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What do you guys think of this study?

Discussion in 'Kava Lounge' started by Larp Jango, Aug 6, 2019.

  1. Larp Jango

    Larp Jango Member

  2. Kapmcrunk

    Kapmcrunk The Kaptain of Crunk KavaForums Founder

    Hmm, Brazil. @Krunʞy how's the kava in Brazil?

    The only thing I can say about this study is that if this were universally true, you would see many many people, those here included and myself, popping up on liver tests as having issues.

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    The bilirubin in these charts is extremely high. Quite unlike anything we've seen with kava drinkers. A normal level is 1.2mg/dl so if I had my 2 cents to add I would say this person had issues with the liver far before they ever found kava. Looks like the patient went almost up to 30mg/dl
    kasa_balavu likes this.
  3. Alia

    Alia 'Awa Grower/Collector

    Regarding this paper posted by- @ Larp Jango
    It seems they are referring to an extract of kava, not kava. If that is correct then we cannot be sure what was in it. If an extract then all bets are off and I think it was an extract so to repeat myself- Not Kava . A much smarter, than me, friend of mine said this--
    "My issue with it is that I don't agree with how they use the RUCAM scale. They make at least one error in their assessment that contradicts the data included in the article itself. They say the ALT levels dropped by 50% within 8 days, but their own graph shows that this doesn't happen until about day 12. But also, that measure is supposed to indicate recovery after the person stops taking the drug in question. That isn't what happened. Instead, the patient's liver failed. So even if the ALT levels are decreasing, what does that mean given that the patient had to have a transplant when the ALT levels according to their graph were at their lowest? And does it make sense to talk about recovery within 30 days given the medical complications post-transplant, which included kidney failure? My take on that is that the second item on the scale should be rated 0 rather than +3, giving an overall score of 5 which is "possible" rather than "probable". Alternately, if you want to say that the patient did have a >50% decrease in ALT after day 30, then it should at most be rated +2. But given the course of the case I'm not sure that's how the scale is meant to be applied".
    Last edited: Aug 6, 2019
  4. kasa_balavu

    kasa_balavu Yaqona Dina

  5. Krunʞy

    Krunʞy . Admin

    I think the lack of knowledge here in Brazil has a lot to do with this study and perhaps it's findings. The lack of quality kava and testing here are quite obvious. So much so, after that experience here on that kava I purchased, I came to the conclusion that it's not worth the risk here, unless it is coming from a reputable vendor in the US.
    While this is very true, it also applies to other hebal alternatives. The average Brazilian here relies on word of mouth and often take advice from "Vendors" who are unqualified to give advice with many of these uncommon herbs, like kava.
    Kapmcrunk likes this.
  6. Kapmcrunk

    Kapmcrunk The Kaptain of Crunk KavaForums Founder

    Alia likes this.
  7. verticity

    verticity I'm interested in things

    A full text draft of the case report is available here:
    https://sci-hub.tw/https://doi.org/10.1016/j.phymed.2018.08.011

    TL/DR: It's possibly this actually is a rare case of liver failure caused by some kind of kava product. But reading the article raises many unanswered questions, and the possibility of drug interactions or preexisting conditions seems more likely to me than the abstract suggests. Also it's not clear what kind of kava product was actually involved here. Obviously it was not traditional kava as we know it.

    Description of the patient's initial presentation and other medications:

    "Female, 45 years old, admitted to a small hospital on 09/05/2016 with symptoms of nausea and jaundice since 09/03/2016. Computed tomography of abdomen within normality. Total bilirubin: 12.40mg/dl; direct bilirubin: 10.40mg/dl; Alanine methyltransferase: 2459 U/L; international normalized ratio: 1.76(Graph 1). In anamnesis, the patient disclaims alcoholism and smoking. Previous use of continuous drugs: omeprazole 20mg QD for 4 years and bromazepam 3mg QD for 2 years. Patient reports stop using bromazepam and self-medicating with herbal kava medicine 100mg QD at night. The symptoms started 52 days after the onset of kava use. On 09/05/2016, after hospital admission, the kava medication was suspended. Infectious diseases, such as hepatitis A, B, C, cytomegalovirus, Epstein bar virus, leptospirosis, and herpes, were excluded."

    So the patient said that she had been taking 2 medications every day ("QD") for several years: omeprazole and bromazepam. The paper doesn't say if the patient had any liver tests done during the prior 2-4 years when she was on those medications. According to the patient's self-report she then stopped taking the bromazepam when she started taking some sort of kava product, and then a couple months later started experiencing severe liver symptoms. The paper doesn't say if she kept taking the omeprazole during this time. The "Concomitant drug/herb" item on the RUCAM form in Fig. 1 is marked in a way that seems to indicate they didn't think the patient's prior use of bromazepam or possibly continuing use of omeprazole was significant. Specifically "Concommitant drug/herb with incompatible time to onset" is marked with 0, but my question is how can they be certain that the onset time was not earlier without having test results from the prior years, in which case that item would be -1 or -2 subtracted from the total.. And both of those meds have had their own reported liver issues:

    Omeprazole AKA Prilosec is used for gastric reflux. The NIH Livertox database gives it a rating of "B (rare but likely cause of clinically apparent liver injury)": https://livertox.nlm.nih.gov/Omeprazole.htm

    Bromazepam is a benzodiazapine that is not available in the US, so there isn't any info on the NIH Livertox site, but the Wikipedia article on bromazepam has this: "Leukopenia and liver-damage of the cholostatic type with or without jaundice (icterus) have additionally been seen; the original manufacturer Roche recommends regular laboratory examinations to be performed routinely."

    Another thing the paper is not really clear about is what kind of kava product or extract these capsules actually were. It has this confusing description of the chemical analysis:

    "The quality control reports indicated extraction with methanol, and all the chemical and microbiological requirements were met. The capsules used by the patient were submitted to constituents and contaminants investigation. Chemo-profiling was performed by HPLC/ESI-MS/MS.The drug used by the patient was compared to a sample purchased at the same pharmacy a few months later. In this study, the drug purchased by the researchers was considered the control. Both medicines were 100-mg kava capsules. For the possible contaminants, Aflatoxins(AfB1, AfB2, AfG1, AfG2 e AfM1) and Ochratoxin A werere searched by HPLC/ESI-MS/MS, with the Multiple Reaction Monitoring method. The results showed that all Kavalactones, Flavocaine B, Pipermetistina, and other specifications were within the standards. Similarly, the research for Aflatoxins and Ochratoxin A was negative. Graph 2 shows that there was some reduction in the concentration of constituents in the patient sample, however, this can be attributed to the natural degradation of the drug. Besides, the environmental conditions in which the plant developed could also contribute to the constituents variation (Graphs2 and 3). We reject the hypothesis that there are high concentrations of the kava active compounds. However, we cannot accurately state that the capsule had 100 mg of kava since the control used was not a standard."

    Comments:

    "The quality control reports indicated extraction with methanol" - WTF?? Does that mean the product was a methanol-based extract??!! I certainly hope not because methanol is highly toxic and that should not be legal anywhere.. More likely it means the analytical method used methanol extraction, which would be an irrelevant detail and does not answer the question I really want to know of how the product was made.

    "The results showed that all Kavalactones, Flavocaine B, Pipermetistina, and other specifications were within the standards." - So they measured KLs, FKB and PM and found they were "within standards" but what does that mean? How much KL, FKB and PM was there in absolute terms? The paper doesn't say. Does Brazil actually have standards for acceptable levels of FKB and pipermethystin in kava products? Really? Are those levels some number higher than 0?

    All this analysis really concludes is that yes, the product contained some kavalactones in proportions suggestive of a non-noble chemotype, but not a lot of those, plus possibly unknown quantities of FKB and pipermethystin that we are assured were within some unknown standard, was free of mold toxins, and the capsules the patient had were the same as some other ones they bought in a store, but did not compare to any real standard references?
    Last edited: Aug 7, 2019
  8. El Guapo510

    El Guapo510 Member

    In my highly anecdotal and non-expert level comment: Benzodiazepines and omeprazole are both metabolized in the liver by the CYP450 enzymes neither of which combined would harm someone otherwise healthy. Again, I can only speak for myself, but I take omeprazole and propranolol with Kava (traditional prep) liver tests have been fine. I would be more concerned about the potentiating effects (increased sedation, etc) of mixing benzodiazepines and kava than I would metabolic effects as long as you are otherwise healthy. To me, it sounds more like a questionable kava product they are using plus we have no idea what her previous medical history has been or if she drinks alcohol. In some of those German studies from back in 2000 the patients reported consuming 6-10 alcoholic drinks per day along with the Kava (I have no citations for that I just remember reading it somewhere so take it with a grain of salt). Anyway, my take-away is there is simply not enough information to make any good assumption let alone an evidence-based answer.
    Last edited: Aug 20, 2019 at 7:52 AM
    verticity likes this.
  9. verticity

    verticity I'm interested in things

    I agree when you say that the cause of this case report is unknown and probably unknowable with certainty.. You are also right that all of those meds are generally safe for healthy people, and I didn't mean to imply that they were not. The liver issues reported for all three things (benzos, omeprazole and kava) are extremely rare and idiosyncratic. If the starting point is someone who is healthy, there would be no reason to avoid any of them (setting aside concern about the addictive potential of benzos). Combining different medications or combining meds with kava should always be done with caution because there is always the potential for interactions via CYP450 enzymes, but still for the vast majority of otherwise healthy people that combination would not be a huge red flag.

    But the issue with this article is that it is a case report of one person who did not start out healthy. The patient showed up at a hospital with a failing liver, and the doctors had to retroactively figure out why. They ruled out the most common causes such as alcoholism or hepatitis, and concluded that the most likely cause for the liver failure was the kava product the patient had been taking right before they came in. And it's possible that really is the case, but there are several things that raise significant doubt in my mind. In a nutshell:
    1) The patient's liver health was not assessed prior to starting the kava extract product. We don't know if they had a pre-existing condition.
    2) The patient was taking 2 other medications that also have had very rare case reports of causing liver issues.
    3) The quality control of this "kava extract product" seems highly questionable.