Emerging Controversy Around Tudei Kava

PrintAh, Tudei kava. Perhaps no varietal of kava is getting more attention or press at the moment. Unfortunately a lot of it is currently bad press, as some distinguished kava researchers such as Vincent Lebot have come forward with recommendations against drinking kava made from Tudei varieties. I was frankly shocked at how quickly Tudei kava rose in notoriety as being somehow harmful, even though the science on why it might be so is still in its initial stages. I don’t think I was alone, either: many growers, retailers and connoisseurs in the kava community were blindsided by the emerging controversy surrounding Tudei kava strains. Over the past year I’ve seen two rough camps develop, divided between those who have sworn off Tudei kava and those who are still skeptical of the supposed evidence against Tudei kava. But before I can get into the controversy, I should probably break down a few things for our readers. Like what is Tudei kava?

What is Tudei Kava?

First of all, the term Tudei or Tuday kava doesn’t refer to just one strain, but actually a group of kava strains that are classified as “ignoble” according to Vanuatu’s kava export laws [1]. Tudei kava strains tend to have dark green stems and leaves, often with lighter green spots on the leaves. They also usually grow and mature quickly compared to other kava strains. Some people prize Tudei kava varieties for their perceived long-lasting effects—the effects can reportedly last as long as two days, hence the name—which are probably due to higher levels of large, slow-to-metabolize kavalactones such as dihydromethysticin in the kava root [2]. However, the longer-lasting effects can sometimes also be accompanied by undesirable side effects such as nausea and drowsiness [1], so the kava community is really split on whether the enjoyable parts of the Tudei experience outweigh the less pleasant aspects!

In Vanuatu, Tudei kava cultivars such as Isa and Palisi are actually banned from export by law (although one can still find them, or kava vendors claiming to sell them, online). This is because only “noble” kava cultivars with a specific chemotype are legal to export or process into kava supplement products. The explanation indigenous ni-Vanuatu people give for this is that Tudei or ignoble strains like Isa are reserved for ritual and medicinal use, and are considered too potent to be everyday drinking kavas [1]. There has even been a persistent rumor in some kava circles that Tudei kava is actually Piper wichmannii, the wild form of kava, and some vendors have exploited this hearsay to add an air of potency and exoticism to the the kava they sell. However, no genetic or morphological evidence has ever substantiated the claim that Tudei kava is P. wichmannii [2]. The Tudei strains may be chemically close to P. wichmannii in their ratios of kavalactones though, which could be where this claim originated.

The Emerging Tudei Kava Controversy:

I first became aware of the doubts surrounding Tudei kava from a post made on Kava Lounge by Andrew Procyk, owner of Vanuatu Kava Bar in Asheville, North Carolina and the recently opened Noble Kava Bar in Boone, North Carolina. He linked to a video featuring semi-famous kava luminary Vincent Lebot, in which Lebot recommends against drinking Tudei kava strains such as Isa and Palisi on the basis that they contain significant amounts of flavokavain B. His recommendation was based on data that suggest flavokavain B can be cytotoxic to human liver cells in lab tests [3].

Sigh. I thought the kava liver safety scares were over after the World Health Organization determined kava to be safe back in 2007 [4], but apparently not. The good news, though, is that Lebot and other kava researchers agree there is no detectable flavokavain B in the roots of noble kava cultivars [3]—those traditionally consumed nightly in the South Pacific as part of kastom—so even if flavokavain B turns out to be something to avoid, you don’t have to swear off noble kavas bought from scrupulous vendors. So, what’s the big deal with flavokavain B?

Flavokavains A, B, and C (also spelled flavokavins or flavokawains) are not kavalactones but are actually chalconoid compounds; precursors to the flavonoids found in many pigmented food plants like dark berries and dark orange or green vegetables [5]. Flavonoids have become darlings in the nutrition science world because research has shown that many of them provide significant health benefits like lowering inflammation in tissues and acting as antioxidants. Similarly, there is evidence the flavokavains in Tudei kava might be antifungal, antibacterial, and antioxidant [5]; Dr. Xiaolin Zhi at University of California Irvine has even discovered a tumor-preventive potential of flavokavain A in lab tests on mice [6]!

Seems good so far, doesn’t it? Unfortunately, the research also suggests there are two big problems specifically with flavokavain B. First, Dr. Chris Xing of the University of Minnesota has stated that flavokavain B may deplete glutathione, an antioxidant, liver-protective enzyme [7]. In a recent video interview featured on Natural Products Insider, Xing said, “[T]hat compromises liver function for detoxification… which may contribute to the observed hepatotoxicity among kava users”. As an antioxidant, glutathione plays a crucial role in scavenging free radicals produced by mitochondria (the organelles responsible for cellular respiration), and a severe enough deficit of glutathione can be fatal for cells [8].

Even more troubling, this 2010 paper [9] found that flavokavain B also has direct toxic effects on two human liver cell lines: I’ll try not to get too technical, but the researchers found that adding flavokavain B to cultured liver cells inhibits a protein signaling pathway regulated by nuclear factor kappa B (NF-κ B) that is involved in preventing cell death caused by tumor necrosis factor alpha (TNF-α). Under healthy conditions, these two signaling pathways balance each other, but when flavokavain B is added it knocks out the NF-κ B pathway, leading to apoptosis (death) of the treated liver cells.

Two things about this study stood out to me. One was that the researchers experimented with altering different parts of this process and discovered that adding exogenous glutathione rescued the liver cells from flavokavain B-induced cell death, even when the process had already been set in motion in the treated cells [9]. I couldn’t help but be reminded of studies of kava I’ve come across stating that brews prepared using traditional cold water steeping were found to extract glutathione into the water along with the kavalactones [10]. The Kava Guru finds it hard to believe that these two pieces of data are a coincidence!

Final Verdict—Should You Avoid Tudei Kava?

Well… it’s complicated. The paper described above reports the mechanism of toxicity for flavokavain B extracted from kava kava root using an organic solvent. It’s important to remember that the amount of flavokavain B present in the extract used does not necessarily match the amount that would be found in a traditionally prepared aqueous kava brew, or a kava extract prepared using a modern solvent such as supercritical cold CO2. It’s well known that ethanol and acetone, two once-common solvents used to extract kava, extract everything in the root, not just the kavalactones, and that could include much higher levels of potentially harmful flavokavain B [8].

In fact, on page 5, table 1 of the paper, the researchers compare concentrations of flavokavain B in aqueous kava brews versus acetone- and ethanol-extracted kava extracts: kava extracts made with a 60% acetone extract contained 26 mg of flavokavain B per 1 gram of kava used, while a pure acetone extract contained 33.7 mg/g, and a 95% ethanol extract contained 32.3 mg/g [9]. How much flavokavain B did a traditional water-based Tudei kava brew contain? 0.2 mg/g [9]! What surprises me most about this outcome is that it suggests solvent-extracted kava extracts may actually have had a role in some of the liver toxicity cases of the early 2000s, a theory I thought had been debunked until now.

The very small amount of flavokavain B in an aqueous Tudei kava brew should, I think, at least give one pause before totally condemning Tudei kava as unsafe. Furthermore, in a co-op paper with Samuel X. Qiu and Rolf Teschke, Vincent Lebot explored three possible explanations for the idiosyncratic liver toxicity found in some kava users in the early 2000s [11]. One of those possible mechanisms was the presence of flavokavain B from Tudei kava, and the other two were the presence of pipermethystine from the aerial parts of kava, and possible contamination of kava roots with mold toxins (aflatoxins). In their results, the researchers noted that although both flavokavain B and pipermethystine have been shown to kill liver cells in lab tests, neither compound was detected in the commercial kava extracts tested at levels that would be of concern to human health [11]. They couldn’t detect pipermethystine at all in the extracts they tested. As for flavokavain B, even in the kava extracts where it was present, Lebot et al report that the concentration was much too low to cause harm in their experimental tests on liver cells. The conclusion of the paper states that contamination with mold aflatoxins due to poor storage conditions of the kava tested is actually the most likely explanation for the liver toxicity seen in 2002 and earlier cases [11].

Of course, no one should ignore that flavokavain B has been shown to have a detrimental effect on liver cells. But rather than state unequivocally that Tudei kavas are dangerous to consume, we have to look at all the factors in their preparation in order to make an informed choice about consuming them. A Tudei kava that has been solvent extracted and probably contains significant levels of flavokavain B might be wise to avoid. While Tudei kavas are consumed in the South Pacific, these cultures have traditionally only steeped the roots in water, and restricted them to occasional ceremonial and medicinal use rather than everyday drinking. It seems now that there is sound science behind the tradition.

REFERENCES

1. “Kava Definitions”. Kava Forums: Connecting Kava Lovers Around the World. Last modified May 30th, 2014. http://www.kavaforums.com/forum/wiki/kava-definitions/.

2. “Tudei Kava”. Kona Kava Farm. Accessed July 2nd, 2014. http://www.konakavafarm.com/kava-tudei.html.

3. Procyk, Andrew. “Drinking Tudei? Someone thinks you should probably stop.” The Kava Lounge: Science of Kava. Posted August 25th, 2013. http://kavalounge.yuku.com/topic/1576/Drinking-tudei-Someone-thinks-you-should-probably-stop#.U6iUeBZBm1A.

4. “WHO says Kava is Safe!” Kona Kava Farm Blog. Accessed July 2nd, 2014. http://www.konakavafarm.com/blog/kava-news/who-says-kava-is-safe/.

5. “Simple Test for Checking if your Kava is Tudei”. Kava Forums: Connecting Kava Lovers Around the World. Last modified May 26th, 2014. http://www.kavaforums.com/forum/threads/simple-test-for-checking-if-your-kava-is-tudei-please-read-if-youre-new-to-kava.2451/.

6. Vasich, Tom. “Can Kava Kava Cure Cancer?” UC Irvine News. Accessed June 29th, 2014. http://news.uci.edu/features/can-kava-cure-cancer/.

7. “New Science May Boost Kava Market” Insider TV: Natural Products Insider. Accessed July 2nd,2014. http://www.naturalproductsinsider.com/videos/2014/05/insider-tv-new-science-may-boost-kava-market.aspx.

8. “Dr. Xing: ‘Hepatotoxic Risk due to wrong cultivar […] and that Cultivar is Tudei Kava”. Kava Forums: Connecting Kava Lovers Around the World. Last modified May 28th, 2014. http://www.kavaforums.com/forum/threads/dr-xing-hepatotoxic-risk-due-to-wrong-cultivar-and-that-cultivar-is-tudei-kava.2557/.

9. Ping Zhou, Shimon Gross, Ji-Hua Liu, Bo-Yang Yu, Ling-Ling Feng, Jan Nolta, Vijay Sharma, David Piwnica-Worms, and Samuel X. Qiu. December 2010. “Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-kB and MAPK signaling pathways”. Federation of American Societies for Experimental Biology Journal 24 (12): 4722-4732.

10. Whitton, PA, A Lau, A Salisbury, J Whitehouse, and CS Evans. October 2003. “Kavalactones and the kava kava controversy”. Phytochemistry 64 (3): 673-9.

11. Teschke, Rolf, Samuel X. Qiu, and Vincent Lebot. September 2011. “Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits”. Digestive and Liver Disease 43 (9): 676-81.

More Evidence Suggests Kava Does not Cause Liver Problems When Used Correctly

KG-Kava Studies 211X300We have all heard of and are plagued by the infamous “German Study”, and others studies, that indicate that kava kava might cause liver problems (hepatotoxicity) – but, I am pleased to yet again offer some new insight into the fallible nature of those studies. Recently, at an Oxford annual conference on the ‘science of botanicals’, a presentation was given on new research findings about Kava that offer further evidence to suggest that pure kava kava, used correctly, does not cause liver damage! And furthermore, that Kava is actually a healthy and desirable dietary supplement, when used correctly.

At the annual Oxford conference – the International Conference on the Science and Regulation of Botanicals (ICSB), hosted by the National Center for Natural Product Research (NCNPR) – Chris Xing, Ph.D, an assistant professor at the University of Minnesota, gave a presentation on recent research findings with regard to Kava that outlined just how the German studies could have been wrong [4].

In an interview with Steve Myers – Senior Editor of Natural Products INSIDER – Dr. Xing discusses the highlights of the presentation at some length. According to Dr. Xing, it’s possible that those studies used a strain or cultivar called “Tudai Kava”. This particular strand carries a high amount of a chemical that “compromises liver function or detoxification function that may contribute to the observed hepatotoxicity among kava users” [4].

Dr. Xing and his associates, believe that the hepatotoxic cultivar “… got into the market mainly because it grows faster and offered a higher yield” [4], which stands as a warning to all of us to always do research about a product before using it! It is important to realize that, like with anything, companies will always find ways to make money faster and sometimes the ways companies choose to do this might not always be beneficial to the consumer, and can sometimes even be damaging!

According to Dr. Xing the hepatotoxicity reports then, which were very few as it is, are “probably due to a wrong cultivar, not recommended for traditional use” [4].   This information is consistent with other studies and findings on Kava that indicate the failings of the German studies. For example, an article in the Journal of Toxicology – “Liver function test abnormalities in users of aqueous Kava extracts” – discusses how island populations that have been using kava kava for centuries have no reports of problems with liver function directly related to kava use [2].

We are all very fortunate that these findings are surfacing and the reputation of Kava is being rectified, as it does provide many benefits to people, such as relaxation and anxiety relief. As Dr. Xing says, “We believe that Kava, with proper standardization, removing its hepatotoxic species…will benefit humans as an anxiolytic and dietary supplement”.

“Kava kava had a rise and a fall, and right now it looks like it’s coming back”, says Dr. Xing in his interview with Myers of INSIDER [4]. And this is wonderful news for everyone, because kava kava provides a wonderful alternative to harmful pharmaceuticals used to combat anxiety and stress-related symptoms.

Some sources, such as statisticbrain.com and the American Psychology Association (APA), indicate a rise in stress, anxiety and other related symptoms, as well as that over 70% of the United States of America’s population suffers from such symptoms [1]. Many people turn to medicinal means to combat the pain and suffering they experience as a result of mental health problems – like stress, anxiety and related symptoms. In the Western world these medicinal means have traditionally been pharmaceutical or at the very least synthesized chemical solutions. But, these solutions are damaging people’s bodies and minds! There have been reports of pharmaceuticals, like Prozac, causing brain damage that results in the development of tics and other neurological disorders [3]. Yuck, how terrible!

Fortunately, the scientific and medical community is coming to terms with the real problems that pharmaceutical and chemical solutions can cause, and more and more people are turning to natural alternatives like kava kava as an answer to their problems. I am so grateful that a better understanding of Kava is being brought to the forefront of the scientific community by Dr. Xing and others like him, so that people can see and experience just how wonderful Kava is as a healthy supplement option!

Sources:

1. American Psychological Association – American Institute of Stress, NY.  July 28, 2013. Online: http://www.statisticbrain.com/stress-statistics/

2. Clough AR, Bailie RS, Currie B.  “Liver function test abnormalities in users of aqueous kava extracts”.  Journal of Toxicology. 2003. 41(6):821-9. http://www.ncbi.nlm.nih.gov/pubmed/14677792

3. Lamvert, Craig. “The Downsides of Prozac”. Harvard Magazine, June 2000. Online: http://harvardmagazine.com/2000/05/the-downsides-of-prozac-html

4. INSIDER T.V. “New Science May Boost Kava Market”. Online: http://www.naturalproductsinsider.com/videos/2014/05/insider-tv-new-science-may-boost-kava-market.aspx

Pure Kava Kava Does Not Cause Liver Damage

Dear Kava Guru,

Can Kava really cause liver damage?

Linda, Carson City, CA

To answer your question simply – there hasn’t been any formal or concrete evidence to indicate that pure kava kava causes liver damage or toxicity. In fact, South Pacific Island populations have been using kava kava (Piper Methysticum) for centuries on end without any known incidences of liver damage [2].

Now for lengthier Kava Guru wisdom on the topic of liver damage:

Kava kava has effects that are said to be similar to those felt from the consumption of alcohol – alleviation of stress, mood elevation, contentment, and overall relaxation.  Kavalactones, the kava compounds believed to grace us with those benefits, have been shown to have anesthetic and muscle relaxation effects as well [1]. Given these much sought-after qualities, it’s no wonder it has been used as a remedy for anxiety, insomnia and other neurological disorders and is steadily growing in popularity!

Additionally, kava kava has been shown to actually improve cognitive functioning, making it a worthy alternative to other neurological medications that impair cognitive functionality. For instance, the University of Maryland Medical Center recently published an article that documents a 2004 case study.  This case suggests that 300mg of kava kava can actually improve cognitive functioning while alleviating anxiety.  As the article also indicates, this is quite a significant result given that standard anti-anxiety medications, like diazepam (Valium), have been proven to cause cognitive impairment [7].

This information could substantiate the reasoning behind the recent evidence that pharmaceutical giants  have conducted false and corrupt reports about kava kava and liver damage, in order to have them banned from hosting countries.   Given that kava kava has become an increasingly popular anti-anxiety, and insomnia remedy, with the added benefit of cognitive improvement – it’s no wonder that some may think that pharmaceutical companies might have a vested economic interest in devaluing kava kava.

Not to mention that there are even reports about “fake kava” being distributed that are actually chemical elixirs intended to induce a “high” and have nothing to do with kava at all! These elixirs are reported to cause some pretty serious health risks due to the types of toxic chemicals used in their preparation and these cases have been lumped in along with other information regarding kava – and it’s not even kava! Inevitably these types of cases end up in skewed and misinformed data regarding kava.

According to LiverTox and the World Journal of Gastroenterology, there are some documented cases indicating that some individuals have had liver damage and in a few cases required liver transplants after using kava kava [2,3].   However, several other sources, including the American Association of Family Pharmacists (AAFP) and the Journal of Toxicology have indicated that there is no evidence of permanent liver damage [5].  Additionally, Yadhu Singh – an author that writes extensively on the subject of Kava – states that these problems were not encountered with the traditionally prepared beverage, which was prepared as a water infusion.  Commercialized Kava extracts, that are extracted with organic solvents, are the source of Kava used in the potential cases of liver toxicity [4].  Further yet, a professor out of  Menzies University – Medical School has studied aboriginal populations of Australian Northern Territories, who were first introduced to kava kava as an alternative to drinking alcohol in the 1980’s, and there were no records of hepatotoxicity related to kava kava during  those studies.   And interestingly enough, the subjects of these particular cases ingested a substantially larger amount of kava kava (10-50 times) than what is recommended by European standards [9].

However, the same studies do address a temporary change in liver functionality.   This change in liver function – namely, fluctuations in the liver enzymes gamma-glutamyl transferase and alkaline phosphatase [2] – may allow for some understanding about the misrepresentation of kava kava with regard to liver damage.  Furthermore, it is important to note that changes that do occur from using kava kava, are temporary – that is, liver functions become normal after a short period of time after using kava kava. Additionally, there is some indication that kava kava ingestion could disable certain enzymes, such as cytochrome P450 and  cyclooxygenase [10]. It is possible that due to the change in liver function, enzymes normally used in the metabolizing of ethanol and other substances may not properly function during the short period of time that kava kava is in the system.  As a result, consumption of alcohol or drugs while taking kava kava could result in liver toxicity.  It is possible that the subjects of documented liver damage cases had a history of alcohol or drug abuse, and that they either had damaged livers prior to the case studies or that they were actively using other substances during the studies.  This toxicity then is not necessarily due to kava kava itself, but is more likely due to the misuse of kava kava with other substances.   It would be wise then to not use kava kava with other substances, and this recommendation does not differ from the solo-usage requirements of other medicinal remedies [6,7].

There is also a body of evidence indicating that cases of kava kava liver damage or toxicity, if any, are due to an improper usage of the plant itself.  The AAFP suggests that cases of liver damage may arise from use of parts of the plant other than the root.   The leaves, stem and other aerial parts of kava kava that are not directly derived from the root, do come up in some bodies of evidence as poisonous or toxic.  Additionally, there is evidence to suggest that the kava extracts, used by the subjects in many of the cases of liver damage, could have been impure (tainted with other substances). Many commercial kava kava extracts contain as much as %60 ethanol, and are labeled as “standardized” simply on the basis that they contain a prerequisite amount of a given substance (in this case, kava kava) [9]. This suggests poor-quality and/or contaminated kava kava raw material, as a possible explanation for toxicity – not pure kava kava derived only from the plant’s roots [5,6,7].

In his discussion of prospective considerations with regard to hepatotoxicity (liver toxicity) due to kava kava, Rolf Teschke thoroughly addresses all of the above reasons for the misinformation surrounding kava kava.  Teschke indicates that in the cases where liver damage has been linked to kava kava, there was evidence of co-medication and improper adherence to dosage recommendations.  He furthermore addresses the possibility that the incorrect, and toxic, parts of the plant were used in those studies.  “By improving kava quality [purity] and adherence to therapy recommendation under avoidance of co-medication, liver injury by kava should be a preventable disease…” (Teschke, p. 1270).

Furthermore, the Journal of Toxicology not only indicates that there have been no cases of liver damage directly and undeniably linked to kava kava, but also that there is no evidence of liver toxicity or damage in Pacific Island populations – populations that have traditionally and properly been using kava kava for centuries [2].

Also, like with pretty much anything, overly high dosages are likely to play a factor in cases of toxicity.  If you take too much kava kava, no matter the source – there are likely to be negative consequences.  It’s probably similar to how a glass of red wine a day has been proven to alleviate stress and be beneficial in other ways – and yet, as we all know, too much alcohol can be quite damaging to our livers!

Kava Guru thinks it breaks down to this: anything in large quantities, or used incorrectly, is going to reap unhealthy results.  Sources suggest that small to moderate dosages of pure kava kava root – not the stem or leaf – do have benefits and are a solid alternative to pharmaceutical methods for alleviation of anxiety, insomnia, pain and other neurological problems.

And if you take nothing else away from reading this, do remember the following three bits of wisdom:

1)   Do not combine kava kava with drugs or alcohol.  Like with most – if not all – other medicinal substances this can not only interfere with the benefit of kava kava, but could also cause liver damage (as stated in more detail above).

2)   Moderate and monitor your use!  If your intended use is for a longer duration of time – such as for medicinal purposes – then do ensure that you seek out a physician specialized in medicinal plants for advice on dosage amounts and duration.

3)  And, as any guru of any product would remind you – always do your research on the vendor! Only buy kava kava from those companies that give you a guarantee that their product is pure kava kava made strictly from the root of the plant.  If they cannot vouch for their purity, that’s probably an assurance that the product is not pure.

If you follow those three points of wisdom, you will be sure to revel in the benefits of kava kava – a comfort that has been quietly enjoyed by the traditional people of the South Pacific islands for many upon many blissfully peaceful centuries.

Mahalo,

Keith @ Kava Guru

REFERENCES:

1. Cassileth, Barrie, PHD.  “Oncology”. United Business Media LLC, San Francisco: April 15, 2011. Vol. 25-4 p. 384-385.

2. Clough AR, Bailie RS, Currie B.  “Liver function test abnormalities in users of aqueous kava extracts”.  Journal of Toxicology. 2003. 41(6):821-9. http://www.ncbi.nlm.nih.gov/pubmed/14677792

3. Fu S, Korkmaz E, Braet F, Ngo Q, Ramzan I. “Influence of Kavain on Hepatic Ultrastructure”. World Journal of Gastroenterol. January 28, 2008: 14(4): 541-546. http://www.sciencedaily.com/releases/2008/02/080222111446.htm

4. Singh, N. Yadhu. “Potential for Interaction of Kava and St. John’s Wort with Drugs”. Journal of Ethnopharmacology, 2005.  Vol 100, p. 108-113.

5. Saeed, Bloch, and Diana Antonocci.  “Herbal and Dietary Supplements for Treatment of Anxiety Disorders”.  Association of American Family Physicians, Aug 15, 2007: 76(4) p. 549-556.  http://www.aafp.org/afp/2007/0815/p549.html

6. Teschke, Rolf, MD. “Kava Hepatotoxicity: pathogenetic aspects and prospective considerations”. Liver International: October, 2010. Vol. 30-9, p. 1270-1279.

7. University of Maryland Medical Center. “Kava Kava”. Last modified: May 07, 2013. http://umm.edu/health/medical/altmed/herb/kava-kava

8. U.S. National Library of Medicine. “Kava Kava – Piper Methysticum”.  Last modified: March 03, 2014. www.livertox.nlm.nih.gov/KavaKava.htm

9. Whitton, Lau, Salisbury, Whitehouse and Christine S. Evans. “Kava Lactones and the Kava-Kava Controversy”. Pergamon: June 5, 2003. Phytochemistry (64) p. 673-679.

10. Wikipedia. “Kava-Toxicity and Safety”. Last modified: February 21, 2014. http://en.wikipedia.org/wiki/Kava#Toxicity_and_safety