Zhu Q, Ma Y, Wu J, Sun J, Tang Y.

  1. Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growth.

Int J Cancer. 2010 Oct 15;127(8):1758-68. doi: 10.1002/ijc.25210.

Tang Y1, Li X, Liu Z, Simoneau AR, Xie J, Zi X.

  1. Abstract 5678: Kavalactone yangonin induces autophagy, inhibits TSC-mediated translation initiation and acts synergistically with a kava chalcone flavokawain A on growth inhibition in bladder cancer UMUC-3 cells AACR; Cancer Res 2010 Apr vol 70, issue 8 DOI:1158/1538-7445. 

Zhongbo Liu, Xuesen Li, Anna Simoneau and Xiaolin Zi

  1. Effects of the kava chalcone flavokawain A differ in bladder cancer cells with wild-type versus mutant p53. Cancer Prev Res (Phila). 2008 Nov;1(6):439-51. doi: 10.1158/1940-6207.CAPR-08-0165.

Tang Y1, Simoneau AR, Xie J, Shahandeh B, Zi X.

  1. Kava, a tonic for relieving the irrational development of natural preventive agents. Cancer Prev Res (Phila). 2008 Nov;1(6):409-12. doi: 10.1158/1940-6207.CAPR-08-0172.

Agarwal R1, Deep G.

  1. Flavokawains B and C, melanogenesis inhibitors, isolated from the root of Piper methysticum and synthesis of analogs. Bioorg Med Chem Lett. 2015 Feb 15;25(4):799-802. doi: 10.1016/j.bmcl.2014.12.082. Epub 2015 Jan 3.

Jeong HJ1, Lee CS2, Choi J3, Hong YD2, Shin SS2, Park JS2, Lee JH2, Lee S4, Yoon KD5, Ko J6.

  1. The Combination of Flavokawain B and Daunorubicin Induces Apoptosis in Human Myeloid Leukemic Cells by Modifying NF-κB. Anticancer Res. 2018 May;38(5):2771-2778.  Lee JJ1, Koh KN2, Park CJ3, Jang S3, Im HJ4, Kim N5.
  2. Kava and kava hepatotoxicity: requirements for novel experimental, ethnobotanical and clinical studies based on a review of the evidence.

Phytother Res. 2011 Sep;25(9):1263-74. doi: 10.1002/ptr.3464. Epub 2011 Mar 28.  Teschke R1, Qiu SX, Xuan TD, Lebot V.

  1. Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits. Dig Liver Dis. 2011 Sep;43(9):676-81. doi: 10.1016/j.dld.2011.01.018. Epub 2011 Mar 4.

Teschke R1, Qiu SX, Lebot V.

  1. Are mould hepatotoxins responsible for kava hepatotoxicity? Phytother Res. 2012 Nov;26(11):1768-70. doi: 10.1002/ptr.4620. Epub 2012 Feb 8.

Rowe A1, Ramzan I.

  1. Kava hepatotoxicity solution: A six-point plan for new kava standardization. 2011 Jan 15;18(2-3):96-103. doi: 10.1016/j.phymed.2010.10.002. Epub 2010 Nov 26.  Teschke R1, Sarris J, Lebot V.
  2. Kava hepatotoxicity solution: A six-point plan for new kava standardization. 2011 Jan 15;18(2-3):96-103. doi: 10.1016/j.phymed.2010.10.002. Epub 2010 Nov 26.  Teschke R1, Sarris J, Lebot V.
  3. Single-Lab Validation for Determination of Kavalactones and Flavokavains in Piper methysticum (Kava). Planta Med. 2018 Nov;84(16):1213-1218. doi: 10.1055/a-0637-2400. Epub 2018 Jun 25.  Liu Y1, Lund JA2, Murch SJ2, Brown PN1.