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Does Valtrex block mitochondrial reproduction?

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by JalapenoLuv, Oct 18, 2014.

  1. JalapenoLuv

    JalapenoLuv

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    Valtrex is an antiviral drug which was shown in a pilot study to improve mental symptoms and fatigue after taking it for six months. The improvements lasted three months more after patients stopped taking it but longer outcomes data isn't available.

    Mitochondrial damage is a hallmark of CFS. One concern I have about Valtrex is that it has been found to prevent mitochondrial reproduction. Over time, this should lead to a lowering of the total number of mitochondria in affected cells and a worsening of CFS fatigue symptoms.

    “Mitochondrial DNA synthesis in Molt-4 cells was particularly sensitive to ddC. The ratio of mitochondrial to cellular DNA was decreased 80% after 5 days of treatment with 0.05 puM ddC; however, there was no apparent increase in the doubling times of the treated cells. (Martin, JL. Antimicrob. Agents Chemother. 1994, 38(12):2743)."
     
  2. Sidereal

    Sidereal Senior Member

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    Valtrex is not valganciclovir (Valcyte). Very different drugs.
     
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  3. Ema

    Ema Senior Member

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    What does ddc have to do with Valtrex?
     
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  4. JalapenoLuv

    JalapenoLuv

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    Sorry, I listed the wrong generic name; but it is Valtrex (valacyclovir). Valtrex uses a DNA polymerase inhibitor called
    thymidine kinase which is listed on Martin's paper as reference 16. Martin writes:

    "Thymidine analogs were also examined as inhibitors of mitochondrial DNA synthesis. FLT reduced the ratio of mitochondrial to cellular DNA by 59% after 7 days of treatment...Significant cell death was observed after 5 days of treatment..." (Ibid. Martin p. 2745.)
     
  5. JalapenoLuv

    JalapenoLuv

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    All of the thymidine analogs were inhibitors. I believe that this shows that valtrex does this.
     
  6. Ema

    Ema Senior Member

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    I don't find this paper to be conclusive evidence of much of anything much less that Valtrex inhibits the mitochondria.

    Where does it say that Valtrex is a thymidine analog?
     
  7. JalapenoLuv

    JalapenoLuv

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    It's on RX list (link above THYMIDINE KINASE).
     
  8. Ema

    Ema Senior Member

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    It says:

    Valacyclovir is a nucleoside analogue DNA polymerase inhibitor.

    Please copy the specific part where it says it is a thymidine analog.
     
  9. JalapenoLuv

    JalapenoLuv

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    Microbiology
    Mechanism of Action
    Valacyclovir is a nucleoside analogue DNA polymerase inhibitor. Valacyclovir hydrochloride is rapidly converted to acyclovir which has demonstrated antiviral activity against HSV types 1 (HSV-1) and 2 (HSV-2) and VZV both in cell culture and in vivo.

    The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue.
     
  10. Ema

    Ema Senior Member

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    How does having an affinity for viral TK make it a thymidine analog?
     
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  11. JalapenoLuv

    JalapenoLuv

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    Ask a pharmacist to explain it to you.
     
  12. Ema

    Ema Senior Member

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    Or you could actually prove your case.

    There's no evidence I can find to support your claims that Valtrex is toxic to mitochondria in people.

    If you'd like to actually connect the dots, I'm more than happy to reconsider. Otherwise, it's just reaching.
     
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  13. JalapenoLuv

    JalapenoLuv

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    On page 2743 of Martin, the Materials and Methods section lists acyclovir, so it was tested. It is toxic to mitochondria.
     
    Last edited: Oct 18, 2014
  14. Ema

    Ema Senior Member

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    The Materials and Methods section lists the abbreviation for acyclovir...it says nothing about how it was tested.

    If you look down to Table 3, it is not listed as one of the compounds that was tested.

    But regardless, the researchers themselves say that nothing can be derived from these results regarding toxicity to the mitochondria in real life.

    Further the conclusion goes on to say:

    So you can't just lump them all together, even if they had proven one nucleoside analog to be toxic to the mitochondria because they don't all act in the same way.
     
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  15. JalapenoLuv

    JalapenoLuv

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    The precautionary principle—that any action designed to reduce risk should not await scientific certainty—applies here. Just because something may not be predictive in vivo, you have to take in vitro experimentation seriously.

    Martin described the effect as potent.

    A look at table 2 shows the data.

    He said that AZTTP didn't have an effect and it's K value for polymerase alpha was 140, the highest of the group. ACVTP (valtrex)'s effect on the other hand he called potent, and it is listed as 0.96. That is a difference of 140x!

    Frankly, this really scares me. The doses given for CFS patients are very high, 1-1.5g 3x/day. So I can't see this being safe in any way.

    The prudent thing to do is to not use the drug until it is proven nontoxic to human mitochondria in vivo.

    I have used it and my impressions are that it decreased my mitochondrial function by 75%, just as the study predicted. I experienced fatigue and decreased urge to breathe. However, I realize that my observations are not applicable to the side effects reported because of the uniqueness of the experimental regimen I am doing. Simply, most CFS patients aren't recovering their mitochondria count and the lack is masking any increases in fatigue. More fatigue on top of existing fatigue isn't perceptible.

    It is very risky to take this drug in light of this negative in vitro data. Moreover, perceived fatigue improvements haven't been documented to last longer than three months.

    Having done it myself, I do not recommend this treatment.

    Here are comments from other PR members who had fatigue from valtrex:

    One of the limitations for Valtrex is immunocompromised patients:

    I did a survey where 45% of the CFS patients reported they aren't getting fevers and head colds, indicating their immune systems are compromised. Therefore, this is a second reason why valtrex would be contraindicated.
     
    Last edited: Oct 18, 2014
  16. Ema

    Ema Senior Member

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    That's fine if a treatment is not for you.

    But this study does not say *any* of the things you attribute to it as far as I can see.

    I'm all for a case study but even I have to scratch my head over how one could possibly discern a 75% decrease in mito function.

    Please don't present something as a fact when it is not. It just muddies the waters because this paper does not even prove that Valtrex or acyclovir is toxic in vitro. Ddc is not the same as Valtrex.
     
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  17. JalapenoLuv

    JalapenoLuv

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    That was my error, using the figure for dGTP in the Polymerase alpha column you actually get a value of 96.4% reduction comparing ddGTP (27) to ACVTP (0.96).

    Again not respecting the precautionary principle and ignoring data puts patients at risk. I won't do that and I'm not misleading people about these effects.

    80% of drugs approved by the US FDA are withdrawn at five years. I have no doubt that pharmaceutical companies lobby hard to get data like this ignored, especially when the indication for it is short term use. Using valtrex long term is off label and unapproved.

    I'm curious what Dr. Edwards thinks about the valtrex study.
     
    Last edited: Oct 18, 2014
  18. Sushi

    Sushi Moderation Resource Albuquerque

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    I think that statement is misleading. First of all, that survey and only 11 votes--total--from members on this forum. 5 indicated that they no longer get fevers and/or head colds. This cannot really be said to represent 45% of "the CFS patients."

    Also, of those who responded, several had tests showing that their immune systems were partially hyperactive. They and their doctors thought that this was a likely explanation for them not getting colds and fevers.

    Sushi
     
  19. JalapenoLuv

    JalapenoLuv

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    Formally the survey needed 30 people to be statistically significant and it isn't controlled so it has to be seen with that limitation. An ideal study would be to take 80 patients and inject them with pyrinogens to see if they can get a fever. But the point is that many people are reporting they have signs of immune compromise.
     
  20. Ema

    Ema Senior Member

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    I'm not ignoring data but I'm not creating it either where it is not. I'm all for further study of Valtrex. If indeed, it could be shown to be toxic to mitochondria, that would be important information.

    The benefits of reducing long standing chronic infections would still have to be weighed against these potential risks though. I think for some people, the benefits obviously outweigh the risk considering that a substantial number of people have improved on antivirals.
     
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