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Unlocking the Potential of Kava:

Are Claims of Kava’s Health Benefits Supported by the Research?

Kava for improved sleep? Kava to prevent cancer? Kava to cure cancer? Kava to relieve anxiety? Kava for insomnia? Kava as an anti-parasitic? Kava to combat Covid-19? Kava for creative inspiration? Kava to aid digestion? Kava as an anti-inflammatory? Kava for pain relief? Kava as a muscle relaxant? Kava to improve brain function?

There are lot of reasons why people choose to use kava, but let’s be clear about this from the outset: We don’t sell kava on the basis of health benefits, including for any of those purported above. We recommend buying kava purely to enjoy the experience that comes from drinking it, and we are not able to confirm or disprove whether any of the claims about kava are true or not – you will need to find that out for yourself.

At Root & Pestle, we like to unwind at the end of a long day with a few shells of our favourite single cultivar kavas or chill out with mates at a local nakamal. We think it is unwise and potentially dangerous to forgo modern, licensed medical care in lieu of natural products, and we believe that you should be seeing a legitimate health care practitioner for medical advice. Whether you’re talking about healing herbs or other alternative medicines and therapeutic strategies, we believe you should always first and foremost follow the advice of your medical doctor. If you aren’t feeling well, see a GP. Just because plenty of people believe something is good for you, doesn’t necessarily make it so, even if you read it on the internet… but does that mean it’s total bogus?

Before we get into it, once again – Please don’t buy kava to cure yourself of whatever ails you – that’s not what we sell it for! We make no claims about the potential health benefits of kava, and we aren’t recommending that you buy it for use as part of a medical treatment regime.

So where did all this talk about the wonders of kava come from, and is it mumbo jumbo, or is it perhaps wise to include drinking kava as part of your healthy lifestyle?

If you’ve spent much time investigating the potential benefits of kava, it wouldn’t surprise us to find out that you may have heard that consuming drinks made from kava root will lower anxiety and improve sleep, or that drinking kava provides other health benefits of some kind.

With more than 40 bioactive compounds having been isolated and identified from Piper methysticum (kava), including chalcones, alkaloids, steroids, long-chained fatty acids, and others (Parmar, V.S.; Jain, S.C.; Bisht, K.S.; Jain, R.; Taneja, P.; Jha, A.; Tyagi, O.D.; Prasad, A.K.; Wengel, J.; Olsen, C.E. Phytochemistry of the genus Piper. Phytochemistry 1997, 46, 597-673.), it is no surprise that there will be molecular interactions within the human body, and downstream effects which influence the mind.

Although there may be a general belief that certain kavalactones are directly related to certain subjective effects of the kava drinking experience (such as a kavain-rich kava allegedly necessitating the subsequent beverage be resultant in a “heady” experience), the effects may actually be the result of a synergy of the six major kavalactones (Spinella, M. The Importance of Pharmacological Synergy in Psychoactive Herbal Medicines. Altern. Med. Rev. 2002, 7 (2), 130-137. PMID: 11991792. https://pubmed.ncbi.nlm.nih.gov/11991792/ and Xuan, T.D.; Fukuta, M.; Wei, A.C.; Elzaawely, A.A.; Khanh, T.D.; Tawata, S. Efficacy of extracting solvents to chemical components of kava (Piper methysticum) roots. J. Nat. Med. 2008, 62, 188-194.). Because of this, a particular effect may not be attributable to only the quantity (or ingestion) of any one compound alone, but rather may be conferred only as part of the total “cocktail” of kavalactones. This suggests to us that the story has the potential to become quite complex in regard to associating particular effects with particular compounds, and also means that the results of a study about the potential interactions one compound may have within the body may not be applicable when taken out of the context within which the research was conducted. From our perspective, the jury is still out on exactly how this stuff works, despite the huge swaths of experimental research already conducted.

Most kava growers, producers, distributors, retailers, bars, nakamals, and kava lounges sell kava root and kava powder based drinks purely for use as a lifestyle beverage and make no claims about its ability to improve sleep, relieve anxiety, prevent cancer, treat intestinal worms, alleviate chronic inflammation, or provide any other medical benefit. Root & Pestle is not a clinic, medical centre, nutritional institute, or health research agency, and we too only promote drinking kava for people to enjoy their own subjective experience of the pleasant feelings its fans say it supports.

What we can tell you is that kava, and in particular kavalactones, the compounds in kava principally responsible for its psychoactive effects, have had quite a bit of interest from the scientific community, and that plenty of research has been conducted, with many interesting findings made, and that this work is ongoing and final conclusions remain to be drawn. We haven’t verified the veracity of any medical claims about kava which have been published in the many peer-reviewed scientific journals, and we have only read a few hundred of the multitude of studies about the various kavalactones which are in ready supply in kava root powder drinks. Because of this, and because we are producing kava as a food supplement and not as a medicine, we are not really in a position to say which research is the highest quality, most believable, or needs the most follow-up, but we can say that we have read countless fascinating experiments along with the results published by their researchers, and that we believe that if you’re interested in journeys of discovery, you might want to take a dive into the literature for yourself.

To get you started on your voyage of enlightenment in regard to the botanical wonder that is kava, you might want to look up some of the research papers below. Google Scholar (https://scholar.google.com/) usually has direct links, if any of these articles haven’t got an active one.

The results of peer-reviewed studies are often “pay to access”, but in many cases it may be possible to look up the institutions where the authors are based, use their publicly available staff directory to get an email address (or use the address for correspondence published directly on many of the articles themselves) and email the folks who did the research directly, asking politely if it would be possible to send a copy of their work, free of charge, out of personal interest. In our experience, most scientific authors have felt happy to have been asked by members of the public to read their work, but please forgive them if they are unable to oblige.

We do not endorse or support any of the research or findings published in the below papers – we have simply collated a small assortment to potentially spark your interest in a journey of discovery of what many people regard as a robust source of information these days. Please take everything you read with a grain of salt, as no one is perfect and everyone makes mistakes, and double check for conflicts of interests to be more confident that the published findings are not biased. We have had nothing to do with any of the research or published findings we’ve mentioned below, and we have no affiliation with any of the authors or institutions. You will likely have no problem finding many other potentially trustworthy sources of information about research related to kava and kavalactones, and we encourage you to do your due diligence and critically examine all of the available information before you decide if kava, or any other natural product, is right for you.

Again, we don’t support or condone (or refute) any of the findings from any of these sources, and we aren’t representing any of the claims made as correct or valid – we’re just letting you know that some research has been done, and we have quoted a few things from various research articles we’ve found. We are not giving summaries of findings or making any interpretations from these works, and we have no stated opinion on any of the experiments conducted or findings made by any of the researchers or institutions who carried out any of this work, nor are we expressing any opinions about anything said by any of the authors we cite here – we’ll leave all of that up to you. We have come across interesting research and fascinating anecdotes in books too, and we’ve included a handful of those as well, purely for entertainment purposes.

Good luck and have fun learning about kava and kavalactones!

So, What do Academics, Researchers, Scientists, Scholars, and Respected Authors (with no connection to Root & Pestle) Have to say About Kava or its Constituents for:

– Inhibiting Covid-19?

Davella, Rakesh; Gurrapu, Swapna; Mamidala, Estari. Phenolic compounds as promising drug candidates against COVID-19 – an integrated molecular docking and dynamics simulation study. Materials Today: Proceedings. 2022;51(1):522-527. Available at: https://doi.org/10.1016/j.matpr.2021.05.595.

“…Methysticin, Kavain and Dihydrokavain…interacted well in the key protease’s active site showing that they may inhibit COVID19…”

– Preventing or Reversing Greying Hair?

Matsuda, Hideto; Hirata, Noriko; Kawaguchi, Yoshiko; Naruto, Shunji; Takata, Takanobu; Oyama, Masayoshi; Iinuma, Munekazu; Kubo, Michiyoshi. Melanogenesis Stimulation in Murine B16 Melanoma Cells by Kava (Piper methysticum) Rhizome Extract and Kavalactones. Biological and Pharmaceutical Bulletin 2006, 29(4), 834-837. DOI: 10.1248/bpb.29.834. Available at: https://pubmed.ncbi.nlm.nih.gov/16595931/.

“For the development of gray hair prevention agent, we have carried out a screening program to find a potential stimulant of melanogenesis from the natural resources … The extract of rhizomes of P. methysticum (Kava) exhibited the significant activity with slight increment of cell proliferation at concentration of 10 mg/ml”

– Improved Brain Function, Cognition, and Neuroprotection?

Volgin, Andrey; Yang, LongEn; Amstislavskaya, Tamara; Demin, Konstantin; Wang, Dongmei; Yan, Dongni; Wang, Jingtao; Wang, Mengyao; Alpyshov, Erik; Hu, Guojun; Serikuly, Nazar; Shevyrin, Vadim; Wappler-Guzzetta, Edina; de Abreu, Murilo; Kalueff, Allan. DARK Classics in Chemical Neuroscience: Kava. ACS Chemical Neuroscience. 2020, 11, 3893-3904.

“In humans, kava consumption evokes robust psychoactive effects, inducing improved recognition memory and anxiolysis”

“Subjective sensations after kava intake progress from slight numbness of the tongue and lips (due to an anesthetic action of kavalactones), increased sociality and thinking, sense of peace and harmony, muscle relaxation, to a sense of health and happiness.”

“The low addictive potential, low neurotoxicity, and seemingly lacking overt withdrawal-like effects of kava are also interesting in regard to its potential as a medicine”

Pedrosa, Elaine Cristina Gurgel Andrade; Bezerra, Ana Paula Carvalho; da Costa, Ianara Mendonça; Pinheiro, Francisco Irochima; Guzen, Fausto Pierdoná. Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a systematic review. Journal of Pharmaceutical and Chemical Biological Sciences, 2020, 2(1), 55-84. DOI:10.36619/jpcbs.2020.2.56.80. ISSN:2674-886X.

“Results: Piper Methysticum demonstrated significant positive responses to reduce oxidative stress and neuroinflammation in neurodegenerative diseases. In addition, Piper methysticum extract can have anti-ischemic and anticonvulsant effects mediated by blocking the Na+ channel voltage, as well as behavioral changes similar to anxiolytics and significant sedation. Conclusion: Thus, considering that Piper methysticum proves to be effective and has a phytotherapeutic potential to act as an adjuvant or alternative to existing drugs.”

 

Tzeng, Yi-Ming; Lee, Ming-Jen. Neuroprotective Properties of Kavalactones. Neural Regeneration Research. 2015, 10(6), 875-877. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498339/.

“Recent studies on the mechanisms of action for isolated kavalactones have revealed other neuroprotective activities…These findings suggest that the use of kava might also be beneficial for the treatment of many degenerative diseases or nervous system conditions…One of the neuroprotective effects of kavalactones is mediated by the P38/nuclear factor-kappaB (nuclear factor-κB)/cyclooxygenase 2 (COX2) signaling pathway…Another important neuroprotective pathway recently demonstrated is the kavalactone-mediated upregulation of antioxidation enzymes”

 

Cairney, Shane, Alan R. Clough, Paul Maruff, Alexander Collie, Bart J. Currie, and Jan Currie. “Saccade and cognitive function in chronic kava users.” Neuropsychopharmacology 28, no. 2 (2003): 389-396. doi:10.1038/sj.npp.1300052. PMID 12589393.

“…there is no conclusive evidence that kava interferes with normal cognitive processes… Despite collecting data from among the heaviest reported kava drinkers in the world, we found no impairment in cognitive or saccade function in individuals who were currently heavy kava users (and had been for up to 18 years), nor was there any impairment in individuals who had been heavy kava users in the past but had abstained for longer than 6 months…we have found no evidence of brain dysfunction in heavy and long-term kava users.”

 

LaPorte, Elizabeth; Sarris, Jerome; Stough, Con; Scholey, Andrew. Neurocognitive effects of kava (Piper methysticum): a systematic review. Human Psychopharmacology. 2011, 26 (2), 102-111. doi: 10.1002/hup.1180. ISSN 1099-1077. PMID 21437989. S2CID 44657320. Available at: https://onlinelibrary.wiley.com/doi/abs/10.1002/hup.1180.

“Results: …kava significantly improved visual attention and working memory processes… Potential enhanced cognition may be attributed to the ability of kava to inhibit re-uptake of noradrenaline in the pre-frontal cortex… Conclusions: The majority of evidence suggests that kava has no replicated significant negative effects on cognition”

 

Backhauss, Claudia; Krieglstein, Josef. Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents. European Journal of Pharmacology. 1992, 215, 265-269. DOI: 10.1016/0014-2999(92)90037-5 Available at: https://pubmed.ncbi.nlm.nih.gov/1396990/

“In conclusion, the kava extract exhibited neuroprotective activity, which was probably mediated by its constituents methysticin and dihydromethysticin.”

 

Münte, Thomas F.; Heinze, Hans J.; Matzke, Matthias; Steitz, Johanna. Effects of Oxazepam and an Extract of Kava Roots (Piper methysticum) on Event-Related Potentials in a Word Recognition Task. Neuropsychobiology 1993, 27 (1), 46-53. DOI: 10.1159/000118952. Available at: https://pubmed.ncbi.nlm.nih.gov/8515824/.

“Oxazepam led to a reduction of a negative component in the 250-500 ms range for both old and new words and to a reduction of the old/new difference in the ERP associated with a significantly worse recognition rate. Kava on the other hand showed a slightly increased recognition rate and a larger ERP difference between old and new words.”

 

Krum, Barbara Nunes; de Freitas, Catiuscia Molz; Ceretta, Ana Paula Chiapinotto; Barbosa, Caroline Pilecco; Reis, Elizete de Moraes; Scussel, Rahisa; Corneo, Emily da Silva; Machado-de-Avila, Ricardo Andrez; Boligon, Aline Augusti; Fachinetto, Roselei. Kava decreases the stereotyped behavior induced by amphetamine in mice. Journal of Ethnopharmacology, 2021, 265, 113293. DOI: 10.1016/j.jep.2020.113293. Available at: https://doi.org/10.1016/j.jep.2020.113293.

“Conclusion: The results showed that Kava extract decreased the stereotyped behavior induced by AMPH at the same dose that promotes anxiolytic effects, which could be useful to minimize the psychotic symptoms in patients.”

Leitzman, Petra; Narayanapillai, Sreenivasan C.; Balbo, Silvia; Zhou, Boyang; Upadhyaya, Pramod; Shaik, Aleem A.; O’Sullivan, M. Gerard; Hecht, Stephen S.; Lu, Jia; Xing,

– Counteracting Carcinogens and Helping to Quit Smoking?

Wang, Yi; Narayanapillai, Sreekanth C.; Tessier, Katelyn M.; Strayer, Lori G.; Upadhyaya, Pramod; Hu, Qi; Kingston, Rick; Salloum, Ramzi G.; Lu, Junxuan; Hecht, Stephen S.; Hatsukami, Dorothy K.; Fujioka, Naomi; and Xing, Chengguo. 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. February 26, 2020; DOI: 10.1158/1940-6207.CAPR-19-0501. Available at: http://cancerpreventionresearch.aacrjournals.org/.

“Kava increased urinary excretion of total NNAL and reduced urinary 3-methyladenine in participants, suggestive of its ability to reduce the carcinogenicity of NNK. Kava also reduced urinary total nicotine equivalents, indicative of its potential to facilitate tobacco cessation. Plasma cortisol and urinary total cortisol equivalents were reduced upon kava use, which may contribute to reductions in tobacco use. These results demonstrate the potential of kava intake to reduce lung cancer risk among smokers” Xing, Chengguo; Malaty, John; Malham, Melissa Bou; Nehme, Anna Maria Abi; Freeman, Breanne; Huo, Zhiguang; Firpi-Morrel, Roberto; Salloum, Ramzi G. Reducing Tobacco- Associated Lung Cancer Risk: A Study Protocol for a Randomized Clinical Trial of AB-Free Kava. Trials 2023, 24 (36). Available at: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07081-x

“The goal of this project is to develop a safe and effective kava-based intervention to enable tobacco cessation and reduce lung cancer risk, which will improve the health of smokers.”

The complete results of this clinical trial are expected to be published in the near future.

– Pain Relief?

Jamieson, D.D.; Duffield, P.H. The antinociceptive actions of kava components in mice. Clinical and Experimental Pharmacology and Physiology. 1990;17:495-507. doi: 10.1111/j.1440-1681.1990.tb01349.x. PMID: 2401103.

“…kawain, dihydrokawain, methysticin and dihydromethysticin were found to be very effective in producing analgesia…analgesia produced by kava occurs via non-opiate pathways”

– Prevention and Treatment of Alzheimer’s disease?

Wruck, Christoph J.; GÖtz, Mario E.; Herdegen, Thomas; Varoga, Deike; Brandenburg, Lars-

Ove; Pufe, Thomas. Kavalactones Protect Neural Cells against Amyloid β Peptide-Induced

Neurotoxicity via Extracellular Signal-Regulated Kinase 1/2-Dependent Nuclear Factor

Erythroid 2-Related Factor 2 Activation. Molecular Pharmacology 2008, 73(6), 1785–1795. https://doi.org/10.1124/mol.107.042499.

“Our results demonstrate that kavalactones attenuate amyloid β -peptide toxicity by inducing protective gene expression mediated by Nrf2 activation in vitro. These findings indicate that the use of purified kavalactones might be considered as an adjunct therapeutic strategy to combat neural demise in Alzheimer disease and other oxidative stress-related diseases.”

– Prevention and Treatment of Cancer?

Ding, Yan; Hou, Ruilin; Yu, Jianqiang; Xing, Chengguo; Zhuang, Chunlin; Qu, Zhuo. Dietary Phytochemicals as Potential Chemopreventive Agents against Tobacco-Induced Lung Carcinogenesis. Nutrients 2023, 15(3), 491. Available at: https://doi.org/10.3390/nu15030491.

“Our group has carried out continuous chemoprevention studies on kava for lung cancer. The results displayed that dietary kava led to statistically significant lower lung tumor multiplicities in NNK plus BaP-treated A/J mice [55]. It is worth mentioning that diets containing kava reduced lung adenomas multiplicity by approximately 99%. Furthermore, daily gavage of kava blocked lung adenoma formation by decreasing DNA damage in lung tissues of O6-methylguanine (O6-mG) [52]. Moreover, mice that were fed diets containing kava suppressed lung tumorigenesis in A/J mice via inhibition of cell proliferation, enhancing apoptosis, and also inhibiting the activation of NF-κB [53]. In addition, kava and its component methysticin suppressed NF-κB activation in lung adenoma tissues with minimum toxicity [56].

Xu, Xia; Tian, Xuejiao; Song, Liankun; Xie, Jun; Liao, Joseph C.; Meeks, Joshua J.; Wu, Xue-Ru; Gin, Greg E.; Wang, Beverly; Uchio, Edward; Zi, Xiaolin. Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation. Biomolecules 2023, 13(3), 521. Available at: https://doi.org/10.3390/biom13030521.

Epidemiological evidence suggests that kava (Piper methysticum Forst) drinks may reduce the risk of cancer in South Pacific Island smokers… Here we show that dietary feeding of kawain (a major active component in kava root extracts) to mice either before or after hydroxy butyl(butyl) nitrosamine (OH-BBN) carcinogen exposure slows down urinary bladder carcinogenesis and prolongs the survival of the OH-BBN-exposed mice… In addition, kava root extracts and the kavalactones kawain and methysticin all increase the levels of H3K4 mono- and di-methylation, leading to inhibitory effects on cell migration. Taken together, our results suggest that modification of histone lysine methylation may represent a new approach to bladder cancer prevention and treatment and that kavalactones may be promising agents for bladder cancer interception in both current and former smokers.

Tabudravu, Jioji N.; Jaspars, Marcel. Anticancer Activities of Constituents of Kava (Piper Methysticum). South Pacific Journal of Natural and Applied Sciences. 2005;23:26-29. Available at: https://www.publish.csiro.au/sp/pdf/SP05005.

“Crude extracts of kava (Piper methysticum G. Forster, Piperaceae) showed good activity against ovarian tumour and leukaemia cancer cell lines.”

Li, Xuesen; Song, Liankun; Xu, Shan; Tippin, Matthew; Meng, Shuan; Xie, Jun; Uchio, Edward; Zi, Xiaolin. 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. 2021;5:163-172. doi: 10.20517/jtgg.2021.22. PMID: 34368644. Available at: https://pubmed.ncbi.nlm.nih.gov/34368644/.

“Conclusion: Our results suggest that consumption of kava products through diet can delay prostate cancer development and progression and that kavalactones may be a new structure model for developing a potent dual inhibitor of LSD1 and MAO-A.”

Johnson, Thomas E.; Hermanson, David; Wang, Lei; Kassie, Fekadu; Upadhyaya, Pramod; O’Sullivan, Michael G.; Hecht, Stephen S.; Lu, Junxuan; Xing, Chengguo. Lung Tumorigenesis Suppressing Effects of a Commercial Kava Extract and Its Selected Compounds in AJ Mice. The American Journal of Chinese Medicine. 2011;39(4):727-742.

“Analyses of lung adenoma tissues derived from kava treated animals revealed that kava significantly inhibited adenoma cell proliferation while it had no detectable effect on cell death, indicating that kava primarily suppressed lung tumorigenesis in A/J mice via inhibition of cell proliferation… Kava at all dosages and treatment regimens did not induce detectable adverse effects”

“Epidemiological data suggest that kava may lead to a decreased risk for lung cancer development in both smokers and ex-smokers (Henderson et al., 1984; Tuomilehto et al., 1986; Steiner, 2000; Imai et al., 1997)”

Botello, Jordy F.; Corral, Pedro; Bian, Tengfei; Xing, Chengguo. Kava and its Kavalactones Inhibit Norepinephrine-induced Intracellular Calcium Influx in Lung Cancer Cells. Planta Medica. 2019. Available at: https://doi.org/10.1055/a-1035-5183.

“…kava consumption may reduce human cancer risk, and in vitro and in vivo models suggest chemopreventive potential against carcinogen-induced tumorigenesis… our study suggests a novel mechanism through which kava and its ingredients potentially offer the anxiolytic and cancer-preventive activity”

Liu, Zhongbo; Song, Liankun; Xie, Jun; Wu, Xue-Ru; Gin, Greg E.; Wang, Beverly; Uchio, Edward; Zi, Xiaolin. Kavalactone Kawain Impedes Urothelial Tumorigenesis in UPII-Mutant Ha-Ras Mice via Inhibition of mTOR Signaling and Alteration of Cancer Metabolism. Molecules 2023, 28(4), 1666. Available at: https://doi.org/10.3390/molecules28041666.

“…mice fed with kawain food showed significantly more enrichment of serotonin and less abundance of xylulose, prostaglandin A2, D2 and E2 compared to those from control diet- fed mice, suggesting decreased shunting of glucose to the pentose phosphate pathway (PPP) and reduced inflammation. In addition, kawain selectively inhibited the growth of human bladder cancer cell lines with a significant suppression of 4E-BP1 expression and rpS6 phosphorylation. These observations indicate a potential impact of kawain consumption on bladder cancer prevention by rewiring the metabolic programs of the tumor cells.”

Celentano, Antonio; Yiannis, Callisthenis; Paolini, Rita; Zhang, Pangzhen; Farah, Camile S.; Cirillo, Nicola; Yap, Tami; McCullough, Michael. Kava constituents exert selective anticancer effects in oral squamous cell carcinoma cells in vitro. Nature. Scientific Reports. 2020;10:15904. Available at: https://doi.org/10.1038/s41598-020-73058-4.

“Treatment of malignant and normal oral keratinocyte cell lines with three of the identified constituents, 10 μg/ml FKA, 2.5 μg/ml FKB and 10 μg/ml yangonin, showed a significant reduction in cell proliferation in both H400 and BICR56 cancer cell lines but not in normal OKF6 cells. Remarkably, the same Kava constituents induced a significant reduction of OSCC cell migration and invasion. We have demonstrated, for the first time, that Kava constituents, FKA, FKB and yangonin have potential anticancer effects on OSCC. This highlights an avenue for further research of Kava constituents in the development of future cancer therapies to prevent and treat OSCC”

Li, X; Liu, Z; Xu, X; Blair, C.A.; Sun, Z; Xie, J; Lilly, M.B.; Zi, X. Kava components down- regulate expression of AR and AR splice variants and reduce growth in patient-derived prostate cancer xenografts in mice. PLoS One. 2012;13(2):24. doi: 10.1371/journal.pone.0031213. Available at: https://pubmed.ncbi.nlm.nih.gov/22347450/.

“Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold… The kava root extract and flavokawain B reduce tumor growth, AR expression in tumor tissues and levels of serum PSA in the patient-derived PCa xenograft models. These results suggest a potential usefulness of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR.”

Steiner, Gerd G. The correlation between cancer incidence and kava consumption. Hawaii Medical Journal. 2000;59:420-422. PMID: 11149250. Available at: https://europepmc.org/article/med/11149250

“Results/conclusions: The data indicates that the more kava consumed by a population the lower the cancer incidence for that population. The data suggests there is a close inverse relationship between cancer incidence and kava consumption”

Einbond, Linda S., Negrin, Adam, Kulakowski, Daniel M., Wu, Han-An, Antonetti, Valeria, Jalees, Farah, Law, Wing, Roller, Matthias, Redenti, Sara, Kennelly, Edward J., and Balick, Michael J. Traditional preparations of kava (Piper methysticum) inhibit the growth of human colon cancer cells in vitro. Journal of Toxicology and Environmental Health, Part A Current Issues, 2017, vol. 80, no. 3, pp. 146-154. doi: 10.1080/15287394.2016.1242515. Available at: http://dx.doi.org/10.1016/j.phymed.2016.11.002.

“Background: Epidemiological studies indicate there is low incidence of colon cancer in the South Pacific islands, including Fiji, West Samoa, and Vanuatu. Cancer incidence has been shown to be inversely associated with kava (Piper methysticum G. Forst.) ingestion”

“Results: Traditional preparations of kava inhibit the growth of breast and colon cancer cells.”

“Since kava is prepared in Micronesia by squeezing the extract through sea hibiscus bark, we assayed the growth inhibitory activity of combinations of kava and sea hibiscus sap and found that sea hibiscus enhanced the growth inhibitory effect of kava.

Conclusion: Our results show that traditional kava, alone or combined with sea hibiscus, displays activity against human cancer cells and indicate it will be worthwhile to develop and further analyze these preparations to prevent and treat colon and other cancers”

Cunha, Marcos R. R., Tavares, Mariana T., Fernandes, Thais B., Parise-Filho, Roberto. Peppers: A “Hot” Natural Source for Antitumor Compounds. Molecules. 2021 Mar 10;26(6):1521. DOI: 10.3390/molecules26061521. PMID: 33802144. Available at: https://pubmed.ncbi.nlm.nih.gov/33802144/.

“In this review, we highlight naturally occurring secondary metabolites of peppers with cytotoxic effects on cancer cell lines”

Celentano, Antonio; Tran, Andrew; Testa, Claire; Thayanantha, Krishen; Tan-Orders, William; Tan, Stephanie; Syamal, Mitali; McCullough, Michael J.; Yap, Tami. The protective effects of Kava (Piper Methysticum) constituents in cancers: A systematic review. Journal of Oral Pathology and Medicine. 2019 Jun 5; 00:1-20. DOI: 10.1111/jop.12900. Available at: https://onlinelibrary.wiley.com/doi/10.1111/jop.12900.

“Results: Of 39 papers that met the inclusion criteria, 32 included in vitro models and 13 included animal studies. A total of 26 different cancers were assessed with 32 studies solely assessing epithelial cancers, 6 mesenchymal cancers and 1 study including both. There was only one report assessing an OSCC cell line. Antiproliferative properties were demonstrated in 32 out of 39 papers. The most researched constituent of kava was flavokavain B followed by flavokavain A. Both were associated with increased expression of pro‐apoptotic proteins and decreased expression of anti‐apoptotic proteins. Further, they were associated with a dose‐dependent reduction of angiogenesis.

Conclusion: There was heterogeneity of study models and methods of investigation across the studies identified. Components of kava appear to present an area of interest with chemotherapeutic potential in cancer prevention and treatment, particularly for epithelial neoplasms. To date, there is a paucity of literature of the utility of kava components in the prevention and treatment of oral squamous cell carcinoma”

Yang, Xueqin; Zan, Tao; Yan, Huiyu; Liu, Baohua. UPLC-MS/MS determination of flavokawain B, a novel anti-tumor chemotherapeutic agent in rat plasma and its application to a pharmacokinetic study in rats. Biomedical Chromatography. 2018; e4391. Available at: https://doi.org/10.1002/bmc.4391.

“Flavokawain B (Figure S1) is a naturally occurring chalcone that can be isolated from the kava‐kava plant (Dharmaratne, Nanayakkara, & Khan, 2002). This compound is known to have promising anti‐inflammatory, antinociceptive and antitumorigenic properties (Abu et al., 2013; Lin, Kumar, Tseng, & Wang, 2009). It also has been reported to have significant antitumor activity against osteosarcoma, breast cancer, prostate cancer, oral carcinoma and lung cancer cells (Abu et al., 2015; An et al., 2012; Hseu et al., 2012; Ji et al., 2013; Tang et al., 2015)”

Da Silva, Thaís Teixeira; Martins, Júlia Braga; De Brito Lopes, Maria Do Socorro; De Almeida, Pedro Marcos; Sá, José Luiz Silva; Martins, Francielle Alline. Modulating effect of DL-kavain on the mutagenicity and carcinogenicity induced by doxorubicin in Drosophila melanogaster. Journal of Toxicology and Environmental Health, Part A: Current Issues. 2021 Jun 27;84(12):769-782. Available at: https://doi.org/10.1080/15287394.2021.1942354.

“Kavain, kavalactone, present in Piper methysticum [kava] exhibits anticonvulsive, analgesic, anxiolytic, antiepileptic, antithrombotic, anti-inflammatory and antioxidant properties…when kavain was combined with DXR [chemotherapeutic drug, doxorubicin] synergistic induction of tumors by the chemotherapeutic drug occurred indicating that kavain enhanced the carcinogenic action of DXR”

Chen, George G., and Lai, Paul B.S. Novel Apoptotic Regulators in Carcinogenesis. Springer Dordrecht Heidelberg New York London, 2012. ISBN 978-94-007-4916-0, ISBN 978-94-007-4917-7, DOI 10.1007/978-94-007-4917-7. Library of Congress Control Number: 2012946196.

“Flavokawain A and B are naturally-occurring chalcones existing in several plant products, including Piper methysticum Forst. (Kava)… These plant products have been safely used as herbal medicine, social drink and food for thousands of years and have beneficial potentials of promoting general health. Flavokawain A and B have recently been identified as novel apoptosis inducers against many cancer cells”

Kłósek, M., Kuropatnicki, A. K., Szliszka, E., Korzonek-Szlacheta, I., & Król, W. (2017). Chalcones Target the Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) Signaling Pathway for Cancer Chemoprevention. In Nutrition and Functional Foods for Healthy Aging (pp. 233-244). Academic Press. Available at:https://www.sciencedirect.com/science/article/pii/B9780128053768000204.

“Chemoprevention is one of the most promising approaches for arresting many types of cancer cells or reversing the process of carcinogenesis. Preclinical and epidemiological studies have shown that chalcones can inhibit cancerogenesis at very early stages”

Tang, Yaxiong; Li, Xuesen; Liu, Zhongbo; Simoneau, Anne R.; Xie, Jun; Zi, Xiaolin. 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. International Journal of Cancer. 2010 Aug 20;127(8):1758- 68. doi: 10.1002/ijc.25210. Available at: https://onlinelibrary.wiley.com/doi/10.1002/ijc.25210.

“We have shown that flavokawain B (FKB), a kava chalcone, is about 4- to 12-fold more effective in reducing the cell viabilities of androgen receptor (AR)-negative, HRPC [hormone- refractory prostate cancer] cell lines DU145 and PC-3 than AR-positive, hormone-sensitive prostate cancer cell lines LAPC4 and LNCaP, with minimal effect on normal prostatic epithelial and stromal cells. FKB induces apoptosis with an associated increased expression of proapoptotic proteins: death receptor-5, Bim and Puma and a decreased expression of inhibitors of apoptosis protein: XIAP and survivin. Among them, Bim expression was significantly induced by FKB as early as 4 hr of the treatment… Furthermore, FKB treatment of mice bearing DU145 xenograft tumors results in tumor growth inhibition and increases Bim expression in tumor tissues. Together, these results suggest robust mechanisms for FKB induction of apoptosis preferentially for HRPC and the potential usefulness of FKB for prevention and treatment of HRPC in an adjuvant setting.

Zi, Xiaolin and Simoneau, Anne R. Flavokawain A, a novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of Bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in mice. Cancer Research. (April 2005) 65(8): 3479–86. https://doi.org/10.1158/0008-5472.CAN-04-3803. Available at: https://pubmed.ncbi.nlm.nih.gov/15833884/.

“…our data suggest that flavokawain A may have a dual efficacy in induction of apoptosis preferentially in bladder tumors. Finally, the anticarcinogenic effect of flavokawain A was evident in its inhibitory growth of bladder tumor cells…”

Rossette, Mariana C.; Moraes, Débora C.; Sacramento, Erika K.; Romano-Silva, Marco Aurélio; Carvalho, Juliana L.; Gomes, Dawidson A.; Caldas, Hanna; Friedman, Eitan; Bastos-Rodrigues, Luciana; De Marco, Luiz. The In Vitro and In Vivo Antiangiogenic Effects of Flavokawain B. Phytotherapy Research. 2017 Oct;31(10):1607-1613. doi: 10.1002/ptr.5891. Available at: https://pubmed.ncbi.nlm.nih.gov/28816367/.

“Flavokawain B (FKB), a chalcone isolated from the root extracts of kava-kava plant, inhibits proliferation and causes apoptosis in vitro and in vivo of various cancer cell lines.”

Li, Xuesen; Pham, Victor; Tippin, Matthew; Fu, Dongjun; Rendon, Raymond; Song, Liankun; Uchio, Edward; Hoang, Bang H.; Zi, Xiaolin. Flavokawain B targets protein neddylation for enhancing the anti-prostate cancer effect of Bortezomib via Skp2 degradation. Cell Communication and Signaling. 2019 Mar 18;17(1):25. Available at:https://biosignaling.biomedcentral.com/articles/10.1186/s12964-019-0338-2.

“Flavokawain B (FKB) has been identified from kava root extracts as a potent apoptosis inducer for inhibiting the growth of various cancer cell lines, including prostate cancer… Conclusion: These findings provide a rationale for further investigating combination of FKB and Bortezomib for treatment of RB deficient, castration-resistant prostate cancer.”

Abu, Nordin; Akhtar, Muhammad Nadeem; Yeap, Swee Keong; Lim, Kian Lam; Ho, Wan Yong; Abdullah, Mohd Puad; Ho, Chai Ling; Omar, Abdul Rahman; Ismail, Jamil; Alitheen, Noorjahan Banu. 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 Complementary and Alternative Medicine 2016, 16, 86. DOI: 10.1186/s12906-016-1046-8. Available at: https://pubmed.ncbi.nlm.nih.gov/26922065/.

“Flavokawain B is a unique chalcone, which can be found in the roots of the kava-kava plant. In this study, the operational mechanism of the anti-cancer activity of a synthetic Flavokawain B (FKB) on two breast cancer cell lines, MCF-7 and MDA-MB231 was investigated… Conclusion: Our findings suggested that FKB also regulated several receptor tyrosine kinases. Overall, FKB is not only a potential candidate to be an anti-cancer agent, but as an anti-metastatic agent as well.”

Abu, Nadiah, Noor Embi Mohamed, Swee Keong Yeap, Kian Lam Lim, Muhammad Nadeem Akhtar, Ahmad Jefri Zulfadli, Boo Beng Kee, Mohd Puad Abdullah, Abdul Rahman Omar, and Norhaizan Mohd Esa Alitheen. “In Vivo Antitumor and Antimetastatic Effects of Flavokawain B in 4T1 Breast Cancer Cell-Challenged Mice.” Drug Design, Development and Therapy 9 (2015): 1401–17. doi: 10.2147/DDDT.S67976. PMID: 25834398. Available at:https://pubmed.ncbi.nlm.nih.gov/25834398/.

“Breast cancer is one of the major causes of cancer-related deaths in the world today. Any potential treatment should not only impede the growth of the tumor, but also modulate the immune system efficiently and inhibit the formation of secondary tumors. As presented in our study, FKB induced apoptosis in 4T1 tumors in vivo, as evidenced by the terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining of the tumor. FKB also regulated the immune system by increasing both helper and cytolytic T- cell and natural killer cell populations. In addition, FKB also enhanced the levels of interleukin 2 and interferon gamma but suppressed interleukin 1B. Apart from that, FKB was also found to inhibit metastasis, as evaluated by clonogenic assay, bone marrow smearing assay, real-time polymerase chain reaction, Western blot, and proteome profiler analysis. All in all, FKB may serve as a promising anticancer agent, especially in treating breast cancer.”

Sakai, Takatoshi; Eskander, Ramez N.; Guo, Yiran; Kim, Kevin J.; Mefford, Joel; Hopkins, Joseph; Bhatia, Neil N.; Zi, Xiaolin; Hoang, Bang H. Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines. Journal of Orthopaedic Research. 2012 Jul;30(7):1045-50. DOI: 10.1002/jor.22050. PMID: 22213202. Available at: https://pubmed.ncbi.nlm.nih.gov/22213202/.

“Synovial sarcomas (SS) are soft tissue sarcomas with poor prognosis, displaying a lack of response to conventional cytotoxic chemotherapy. Although SS cell lines have moderate chemosensitivity to isofamide and doxorubicin therapy, the clinical prognosis is still poor. In this article, we showed that flavokawain B (FKB), a novel chalcone from kava extract, potently inhibits the growth of SS cell lines SYO-I and HS-SY-II through induction of apoptosis…”

An, Jie; Gao, Yan; Wang, Jun; Zhu, Qianqian; Ma, Yanhui; Wu, Jianfeng; Sun, Jian; Tang, Yuping. Flavokawain B induces apoptosis of non-small cell lung cancer H460 cells via Bax- initiated mitochondrial and JNK pathway. Biotechnology Letters. 2012 Oct;34(10):1781-8. DOI: 10.1007/s10529-012-0976-6. PMID: 22729748. Available at: https://pubmed.ncbi.nlm.nih.gov/22729748/.

“…Together, these results suggest the anti-lung cancer potential of flavokawain B for the prevention and treatment of lung cancer.”

Phang, Chung-Weng; Gandah, Nur Ashikhin; Abd Malek, Sri Nurestri; Karsani, Saiful Anuar. Proteomic analysis of flavokawain C-induced cell death in HCT 116 colon carcinoma cell line. European Journal of Pharmacology. 2019, 853, 388-399. DOI: 10.1016/j.ejphar.2019.04.032. https://pubmed.ncbi.nlm.nih.gov/31014923/.

“Our results have provided novel insights into the potential molecular mechanisms underlying FKC-induced apoptosis or cell death in colon cancer cells”

Phang, Chung-Weng; Karsani, Saiful Anuar; Sethi, Gautam; Abd Malek, Sri Nurestri. Flavokawain C Inhibits Cell Cycle and Promotes Apoptosis, Associated with Endoplasmic Reticulum Stress and Regulation of MAPKs and Akt Signaling Pathways in HCT 116 Human Colon Carcinoma Cells. PLoS One 2016, 11 (2), e0148775. PMID: 26859847; PMCID: PMC4747580. https://doi.org/10.1371/journal.pone.0148775. Available at: https://pubmed.ncbi.nlm.nih.gov/26859847/.

“Flavokawain C (FKC) is a naturally occurring chalcone which can be found in Kava (Piper methysticum Forst) root. The present study evaluated the effect of FKC on the growth of various human cancer cell lines and the underlying associated mechanisms. FKC showed higher cytotoxic activity against HCT 116 cells in a time- and dose-dependent manner in comparison to other cell lines (MCF-7, HT-29, A549 and CaSki), with minimal toxicity on normal human colon cells.”

Phang, Chung-Weng; Karsani, Saiful Anuar; Abd Malek, Sri Nurestri. Induction of Apoptosis and Cell Cycle Arrest by Flavokawain C on HT-29 Human Colon Adenocarcinoma via

Ji, Tianhui; Lin, Chia-Lung; Krill, Lorraine S.; Eskander, Ramez; Guo, Yizhi; Zi, Xiaolin; Hoang, Bang H. Flavokawain B, a kava chalcone, inhibits growth of human osteosarcoma cells through G2/M cell cycle arrest and apoptosis. Molecular cancer. 2013 Jun 10;12:55. PMID: 23764122; DOI: 10.1186/1476-4598-12-55; Available at: https://pubmed.ncbi.nlm.nih.gov/23764122/.

“Conclusions: Taken together, our evidence of apoptosis and cell cycle arrest by FKB treatment with less toxicity than the standard treatments provides an innovative argument for the use of FKB as a chemotherapeutic and chemopreventive compound…”

Zhao, Xianming; Chao, Yimin L.; Wan, Qingbiao; Chen, Xueqin M.; Su, Peng; Sun, Jielin; Tang, Yuping. 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. Canadian journal of physiology and pharmacology. 2011 Dec; 89(12):875-83. PMID: 22115332; DOI: 10.1139/y11-088. Available at: https://pubmed.ncbi.nlm.nih.gov/22115332/.

“Novel effective drugs are still urgently needed in the prevention and treatment of oral adenoid cystic carcinoma (ACC). In this study, we have assessed the antitumor potential and molecular mechanisms of flavokawain B (FKB) as a kava chalcone on the ACC-2 cell line in vitro. The results demonstrated that FKB could significantly inhibit the cell proliferation of ACC-2 in a dose-dependent manner that was associated with induced apoptosis and cell cycle G2-M arrest, and the half maximal inhibitory concentration (IC50) of flavokawain-B treatment for 48 h was estimated to be 4.69 ± 0.43 μmol/L… hese results suggest Bim may be one of the potential transcriptional targets, and suggests the potential usefulness of FKB for the prevention and treatment of ACC.”

Phang, Chung-Weng; Malek, Sri Nurestri Abd; Karsani, Saiful Anuar. Flavokawain C exhibits anti-tumor effects on in vivo HCT 116 xenograft and identification of its apoptosis-linked serum biomarkers via proteomic analysis. Biomedicine & Pharmacotherapy. 2021 May; 137:110846. PMID: 33761587. DOI: 10.1016/j.biopha.2020.110846. Available at: https://doi.org/10.1016/j.biopha.2020.110846.

“Our results showed that FKC treatment significantly inhibited HCT 116 tumor growth. In vivo toxicity studies showed that administration of FKC did not cause damage to major organs and had no significant effect on body weight. FKC was found to induce apoptosis in tumor, and this was associated with increased expression of cleaved caspase-3 and decreased expression of Ki67 in tumor tissues. Our proteomic analysis identified five proteins that changed in abundance – Ig mu chain C region (secreted form), GRP78, hemopexin, kininogen-1 and apolipoprotein E. Overall, our findings demonstrated the potential of FKC as an anti-cancer agent for the treatment of colon carcinoma.”

Enhancement of Reactive Oxygen Species Generation, Upregulation of p21, p27, and GADD153, and Inactivation of Inhibitor of Apoptosis Proteins. Pharmacognosy Magazine 2017, 13 (Suppl 2), S321-S328. PMID: 28808400. https://doi.org/10.4103/0973- 1296.210180. Available at: https://www.phcog.com/article.asp?issn=0973- 1296;year=2017;volume=13;issue=50;spage=321;epage=328;aulast=Phang.

“Chalcones have been shown to exhibit anti-cancer properties by targeting multiple molecular pathways. It was, therefore, of interest to investigate flavokawain C (FKC), a naturally occurring chalcone, which can be isolated from Kava (Piper methysticum Forst) root extract… FKC markedly decreased the cell viability of HT-29 cells and the cells showed dramatic changes in cellular and nuclear morphologies with typical apoptotic features. The induction of apoptosis correlated well with the externalization of phosphatidylserine, DNA fragmentation, decreased mitochondrial membrane potential, activation of caspases, and PARP cleavage. This was associated with an increase in reactive oxygen species and a decrease in SOD activity. The protein levels of XIAP, c-IAP1, and c-IAP2 were downregulated, whereas the GADD153 was upregulated after FKC treatment. FKC induced cell cycle arrest at the G1 and G2/M phases via upregulation of p21 and p27 in a p53- independent manner. Our results provide evidence that FKC has the potential to be developed into chemotherapeutic drug for the treatment of colon adenocarcinoma.”

Abu, Nadiah; Ho, Wan Yong; Yeap, Swee Keong; Akhtar, M. Nadeem; Abdullah, Mohd Puad; Omar, Abdul Rahman; Alitheen, Noorjahan Banu. The Flavokawains: Uprising Medicinal Chalcones. Cancer Cell International 2013, 13, 102. https://doi.org/10.1186/1475- 2867-13-102. Available at: http://www.cancerci.com/content/13/1/102https://cancerci.biomedcentral.com/articles/10.1186/1475-2867-13-102 .

“…All three flavokawains may hold promising anti-cancer effects. It has also been revealed that both flavokawain A and B are involved in the induction of cell cycle arrest in several cancer cell lines… Most of the studies reveal that the flavokawains induce apoptosis instead of necrosis in cancer cell lines. This is generally a promising factor if it is further developed into the commercial line… The flavokawains also exhibited anti-cancer activities in xenograft models. Even though there have been reports regarding the liver toxicity induced by flavokawain B, this assertion has been refuted.”

Vivek R. Yadav, Sahdeo Prasad, Bokyung Sung, and Bharat B. Aggarwal. The role of chalcones in suppression of NF-κB-mediated inflammation and cancer. International Immunopharmacology. 2011, 11(3), 295-309. DOI: 10.1016/j.intimp.2010.12.006. Available at: https://doi.org/10.1016/j.intimp.2010.12.006 https://www.sciencedirect.com/science/article/pii/S1567576910004091.

“…Some of the most significant chalcones identified from these plants include flavokawin, butein, xanthoangelol, 4-hydroxyderricin, cardamonin, 2’,4’-dihydroxychalcone, isoliquiritigenin, isosalipurposide, and naringenin chalcone…Inflammatory pathways have been shown to mediate the survival, proliferation, invasion, angiogenesis and metastasis of tumors. How these chalcones modulate inflammatory pathways, tumorigenesis and immune system is the focus of this review.”

Leitzman, Petra; Narayanapillai, Sreenivasan C.; Balbo, Silvia; Zhou, Boyang; Upadhyaya, Pramod; Shaik, Aleem A.; O’Sullivan, M. Gerard; Hecht, Stephen S.; Lu, Jia; Xing, Chengguo. Kava blocks 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in association with reducing O6-methylguanine DNA adduct in A/J mice. Cancer Prevention Research. 2014 Jan;7(1):86-96. doi: 10.1158/1940-6207.CAPR-13-0301. PMID: 24403291

“Kava treatments covering the initiation stage reduced the multiplicity of lung adenomas by approximately 99%”

“Kavalactone-enriched fraction B fully recapitulated kava’s chemopreventive efficacy, whereas kavalactone-free fractions A and C were much less effective. Mechanistically, kava and fraction B reduced NNK-induced DNA damage in lung tissues with a unique and preferential reduction in O(6)-methylguanine (O(6)-mG), the highly tumorigenic DNA damage by NNK, correlating and predictive of efficacy on blocking lung adenoma formation. Taken together, these results demonstrate the outstanding efficacy of kava in preventing NNK-induced lung tumorigenesis in A/J mice with high selectivity for the initiation stage in association with the reduction of O(6)-mG adduct in DNA. They also establish the knowledge basis for the identification of the active compound(s) in kava”

Xing, Chengguo; Freeman, Breanne; Mamallapalli, Jessica; Lynch, Allison. Potential of kava in reducing lung cancer risk and associated disparities: Mechanism-based biomarker discovery and analysis. Cancer Research. 2024, 84(6 Supplement), 1015-1015. https://doi.org/10.1158/1538-7445.AM2024-1015

“Results and Analysis: One-week of kava significantly reduced the level of nicotine exposure among smokers… Biomarkers for stress (plasma cortisol and urinary total cortisol equivalents (TCE)) were significantly reduced upon one-week kava use… One-week kava exposure also increased urinary excretion of total NNAL and reduced urinary 3-methyladenine (3-mA) in participants, suggestive of its ability to reduce the carcinogenicity of nicotine-derived nitrosamine ketone (NNK)… Such biomarkers may also facilitate the translational development of effective and targeted interventions, such as kava, which may not only reduce lung cancer risk but also mitigate the associated disparities…”

– Menopause?

De Leo, Vincenzo; la Marca, Antonio; Morgante, Giuseppe; Lanzetta, Danila; Florio, Pasquale; Petraglia, Felice. Evaluation of combining kava extract with hormone replacement therapy in the treatment of postmenopausal anxiety. Maturitas 2001, 39(2), 185-188. https://doi.org/10.1016/S0378-5122(01)00197-9.

“Results: A significant reduction in HAMA score was observed in all four groups of women. The reduction was more significant in groups taking kava extract than in groups on hormones only. Discussion: The combined use of hormone replacement therapy and kava extract seems to be effective against menopausal anxiety. Kava extract accelerates resolution of psychological symptoms…”

Sun, Jidong. Morning/Evening Menopausal Formula Relieves Menopausal Symptoms: A Pilot Study. The Journal of Alternative and Complementary Medicine 2004, 9(3), 441-449. https://doi.org/10.1089/107555303765551624.

“Results: Morning/evening menopause formula (morning capsule contains panax ginseng, black cohosh, soy, and green tea extracts; evening capsule contains black cohosh, soy, kava, hops, and valerian extracts) significantly reduced the number of hot flashes. The reduction in the number of hot flashes was observed as early as at the end of the second week. At the end of the second week, the number of hot flashes was reduced by 47%. The morning/evening menopause formula also significantly reduced the GCS total and subscale scores. At the end of the eighth week, the vasomotor, anxiety, and depression scores of GCS were reduced by 50%, 56%, and 32%, respectively. Furthermore, the morning/evening menopause formula significantly reduced global PSQI score and scores in five components (sleep quality, sleep latency, sleep duration, sleep disturbance, and daytime dysfunction) by 18%-46%. Conclusions: This study suggests that the morning/evening menopausal formula is safe and effective for relieving menopausal symptoms including hot flashes and sleep disturbance.”

– Treating Anxiety and Stress Relief?

Ashwin Dhanrajji Porwal, Paresh Manilal Gandhi, Deepak Kamlakar Kulkarni, Gajanan Bhagwan Bhagwat, Pravin Prakash Kamble. Complementary and alternative medicine in patients with irritable bowel syndrome: A Pilot Study. World Journal of Advanced Research and Reviews, 2023, 19(03), 363–369. Available at: https://doi.org/10.30574/wjarr.2023.19.3.1808
“The result showed a significant reduction in anxiety and improved sleep quality with the use of Kava…”
Kilham, Christopher. Kava: Medicine Hunting in Paradise: The Pursuit of a Natural Alternative to Anti-Anxiety Drugs and Sleeping Pills. Inner Traditions / Bear & Co. 1 June 1996. ISBN 9780892816408. Available at: https://books.google.vu/books/about/Kava_Medicine_Hunting_in_Paradise.html?id=783SJS FvoucC&redir_esc=y.

Bilia, Anna R.; Gallori, Sandra; Vincieri, Franco F. Kava-kava and anxiety: growing knowledge about the efficacy and safety. Life Sciences. 19 April 2002, Volume 70, Issue 22, Pages 2581-2597. Available at: https://pubmed.ncbi.nlm.nih.gov/12269386/.

“Unlike other substances used for these purposes, kava-kava has been shown to have minimal negative effects, and possibly positive effects, on reaction time and cognitive processing. Furthermore, it decreases anxiety without the loss of mental acuity. Although kava-kava has been found to be very effective, well tolerated, and non-addictive at therapeutic dosages, potential side effects can occur when very high doses are taken for extended periods.”

Sharma, Ankit; Anchariya, Rahul; Dubey, Chetan. A Review on Anti-Stress Activity of Piper Methysticum. Asian Journal of Pharmaceutical Research and Development. 2020. Vol 8:4. Available at: https://ajprd.com/index.php/journal/article/view/688.

“…kavalactones are responsible for biological activity which include local anaesthetic, antispasmodic, Musculo-relaxant, antimycotic, sedative, anticonvulsive, analgesic, antianxiety and neuroprotective effects… Based on clinical studies Kava shows its efficacy within one week at moderate dose.”

Sonani, Snehal; Dudhamal, Tukaram S. “Pharmacological activity of Ayurveda herbal medicines in anxiety and depression: A review.” Journal of Ayurveda and Integrative Medicine 2023, 8(2), 113-123. Available at: https://www.jdrasccras.com/article.asp?issn=2279-0357;year=2023;volume=8;issue=2;spage=113;epage=123;aulast=Sonani.

“Some drugs were found to be more effective in psychotropic activity, i.e., Kava (Piper methysticum G. Forst.) and Klamath Weed (Hypericum perforatum L.) for anxiety and depression disorders, respectively.”

Sarris, Jerome; LaPorte, Emma; Schweitzer, Isaac. Kava: a comprehensive review of efficacy, safety, and psychopharmacology. Australian and New Zealand Journal of Psychiatry. 2011; 45:27–35. Available at: https://pubmed.ncbi.nlm.nih.gov/21073405/.

“The current weight of evidence supports the use of kava in treatment of anxiety… Use of traditional water soluble extracts of the rhizome (root) of appropriate kava cultivars is advised, in addition to avoidance of use with alcohol and caution with other psychotropic medications”

Pittler, Max H.; Ernst, Edzard. Kava extract versus placebo for treating anxiety. Cochrane Database of Systematic Reviews. 2003, Issue 1. Art. No.: CD003383. Available at: https://www.cochrane.org/CD003383/DEPRESSN_kava-extract-for-treating-anxiety.

“The meta-analysis of seven trials suggests a significant treatment effect for the total score on the Hamilton Anxiety Scale in favour of kava extract. Few adverse events were reported in the reviewed trials, which were all mild, transient and infrequent… Compared with placebo, kava extract is an effective symptomatic treatment for anxiety…”

Sarris, Jerome; Stough, Con; Bousman, Chad; Wahid, Zahra; Murray, Greg; Teschke, Rolf; Dowell, Ashley; Ng, Chee; Schweitzer, Isaac. Kava in the treatment of generalized anxiety disorder: A double-blind, randomized, placebo-controlled study. Journal of Clinical Psychopharmacology. 2013. 33 (5): 643–48. Available at: https://pubmed.ncbi.nlm.nih.gov/23635869/.

“Results revealed a significant reduction in anxiety for the kava group compared with the placebo group”

Garrett, Kennon M.; Basmadjian, Garo; Khan, Ikhlas A.; Schaneberg, Brian T.; Seale, Thomas W. Extracts of kava (Piper methysticum) induce acute anxiolytic-like behavioral changes in mice. Psychopharmacology. 2003. 170 (1): 33–41. Available at: https://pubmed.ncbi.nlm.nih.gov/12845414/.

“Kava has been used for centuries by Pacific Islanders for its tranquilizing and sedative effects. Recent clinical trials suggest that kava has therapeutic value for the treatment of anxiety.”

“Results: Kava extract produced statistically significant dose-dependent anxiolytic-like behavioral changes…

Conclusions: Kava extracts produce significant murine anxiolytic-like behavioral changes and sedation that are not mediated through the benzodiazepine binding site on the GABA(A) receptor complex.”

Savage, Karen; Sarris, Jerome; Hughes, Matthew; Bousman, Chad A.; Rossell, Susan L.; Scholey, Andrew; Stough, Con; Suo, Chao. Piper Methysticum (Kava) Attenuates Dorsal Anterior Cingulate Cortex GABA Levels in Generalised Anxiety Disorder. Available at SSRN: https://ssrn.com/abstract=4348556 or http://dx.doi.org/10.2139/ssrn.4348556

“Compared with placebo, the Kava group had a significant reduction of dACC GABA (p = .049) at eight weeks.”

Savage, Karen M.; Stough, Con K.; Byrne, Gerard J.; Scholey, Andrew; Bousman, Chad; Murphy, Jenifer; Macdonald, Patricia; Suo, Chao; Hughes, Matthew; Thomas, Stuart; Teschke, Rolf; Xing, Chengguo; Sarris, Jerome. Kava for the treatment of generalised anxiety disorder (K-GAD): study protocol for a randomised controlled trial. Trials. 2015, 16 (1), 493. https://doi.org/10.1186/s13063-015-0986-5. Available at: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-015-0986-5

This protocol has been implemented and the results of the randomised controlled trial are currently being reported as research groups release the findings of their studies. Please review the K-GAD study upon completion to see the latest results on kava’s promise as an anxiolytic.

– Use as an Antidepressant?

Sarris, Jerome; Kavanagh, David J.; Byrne, Gerard; Bone, Kerry M.; Adams, Jonathon; Deed, Gary. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology (Berl). 2009. 205(3):399–407. Available at: https://pubmed.ncbi.nlm.nih.gov/19430766/

“Results: …The pooled effect of Kava vs. placebo across phases was highly significant (p < 0.0001), with a substantial effect size (d = 2.24, eta(2)(p)). Pooled analyses also revealed highly significant relative reductions in Beck Anxiety Inventory and Montgomery-Asberg Depression Rating Scale scores. The aqueous extract was found to be safe, with no serious adverse effects and no clinical hepatotoxicity.

Conclusions: The aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression.”

Munir, Samman; Shahid, Aqsa; Aslam, Bilal; Ashfaq, Usman Ali; Akash, Muhammad Sajid Hamid; Ali, Muhammad Akhtar; Almatroudi, Ahmad; Allemailem, Khaled S.; Rajoka, Muhammad Shahid Riaz; Khurshid, Mohsin. The Therapeutic Prospects of Naturally Occurring and Synthetic Indole Alkaloids for Depression and Anxiety Disorders. Evidence- Based Complementary and Alternative Medicine. 2020. Available at: https://doi.org/10.1155/2020/8836983.

“Piper methysticum is used as a beverage named kava, which gives a happy state of mind while decreasing anxiety and fatigue… [DHM] facilitates an anxiolytic effect and serves as an antidepressant medicine. Double-blind, placebo-controlled investigations revealed that kavalactone compounds exert antianxiety activities without decreasing the motor and mental functions as well as by improving the sleep quality. Kavalactones have also been used as an alternative to the use of benzos in the treatment of depression”

Muszyńska, Bożena; Łojewski, Maciej; Rojowski, Jacek; Opoka, Włodzimierz; Sułkowska- Ziaja, Katarzyna. Natural products of relevance in the prevention and supportive treatment of depression. Psychiatria Polska. 2015;49(3):435-453. PL ISSN: 0033-2674 (PRINT), ISSN: 2391-5854. Available at: http://dx.doi.org/10.12740/PP/29367.

“P. methysticum is an antidepressant plant.”

Hamid, Hazrulrizawati A.; Ramli, Aizi N. M.; Yusoff, Mashitah M. Indole Alkaloids from Plants as Potential Leads for Antidepressant Drugs: A Mini Review. Frontiers in Pharmacology. 2017;8:96.

“A majority of the selected plants species reviewed were studied at in vivo level, a few study in vitro and only kava had undergone clinical trials… Dihydromethysticin is one of the six major kavalactones found in the kava plant… It contributes toward anxiolytic activity and act as antidepressant drugs. Double-blind placebo-controlled studies demonstrated that kavalactones effect anxiolytic activities without depressing mental and motor functions and improves the quality of sleep. Kavalactones is an alternative to replace the usage of benzodiazepines in depression therapy (Malsch and Kieser, 2001).”

Malsch, U.; Kieser, M. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Psychopharmacology. 2001;157:277-283. doi: 10.1007/s002130100792.

“A 5-week randomized, placebo-controlled, double-blind study was carried out to investigate the efficacy of kava-kava special extract WS®1490 in non-psychotic nervous anxiety, tension and restlessness states… WS®1490 was superior to placebo regarding the HAMA (P=0.01) and Bf-S (P=0.002) total scores and all secondary efficacy measures”

– Insomnia and Improved Sleep?

Wheatley, David. Stress-induced insomnia treated with kava and valerian: singly and in combination. Human Psychopharmacology. 2001;16(4):353-356. doi:10.1002/hup.299. ISSN: 1099-1077. PMID: 12404572. S2CID: 37457833. Available at: https://doi.org/10.1002/hup.299 https://onlinelibrary.wiley.com/doi/10.1002/hup.299.

“Total stress severity was significantly relieved by both compounds individually…These results are considered to be extremely promising…”

Singh, Yadhu N.; Singh, Nirbhay N. Therapeutic potential of kava in the treatment of anxiety disorders. CNS Drugs. 2002;16(11):731-743. doi:10.2165/00023210-200216110-00002. PMID: 12383029. S2CID: 34322458.

“Clinical studies have shown that kava and kavalactones are effective in the treatment of anxiety at subclinical and clinical levels, anxiety associated with menopause and anxiety due to various medical conditions.”

“Its biological effects, due to a mixture of compounds called kavalactones, are reported to include sedative, anxiolytic, antistress, analgesic, local anaesthetic, anticonvulsant and neuroprotective properties”

– Anti-Inflammatory Properties?

Yang, Hui-Ling; Yang, Tsung-Ying; Gowrisankar, Yenuganti V.; Liao, Chien-Hung; Liao, Jiunn-Wang; Huang, Pei-Jane; Hseu, You-Cheng. Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2/ARE-Mediated Antioxidant Genes and Inhibition of ROS/NFκB Signaling Pathways in Primary Splenocytes.Oxidative Medicine and Cellular Longevity. 2020;2020:3476212. Available at: https://doi.org/10.1155/2020/3476212

“Flavokawain A (FKA) is a novel chalcone derived from the kava plant that is known to have medicinal properties. This study was aimed at demonstrating the antioxidant molecular mechanisms mediated by FKA on lipopolysaccharide- (LPS-) induced inflammation… We conclude that with its potent antioxidant and antiinflammatory properties, chalcone flavokawain A could be a novel therapeutic agent in the treatment of inflammation associated diseases”

Park, Chung; Han, Jong-Min. Anti-inflammatory Effects of Flavokavain C from Kava (Piper methysticum) Root in the LPS-induced Macrophages. Journal of the Society of Cosmetic Scientists of Korea. 2016;42(4):311-320.

“Abstract: Kava (Piper methysticum, P. methysticum) is used as traditional herbal medicine for urogenital diseases, rheumatisms, gastrointestinal problems, respiratory irritations, and pulmonary pains. We identified a flavokavain C (FKC) from P. methysticum, which showed anti-inflammatory activity on nuclear factor κB (NF-κB)-dependent nitric oxide (NO) production and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. FKC inhibited accumulation of reactive oxygen species (ROS), such as hydrogen peroxide, and was able to dose-dependently reduce the LPS-induced NO production and the expression of various inflammation-associated genes (iNOS, IL-1β, IL-6) through inhibition of NF-κB and MAPKs (ERK and JNK). In conclusion, these results indicate that FKC may have the potential to prevent inflammation process including NF-κB and MAPKs pathways, and it could be applicable to functional cosmetics for anti-inflammation and antioxidant properties.”

– Reducing Inflammation in Patients Undergoing Active Cancer Treatment?

Yiannis, Callisthenis; Huang, Kevin; Tran, An Nhien; Zeng, Cathy; Dao, Emily; Baselyous, Oliver; Mithwani, Muaaz Adil; Paolini, Rita; Cirillo, Nicola; Yap, Tami; McCullough, Michael; Celentano, Antonio. Protective effect of kava constituents in an in vitro model of oral mucositis. Journal of Cancer Research and Clinical Oncology. 2020;146:1801-1811. Available at: https://doi.org/10.1007/s00432-020-03253-3.

“Conclusion: This was the first study to identify the anti-oxidative effects and safety of FKA and kavain with regard to oral keratinocytes, highlighting their potential use in the development of a preventative treatment for oral mucositis.”

– Liver Protection?

Dong, Renchao; Yang, Xiaobo; Wang, Changyuan; Liu, Kexin; Liu, Zhihao; Ma, Xiaodong; Sun, Huijun; Huo, Xiaokui; Fu, Ting; Meng, Qiang. Yangonin protects against non-alcoholic fatty liver disease through farnesoid X receptor. Phytomedicine 2019, 53, 134-142. doi: 10.1016/j.phymed.2018.09.006. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0944711318302873.

“Non-alcoholic fatty liver disease (NAFLD) is currently evolving as the most common liver disease worldwide… To date, no effective drug therapies for this condition have been approved.

Results: Yangonin had obvious protective effects… yangonin attenuated lipid accumulation in the liver… Furthermore, yangonin modulated blood glucose homeostasis… Also, yangonin increased insulin sensitivity…

Conclusions: Yangonin protects against NAFLD due to its activation of FXR signalling to inhibit hepatic lipogenesis and gluconeogenesis, and to promote lipid metabolism and glycogen synthesis, as well as insulin sensitivity.”

Kong, Lina; Dong, Renchao; Huang, Kai; Wang, Xiaohui; Wang, Dalong; Yue, Nan; Wang, Changyuan; Sun, Pengyuan; Gu, Jiangning; Luo, Haifeng; Liu, Kexin; Wu, Jingjing; Sun, Huijun; Meng, Qiang. Yangonin Modulates Lipid Homeostasis, Ameliorates Cholestasis and Cellular Senescence in Alcoholic Liver Disease via Activating Nuclear Receptor FXR. Phytomedicine. 2021 Sep;90:153629. Available at: https://pubmed.ncbi.nlm.nih.gov/34304130/.

“Alcoholic liver disease (ALD) is a progressive disease beginning with simple steatosis but can progress to alcoholic steatohepatitis, fibrosis, cirrhosis, and even hepatocellular carcinoma… It is unfortunately that there are currently no approved therapeutic drugs against ALD… Conclusions: YAN exerted significant hepatoprotective effects against liver injury triggered by ethanol via FXR-mediated target gene modulation.”

“Yan has protective effect against alcoholic liver disease.”

“Yan alleviated lipid metabolism disorder and hepatic steatosis via inhibition of SREBP-1c, FAS and SCD1 protein expression.”

Dong, Renchao; Wang, Xiaohui; Wang, Lu; Wang, Changyuan; Huang, Kai; Fu, Ting; Liu, Kexin; Wu, Jingjing; Sun, Huijun; Meng, Qiang. Yangonin Inhibits Ethanol-Induced Hepatocyte Senescence via miR-194/FXR Axis. European Journal of Pharmacology. 2021, 890, 173653. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0014299920307457.

“- Yan alleviated ethanol-induced liver injury via inhibition of cellular senescence.

– MiR-194 inhibition and FXR activation improved ethanol-exposed hepatocytes damage and cellular senescence.

– Yan prevent liver injury via regulating miR-194/FXR axis from ethanol exposure.”

– Improved Gut Health?

Wang, Jie; Gao, Lu; Zhang, Yan; Huang, Yufang. Kava and its compounds: potential effects on neurological diseases and gut microbiota. Journal of Functional Foods 2021, 80, 104451.

“The results suggest that kava and its active components may be used as a potential therapeutic agent for neurological diseases, such as Parkinson’s disease and Alzheimer’s disease, which are associated with gut microbiota dysbiosis.”

Sarris, Jerome; Byrne, Gerard J.; Cribb, Luke K. Kava: A Comprehensive Review of Efficacy, Safety, and Psychopharmacology. Australian and New Zealand journal of psychiatry 2011, 45 (1), 27-35. DOI: 10.3109/00048674.2010.522554. Available at: https://journals.sagepub.com/doi/abs/10.3109/00048674.2010.522554.

“…kavalactones may have antispasmodic effects on smooth muscle, which could be useful in conditions such as irritable bowel syndrome.”

Ma, Yunfeng; Han, Hyeun-Kyoo; Eun, Ju Seong; Kim, Hyun-Soo; Jeong, Jin-Hyung; Kim, Youngsoo. Kavalactones isolated from Piper methysticum inhibit pro-inflammatory cytokine production in lipopolysaccharide-stimulated RAW264.7 macrophages by targeting NF-κB, STAT3, and the PI3K/Akt/mTOR pathway. Journal of Functional Foods 2020, 65, 103741. Available at: https://www.sciencedirect.com/science/article/abs/pii/S1756464620306251.

“In conclusion, our results suggest that KLs [kavalactones] isolated from Piper methysticum possess anti-inflammatory activity by downregulating the expression of pro-inflammatory cytokines through the NF-κB, STAT3, and PI3K/Akt/mTOR pathways. Therefore, KLs could be used as potential therapeutic agents against inflammatory diseases.”

Korczak, Maciej; Pilecki, Maciej; Granica, Sebastian; Gorczynska, Aleksandra; Pawłowska, Karolina A.; Piwowarski, Jakub P. Phytotherapy of Mood Disorders in the Light of Microbiota-Gut-Brain Axis. Phytomedicine 2023, 111 (154642).

– Anthelmintic Treatment Against Parasitic Worms?

Otoguro, Kazuhiko; Iwatsuki, Masato; Ishiyama, Aki; Namatame, Miyuki; Nishihara- Tsukashima, Aki; Kiyohara, Hiroaki; Hashimoto, Toshihiro; Asakawa, Yoshinori; O ̄mura, Satoshi; Yamada, Haruki. In Vitro Antitrypanosomal Activity of Some Phenolic Compounds from Propolis and Lactones from Fijian Kawa (Piper methysticum). Journal of Natural Medicines 2012, 66, 558-561. DOI: 10.1007/s11418-011-0613-z. Available at: https://link.springer.com/article/10.1007/s11418-011-0613-z.

“…dihydrokawain exhibited high or moderate selective and potent antitrypanosomal activity… Dihydrokawain showed the highest antitrypanosomal activity, with an IC50 value of 0.63 μg/ml, and its activity was 2.5 to 3.6-fold more potent than suramin and eflornithine respectively”

Herath, H.M.P. Dilrukshi; Preston, Sarah; Jabbar, Abdul; Garcia-Bustos, Jose; Addison, Russell S.; Hayes, Sasha; Ralid, Topul; Wang, Tao; Koehler, Anson V.; Chang, Bill C.H.; Hofmann, Andreas; Davis, Rohan A.; Gasser, Robin B. Selected α-Pyrones from the Plants Cryptocarya novoguineensis (Lauraceae) and Piper methysticum (Piperaceae) with Activity against Haemonchus contortus in Vitro. International Journal of Parasitology: Drugs and Drug Resistance 2019, 9, 72-79. DOI: 10.1016/j.ijpddr.2018.12.006. Available at: https://pubmed.ncbi.nlm.nih.gov/30739078/.

“we screened 7500 plant extracts for in vitro-activity against the barber’s pole worm, Haemonchus contortus, a highly significant pathogen…

…kavalactones induced a lethal, eviscerated (Evi) phenotype in treated exsheathed third- stage larvae …in an irreversible manner.”

Herath, H.M.P. Dilrukshi; Taki, Aya C.; Nguyen, Nghi; Garcia-Bustos, José; Hofmann, Andreas; Wang, Tao; Ma, Guangxu; Chang, Bill C.H.; Jabbar, Abdul; Sleebs, Brad E.; Gasser, Robin B. Synthetic Kavalactone Analogues with Increased Potency and Selective Anthelmintic Activity against Larvae of Haemonchus contortus In Vitro. Molecules 2020, 25, 2004. DOI: 10.3390/molecules25082004. Available at: www.mdpi.com/journal/molecules.

“In a previous investigation, we had identified three kavalactones that inhibit larval development of Haemonchus contortus in an in vitro-bioassay. In the present study, we synthesized two kavalactones, desmethoxyyangonin and yangonin, as well as 17 analogues thereof, and evaluated their anthelmintic activities… These findings confirm the previously- identified kavalactone scaffold as a promising chemotype for new anthelmintics and provide a basis for a detailed SAR investigation focused on developing a novel anthelmintic agent”

– Natural Control Against Crop Pests?

Lestari, Martina S.; Himawan, Toto; Abadi, A. Latief; Retnowati, Rurini. Consumption Efficiency of Leaf Extracts of Piper methysticum G. Forst Against Larvae of Plutella xylostella L. (Lepidoptera: Plutellidae). In Proceedings of International Workshop and Seminar: Innovation of Environmental-Friendly Agricultural Technology Supporting Sustainable Food Self-Sufficiency; ISBN 978-602-344-252-2, DOI: 10.5281/zenodo.3345841; 2019; p 695.

“These plants are effective as antifugal, antibiotics, antiseptic, antimicrobial and narcotic as well as effective for controlling fungal Alternaria solani Ell. & Mart. (Pleosporaceae). Botrytis cinerea (De Bary) Whetzel. (Sclerotiniaceae). Ceratocystis ulmi Buism. Sclerotinia fructicola G.Winter. (Sclerotiniaceae) (Grainge and Ahmed. 1988)”

– Herbicidal and Antifungal Properties?

Xuan, Tran Dang; Elzaawely, Abdelnaser Abdelghany; Fukuta, Masakazu; Tawata, Shinkichi. Herbicidal and Fungicidal Activities of Lactones in Kava (Piper methysticum). Journal of Agricultural and Food Chemistry 2006, 54(3), 720–725. Available at: https://doi.org/10.1021/jf0519461.

“These six major lactones in kava roots showed great herbicidal and antifungal activities. Growth of lettuce and barnyardgrass were significantly inhibited at 1−10 ppm, and four plant fungi including Colletotrichum gloeosporides, Fusarium solani, Fusarium oxysporum, and Trichoderma viride were significantly inhibited at 10−50 ppm.”

– Anticonvulsant Properties?

Jaiswal, Yogini; Shaikh, Mohd. Farooq; Wang, Ilya; Yong, Yanning; Lee, Vanessa Lin Lin; Williams, Leonard. Evaluation of Anti-Convulsive Properties of Aqueous Kava Extract on Zebrafish Using the PTZ-Induced Seizure Model. Brain Sciences 2020, 10, 541. DOI: 10.3390/brainsci10080541. Available at: www.mdpi.com/journal/brainsci.

“The results indicate that aqueous extract of Kava stems without peel after 45 min of pre- treatment exhibited anti-convulsive potential at the dose of 50 mg/L. This study provides evidence to the anti-convulsive properties of peeled Kava stems and its potential for investigation and design of candidate anti-convulsive drugs…This effect is comparable to the therapeutic effects of diazepam in terms of seizure intensity and onset time”

– Improved Sexual Function?

Sarris, Jerome; Stough, Con; Bousman, Chad A.; Wahid, Zahra T.; Murray, Greg; Teschke, Rolf; Savage, Karen M.; Dowell, Ashley; Ng, Chee; Schweitzer, Isaac. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction and sexual effects. Phytotherapy Research. 2013 Nov; 27 (11), 1723-1728. https://doi.org/10.1002/ptr.4916. Available at: https://pubmed.ncbi.nlm.nih.gov/23348842/.

“The study design was a 6-week, double-blind, randomized controlled trial (n = 75) involving chronic administration of kava… or placebo for participants with generalized anxiety disorder. Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava. No differences in withdrawal or addiction were found between groups. Interesting, kava significantly increased female’s sexual drive compared to placebo (p = 0.040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males. Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole sample.”

Brunetti, Pietro; Lo Faro, Alfredo Fabrizio; Tini, Anastasio; Busardò, Francesco Paolo; Carlier, Jeremy. Pharmacology of Herbal Sexual Enhancers: A Review of Psychiatric and Neurological Adverse Effects. Pharmaceuticals (Basel) 2020, 13(10), 309. DOI: 10.3390/ph13100309. Available at: https://pubmed.ncbi.nlm.nih.gov/33066617/.

“The plant has also been used in traditional medicine, first as a treatment for venereal diseases, then later as a sedative and treatment for anxiety and sleep disorders, to decrease fatigue, and to relieve pain… Kava extracts produce a similar activity profile as that of benzodiazepines, which interact with GABA receptors, inhibit the MAO-B, and inhibit dopamine and noradrenaline reuptake in the CNS, inducing libido-enhancing properties”

Gupta, Ramesh C.; Lall, Rajiv; Srivastava, Ajay. Nutraceuticals Efficacy, Safety, and Toxicity Second Edition; Elsevier: 2020; ISBN: 978-0-12-821038-3.

“Prepared from the rhizome of a tropical shrub (Piper methysticum Forst F.), kava has been used for hundreds of years in beverages for social and recreational events in the South Pacific (IARC, 2016). In Europe, kava has been used as a diuretic, as well as a treatment for gonorrhoea and nervous disorders. In recent years kava has been used as a dietary supplement for therapeutic purposes in Europe and the United States to relieve tension, anxiety, stress, and restlessness.”

Presented here is just the tip of the research iceberg. We hope that it inspires you to do some digging around for yourself. Again, the links, papers, and quotations above are just snippets of what’s available, and we at Root & Pestle are not promoting one idea over another or making any claims about kava, other than that it is a fascinatingly fantastic beverage. We would love to increase awareness about this remarkable plant, but we don’t represent any of our products as replacements for professional medical care. Remember that if you have medical questions, it is best to speak to your health care practitioner. We drink kava because we enjoy how we feel after a couple of shells. We hope you will enjoy our kava too!

The team at R&P.

These statements have not been evaluated by the Food and Drug Administration.  This product is not intended to diagnose, treat, cure or prevent any disease.