High GGT and ALP

[Kava Drinker]

Hi

Does anyone know what might be the implications and consequences of elevated GGT and possible ALP. It been well reported that heavy to moderate kava drinking can raise GGT. This has been shown in Clough 2003 and the Hawaiian study which also found ALP to be elevated. Kava is not supposed to be hepatoxic however this enzymes are a marker for liver disease/damage so it they are elevated I can not see why damage is not done? I have read that GGT is a very sensitive detector towards liver damage. The WHO report on kava said that a high GGT level is a indicator of cholestasis and problems with bile ducts and the flow of bile. A have heard people give out about this before so this could be further evidence for damage even though its hard to directly say it was caused by kava. I have read aswell of ALP and GGT are both raised at the same time it nearly confirms liver damage. So does kava really not cause liver damage?
Some people say they can be elevated without damage. My doctor says a raise in these enzymes is a indicator of damage and she would recommend to stop using kava of they are elevated.

Is there any hypothesis out there for the enzymes being raised but not causing damage.


Thanks

 

[sɥɐʞɐs]

@Henry might have some info for you. I know it's been discussed to some degree here.

From what I can recall, GGT isn't a good indicator of true damage, and as such, isn't typically included on blood panel/liver tests in the US.
Almost every test result that long time daily drinkers have posted shows no elevation in liver enzymes and sometimes even a reduction...but like I said, GGT isn't included on these tests.

 

[Kava Drinker]

thanks for your reply.
I read that thread. I find it worrying as my doctor said it shows damage. as i understand its quite a sensitive indicator to cholestasis but not to hepatocellular damage. GGT is not used by some places not because it does not indicate damage but because it does not specfically indicate damage. why would they use it at all if it did not detect damage.?

what about ALP. nearly all studies out there also detected a increase in ALP. usually if ALP and GGT are elevated it is very likely for some damage or at least that what it says online.
"http://www.medscape.com/viewarticle/413420"

" GGT rise usually parallels changes in ALP in liver disease; elevations in both ALP and GGT help confirm the likelihood of a hepatic disorder."

https://www.healthline.c...-glutamyl-transpeptidase

" The GGT test is currently the most sensitive enzymatic indicator of liver damage and disease. "



throughout the years there has been many studies to support raised GGT and ALP. And while this forum is useful I do not know if it would carry the same weight as the peer reviewed published studies.


" The first study to report abnormal GGT among kava drinkers was by Mathews et al. with no quantification of the amount of kava used or rates of GGT abnormality (17). Cairney et al. (9) reported that among Australian Aboriginal kava drinkers, 73% had elevated GGT and 65% had elevated alkaline phosphatase levels. Clough et al. (19) also reported on Australian Aboriginal kava drinkers and reported elevation in GGT in 61% and alkaline phosphatase levels in 50%. Another study by Clough et al. (7) found abnormal GGT in 48% and alkaline phosphatase in 37% of their Australian Aboriginal subjects. Russmann et al. found 85% of the kava drinkers in New Caledonia in the South Pacific had abnormal GGT levels"

"The elevated levels of the liver enzymes mostly returned to normal levels after 1–2 months (for alkaline phosphatase), and 1 year (for GGT) of kava abstinence, respectively (19)."



this is what my doctor told me. "
with high GGT levels glutathione and intracellular vitamin stores gets depleted. this is a big factor in free radical production. Reactive oxygen species also oxidize HDL (cholesterol) to LDL which usually result in inflammatory response and immune reaction in the liver. This leads to fatty liver , which is the same thing that happens with alcoholics or people who ingest simple sugars from other sources in very large amounts (obese people)

Just imagine your liver slowly cooking throughout life like any other cell, now imagine speeding up the cooking,. This is what increasing GGT does (simplified)."





"Cholestasis can be due to either defective bile formation in hepatocytes or disruption to bile secretion and flow within bile ducts [45]. Mechanisms of noninflammatory cholestasis include inhibition of cellular proteins and transporters. Direct or indirect activation of Kupffer cells and their subsequent release of pro-inflammatory cytokines, growth factors, and reactive oxygen species is a cause of inflammatory cholestasis, which may involve hepatocytes or bile ducts [46]. In the absence of hyperbilirubinaemia, elevations in GGT and ALP are more likely to be due to bile duct inflammation. Each of these mechanisms could be precipitated by kava extracts and are possible explanations for the cholestasis observed in chronic, indigenous, kava users."
https://www.ncbi.nlm.nih.gov/pubmed/21541070
this says cholestasis was found in users but I thought kava does not do liver damage.?

so I am very confused with the claims of kava is not bad for the liver.

 

[verticity]

Hi, I think we discussed this here:
http://kavascience.org/posts/t64-GGT-levels

Basically the deal with kava and the liver is: epidemiological studies show that liver damage caused by kava is very uncommon, but can happen on rare occasions. The reason for this is not known, although there are lots of theories about what component of kava might be responsible, or whether it is molds on the kava or something.

Now, GGT can be indicative of liver disease, but it can also be elevated by various medications, by alcohol or tobacco use, and can also indicate problems that are not related to the liver, such as pancreatitis, heart disease or cancer. In other words, the fact that GGT and ALP are high does indicate that there might be reason for concern, but it is not conclusive proof that you have a disease. Kava might be the cause of the elevation, but it might be caused by something else, for example, if you drink alcohol.

But the bottom line is your doctor who knows you and your medical history has looked at your blood work, and on the basis of that she is concerned and has specifically recommended that you stop using kava (or I think that is what you are saying; not sure if you are posing a hypothetical). If that is the case, you should probably listen to her. We have a lot of people here who are knowledgeable about kava, be we are not doctors, and I wouldn't presume to contradict your doctor if she gives you a specific recommendation. So maybe stop the kava for a while, get your liver checked again and see if the problem is resolved. If not, there could be some other cause, which in any case would be good to get to the bottom of.

 

[Kava Drinker]

I thought I would post it here to see if anyone knew something I did not know to explain it.

from the studies out there and my own personal experience kava seems to alter GGT and ALP. I do take on board that even a GGT increase probably does not indicate liver damage but this just makes me confused due to what I said in the first post and there does not seem to be any ideas out there to why it might elevate this and not do damage.

I have talked to a lot of people about this as well as the liver and alcohol and I would honestly say from my experience 99% of the time, ( from other substances raising it or just naturally high GGT and ALP) if you have a very elevated GGT and ALP there is usually damage to the liver but this seems to contradict kava so again it does not make sense to me but I guess there is just not enough studies on this. It also did not make much sense to the authour of the Hawaii study and I was wondering if there had been any advancement of the knowledge in this area since 2007 when the study was done but there appears to be none what so ever.

Until there is more knowledge on this topic (probably wont happen ever)I will probably just stop taking it and I will just probably go back to benzos.

 

[Kava Drinker]

how often do you drink kava ? Ive never heard of much damage to the kidneys by benzos but there are safer gaba/sedative drugs out there probably than kava is really what I meant. on livertox there is nothing i can find saying benozs raise GGT or any other liver enzyme and have only been associated with "extremely rare" liver problems.?

i do not know why some doctors then are so concerned about GGT. what about ALP if that was raised should there be concern? why bother use GGT and ALP if raises in both does not detect liver damage?

 

[Kava Drinker]

http://www.healtheiron.com/about-ggt

 

[SelfBiasResistor]

How high are your numbers? I'm a heavy kava drinker and have never had high ALP. My ALP levels are actually pretty stable, even with with daily kava usage in the 10-14 Tbsp range (single session since I don't respond to low doses). GGT has never been part of the routine testing. I've had blood screens every six months for the past 3 years...

 

[verticity]

Here is a detailed article that puts GGT in perspective in the overall diagnosis of liver problems:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC545762/

It would seem important to consider the overall picture if you have concerns, not just focus on the isolated enzymes. If your doctor is concerned, she should have an ultrasound done to see if there is actually anything physically wrong, such as fatty liver. I would defer to whatever advice your doctor gives, but would also caution you that benzodiazapines are far from harmless. In particular addiction and withdrawal, as well as memory loss and behaviorial disinhibition, can be real problems--problems that kava does not have at all.

 

[kasa_balavu]

AFAIK the Australian studies were done in communities living in poverty. A terrible diet and alcohol abuse also contribute to poor liver health. There are similar questions about the Hawaiian study.
Anyone here know the truth of this?

 

[verticity]

AFAIK the Australian studies were done in communities living in poverty. A terrible diet and alcohol abuse also contribute to poor liver health. There are similar questions about the Hawaiian study.
Anyone here know the truth of this?

I think the Australian studies were flawed for that reason: they claim to control for alcohol use, but I'm skeptical of that because in fact they found that "Kava use was associated with alcohol use (P < 0.001), cannabis use (P < 0.001) and a history of petrol sniffing(P = 0.035)" *, and it does seem that the overall health of the subjects and controls was fairly poor. The Hawaiian study was mainly Tongans living in Hawaii. They were very heavy kava drinkers, but the study did I think do a better job of controlling for alcohol use, and also for ethnicity and level of education, which would be good proxies for poverty level. Also the overall rates of poly-substance use in the Hawaiian study seem to be lower, and overall health generally better. The main problem with it is that the number of people in the study was relatively small.

I have attached the text of both the Hawaiian and Australian studies so people can asses them for themselves...

* So naturally the response of the local authorities in the Aboriginal areas of Australia has been to ban both alcohol and kava, leaving petrol sniffing as the only legally available option...

 

[verticity]

...on livertox there is nothing i can find saying benozs raise GGT or any other liver enzyme and have only been associated with "extremely rare" liver problems.?
...

Livertox says this about benzos in general:

"Benzodiazepine therapy is uncommonly associated with serum enzyme elevations, and clinically apparent liver injury from the benzodiazepines is quite rare. Alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, flurazepam and triazolam have been linked to rare instances of cholestatic liver injury but the other benzodiazepines have not. The absence of reports of this rare adverse event, however, may be due to the fact that these other benzodiazepines are not as commonly or continuously used. Alternatively, the use of the sleeping aids in intermittent and low doses may favor their lack of hepatic injury."
https://livertox.nih.gov/BenzodiazepineDrugs.htm​

In other words, benzos can cause elevated liver enzymes and very rarely liver damage, which is pretty similar to the situation with kava.

The page for Valium, for example, has this:

"Like other benzodiazepines, diazepam is rarely associated with serum ALT elevations during therapy. Furthermore, clinically apparent liver injury from diazepam is exceedingly rare. A small number of cases of hepatic injury have been described in patients on oral diazepam, but the clinical pattern has varied. The onset of injury has ranged from 1 to 6 months, and pattern of serum enzyme elevations has typically been cholestatic or mixed. Fever and rash are uncommon as is autoantibody formation. In large surveys and case series of clinically apparent drug induced liver injury, diazepam and other benzodiazepines are usually not listed. There have been no case reports of hepatotoxicity from diazepam since the 1980s."

Likelihood score: D (Possible but rare cause of clinically apparent liver injury)"
https://livertox.nih.gov/DiazepamOral.htm​

That situation actually sounds very similar to kava: A small number of cases reported in the past. The site doesn't mention GGT wrt benzos, but my understanding also is that ALT elevation is a more direct indicator of liver injury than GGT.

 

[Kava Drinker]

I have been told it is unlikely the tongans from the Hawaii study drunk much alcohol at all considering isnt it against their religion. so the hawaii study is a good one to go off and it clearly indicates a positive relationship between kava consumption and high GGT and ALP. i think of the top of my head if you drunk kava you were 8 times more likely to have above the range ALP. it was 3% elevated (control) as apposed to 26%(kava group). that is quite significant.

there is alot of evidence showing kava raises GGT and probably ALP. this has been demonstrated in australia,new zealand new caledonia hawaii and various other sources and it seems to be the common denominator in nearly all of the reports so it is very unlikely for outside/external factors to be causing it.

My ALP is not above really the range it should be in but it was raised as it is lower when I do not drink kava.

When you read them GGT articles it pretty scary
"Liver and bone diseases are the most common causes of pathological elevation of ALP levels" "Cholestasis enhances the synthesis and release of ALP, " Elevated GGT levels can be observed in a variety of nonhepatic diseases, including chronic obstructive pulmonary disease and renal failure, and may be present for weeks after acute myocardial infarction. Increased serum levels observed in alcoholic liver disease can be the result of enzyme induction and decreased clearance. In these patients, GGT serum levels can be markedly altered (> 10 times the upper reference value), whereas ALP levels may be normal or only slightly altered (GGT/ALP ratio > 2.5). "Furthermore, an increase in GGT levels in patients with chronic liver disease is associated with bile duct damage and fibrosis"

so increases in GGT seems to be more associated with bile duct problems as well as heart problems. surely It is quite rational to be worried after reading that if you have high GGT. But many of you are not concerned.

Given the widespread use of benzos (more than kava) there is really no documentation of liver problems unless you already had liver problems and if you type in raised enzymes in goggle from benzos you will find nothing from the odd case there is no trend. however with kava there is a strong positive trend. I think it is clear Benzos have less of a chance of being harmful to the liver than kava. also my enzymes are never raised on zimovane. there are new benzos out there with less addiction problems and less memory problems like pryazolam with no connection to phsyical damage and may well be a better alternative to kava as I see it and maybe something people should consider if they have raised liver enzymes. I have also found magnolia bark to be a better option to kava in high doses and does not affect my liver enzymes like kava.

 

[Kava Drinker]

is someone could provide an explanation to why GGT and ALP is raised i would feel more comfortable but no one can. I heard tesche say it could be related to BMI as there is a inverse relationship between GGT and BMI and Kava drinkers have low BMI but some of the GGT levels on the studies are off the charts and BMI does not affect it that much. Ive been told by health offcials that high GGT levels are quite bad and not just for liver damage but it can indicate a serious number of problems. including heart health(there seems to be high rates of heart problems in kava drinkers) kidney health and overall mortality rates which was explained in what I posted earlier that high GGT rates is associated with death.


"
When GGT concentrations exceeded the lowest 25% to 35% of normal population ranges, disease risks grow in proportion to increases in GGT. People faced increased disease risk once GGT rose above the “low-normal” range for their gender. Medical researchers describe this phenomenon as a “dose-response relationship,” essentially, the higher the GGT concentration, the greater the risks of future diseases and premature mortality, even when GGT levels were still well-within "normal" laboratory ranges.

The high end of normal GGT laboratory ranges are generally 50–70 U/L for men and 40–45 U/L for women. Although GGT correlates with other risk factors, most research has demonstrated that elevated GGT, independent of other risk factors, predicts increased disease risk and mortality. "

 

[Kava Drinker]

so drink it if you want a increased mortality percentage

 

[Kava Drinker]

its also quite worrying that you do not drink it that much at all and your GGT is raised.

do you know any studies on this or where I could find sarris's study?

observational studies have limiatations especially when it comes to death.

i am well aware that correlation is not causation but what I have learned in statistics is that if there is correlation it suggests it is more likely the factor causes it than not.

many studies have indicated high ALP like both from cloughs two studies , the hawaii study , mathews study, cairney and I also think a new caledonia study. and not just slight increases very big increases like 3% raised (control) vs 26 raised (kava drinkers)

also in the Hawaii study they did not look at liver damage so it does not prove the people with high GGT did not have liver damage. all they looked at was liver enzymes and they did not detections for cholestasis or liver damage so it could of been there.

where can I find the new zealand Goverment study?

 

[Kava Drinker]

http://jech.bmj.com/content/58/2/140

kava also raises cholesterol which can lead to blockages and heart attacks. GGT may have significant affect in detecting these heart abnormalities.

 

[Kava Drinker]

3 times a week does not seem like that much to raise these enzymes and i only thought it would happen with daily use.

we will just have to disagree then. i could talk about this all they as you could probably aswell.

do you know where i could find the new zealand study and sarris study.

In fiji doctors have also said there seems to be a correlation between heart disease and heavy kava use, this was not a study its just a trend the doctors there are seeing.

you are one case. have you ever got a liver ultarsound/mri/CAT scan. or for that matter I do not think many people at all on this have got them. there may well be light damage done to their gall bladder/bile duct/cholestasis. i have seen a few reports of kindney stones on this which GGT is also a indicator. what a coincidence. there seems to be so many coincidences when discussing this.

 

[Kava Drinker]

"However, there have been no systematic studies into sub-clinical forms of liver toxicity in Pacific Island countries, so it is possible that mild toxicity could be present without having been recognised (Moulds and Malani, 2003)."

"In this case no evidence for irreversible liver damage was found" does this mean damage was found but that it was reversible?
this new zealand report also seems to think not just GGT levels are raised but also ALP.

they also report a woman with liver damage from passion flower and kava. passion flower is usually associated with liver damage. she had to get a liver transplant.


is there a thread on the kava forums about harm reduction and kava use?

 

[Kava Drinker]

as in drink a lot of water, take milf thistle, any supplements that prevent cholestasis and the skin thing and bile disorders and kidney stones and immune modulation and any other supplements that might make your liver enzymes normal and are good for over all health of liver? is there any list on the kava forums or any other external sites you know that has a list of these actions you can do to minimise adverse reactions.

like for example with marijuana there is a list of things you can do like take fish oil,Alpha GPC and various other things.