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Treating CMV with Bovine Lactoferrin

PhoenixBurger

Senior Member
Messages
202
While trying to get my CMV under control, I have been doing a lot of research on possibly helpful supplements. There was a surprising amount of actual data on a few of them and I wanted to share this one in particular, which seemed to be the rock star of them all:

Lactoferrin:

Lactoferrin-mediated protection of the host from murine cytomegalovirus infection by a
T-cell dependent augmentation of natural killer cell activity.
http://www.ncbi.nlm.nih.gov/pubmed/8920822

This was an *in vivo* study showing that Lactoferrin prevented CMV activity. There are other studies showing that Lactoferrin effectively blocks entry of CMV into new cells when it reactivates.

This PDF file discusses it in a bit more depth:
http://bit.ly/1FjNGvU

So if you are trying to keep your CMV down, this may be an outstanding resource.
My research has also revealed the following are significant in beating CMV as well:

Monolaurin supplements
Vitamin A supplements (careful on this one with dosing, I think I remember reading you can take too much)
Quercetin

You can google those words and CMV for more info.

You can get all of these on Amazon or wherever.

@heapsreal figured you'd find this informative.
 

heapsreal

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I think antivirals are the gold standard. I think all the herbal type things like the lactoferrin, colostrum etc etc all look really good on paper but in reality arent as good as antiviral meds, but i think they are a good adjunct to antivirals.

I have been on ahcc for only a short while and have been using lysine which is suppose to have antiviral properties against herpes viruses. I took a short break off famvir to see how effective they would be but i ended up with a return of viral symptoms within a week. Its possible that once u have your viral load low enough and your immune system is responding then these herbal/natural types supps will be effective on their own??

Im going to continue with the AHCC a few more months as i have only been on a a few weeks, its suppose to increase nk function and numbers as well as improve immune function overall. I do plan to get some immune testing done down the track and see if there are changes on labs. I will also try another stint off famvir to see if it can help on its own.

Another interesting supp that may be helpful is artesunate, @Ema sent me an interesting link to some info on it, i have only glanced through it so far. Hopefully she can post a link. It was a popular supplement a few years ago and may find some threads on it.

Its possible that maybe a good combo of antiviral supps could be effective, we are the lab rats that have to work this out.

cheers!!
 

Ema

Senior Member
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I think the dose of artesunate may be really critical in whether or not it has any effect. Higher doses than typically used seen to be required. Of course, that ups the cost considerably too.

Also, art seems to need to be pulsed in order to maintain effectiveness.

It may also need to be taken away from Vit C and other antioxidants since it works by generating ROS. But I'm not clear on that detail because the cancer research says it works synergistically with C. The parasite studies also seem to show it working in the presence of C as well.
 

heapsreal

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I think the dose of artesunate may be really critical in whether or not it has any effect. Higher doses than typically used seen to be required. Of course, that ups the cost considerably too.

Also, art seems to need to be pulsed in order to maintain effectiveness.

It may also need to be taken away from Vit C and other antioxidants since it works by generating ROS. But I'm not clear on that detail because the cancer research says it works synergistically with C. The parasite studies also seem to show it working in the presence of C as well.


I wanted to ask u about antioxidants and artesunate. If I remember rightly artesunate killed infected cells by increasing oxidation in them. It was thought antioxidants may reduce the effectiveness of them.

They may have done a treatment like 3days in a row then rest of the week off, but cant quite remember.

Im still looking into antiretroviral drugs as they are cheaper than valcyte and dont have the side effect of neutropenia that I get from valcyte. I will hopefully have more time off soon to look into this further and then talk things over with my doctor.
 

shannah

Senior Member
Messages
1,429
You can get all of these on Amazon or wherever.

I've been finding lactoferrin helpful at high doses. Would very much like to go higher but the cost is really prohibitive.

Been trying to source a bulk supplier but haven't managed to find one yet.

Anyone managing to secure this at a reasonable cost?
 

PhoenixBurger

Senior Member
Messages
202
@shannah - that would make sense. In the study above they did 1mg per 1gram of body weight. For me (185lbs) thats something like 38,000mg !!!!!!!!!!!

If you google Lactoferrin Hep C dose ... they tend to hover around 1,000 to 3,500 mg per day as a treatment dose.
 

shannah

Senior Member
Messages
1,429
@shannah - that would make sense. In the study above they did 1mg per 1gram of body weight. For me (185lbs) thats something like 38,000mg !!!!!!!!!!!

If you google Lactoferrin Hep C dose ... they tend to hover around 1,000 to 3,500 mg per day as a treatment dose.

Thanks @PhoenixBurger. I've been at 1750 mg daily for a long while now. Would like to go higher but this is an expensive supplement.
 

heapsreal

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Hard to find bulk powder lactoferrin but there are places that sell colostrum, but not sure what dose u would need to get the bigger doses of lactoferrin??
 

Ema

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I wanted to ask u about antioxidants and artesunate. If I remember rightly artesunate killed infected cells by increasing oxidation in them. It was thought antioxidants may reduce the effectiveness of them.

Here is one of the papers I found on Vit C and artesunate/artemether.

The authors conclude that Vit C and other antioxidants should not be taken with artemisinin and its derivatives.

However, artemisinin derived antimalarials are claimed by their mode of action to generate free radicals (pro-oxidants) which in turn kill the malaria parasites (Krishna et al.,2004), an effect directly opposite that of ascorbic acid. A

But later they say that Vit C alone also has some effect in killing the parasites.

Furthermore, evaluation of possible therapeutic activity of ascorbic acid doses in suppression of rate of malarial parasite growth was found to be statistically significant (p<0.05) at both low and high doses when compared with the control.

This observed impairment of rapid development of parasitaemia for high dose ascorbic acid is in line with “mega dose ascorbic acid concept” which states that ascorbic acid is capable of suppressing parasitaemia at high dose.

Then they say that it doesn't actually seem to matter about Vit C, because all of the test groups had total parasite clearance.

In all the three groups of artemether/ascorbic acid treatment total parasite clearances were however observed on day 2 to day 5 of drug treatment.

But then they somehow come to the conclusion that Vit C and artemisinin shouldn't be taken together. I'm not sure how they have reached that conclusion based on their data.

This study has shown that in vivo ascorbic acid impairs the activity of artemether in the clearance of P.berghei. This pharmacodynamic interaction observed in mice therefore forbid co-administration of the two pharmacological agents hence pharmacists and prescribers should advice their patients to complete antimalaria use before commencing with ascorbic acid if need be.

Also ascorbic acid when used in high dose has been shown to suppress the rate of progression of parasitaemia in infected mice.

:confused:o_O

And then you get the studies with artemisinin and cancer that say that the two work synergistically together and improve outcomes, like this.

Preliminary data from Bastyr Integrative Oncology Research Center indicates that IV Vitamin C (IVC) in conjunction with IV Artesunate makes a substantial difference in advanced cancers. IV Artesunate is often administered right before high dose IV vitamin C and there is evidence that these therapies work synergistically together.

In patients with Stage 4 Breast cancer, after 1 year the group that received no IV Vitamin C and IV Artesunate had a 74% survival rate. Compared to the IV Vitamin C and IV Artesunate group which had a 90% survival rate after 1 year. By year 2 the results were even more significant as the group that did not receive treatment had a 68% survival rate compared to 90% in the treatment group.

Maybe the mechanism for killing cancer and parasites is different?

Artesunate activates mitochondrial apoptosis by iron catalyzed lysosomal reactive oxygen species production4. In other words, this drug will use the iron within the cancer cells against them.

If anyone can make sense out of this, I'd be appreciative. Right now, I don't see any point of discontinuing my high dose C to take artemisinin but the "common knowledge" is that I would be wrong! :)


They may have done a treatment like 3days in a row then rest of the week off, but cant quite remember.

Yes, 3 days on and 4 days off is most commonly how this is prescribed in the Lyme world. I think that makes sense. I would at least take weekends off.
 

leokitten

Senior Member
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I agree with @heapsreal supplements etc just don't work by themselves in my experience. Like you (I think) I am in the virus subset ME/CFS (if it can be called that) presenting with extremely high antibodies to EBV, CMV, HHV-6.

For antivirals I was on Valcyte + Famvir + Immunovir + supplements (resveratrol, quercetin, AHCC, plus many more) for over a year and it caused huge drops in my titers. I then took a break from Valcyte (as it takes a toll on your body after taking it so long) and Immunovir (because it's expensive and not covered by insurance) but continued to take Famvir and supplements in high doses and just as expected CMV and HHV-6 titers shot back up.

Famvir has ZERO direct antiviral effect on CMV and HHV-6 don't let anyone tell you differently, the drug does not target viral replication at all in betaherpesviruses. It could only ever have a secondary effect by continuing to inhibit EBV and therefore giving your immune system some help so that it can fight these other viruses. Supplements also just are not strong enough even in combination to do much of anything except as @heapsreal said be a good adjunct.

I cannot wait until brincidofovir is FDA approved because this will have more power than Valcyte without any of the toxicity.
 

Ema

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Famvir has ZERO direct antiviral effect on CMV and HHV-6 don't let anyone tell you differently, the drug does not target viral replication at all in betaherpesviruses. It could only ever have a secondary effect by continuing to inhibit EBV and therefore giving your immune system some help so that it can fight these other viruses.

Is this based on your experience or some published research on Famvir and the beta herpes viruses?

Last I checked, most thought Famvir did have some activity, particularly against HHV6, but had just not been put through the testing needed for FDA approval for treating those infections.

Since Valtrex is more potent than Famvir against EBV, it would be nice to know for sure what activity Famvir has against beta herpes viruses.
 

leokitten

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Is this based on your experience or some published research on Famvir and the beta herpes viruses?

Last I checked, most thought Famvir did have some activity, particularly against HHV6, but had just not been put through the testing needed for FDA approval for treating those infections.

People write a lot of things on this site that aren't based on any facts or evidence. Famvir (and Valtrex) have no activity against betaherpesviruses and this is based on the well known mechanism of action of both drugs. Both Valtrex and Famvir work only on herpesviruses which have thymidine kinase (TK), that's how these drugs become activated in virus infected cells (via phosphorylation by TK).

Betaherpesviruses (CMV, HHV-6, HHV-7, HHV-8) do not have TK. This is why drugs like Valcyte were invented because they needed different nucleoside analogues that were activated in betaherpesvirus infected cells by UL97 kinase (analog to TK in betaherpesvirus) and therefore effective at inhibiting their DNA replication.

Since Valtrex is more potent than Famvir against EBV, it would be nice to know for sure what activity Famvir has against beta herpes viruses.

This is not true, there is no evidence that one or the other is more effective against gammaherpesviruses such as EBV.
 

Ema

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People write a lot of things on this site that aren't based on any facts or evidence. Famvir (and Valtrex) have no activity against betaherpesviruses and this is based on the well known mechanism of action of both drugs. Both Valtrex and Famvir work only on herpesviruses which have thymidine kinase (TK), that's how these drugs become activated in virus infected cells (via phosphorylation by TK).

Betaherpesviruses (CMV, HHV-6, HHV-7, HHV-8) do not have TK. This is why drugs like Valcyte were invented because they needed different nucleoside analogues that were activated in betaherpesvirus infected cells by UL97 kinase (analog to TK in betaherpesvirus) and therefore effective at inhibiting their DNA replication.



This is not true, there is no evidence that one or the other is more effective against gammaherpesviruses such as EBV.
So it's based on just your experience then, I take it. There's nothing wrong with that. This site exists for us to share experiences. I am just trying to be clear on your basis for making such a sweeping statement.

The HHV-6 Foundation disagrees with your statement that they have no activity against the beta herpes viruses. Weak activity is still activity.

Do Valtrex or Famvir have any activity against HHV-6?

Valtrex® (Zelitrex®) and Famvir® are the oral forms of acyclovir and penciclovir, respectively. In cell culture, acyclovir has only weak activity against HHV-6. For penciclovir, the activity is even less pronounced.

So apparently, as with many other drugs, there are mechanisms of action outside TK phosphorylation at play that are not yet well elucidated.

I'll have to go back and look for the study I read that indicated Valtrex had greater activity than Famvir. It may have been against HSV1/2 and not EBV. I'll have to double check.
 

heapsreal

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Drugs like famvir and valtrex are used prophylactically to prevent cmv infections in immunosuppressed patients such as those undergoing organ transplant. No links but a quick google will show plenty of evidence.

Famvir is also effective against hepatitis B and said to be an alternative to alpha interferon.

Theres been a few people on here who have seen their viral titres to cmv or hhv6 drop on famvir, probably not as effective as valcyte, but they do work for some and a good alternative for those coming off valcyte treatment to help keep viral load down, similar in a way to it being used prophylacticly in immunosuppressed ?
 

heapsreal

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Its my understanding that changing avs from acyclovir to the prodrug valtrex increases the drugs half life and absorption.

Im guessing the same happens when the prodrug famvir is used instead of penciclovir. valcyte is better absorption and improved etc as its the prodrug to Ganciclovir.

It would be good to have an antiviral with a long half life that it only requires dosing once a day.
 

heapsreal

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People write a lot of things on this site that aren't based on any facts or evidence. Famvir (and Valtrex) have no activity against betaherpesviruses and this is based on the well known mechanism of action of both drugs. Both Valtrex and Famvir work only on herpesviruses which have thymidine kinase (TK), that's how these drugs become activated in virus infected cells (via phosphorylation by TK).

Betaherpesviruses (CMV, HHV-6, HHV-7, HHV-8) do not have TK. This is why drugs like Valcyte were invented because they needed different nucleoside analogues that were activated in betaherpesvirus infected cells by UL97 kinase (analog to TK in betaherpesvirus) and therefore effective at inhibiting their DNA replication.



This is not true, there is no evidence that one or the other is more effective against gammaherpesviruses such as EBV.

Previous studies of herpesvirus infections have indicated that a virus-specified thymidine kinase is required for the initial phosphorylation of acyclovir [acycloguanosine or 9-(2-hydroxyethoxymethyl)guanine] in the formation of acycloguanosine triphosphate. The latter compound accumulates in infected cells and competitively inhibits the viral DNA polymerase. We found that mouse cytomegalovirus, which does not express a thymidine kinase, was sensitive to the antiviral effects of acyclovir at a 50% inhibitory dose of approximately 0.23 microM. Acyclovir was equally effective against mouse cytomegalovirus in normal 3T3 cells and in 3T3 cells deficient in cellular thymidine kinase. Furthermore, the activity of acyclovir could not be reversed by excess thymidine, which easily reversed the antiviral activity of acyclovir against herpes simplex virus. Using a high-pressure liquid chromatography technique that easily detected acycloguanosine triphosphate in cells infected with herpes simplex virus, we could not detect acycloguanosine triphosphate in mouse cytomegalovirus-infected cells. These experiments demonstrated that the activity of acyclovir against mouse cytomegalovirus is not dependent on a thymidine phosphorylation pathway. Additional experiments are underway to determine whether acycloguanosine triphosphate is produced by another pathway in concentrations sufficient to inhibit mouse cytomegalovirus DNA polymerase.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC171322/

It would appear there is more then 1 mechanism of antiviral actions of acyclovir?
 

leokitten

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Both Famvir and Valtrex end up being fairly equipotent in-vivo, please read:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504076/
Mechanism of action
Activation of acyclovir and penciclovir is dependent on viral thymidine kinase found in cells infected with herpesvirus. Penciclovir is rapidly converted to penciclovir-monophosphate by thymidine kinase and then further phosphorylated to penciclovir-triphosphate by other cellular enzymes. Similarly, acyclovir is converted intracellularly to acyclovir-triphosphate, although at a much slower rate. This is due to the 100-fold higher affinity that thymidine kinase has for penciclovir compared to acyclovir, leading to the more efficient phosphorylation of penciclovir and higher intracellular concentrations of penciclovir-triphosphate versus acyclovir-triphosphate (Boyd et al 1987; Vere Hodge and Perkins 1989; Earnshaw et al 1992; Pue et al 1994; Crumpacker 1996).

Both penciclovir-triphosphate and acyclovir-triphosphate are analogues of the naturally occurring nucleoside deoxyguanosine (dGTP) and compete with dGTP as a substrate for viral DNA polymerase. Insertion of these analogues inhibits viral DNA chain elongation, preventing replication of the viral genome. Although both penciclovir-triphosphate and acyclovir-triphosphate act by interfering with DNA polymerase, there are some differences in their inhibitory mechanisms. Penciclovir-triphosphate functions as a short-chain terminator, allowing a small degree of further DNA chain elongation at the 3’ hydroxyl group of its acyclic side chain. Acyclovir-triphosphate, however, is an obligate chain terminator, leading to cessation of DNA chain elongation after its incorporation. Additionally, DNA polymerase has a higher affinity for acyclovir-triphosphate than penciclovir-triphosphate. Despite this fact, in a study simulating physiologic concentration of nucleosides, penciclovir-triphosphate was found to more efficiently inhibit chain elongation by DNA polymerase than acyclovir-triphosphate (Reardon and Spector 1989; Vere Hodge and Cheng 1993; Crumpacker 1996; Bacon et al 2003).

Overall, studies have indicated that penciclovir and acyclovir have similar efficacy versus varicella zoster virus (VZV), HSV-1, and HSV-2. This is possible despite the decreased affinity of DNA polymerase for penciclovir-triphosphate versus acyclovir-triphosphate given the aforementioned increased affinity of thymidine kinase for penciclovir and the 100-fold increased intracellular concentrations of penciclovir-triphosphate (Larsson et al 1986; Earnshaw et al 1992; Vere Hodge and Cheng 1993; Bacon 1996; Crumpacker 1996).

Plaque reduction assays have demonstrated similar activities of penciclovir and acyclovir when the compounds are present continuously (Bacon 1996). However, upon withdrawal of the compounds, inhibition of virus replication was sustained for a greater time period with penciclovir than acyclovir. This sustained antiviral activity of penciclovir-triphosphate is due to increased stability of penciclovir-triphosphate, leading to prolonged intracellular concentrations and half-lives of penciclovir-triphosphate compared to acyclovir-triphosphate. In HSV-1 and HSV-2 infected cells, the half-life of famciclovir is 10 and 20 hours, respectively. For acyclovir, the half-lives are 0.7 and 1 hour (Boyd et al 1987; Bacon 1996; Crumpacker 1996).
 
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