Jak/stat pathway

During recent research to try to figure out why I might be having recurrent infections, I found research that said a damaged STAT 1 pathway renders interferon to be ineffective in its job to fight off infections. If one does have damage to the STAT 1 pathway wouldn't that be a determinant as to whether one (with HCV) would respond or not to any interferon treatment?

[willing]

binding of interferon to a cell receptor is only the first step in exercising its antiviral effect. The signal must somehow travel from the bound receptor to the nucleus to promote transcription of the  interferon-stimulated genes (ISGs) that do the heavy lifting. Jak-Stat is a widely used cell pathway for signal transduction. The virus has figured this out and apparently  blocks methylation of STAT1 thus reducing ifn effectiveness. A Swiss group under M. Heim has been studying this for a while and found that adding the supplements SAMe and Betaine could reverse  this effect. They started a clinical trial in 2006 but as far as I know have not published results yet:
http://clinicaltrials.gov/ct2/show/NCT00310336

Meanwhile however,  CS, a former member here and also former  G3 non-responder used this along with other strategies and was able to dramatically reverse his non-response into super-response. He recently presented a summary of his approach at a hepatitis conference:

http://www.cornwallhepcsupportgroup.org.uk/cocksparrow/StudyPics/CSAbstract.pdf

and
http://www.cornwallhepcsupportgroup.org.uk/cocksparrow/StudyPics/CSPoster.pdf

See also
http://www.ncbi.nlm.nih.gov/pubmed/16557551
http://www.ncbi.nlm.nih.gov/pubmed/18467494

[CoWriter]

Damn it, he took out my real name.  There goes my claim to fame.

But I can't complain.  We're getting lots of attention....from people that want us to help them sell junk LOL.  One woman was selling a product that according to her, contained "reactive molecules" that "reduced oxidative stress, increased gluthathione and supported the immune system".

The "reactive molecules" turned out to be sodium and chlorine.  When you put them together they REACT with each other.(therefore they're reactive molecules LOL) to form sodium chloride....table salt.

She was selling four 32 oz bottles of SALTY WATER for $150.

I hate to think of all the research we did being used to sell lies.

Co

[willing]

Co : yeah, but look on the bright side: that's one supplement for which purity and concentration might agree with  advertised content...

all: CS points out that though the clinical trial on SAMe/betaine supplements  run by M. Heim (NCT00310336) has not yet  published results, a similar trial in the US (NCT00475176) run by the NIDDK now has results in press:

http://www.ncbi.nlm.nih.gov/pubmed/20854821

The results are about as compelling in support of a supplement as any I've seen and make it likely that SAMe, along with Vit.D and coffee, should be taking up space on your kitchen counter while on tx. They enrolled 24 G1 non-responders and put them through two tx starts . First two weeks of soc with no SAMe then  a real  tx supplemented by 1600mg SAMe with two weeks of pre-loading ( and a month of washout between the two). This design let them measure the effect of the supplement in the same individuals - an important plus given that in many cases these effects are relatively minor relative to differences between individuals.  

Two measures of effectiveness were used : (1) the 2nd-phase viral decline (slope of the viral load curve from 48h after 1st shot to day 14 (2) expression levels of three ISGs as measured from PBMC cells collected from patients at time 0 and 24 hours after 1st shot. Given that the whole point of ifn is to get cells to start cranking out ISG proteins, the second measure is directly on point.  The results are impressive : the 2nd phase slope more than  doubled and the measure of expression for the three ISGs increased with significance in excess of 0.05 for the given sample size.  

A couple of patient-useful details : their SAMe supplier was Pharmavite  (no discussion of assessing purity/concentration of the product). The supplement was generally well tolerated, 4/24 complained of gastric disturbance which may have been related to lactose used in tablet prep and improved with lactase.

The question of how much STAT1 methylation is enough remains open. The Heim study, in addition to SAMe was looking at betaine, another methyl-group donor. Also B-vitamins play a role in the  completing the SAMe cycle. Since all patients selected were non-responders (no EVR in previous tx) it's not clear how much the supplement enhances outlook for ifn-responders.

[evangelin]

This post is directed towards those that have been non responders to meds.  I am not advocating anyone starting TX take anything there Dr. doesn't recommend.  After 3 TX failures, Joe and I are out of the box thinkers. Some of it may be wrong and I don't want to lead anyone astray. If the regular recipe works for you then you don't need to take a chance with add-ons.

Willing-
Thanks for sharing that.  I'm giving Joe Sam-E now, along with his other supplements and it most definitely in my tool box if he gets to try Teleprevir.  
Have you ever looked at Vitamin D2 ?  HR came along a few months ago and responded to something I asked in regards to a study showing an hcv replication inhibition with D2 and 2 other substances.   He responded favorably to its use.  I still give Joe D3 also. (he didn't give a thumbs up to retinolic acid- Sp? or the other which I can't remember right now)  I bought a brand from Swanson called Country life-Dry vitamin D2.  Because it doesn't absorb as well as D3 it isn't the recommended type for upping your D levels but for some reason, the virus doesn't seem to like it.  It seems that some very strict vegetarians take this form because of some animal product in D3 (can't remember the particulars)  Hurray- it is cheap.
I hope all these little ideas will have a cumulative effect in deterring the virus.  I feel like I'm in" The Swiss Family Robinson" and I'm laying up traps and coconut bombs for when the pirates show up. :>)  
Have you looked in to Stevia.  CS says if you can buy the right kind ( pure with a high stevioside content) it has an inhibitory effect on the virus.  It looks interesting but the kind of thing that won't make anyone rich, so likely will not be studied much.  CS posted an interesting article on another site but I don't have a clue to how much to give. You might understand it but I don't get it at all.  It looks to be quite safe though and also helps against insulin resistance.
Keep the good ideas flowing. :">)
We have hope,
Ev

[willing]

I remember the post but not the content ( that's a lot of help, right?...) but have   been assuming that as long as one's 25-hydroxy vit. D test is in range, there's not much more to be done. Whether supplements can do more than remediate a shortfall is not clear. In the SAMe study above,  that 1600mg daily had a clear benefit in non-responders but whether it can  further enhance ifn's effect among those with demonstrated ifn sensitivity seems a separate question. Since HCV is busily demethylating STAT1 as part of daily business-as-usual, it could be argued that all hcv-infected are  ifn nonresponders on some level.

Have not yet  looked into Stevia, however have stopped the quercetin.
I had started taking it on the basis of :
http://www.ncbi.nlm.nih.gov/pubmed/19839005

However my last VL was the highest ever, a full log unit higher than previous steady state. Also, concluded that while the results of studies on milk-thistle derived compounds as viral suppressors (principally silibinin) are quite strong, it's not worth spending the money on any of the available  supplements. I'll post  details when I get a minute, but basically the bottom line is that "you can't get there from here" in terms of mg/ml via oral supplements.

[willing]

footnote : looks like if you're going to be adding 1600mg of SAMe to help the ifn along and depressed about the added cost, there's some good news:
"S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial."
http://www.ncbi.nlm.nih.gov/pubmed/20595412

apparently a rare case of beneficial drug interaction