Curcumin

[Hepatitis Researcher]

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.

[willing]

4C : you are too kind, but we all know that already...I hope the new year finds you well.

I followed up on those cannabinoid-receptor refs a bit and it looks like we're safe and won't really have to start smoking joints on a daily basis for the sake of our livers (whew, that's a relief). Back in'05 when the CB1/CB2 receptors were first correlated with fibrosis progression, the report was pretty explicit that daily smoking was a non-no: "Patients with ongoing CHC should be advised to refrain from regular cannabis use". - from PMID-15892090. Ingestion of THC activates both the CB1 and CB2 receptors, with CB1 activation being directly related to fibrosis progression and CB2 to fibrosis reduction: ("we have strong evidence that the cannabinoid system directly affects liver fibrogenesis via activation of CB1 and CB2 receptors with opposite pro- and antifibrogenic effects, respectively" from the reply letter to a comment on that same PMID). So basically you want to bock CB1 and stimulate CB2  "Therefore, overall, our current experimental findings indicate dual opposite effects of cannabinoid receptors on liver fibrogenesis and suggest that selective
antagonists of CB1 and selective agonists of CB2 might open new prospects in the treatment of liver fibrosis."

All that's changed is that the effect of CB2 stimulation has been more conclusively linked to fibrosis regression, eg the Munoz-Luque'07 study above and PMID-17412522 "In keeping with these results, daily cannabis smoking is a risk factor for fibrosis progression in patients with chronic hepatitis C. In contrast, CB2 display antifibrogenic effects, by a mechanism involving reduction of liver fibrogenic cell accumulation. These results may offer new perspectives for the treatment of liver fibrosis, combining CB2 agonist and CB1 antagonist therapy.".

So, the long and the short of it is those poor cirrhotic lab rats didn't get to enjoy a few peaceful tokes after all, instead they had to endure "daily subcutaneous injection of the CB2 receptor selective agonist 3-(1’,1´-Dimethylbutyl)-1-deoxy-Δ8-THC" . It's a  hard life.

gooof : happy new year! how's the remodeling coming? are you thinking about adding curcumin to your supplement list?

[Hepatitis Researcher]

You are very capable of seeing/finding the critical issues. The formulation in the second study that was performed in India on humans is available in the US under two names and has been retested in the US for the reported effect in increasing bioavailibility. Considering that limited  bioavailibility is the problem with curcumin, this would seem to be the preferable form to take for a serious indication.   Good idea to check the LFTs if such doses are actually taken and discuss with your personal. hepatologist.. Dont know about the second one, very interesting.

HCC prevention is an interesting hypothesis, can only be speculated, but not totally unrealistic.

[GoofyDad]

HR - comments on either of the following? Also, would you expect Curcumin to have any influence in the prevention of HCC?

https://lra.le.ac.uk/bitstream/2381/511/1/curcumin%20FINAL2.pdf

http://www.curcumin.co.nz/pdf/Bioavailability_Study_Of_Curcu-Gel.pdf

[Forseegood]

I know with your charms, you'll light up the dreams of fat ladies anywhere! oh, and thanks for posting this article...was looking for stuff re this....be well....

[willing]

I was following up references in that Fu'07 article on rat livers and came across a line of papers implicating the cannabinoid cb2 receptor in improvement in  fibrosis generation. See for example:

Munoz-Luque J, Ros J, Fernandez-Varo G, Tugues S, Morales-Ruiz M, Alvarez CE, Friedman SL, Arroyo V, Jimenez W.

REGRESSION OF FIBROSIS AFTER CHRONIC STIMULATION OF CANNABINOID CB2 RECEPTOR IN CIRRHOTIC RATS.
J Pharmacol Exp Ther. 2007 Nov 20; [Epub ahead of print]
PMID: 18029545

(SL Friedman btw seems to be a  doyen of the fibrosis community)

or
Julien B, Grenard P, Teixeira-Clerc F, Van Nhieu JT, Li L, Karsak M, Zimmer A, Mallat A, Lotersztajn S.

Antifibrogenic role of the cannabinoid receptor CB2 in the liver.
Gastroenterology. 2005 Mar;128(3):742-55.
PMID: 15765409

I've stayed out of the ganja wars around here lately, but last I heard there seemed to be pretty clear evidence linking it to poorer SVR outlook.  Am I hallucinating or do I need to  plan on lighting up a couple of fatties along with those 12 cups of daily coffee I'm supposed to be downing. Not sure I can cope with this....

[willing]

hr: thanks for pointing this out as another potentially valuable supplement. Anyone interested can find the full text of the abstracts hr posted here (both are free access):

http://www.nature.com/bjp/journal/vaop/ncurrent/full/0707580a.html
http://molpharm.aspetjournals.org/cgi/reprint/mol.107.039818v1

Though there seems to be wide-ranging  support for curcumin as an anti-inflammatory, the 1st editorial concludes with:

"Pharmacokinetic studies, however, suggest that oral administration results in low bioavailability. Pharmacologically active concentrations are achievable in tissues that are directly exposed to oral or topical curcumin including the colon, skin, eye and airways (Hsu and Cheng, 2007) and this suggests that alternative routes of administration are necessary for curcumin to be a successful therapy for hepatic fibrosis."

and I wonder how effective is its use as a nutritional supplement. However,  in the 2nd paper, showing protection of rat liver from CCl4 effects, administration was oral :
"Curcumin (200mg/kg, or 400mg/kg body weight) was suspended in sterile PBS and given once daily by gavage."

Overall, I've been very lax about pursuing any nutritional supplements beyond some omega-3 oil and vitamins but given this post I'm beginning to change my mind. My principal objection has always been the lack of clear causal connection between supplement and benefit, absence of definitive studies, lack of certainty about dosage and purity, etc. etc.  However your aguments above are convincing.

Focusing on the virus really is a distraction from the damage caused by inflammation. Even if use of supplements is based on partial and incomplete data, and establishing a definite benefit is likely an impossible goal (in part because of research  funding economics) they may provide the best currently available strategy. Acting on  incomplete information is better than not acting at all:  "we can have a decent hope for clinical effectiveness, provided proper dosage is also obtained"

all: does anyone have a link to the post(s) hr referred to above "I have described the base before. It is a combination of reduced injury, improved  hepatocellular response/defense to injury, and then deactivation of the stellate cell activation pathway that underlies almost all fibrosis". I think it would be a valuable service to re-post this "pyramid" on a regular basis. Preventative action is likely to be of benefit to  nearly everyone on this forum, regardless of SVR status.