Aa
Curcumin
Curcumin is an available substance that has serious potential to prevent or treat liver fibrosis. Oral administration in humans suffer from the limited bioavailibility of regular curcumin preparations. Combinations with biopterin have been shown to enhance curcumin absorption, but only to a limited degree. New curcumin formulations have appeared on the supplement market that claim a very substantially enhanced absorption/bioavailibility. I have not yet found proof of these claims in the peer reviiewed literature, which however does not necessarily mean that this claims have no merit.
Curcumin is a substance that is worth discussing with your treating hepatologist. Not during tx, since it has a clear antiinflammatory effectiveness/mechanism that is likely to counteract some of the immunestimulating effects of IFN. Below are two examples of recent abstracts re its antifibrotic potential.
Curcumin is a substance that is worth discussing with your treating hepatologist. Not during tx, since it has a clear antiinflammatory effectiveness/mechanism that is likely to counteract some of the immunestimulating effects of IFN. Below are two examples of recent abstracts re its antifibrotic potential.
MEDICAL PROFESSIONAL
Curcumin: potential for hepatic fibrosis therapy?
1School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, UK.
The beneficial antioxidative, anti-inflammatory and antitumorigenic effects of curcumin have been well documented in relation to cancer and other chronic diseases. Recent evidence suggests that it may be of therapeutic interest in chronic liver disease. Hepatic fibrosis (scarring) occurs in advanced liver disease, where normal hepatic tissue is replaced with collagen-rich extracellular matrix and, if left untreated, results in cirrhosis. Curcumin inhibits liver cirrhosis in a rodent model and exerts multiple biological effects in hepatic stellate cells (HSCs), which play a central role in the pathogenesis of hepatic fibrosis. In response to liver injury, these cells proliferate producing pro-inflammatory mediators and extracellular matrix. Curcumin induces apoptosis and suppresses proliferation in HSCs. In addition, it inhibits extracellular matrix formation by enhancing HSC matrix metalloproteinase expression via PPARgamma and suppressing connective tissue growth factor (CTGF) expression. In this issue, Chen and co-workers propose that curcumin suppresses CTGF expression in HSC by inhibiting ERK and NF-kappaB activation. These studies suggest that curcumin modulates several intracellular signalling pathways in HSC and may be of future interest in hepatic fibrosis therapy.British Journal of Pharmacology advance online publication, 26 November 2007
Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation.
Saint Louis University.
We previously demonstrated that curcumin, a polyphenolic antioxidant purified from turmeric, up regulated PPARgamma gene expression and stimulated its signaling, leading to the inhibition of activation of hepatic stellate cells (HSC) in vitro. The current study evaluates the in vivo role of curcumin in protecting the liver against injury and fibrogenesis caused by carbon tetrachloride (CCl4) in rats and further explores the underlying mechanisms. We hypothesize that curcumin might protect the liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress, suppressing inflammation and inhibiting activation of HSC. This report demonstrates that curcumin significantly protects the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, and by improving the histological architecture of the liver. In addition, curcumin attenuates oxidative stress by increasing the content of hepatic glutathione, leading to the reduction in the level of lipid hydroperoxide. Curcumin dramatically suppresses inflammation by reducing levels of inflammatory cytokines, including IFN-gamma, TNF-alpha and IL-6. Furthermore, curcumin inhibits HSC activation by elevating the level of PPARgamma and reducing the abundance of PDGF, TGF-beta, their receptors and type I collagen. This study demonstrates that curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by suppressing hepatic inflammation, attenuating hepatic oxidative stress and inhibiting HSC activation. These results confirm and extend our prior in vitro observations and provide novel insights into the mechanisms of curcumin in the protection of the liver. Our results suggest that curcumin might be a therapeutic anti-fibrotic agent for the treatment of hepatic fibrosis.
1School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, UK.
The beneficial antioxidative, anti-inflammatory and antitumorigenic effects of curcumin have been well documented in relation to cancer and other chronic diseases. Recent evidence suggests that it may be of therapeutic interest in chronic liver disease. Hepatic fibrosis (scarring) occurs in advanced liver disease, where normal hepatic tissue is replaced with collagen-rich extracellular matrix and, if left untreated, results in cirrhosis. Curcumin inhibits liver cirrhosis in a rodent model and exerts multiple biological effects in hepatic stellate cells (HSCs), which play a central role in the pathogenesis of hepatic fibrosis. In response to liver injury, these cells proliferate producing pro-inflammatory mediators and extracellular matrix. Curcumin induces apoptosis and suppresses proliferation in HSCs. In addition, it inhibits extracellular matrix formation by enhancing HSC matrix metalloproteinase expression via PPARgamma and suppressing connective tissue growth factor (CTGF) expression. In this issue, Chen and co-workers propose that curcumin suppresses CTGF expression in HSC by inhibiting ERK and NF-kappaB activation. These studies suggest that curcumin modulates several intracellular signalling pathways in HSC and may be of future interest in hepatic fibrosis therapy.British Journal of Pharmacology advance online publication, 26 November 2007
Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation.
Saint Louis University.
We previously demonstrated that curcumin, a polyphenolic antioxidant purified from turmeric, up regulated PPARgamma gene expression and stimulated its signaling, leading to the inhibition of activation of hepatic stellate cells (HSC) in vitro. The current study evaluates the in vivo role of curcumin in protecting the liver against injury and fibrogenesis caused by carbon tetrachloride (CCl4) in rats and further explores the underlying mechanisms. We hypothesize that curcumin might protect the liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress, suppressing inflammation and inhibiting activation of HSC. This report demonstrates that curcumin significantly protects the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, and by improving the histological architecture of the liver. In addition, curcumin attenuates oxidative stress by increasing the content of hepatic glutathione, leading to the reduction in the level of lipid hydroperoxide. Curcumin dramatically suppresses inflammation by reducing levels of inflammatory cytokines, including IFN-gamma, TNF-alpha and IL-6. Furthermore, curcumin inhibits HSC activation by elevating the level of PPARgamma and reducing the abundance of PDGF, TGF-beta, their receptors and type I collagen. This study demonstrates that curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by suppressing hepatic inflammation, attenuating hepatic oxidative stress and inhibiting HSC activation. These results confirm and extend our prior in vitro observations and provide novel insights into the mechanisms of curcumin in the protection of the liver. Our results suggest that curcumin might be a therapeutic anti-fibrotic agent for the treatment of hepatic fibrosis.
I read an article in the Bangkok post a while back about a formula invented in a hospital there for liver disease using cucurmin derived from tumeric, mixed with chili peppers and what they call morning glory, not the same plant that goes by that name here.
So I find this very intersesting although I can't understand the details. Thanks for posting.
So I find this very intersesting although I can't understand the details. Thanks for posting.
MEDICAL PROFESSIONAL
For patients with early cirrhosis and no current chance to eliminate HCV a well designed and complete liver protective and antifibrotic regimen might be their best chance to halt progression and possibly dramatically improve long term prognosis. Curcumin holds a high position insuch a regimen, roughly equal - from our curent point of view - to resveratrol. This is always to be seen on top of the basic approaches ( nutrition/metabolism, eubiosis, glutathione/thiol status, methyldonors).
When several publications, abstracts, posters at meetings and proper fibrosis mechanistic/inhibitory pathways concepts point repeatedly in the same direction, and a substance is additionally GRAS, then we can have a decent hope for clinical effectiveness, provided proper dosage is also obtained. Here we are somewhat in the dark. Unfortunately, clinical trials to prove antifibrotic effectiveness are very expensive, require multiple biopsies, a large time frame and give no hope for a sponsor to derive future income from the results, regardless how positive. Much less can you expect a clinical trial to be undertaken, that would use a combined, much more powerful approach to antifibrosis, that is much more likely to yield good results.
The irresponsible, profit driven "hepatoprotective" claims by many supplement "dealers" furthermore damage the chance of the few substances that have good, realistic research and mainstream scientific concepts behind them, since they dilute the efforts of patients/doctors to navigate and act in practical terms in this extremely difficult but also extremely important topic.
When several publications, abstracts, posters at meetings and proper fibrosis mechanistic/inhibitory pathways concepts point repeatedly in the same direction, and a substance is additionally GRAS, then we can have a decent hope for clinical effectiveness, provided proper dosage is also obtained. Here we are somewhat in the dark. Unfortunately, clinical trials to prove antifibrotic effectiveness are very expensive, require multiple biopsies, a large time frame and give no hope for a sponsor to derive future income from the results, regardless how positive. Much less can you expect a clinical trial to be undertaken, that would use a combined, much more powerful approach to antifibrosis, that is much more likely to yield good results.
The irresponsible, profit driven "hepatoprotective" claims by many supplement "dealers" furthermore damage the chance of the few substances that have good, realistic research and mainstream scientific concepts behind them, since they dilute the efforts of patients/doctors to navigate and act in practical terms in this extremely difficult but also extremely important topic.
Along with some other herbs which surprised me, such as Sho-saiko-to “bupleurum” Curcumin is on the list of herbs to avoid see below. What would be a safe amount?
The following is from HCV & CAM: Dietary Supplements to Avoid http://www.hcvadvocate.org/hepatitis/factsheets_pdf/CAM_avoid.pdf
23Turmeric (curcumin) is probably safe for liver patients unless taken in large doses.
Turmeric (curcumin) is being studied as a possible treatment for hepatitis, but until the evidence is in, avoid or use cautiously.
Blue-green Algae (Spirulina)* is also on the list.
If the Blue-green Algae is as toxic as the varieties we have in Aust I wouldnt go near it.
CS
The following is from HCV & CAM: Dietary Supplements to Avoid http://www.hcvadvocate.org/hepatitis/factsheets_pdf/CAM_avoid.pdf
23Turmeric (curcumin) is probably safe for liver patients unless taken in large doses.
Turmeric (curcumin) is being studied as a possible treatment for hepatitis, but until the evidence is in, avoid or use cautiously.
Blue-green Algae (Spirulina)* is also on the list.
If the Blue-green Algae is as toxic as the varieties we have in Aust I wouldnt go near it.
CS
Thanks once again for your valuable input.
I ordered curcumin for my husband when you first brought it up. I bought it from vitacost online. They have a brand that combines it with a form of piperine claiming it to be more absorbable. This is copied from their product description:
How Does NSI® Turmeric Extract with Bioperine® Work?
Turmeric (Curcuma longa) is an ancient spice native to India and Southeast Asia, best known for its distinctive flavor and yellow color, used in curries and some prepared mustards. Besides being a food additive, turmeric has been used for centuries in Ayurveda, Siddha, Unani, and other traditional medicines as a remedy for stomach and liver ailments.
Curcumin, the active ingredient in turmeric, contains a mixture of powerful phytonutrients known as curcuminoids. Curcuminoids have antioxidant properties, meaning they fight the damaging effects of free radical molecules in the body.
Curcuminoids may play a part in blocking a key biological pathway that causes damage to cells and may lead to their unhealthy, unrestrained growth¹. They shut down nuclear factor kappa B (NF-kB), known to regulate expression of more than 300 genes that promote inflammatory responses which lead to joint inflammation and cell damage. NSI® Turmeric Extract with Bioperine® is standardized to 95% curcuminoids.
Although the therapeutic effects of curcumin are often limited due to its poor absorption in the GI tract, NSI® Turmeric Extract with Bioperine® has been specially formulated with a patented bioavailability enhancer. Bioperine® is a form of piperine, a component of black pepper, found to increase the bioavailability of curcumin twenty-fold².
I remembered reading in Dr. Melissa Palmer's book that piperine had the ability to prevent depletion of glutathione. That sounded like a good combination for our purpose. (husband has cirrhosis) Does this sound good to you?
Sincerely grateful for your help.
I ordered curcumin for my husband when you first brought it up. I bought it from vitacost online. They have a brand that combines it with a form of piperine claiming it to be more absorbable. This is copied from their product description:
How Does NSI® Turmeric Extract with Bioperine® Work?
Turmeric (Curcuma longa) is an ancient spice native to India and Southeast Asia, best known for its distinctive flavor and yellow color, used in curries and some prepared mustards. Besides being a food additive, turmeric has been used for centuries in Ayurveda, Siddha, Unani, and other traditional medicines as a remedy for stomach and liver ailments.
Curcumin, the active ingredient in turmeric, contains a mixture of powerful phytonutrients known as curcuminoids. Curcuminoids have antioxidant properties, meaning they fight the damaging effects of free radical molecules in the body.
Curcuminoids may play a part in blocking a key biological pathway that causes damage to cells and may lead to their unhealthy, unrestrained growth¹. They shut down nuclear factor kappa B (NF-kB), known to regulate expression of more than 300 genes that promote inflammatory responses which lead to joint inflammation and cell damage. NSI® Turmeric Extract with Bioperine® is standardized to 95% curcuminoids.
Although the therapeutic effects of curcumin are often limited due to its poor absorption in the GI tract, NSI® Turmeric Extract with Bioperine® has been specially formulated with a patented bioavailability enhancer. Bioperine® is a form of piperine, a component of black pepper, found to increase the bioavailability of curcumin twenty-fold².
I remembered reading in Dr. Melissa Palmer's book that piperine had the ability to prevent depletion of glutathione. That sounded like a good combination for our purpose. (husband has cirrhosis) Does this sound good to you?
Sincerely grateful for your help.
Many thanks for the heads-up. You've really been working at getting the anti-fibrotic message across and it finally sunk into my brain - I just ordered resveratrol and curcumin. The message took a while to get through to me but your persistence may well have made all the difference to my future well being.
dointime.
dointime.
MEDICAL PROFESSIONAL
That " liver warning" does not sound too dangerous. I am carefully monitoring the literature and meeting posters/presentations not only for effectiveness, but also potential toxicity. Studies in human volunteeers with extremely high doses of curcumin have to date not shown any toxicity within the parameters examined. Two aspects should be kept in mind:
1. Turmeric might have some more toxic compounds in them than purified curcumin, a chemically well defined substance. While the plant might have additional positive effects from the combined use of its ingredients, it might also contain hidden/limiting toxicities.
2. All relevant studies have been done with the purified compound.
3. One should start the use of it slowly increasing and follow the LFTs. This would give early warning re potential neg effects. The end dose should probably be in the range of 1000mg for the new bioavailable formulations, but that is just an educated guess.
1. Turmeric might have some more toxic compounds in them than purified curcumin, a chemically well defined substance. While the plant might have additional positive effects from the combined use of its ingredients, it might also contain hidden/limiting toxicities.
2. All relevant studies have been done with the purified compound.
3. One should start the use of it slowly increasing and follow the LFTs. This would give early warning re potential neg effects. The end dose should probably be in the range of 1000mg for the new bioavailable formulations, but that is just an educated guess.
MEDICAL PROFESSIONAL
What you have is the older version , where biopterin is used to improve availibility. This yields about 1.5 times the absorption compared to regular curcumin. This has been published. The latest version however claims to have 6 times better bioavailibility ( GI absorption) and some data of actual studies ( not published thus far, to my knowledge) were shown to confirm this claim. If true, the effectiveness would be greatly enhanced.
evangelin : The NAC/VitC and ALA will provide/ensure production of plenty of glutathione.
evangelin : The NAC/VitC and ALA will provide/ensure production of plenty of glutathione.
I didnt think it sounded that bad either, but it must have been included for a reason.
Go easy with the Tumeric it is then.
The follow LFTs seems like a good idea when taking anything, apart from that gives me an excuse to do a little more of the monitor thing, which I am a bit slack on lately
Thanks
CS
Go easy with the Tumeric it is then.
The follow LFTs seems like a good idea when taking anything, apart from that gives me an excuse to do a little more of the monitor thing, which I am a bit slack on lately
Thanks
CS
hey thanks for continuing to share your knowledge. so would this be something to add to the other sups that you suggested on an earlier post? if you were stage 1 on bx and had to pick just a few of the sups to take what would you suggest? i'm not into taking a bunch of pills but would like to take just a few with the most benefit. thanks again
One other thing.
Is there any evidence for improved SVR rates when taking AntiOxidents/AntiFibrotics (or anything else for that matter) before TX.
CS
Is there any evidence for improved SVR rates when taking AntiOxidents/AntiFibrotics (or anything else for that matter) before TX.
CS
MEDICAL PROFESSIONAL
The PPC is the only hepatoprotective/antifibrotic substance which has been evaluated together with IFN and it has interestingly improved SVR rates, as posted earlier. It is impossible to predict how strong acting antiinflammatory substances like Curcumin and Resveratrol would impact SVR rates. We have to assume that activation of the innate/adaptive system during SOC depends partly on ancient primitive proinflammatory pathways.
Taking these before Tx should not influence SVRs either way, but there is no way to be sure about that.
Copy: Curcumin and Resveratrol are like the top of the antifibrotic pyramid. I have described the base before. It is a combination of reduced injury, improved hepatocellular response/defense to injury, and then the multiple deactivation of the stellate cell activation pathway that underlies almost all fibrosis production. All that can be done with safe measures and carefully selected GRAS substances, that is the strength of it.
Taking these before Tx should not influence SVRs either way, but there is no way to be sure about that.
Copy: Curcumin and Resveratrol are like the top of the antifibrotic pyramid. I have described the base before. It is a combination of reduced injury, improved hepatocellular response/defense to injury, and then the multiple deactivation of the stellate cell activation pathway that underlies almost all fibrosis production. All that can be done with safe measures and carefully selected GRAS substances, that is the strength of it.
Good to see you here. I am now taking Curcumin, Resveratrol, and Sylmarin antiinflammatories. I also take PPC, N-A-C/vit C, T-M-G, Taurine, a prebiotic and probiotic, ALA, EPA, DHA, cq10, vit e, multi vit no iron.
When I begin tx I plan to continue taking these with the possible exception of the anti inflammatories. Our conversation was unfortunately cut short and I was not able to ask if anything might be added to this regimen, and might this regimen help to REVERSE mild cirrhosis? As always, I look forward to, and highly appreciate your posts. Thank you.
When I begin tx I plan to continue taking these with the possible exception of the anti inflammatories. Our conversation was unfortunately cut short and I was not able to ask if anything might be added to this regimen, and might this regimen help to REVERSE mild cirrhosis? As always, I look forward to, and highly appreciate your posts. Thank you.
Ive been taking tumeric 2 times a days for the since i relapsed,also ive been taking blue green algae ....my LFT`s have been in normal range ever since ive been taking this "FOOD".......BTW Mr Researcher.....whats your views on this blue green algae.....also know as AFA....it releases stem cells from bone marrow and regerates the liver and other parts of our body.
http://www.pharmcast.com/Patents100/Yr2004/Nov2004/110904/6814961_StemCell110904.htm
MEDICAL PROFESSIONAL
This is just a patent and the claim that is made is enormous, without any proof.
As to the quality of the proofreading of this patent: This is pasted directly from it:
" The percentage decrease in the number of circulating stem cells compared to a normal baseline may about 25%, about 50%, about 75%, or even about 100% as compared to a control."
Aha, the algae, actually decrease the circulating stem cells.
the point: If i can detect this unpleasant mistake in the patent text within 1 minute, why havent the inventors or patent examiners seen it?
I will make an extra effort to check if there is any promise to the blue green algae as a liver therapeutic.
As to the quality of the proofreading of this patent: This is pasted directly from it:
" The percentage decrease in the number of circulating stem cells compared to a normal baseline may about 25%, about 50%, about 75%, or even about 100% as compared to a control."
Aha, the algae, actually decrease the circulating stem cells.
the point: If i can detect this unpleasant mistake in the patent text within 1 minute, why havent the inventors or patent examiners seen it?
I will make an extra effort to check if there is any promise to the blue green algae as a liver therapeutic.
MEDICAL PROFESSIONAL
Your regimen is becoming quite complete, provided the dosages are adequate. And of course provided that the weight loss and the ongoing dietary principles ( the metabolic stress avoidance to the liver) are handled with great care.
As for the antifibrotic supplements green tea extract might make it even more complete.
The sum of all these measures has a realistic chance to halt or even reverse mild fibrosis. This needs to be proven on a case by case basis by either paired biopsies or paired fibroscans, properly performed.
As for the antifibrotic supplements green tea extract might make it even more complete.
The sum of all these measures has a realistic chance to halt or even reverse mild fibrosis. This needs to be proven on a case by case basis by either paired biopsies or paired fibroscans, properly performed.
Oh yes, green tea is in there; merely forgot. Resveratrol now at 1000 mg a day with only minor problems. Weight and exercise? Perhaps I could just take another pill! LOL URQ pain has ceased and hope it is the supplements doing the job. In fact I feel so good... I hate to tox! Thanks for taking me down this road. I am thinking of continuing at least Sylmarin on tox, standing at that crossroad and looking for something to tip me one way or the other. Any studies out there on this you could steer me towards?
MEDICAL PROFESSIONAL
Sorry meant to say mild cirrhosis, not fibrosis, of course, above.
Resveratrol 2 x 500 should be quite effective
No studies on tx and supplement interaction are TMK available with notable exception PPC. If you were in this state, we could perform a fibroscan and then while on strict antifibrotic regimen, repeat it in 6 month. If all is stable or even better, you could possibly wait for the combo SOC+ Vertex+Alinia. By early 2011 Telaprevir and more info re Alinia and geno 1 will be available and decent conclusions could be drawn re other genotypes.
Resveratrol 2 x 500 should be quite effective
No studies on tx and supplement interaction are TMK available with notable exception PPC. If you were in this state, we could perform a fibroscan and then while on strict antifibrotic regimen, repeat it in 6 month. If all is stable or even better, you could possibly wait for the combo SOC+ Vertex+Alinia. By early 2011 Telaprevir and more info re Alinia and geno 1 will be available and decent conclusions could be drawn re other genotypes.
Thank you for your response,im not too sure about the explaination they mean ,talking about the % of stem cells and in that paragraph,it is confusing,but i will tell you from personal experience,my own mothwer takes this stuff and her arthritis went away ,almost immeaditaly...excuse my spelling,,...i also have meat lots of people with similar experiences.
Like the sound of that. Hmmm... I know fibroscan is the best test available, but they are not widely available. Is there a second choice alternative that might work? Perhaps another biopsy and bloodwork could be a measuring stick. I see a hemotologist for low platelets (which have improved a little bit of late .88 from .67 in 8 weeks) and my WBC count is 2.8 and not changing. I am concerned that tx will quickly drop me into a position where I would have to stop tox early. So, if I had time to improve these numbers, it may be in my best interest to consider your approach.
you seem to know so much. i am a 40 year old female diagnosed with chronic active hepatitis b i was first diagnose at 25 and was told not to worry. well i have been very sick and have been diagnosed with still active hepatitis b (recently) and gastritis, gastroperesis, esophougus problems and now i have hurting knees that are filling with fluid. the rhuematolgist said even though i am a low positive for rhuematism it is not that and could be the hep b. i am in pain all the time and sick at my stomach daily. i have had bad medical care in my opinion so i set an appointment with a hemotolgist in feb. i also (through a cat scan) was diagnosed with a hemangioma. could it be cancer? and how do they know? i am worried i feel horrible. any help would be so appreciated. thankyou so much Ginny
Hey, This is the first I've ever heard of "good and bad polyphenols". Anyone know anything about this?
February 25th, 2006
Green Tea Polyphenols May Cause Liver Damage in High Doses
SourceURL:http://www.medicalnewstoday.com
The polyphenols present in green tea plants or herbs could pose health risks to humans if extracted and packaged in highly concentrated doses, says a new University of Toronto study published in the current issue of Free Radical Biology and Medicine.
In small mammals, green and black tea phenolics -- a class of chemical compounds found in plants that include polyphenols -- have been proven to contain antioxidants that help reduce the risk of cancer and cardiovascular disease. Findings such as these have helped to make these teas popular choices among health-conscious tea drinkers around the world.
Working with a team of graduate students, Professor Peter O'Brien of the Leslie Dan Faculty of Pharmacy injected low and concentrated doses of polyphenols into mice. At low doses, "good" polyphenols protected the liver or isolated liver cells against oxygen radicals, while "bad" polyphenols caused liver toxicity at high concentrations.
"The low concentration is roughly equivalent to what people consume when they drink green or black tea," O'Brien says. "But the health benefits are not clear as only a small amount of the polyphenols in the teas seems to get absorbed across the intestine. We won't know how much is absorbed or metabolized without running large clinical trials involving humans."
O'Brien has no plans to stop drinking green or black tea anytime soon, but cautions those who might want to exploit the antioxidant and health promoting properties of tea polyphenols against consuming concentrated doses in pill form as this could create more health problems than it might fix.
"New drugs are subjected to exhaustive clinical trials," he says. "Our findings demonstrate that there simply isn't enough known at this time to substantiate green tea's health-promoting properties if taken in high concentrations."
http://www.utoronto.ca
February 25th, 2006
Green Tea Polyphenols May Cause Liver Damage in High Doses
SourceURL:http://www.medicalnewstoday.com
The polyphenols present in green tea plants or herbs could pose health risks to humans if extracted and packaged in highly concentrated doses, says a new University of Toronto study published in the current issue of Free Radical Biology and Medicine.
In small mammals, green and black tea phenolics -- a class of chemical compounds found in plants that include polyphenols -- have been proven to contain antioxidants that help reduce the risk of cancer and cardiovascular disease. Findings such as these have helped to make these teas popular choices among health-conscious tea drinkers around the world.
Working with a team of graduate students, Professor Peter O'Brien of the Leslie Dan Faculty of Pharmacy injected low and concentrated doses of polyphenols into mice. At low doses, "good" polyphenols protected the liver or isolated liver cells against oxygen radicals, while "bad" polyphenols caused liver toxicity at high concentrations.
"The low concentration is roughly equivalent to what people consume when they drink green or black tea," O'Brien says. "But the health benefits are not clear as only a small amount of the polyphenols in the teas seems to get absorbed across the intestine. We won't know how much is absorbed or metabolized without running large clinical trials involving humans."
O'Brien has no plans to stop drinking green or black tea anytime soon, but cautions those who might want to exploit the antioxidant and health promoting properties of tea polyphenols against consuming concentrated doses in pill form as this could create more health problems than it might fix.
"New drugs are subjected to exhaustive clinical trials," he says. "Our findings demonstrate that there simply isn't enough known at this time to substantiate green tea's health-promoting properties if taken in high concentrations."
http://www.utoronto.ca
MEDICAL PROFESSIONAL
In reference to the above quoted article:
o Brien in Torotnto is performing very serious research on the potential toxicity of polyphenols since many years and i follow his work very carefully, it is of excellent academic and scientific quality. The conclusions to be drawn re the practical use of these plant substances need to be done carefully as well and the study of the original papers is necessary to understand the impact of this type of research on practical implications. Secondary internet articles by journalists are likely to be oversimplified and grossly distorted, thus dangerously misleading in either direction.
What follow is the pertinent portion from the actual paper by Dr. OBrien that will show the experimental approach re green tea components ( intraperitoneal, the comparative discussions of oral animal toxicity testing and the toxicities or lack thereof found and the actual concentrations/amounts of the substances used. This needs to be compared to the oral doses offered for humans in at least a semiquantitative fashion.
Quotation "
Due to its central role in drug metabolism, the liver is particularly susceptible to injury following systemic exposure to xenobiotics by ip administration. To test whether hepatocytes are susceptible to tea catechins or gallic acid in vivo as shown here for hepatocytes in vitro, the hepatotoxicity of these dietary phenolics in vivo was therefore tested in mice by ip administration. It was found that the dietary phenolics NDGA, gallic acid, propyl gallate, tannic acid, and EGCG, administered ip, all significantly increased plasma ALT levels, at various doses, compared to the control. The order of hepatotoxic effectiveness found, using a plasma ALT level of approximately 200 U/L (a 4-fold increase compared to control), was as follows: NDGA (50 mg/kg) > tannic acid, EGCG (both approximately 120 mg/kg) > propyl gallate (170 mg/kg) >> gallic acid (500 mg/kg). Surprisingly, the most abundant tea catechin (EGCG) caused death to mice in less than 24 h at a dose of 150 mg/kg. NDGA has previously been shown to have an LD50 (ip), after 5 days, of 75 mg/kg and to cause 100% mortality by ip injection at 100 and 500 mg/kg after 30 h in female Balb/c mice [43]. Interestingly, we found that a lower concentration of EGCG (150 mg/kg) caused 100% mortality in male CD-1 mice in 24 h. NDGA, a polyphenolic component of chaparral tea, has also been implicated in published case studies of hepatotoxicity that developed in users of chaparral tea [17].
However, normal exposure to tea flavonoids or gallic acid occurs by the oral route and the liver is mostly exposed to flavonoid phase II conjugates formed when the flavonoid or gallic acid is transported across the intestinal cell. The ip administration route may therefore normally have no toxic implications. Recently, the no-observed-adverse-effect level for feeding a gallic acid-containing diet for 13 weeks to male F344 rats was found to be 119 mg/kg/day. Centrilobular liver cell hypertrophy was observed at 1.7% gallic acid, whereas hemolytic anemia of weak severity developed at 5% gallic acid [44].
o Brien in Torotnto is performing very serious research on the potential toxicity of polyphenols since many years and i follow his work very carefully, it is of excellent academic and scientific quality. The conclusions to be drawn re the practical use of these plant substances need to be done carefully as well and the study of the original papers is necessary to understand the impact of this type of research on practical implications. Secondary internet articles by journalists are likely to be oversimplified and grossly distorted, thus dangerously misleading in either direction.
What follow is the pertinent portion from the actual paper by Dr. OBrien that will show the experimental approach re green tea components ( intraperitoneal, the comparative discussions of oral animal toxicity testing and the toxicities or lack thereof found and the actual concentrations/amounts of the substances used. This needs to be compared to the oral doses offered for humans in at least a semiquantitative fashion.
Quotation "
Due to its central role in drug metabolism, the liver is particularly susceptible to injury following systemic exposure to xenobiotics by ip administration. To test whether hepatocytes are susceptible to tea catechins or gallic acid in vivo as shown here for hepatocytes in vitro, the hepatotoxicity of these dietary phenolics in vivo was therefore tested in mice by ip administration. It was found that the dietary phenolics NDGA, gallic acid, propyl gallate, tannic acid, and EGCG, administered ip, all significantly increased plasma ALT levels, at various doses, compared to the control. The order of hepatotoxic effectiveness found, using a plasma ALT level of approximately 200 U/L (a 4-fold increase compared to control), was as follows: NDGA (50 mg/kg) > tannic acid, EGCG (both approximately 120 mg/kg) > propyl gallate (170 mg/kg) >> gallic acid (500 mg/kg). Surprisingly, the most abundant tea catechin (EGCG) caused death to mice in less than 24 h at a dose of 150 mg/kg. NDGA has previously been shown to have an LD50 (ip), after 5 days, of 75 mg/kg and to cause 100% mortality by ip injection at 100 and 500 mg/kg after 30 h in female Balb/c mice [43]. Interestingly, we found that a lower concentration of EGCG (150 mg/kg) caused 100% mortality in male CD-1 mice in 24 h. NDGA, a polyphenolic component of chaparral tea, has also been implicated in published case studies of hepatotoxicity that developed in users of chaparral tea [17].
However, normal exposure to tea flavonoids or gallic acid occurs by the oral route and the liver is mostly exposed to flavonoid phase II conjugates formed when the flavonoid or gallic acid is transported across the intestinal cell. The ip administration route may therefore normally have no toxic implications. Recently, the no-observed-adverse-effect level for feeding a gallic acid-containing diet for 13 weeks to male F344 rats was found to be 119 mg/kg/day. Centrilobular liver cell hypertrophy was observed at 1.7% gallic acid, whereas hemolytic anemia of weak severity developed at 5% gallic acid [44].
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