Kava; 200-300 mg can cause severe liver injury

[NO HYPE]

Apart from the useful aspects of kava (in which I enjoy so much), there are some other qualities that put a damper on the fun. Kava is a potent inhibitor of the CYP 450 enzymes [Russman et al. 2005], thereby increasing the potential to experience uncontrolled, pharmacokinetic interactions with other herbs/drugs . Kavain (a biologically active component of kava) has been shown to impair vascular smooth muscle contraction via inhibition of L-type Ca[++] channels [Martin et al. 2002]. More importantly, kava is known to elicit adverse effects on liver homeostasis.

Do the benefits outweigh the negatives? That's for the individual to decide, but in any case.... I would recommend some good liver support to go along with kava.



EXCERPTS FROM:

ISSN 1007-9327 CN 14-1219/R World J Gastroenterol 2008 January 28; 14(4): 541-546
Influence of kavain on hepatic ultrastructure

Kava-kava, or kava, (Piper methysticum Forst.) is a South Pacific plant that has been used by indigenous people as an intoxicating traditional beverage since ancient times[1-4]. Various preparations of kava have been marketed since the 1980s, especially in Europe and North America to manage mild anxiety, tension, and restlessness. Some reports also indicate that kava preparations may have analgesic, spasmolytic, neuroprotective, and antimitotic activities[5-8]. However, a number of case reports have raised serious concerns about kava?s safety. These reports suggest that, occasionally, even normal doses (200-300 mg/d standardized to contain 70% kavalactones) of kava can cause severe liver injury[9-13]. On the basis of these reports, regulatory agencies have banned or restricted sale of kava and kava products in many countries.

The main active constituents believed to be responsible for the pharmacological (and perhaps toxicological) effects of Piper methysticum are the styryl a-pyrones (called kavapyrones or kavalactones). To date, 18 kavalactones have been identified, among these, six major kavalactones constitute approximately 95% of the lipid extract derived from the dried roots and rhizomes; these are kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin. Figure 1 shows kavain?s chemical structure, its molecular formula is C14H14O3, and molecular weight is 230[14-16].

The aim of this study was to investigate whether the major kavalactone, kavain, induces ultrastructural changes and function of the liver instead of biochemical perturbations. This was achieved by examining the vascular, microvascular, and hepatocellular morphological changes that might occur after perfusion of rat livers with kavain. This hypothesis was tested as there are literature evidence that kava might produce general adverse effects on the liver.

Furthermore, additional in vivo experiments might address the intriguing question of whether the effects of kavain on liver tissue are reversible, and may in part explain why patients recover from kava intoxication. Mounting literature evidence is available that dysfunction of the hepatic sinusoid can be reversed by modulating the Kupffer cell population[25] or its activation status[26]. On the other hand, it has been recently shown that acute structural and pathophysiological damage of the liver sinusoidal endothelial lining can revert to normal within days[27].

The current study only examined the effects of one kavalactone, kavain on the liver. Hence it is not possible to conclude whether the other five (dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin) major kavalactones have similar effects individually on the liver. In addition, since kava contains all the six kavalactones in combination, this pilot study has not examined any interactive or synergistic effects of these kavalactones with respect to adverse effects on the liver. It is also not able to be predicted whether kavain and other kavalactones have similar effects on human liver as has been observed here with rat liver.

This study also used only one (10 mg/mL or 43.5 mmol/L) concentration of kavain which was continuously exposed to the livers for 2 h. The choice of this exposure concentration and time was based on literature data. Plasma concentration of total kavalactones was about 33 mg/mL in a fatal human accident subsequent to kava ingestion with alcohol and cannabis[28]. The toxic concentration of kava extracts was 50 mg/mL in rat hepatocytes[29] while kavain toxic concentration (as judged by release of lactate dehydrogenase, LDH) was 125 mg/mL in mouse hepatocytes[30]. Based on this literature data, the kavain concentration in the current study was 10 mg/mL, and the results clearly show liver damage at this concentration. It would therefore be expected that at higher kavain concentrations adverse hepatic effects would be more severe. The exposure time of 2 h reflects literature evidence that livers remain normal during perfusions up to 3 h[18]. The structural changes observed after kavain exposure are therefore genuine as control perfusions revealed normal liver architecture. However, it is not known if the effects of kavain noted here are acute or chronic or if the effects are reversible since the livers were continuously exposed to kavain for 2 h. Since only one kavain concentration was used, it is not known if the effects observed here are concentration-dependent and what the minimum hepatotoxic concentration of kavain is. http://www.wjgnet.com/1007-9327/14/541.asp

[NO HYPE]

Kava root extract is available online, as a potent standardized extract (e.g. 90% kavalactones).

[terracotta]

Canada is one of the countries that has banned kava.

[NO HYPE]

Canada is one of the countries that has banned kava.

I'm wondering how much shelf-life is actually left for the stuff here in the US?

[gmystique]

I wish there was more research on this stuff, anyone know if the kava root powder has the same potential for liver injury?

[SIRT1]

I thought kava was only bad if you consumed the leaves or stems. I thought the roots were fine to take

[Catchol]

Where are the numerous and widespread cases of liver failure that we should see in Western Pacific Islanders who consume large amounts of Kava?

In my opinion, the risks of kava are greatly overstated and are primarily motivated by the pharmaceutical establishment's (of which I'm technically a part of) well-justified fear of highly-effective yet un-patentable drugs.

[Outside backer]

i thought this was proven false

[gmystique]

i thought this was proven false

funny how these new adverse research findings came around the same time the European union lifted their ban of Kava

[1veedo]

I thought kava was only bad if you consumed the leaves or stems. I thought the roots were fine to take

You are correct. The leaves / stems contain a known toxin to the liver but the roots appear perfectly safe. They do increase a couple liver enzymes but there's no reason to suspect it damages the liver, considering there are studies showing that indigenous people who consume kava don't have any increased incidence of liver problems despite consuming pounds of kava root a week. Interesting enough they do have much lower rates of some cancers compared to the rest of the world, even though some populations are heavy cigarette smokers.

[Lag]

Here's some more info on it: http://www.erowid.org/plants/kava/kava.shtml

I recommend staying away from it, or just taking milk thistle right before taking kava, which would help.