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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.