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VITAMIN-E AND RESVERATROL REPLICATE HCV

hello to all and hope my post finds u all in better health and spirit .
I am 38 years old and got infected with hcv 3 years ago ,  i went through the regular tx and relapsed within 2 weeks of completeing ( geno 1a ), anyway i now await the new treatments that are suppose to come out in the next year or two and will decide then as to what needs to be done  .

(i did post once before about the same topic .. but got no feedback except from a genteleman named bill -  thanks bill .)

the only reason i post is to share my story and make others aware of the harm of  "vit e and resveratrol" .
well here we go again ....

last year in december all m liver enzimes were normal ie: ast 30 alt 30 , but i was still hcv + with a viral load of 9000 .
in feburary this year i started feeling a bit weak and decided that juiceing may be a good idea , i started juicing with strawberries , black and green grapes , carrots , pomegranade , and some lemon .
i was also having my regular supplements that include - milk thistle , vit b / c / and a multi vit withought  iron .
after a few days of juicing and feeeling mentally good  i added vitamin e to my supplement list - reading that it was a great anti-oxidant .

well i was due for a lft in march and my report came back with ast= 62 and alt 161 . i continued with the juice and the vit e not realinzing that they could be the culprit .

after 2 weeks of checking again my ast was 106 and alt 320 ... and thereafter another week they went up to ast- 116 and alt = 400 , i paniced and though what is it... what is it ..... here im trying to do everything thats good for my body and liver but whats going on .... then thanx to the mystic law of the universe i tumbeled upon this study .

Quote from the article.

"To date, only a limited number of studies have reported finding an influence of ordinary nutrients on hepatitis C virus (HCV) RNA replication. However, the effects of other nutrients on HCV RNA replication remain largely unknown.

Here, using this OR6 assay system, we comprehensively examined 46 nutrients from four nutrient groups: vitamins, amino acids, fatty acids, and salts. We found that three nutrients-beta-carotene, vitamin D(2), and linoleic acid-inhibited HCV RNA replication and that their combination caused additive and/or synergistic effects on HCV RNA replication. In addition, combined treatment with each of the three nutrients and interferon alpha or beta or fluvastatin inhibited HCV RNA replication in an additive manner, while combined treatment with cyclosporine synergistically inhibited HCV RNA replication. In contrast, we found that vitamin E enhanced HCV RNA replication and negated the effects of the three anti-HCV nutrients and cyclosporine but not those of interferon or fluvastatin. These results will provide useful information for the treatment of chronic hepatitis C patients who also take anti-HCV nutrients as an adjunctive therapy in combination with interferon. In conclusion, among the ordinary nutrients tested, beta-carotene, vitamin D(2), and linoleic acid possessed anti-HCV activity in a cell culture system, and these nutrients are therefore considered to be potential candidates for enhancing the effects of interferon therapy.".

link for the above study  - http://aac.asm.org/cgi/content/short/51/6/2016  

also then i did a little more reading and found this ...

AIM: To elucidate the effect of antioxidants, resveratrol (RVT) and astaxanthin (AXN), on hepatitis C virus (HCV) replication. METHODS: We investigated the effect of recent popular antioxidant supplements on replication of the HCV replicon system OR6. RVT is a strong antioxidant and a kind of polyphenol that inhibits replication of various viruses. AXN is also a strong antioxidant. The replication of HCV RNA was assessed by the luciferase reporter assay. An additive effect of antioxidants on antiviral effects of interferon (IFN) and ribavirin (RBV) was investigated. RESULTS: This is the first report to investigate the effect of RVT and AXN on HCV replication. In contrast to other reported viruses, RVT significantly enhanced HCV RNA replication. Vitamin E also enhanced HCV RNA replication as reported previously, although AXN did not affect replication. IFN and RBV significantly reduced HCV RNA replication, but these effects were dose-dependently hampered and attenuated by the addition of RVT. AXN did not affect antiviral effects of IFN or RBV. CONCLUSION: These results suggested that RVT is not suitable as an antioxidant therapy for chronic hepatitis.

heres the link for the above study - http://www.myhealthfulworld.com/content/an-antioxidant-resveratrol-significantly-enhanced-replication-hepatitis-c-virus

i since have completely stopped taking the vit e and the juice . please note that grapes , peanuts , strawberries and pomegranade all contain high amounts of resvetrol .
I also stopped taking the multivitamin withough iron as it contained vit e ...
i have discussed this topic with a few friends but they dont seem to think resvetrol and vit e can do any harm !!! i wonder !!
but the same hcv community  will come down ure throat if u say u had a beer or a steak .... (  i dont drink or eat red meat anymore ) saying that alcohol replicates hcv ... and iron is bad .. u shouldnt even eat spinich ....
well i would also like to add that 2 weeks of no juice and vit e .... and milk thistle 2 times a day have bought my ast from 116 to 96 , and alt from 400 to 275 .

PLEASE MY FRIENDS  be carefull of what u eat and drink when suffering from hcv ... saying that " its natural " dosent mean its good for us ...  we have a specific disease ....  mud is natural too - would we eat it !!!
people without liver disease can eat and drink all that they want ..including mud -;) ..... but not us ,

i may be wrong and do welcome ure inputs .

also before i leave - i need to ask u all a small question .

as i said earlier - i was infected (  not diagnosed ) with hcv 3 years ago , do i need to get a live biopsy done !!! i dont drink or eat red meat and oily food , my ultra sound shows no enlargement ... but i am tired and have fatgue all the time ....  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 .  .

thanking u and wishing u all well - await ure inputs regarding the bx .. and hope u all find the above studies helpfull.

pacman

  



36 Responses
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92903 tn?1309904711
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.
Helpful - 0
238010 tn?1420406272
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
Helpful - 0
Avatar universal
Thank you, evangelin, I didn't know the difference between D2 and D3
Helpful - 0
Avatar universal
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
Helpful - 0
Avatar universal
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?"
Helpful - 0
Avatar universal
Thank you very much for taking the time to answer. Your expertise is so appreciated.
Ev
Helpful - 0
Avatar universal
MEDICAL PROFESSIONAL
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.
Helpful - 0
Avatar universal
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
Helpful - 0
Avatar universal
MEDICAL PROFESSIONAL
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.
Helpful - 0
577132 tn?1314266526
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
Helpful - 0
179856 tn?1333547362
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
Helpful - 0
238010 tn?1420406272
Could you also weigh in on the finding that Vitamin E enhances HCV RNA replication?

Thanks,

smaug
Helpful - 0
568322 tn?1370165440
"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.
Helpful - 0
Avatar universal
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
Helpful - 0
Avatar universal
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 .
Helpful - 0
Avatar universal
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...
Helpful - 0
Avatar universal
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
Helpful - 0
Avatar universal
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.
Helpful - 0
Avatar universal
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.
Helpful - 0
Avatar universal
its not wrong information,its misinformation the call it.....not a lie or wrong,just mis leading,kind a a white lie in disguise
Helpful - 0
Avatar universal
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  
Helpful - 0
Avatar universal
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  



Helpful - 0
Avatar universal
see..i knew it,,,scewed reports?
Helpful - 0
Avatar universal
MEDICAL PROFESSIONAL
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.

Helpful - 0
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