My overly-simplistic understanding of this process goes something like this: Our liver damage is the result of scarring. The scarring occurs aspart of a mopping-up after our boddy has self-destructed liver cells while trying to chase down the virus.
Thus, it's easy to imagine a situation where a well functioining immune response could potentially hold the viral load lower, while creating more liver damage.
It's not the virus that kills the liver, it's the body's war against the virus.
I've often wondered if a therapy couldn't be developed for non-responders that would help hide the virus, thwarting the immune response and the resulting cellular damage.
So a higher viral load may not necessarily equate to more liver damage. Gotta love living with this stupid virus, things are rarely black and white.
Thank you for your reply, much appreciated as always!
smaug
Thank you, evangelin, I didn't know the difference between D2 and D3
If anyone else is interested, the D2 form is called ergocalciferol on the back label. The D3 form is cholecalciferol. The D2 isn't hard to find. NOW foods, Solaray and Country life are the brands I have found so far.. They are directed towards vegans because the D3 aren't vegan which might help when looking for the right form.
Ev
Dont know if ur being funny and sarcastic,but thanks anywho.
'Come in here, dear boy, have a cigar.
You're gonna go far, fly high,
You're never gonna die,
You're gonna make it if you try;
They're gonna love you?"
Thank you very much for taking the time to answer. Your expertise is so appreciated.
Ev
Vitamin D2- yes D2- has surprisingly shown to be of a stronger antifibrotic acitivity in stellate cell assays than D3 (AASLD and HEPDART ). This has nothing to do with the general health benefits of Vit D3. I would not use beta carotene or linoleic acid, rather omega3s or Polyenylphosphatitylcholine (PPC).
It is unfortunately not possible to give a rational priority between Curcumin and Resveratrol as potentially effective antifibrotics/antiinflammatory compounds in the liver context.
The in vitro study mentioned above by Willig generates some uneasy feelings regards Resveratrol, because the expression of 3 theoretical profibrotic genes in an in vitro human stellate cell line has been increased, but it is entirely unclear if this has meaning in the in vivo setting.There is other research pointing in the opposite direction.
Human patient studies regarding antifibrosis with these natural compounds, comparing them side by side, are not likely to happen, since these studies are very costly.
What about the vitaminD (2), beta carotene, linoeic acid that inhibited the virus in the above study in question? I know you told us extensively about vit D 3 and I think a lot of us have that in place. Are the beta carotene and linoleic acid a safe/good idea?
If I have to choose between resveratrol and curcumin because of the cost, which would you choose? I have had to stop the PPC because of budget restraints for now. If it was the most important, I could cut some of the others and focus on it. Just wondering how you would choose to rank them if you had a child with cirrhosis and had a low income. :>)
I would also like to ask you if you have any thoughts about low -dose Naltrexone? I researched it to the best of my ability and it seemed safe. Joe's 3rd TX attempt was 15 months long with Infergen, Riba, Alinia and he failed to get to undetectable. I gave him LDN afterwards and all I can say is he recovered quicker and better than I would have expected after 15 grueling months. The two previous attempt were only 13 weeks each and I think his recovery was harder and slower. Of course,those were also before taking your supplement list so that may be the REAL difference. We started right back on your liver lovin' list.
Hoping for your valued opinion,
Ev
Regarding the effect of Vitamin E as investigated in the above article: the fivefold increase in replication intensity was achieved at concentrations of Vitamin E that can be expected to occur after supplementation with reasonable amounts, say 300mg. One can only assume they used alpha tocopherol, the method section did not further define the actual substance used beyond the term "Vit E".
Assuming that the replicon model used reflects the situation in vivo in other respects, one would expect that the VL in patients using Vit E would increase, but this is far from certain.
One also wonders about the mechanisms in place. HCV exerts oxidative damage to the hepatocytes and is quite dependent in its synthesis on the lipid metabolism of the liver. Vit E might prevent some of the oxidative damage to these lipids, making them more useful for viral replication , but also it might reduce the cellular stress that the virus exerts, actually reducing hepatocellular damage and stress signaling. All this is speculation and it would be interesting to see if anybody can report a direct influence of start /stop of such supplementation on HCV VLs and ALT levels.
Please explain CYP3A4? And why it is so important with regards to viral treatments?
I know grapefruit has something to do with it but I can't recall it exactly and I can't remember whether it is good or bad to inhibit it's action. I also seem to recall a connection between cigarettes and CYP3A4.
Thank you!
Epi
Pacman if you are to listen to anyone of us HR is the one with the professional expertise - take their advice to heart.
HR - great to see you again! :)
" i would not like to believe that i have cirossis or fibrosis within 3 years of getting infected . "
Pac I wouldn't think this is very likely at all - biopsy is not like you imagine it is more like a big syringe, you dn't feel anything and if you really are concerned you should go for it. They will most likely give you something before hand to make it easier for you. Like I said though I don't think within 3 years is too likely but you do have to take care of your liver. For example I partied and partied for 20 years and did nothing to care for my liver - when I was diagnosed 20/25 years later I was stage 3......but I earned it to be honest. Stupidity - when I was a kid I thought I"d live forever now that I'm getting older I worry about it constantly, youth is truly wasted on the young.
Try not to worry. I'm not sure why your doc won't give you an AD but it seems like it would be a great idea if you could talk him into it and you don't have to stay on it forever. I took paxill and then after treatment stopped.....I'm still nuts ;) but thats ok it's just me.
Deb
Could you also weigh in on the finding that Vitamin E enhances HCV RNA replication?
Thanks,
smaug
"i started drinking grape juice instead of coke"
--------------------------------
Too funny. You drank a bunch of fructose and you're wondering why your liver enzymes went up. Did you not realize that fructose is bad for your liver?
Your liver enzymes went down when you stopped the RVT and Vit E....yes, but you also stopped the juice at the same time.
"i started juicing with strawberries , black and green grapes, carrots, pomegranade, and some lemon"
---------------------------
Did you check to see if any of those fruits inhibits CYP3A4 and whether that would raise the levels of anything else you're taking? Because I believe pomegranade does.
"yes my liver enzimes are high .. but im pretty sure that the reason behind that is the resveratrol and the vit e tablets which i have stopped taking now"
----------------------------- . .
If you approach something with your mind already made up you will miss much....and you may be wrong...and a bunch of people now believe what you told them.
Co.
HI alek , i was taking 400 iu of vit e cap + the multi vit tab i was taking had about 50iu in it too ,
what i think ,messed up things for me was the resveratrol , trying to be healthy ... i started drinking grape juice instead of coke ..... big mistake .. it made my alt go from 160 to 400 in one month .... i would have probably been healthier having coke .. lol
take care and all the best
pacman 1372
Hiya rocker , hope my message finds u in better health and spirit ,
u wrote ....
"dont know about this...i was reading your link to the study and it didnt mention how many patients or any other info like age,sex...nothin...wjats up with that./...and its this a govt run site you posted in that link?..something looks fishy too me"
the answer to that would be - i did the tests at home with a test tube , some of my blood and grape juice and peanuts .... hope thats satisfactory and to ure liking -:) ...
take care and wish u well .
pacman 1372 .
all: pubmed links for the two articles in HR's post are
http://www.ncbi.nlm.nih.gov/pubmed/20066737
http://www.ncbi.nlm.nih.gov/pubmed/20357044
only the 1st (the RVT/HCV one) is free access, but the pubmed-linked pdf seems a bit more legible than one in dointime's link (same content).
HR: always great to see you posting! Point well taken that the concentration at which replication was significantly enhanced in the OR6 and replicon cell lines is much greater than the peak dosage available from ordinary use of RVT as a supplement (from Fig 2 it looks like to get a doubling of HCV rate would require about 8 umol/L, more than 100 times higher than the concentration available from taking a 500mg supplement).
However, the larger question would seem to be why take this particular anti-oxidant if it can (a) promote hcv replication and (b) interfere with ifn/rbv viral suppression . For example why not take astaxanthin, for which they found no HCV enhancing effect? Presumably the answer is RVT's potent anti-fibrotic effects, however their discussion suggests some earlier results have been called into question:
http://www.ncbi.nlm.nih.gov/pubmed/19207580
"Resveratrol amplifies the profibrogenic activation of human hepatic LX-2 stellate cells. "
I have to confess I've let my RVT order lapse, mostly because of cost, but now I'm wondering whether there might be some rationalization for being cheap...
I was so surprised to see your name. Many thanks for explaining this. I am not capable of understanding the explanation but I get what is important to get...keep giving Joe resveratrol.
You pretty much made my day!
Ev
HR, nice to see that you stopped by with your expert opinion. Hope you are well. Please stop back once in awhile.
Rocker, once again thanks for your intelligent reply. You always have so much to add to this forum.
I've found over and over in life that the best thing is moderation. If you just think about how everything in the universe works, left alone, it will seek balance. Extremes are quickly eliminated. This is just the natural order of things.
I'm pretty sure one can't go wrong following this same advice in all areas of your life, including what you ingest.
its not wrong information,its misinformation the call it.....not a lie or wrong,just mis leading,kind a a white lie in disguise
Many thanks for weighing in on this. I wrote my last entry before reading yours. As you can see, I wasn't able to arrive at a realistic conclusion by myself so your intervention has been very helpful.
dointime
I found this link which contains a good discussion:
http://www.wjgnet.com/1007-9327/16/184.pdf
What I make of it is that HR may have been right about resveratrol's anti-inflammatory and anti-fibrotic properties, however this study does indicate that resveratrol enhances hcv replication. The study makes a point of saying not to use resveratrol along with ifn & riba as it could negate their antiviral effects, which is fair enough.
But for those people not on tx, if resveratrol does indeed protect the liver then who cares about a high viral load. But does it in fact? The study says there is still a debate about it's liver protecting properties.
So, insufficient information. I'll have to mull it over whether I should quit taking it after this.
dointime
see..i knew it,,,scewed reports?
Best thing to actually rread the above paper, it is free in full text to everyone. This paper studies the replication of an artificial HCV construct on cultured hepatocytes, in the presence of various concentrations of Resveratrol. it proves nicely that even high doses of RSV are unlikely to have any effect on HCV replication in vivo in man. How so?
On page 187 Fig 2 you will see the effect of increasing micromols of RSV on fold replication of the HCV construct, readout by the luciferase assay.
On page 188 similarlily in fig 4 the effect on the subgenomic replicon cells. RSV in micromols/Liter vs fold replication enhancement. Good work, we assume.
Now there are a few papers that have actually measured, in a reliable well documented HPLC fashion, the achieved RSV concentration in the blood of human subjects after exposure to 250 and 500mg of 99% transResveratrol. In the paper in the American Journal for Clinical Nutrition , published ahead of print March 31st 2010 you find on the forth page in fig 2 the graph of plasma concentrations of RSV as a function of time in these humans to be dose dependent and having for 500mg (quite a high dose!) found the peak concentration of original RSV at 90min after dosing to be 14.4 nanograms/ml or 14.4 micrograms/liter. Knowing the molecular weight of RSV to be 228g/Mol this translates into 14.4/228 micromolar max achievable concentration ,so approx 0.06 micromolar.
If you place this result in the almost linear dependence of replication enhancement foldness of the above paper (see fig 2 AND 4) you will see that the enhancement at this in vivo micromolarity is somewhere between 1 and 5% of starting value, a totally irrelevant phenomenon, if we take everything at face value. In summary, if we trust both papers, there should be no relevant influence by RSV on HCV replication in vivo in man by doses as high as 500mg.
These papers have to be studies in fine details to arrive at realistic conclusions.