Drug treatments and combos for ME/CFS, mitochondrial protection and toxicity

[sometexan84]

All the ME metabolomics and mitochondrial research to date hasn’t found anything abnormal with the functioning of our mitochondria except for this paper I believe:

An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients

The Complex V study is a good one. That's for EBV.

Prusty and Naviaux have shown HHV-6 causes mito dysfunction as well.

EBV and HHV-6 are two of the most (if not THE two most) viruses associated w/ ME/CFS.

I don't understand why people still question whether mitochondrial dysfunction plays a role in CFS..

 

[leokitten]

The Complex V study is a good one. That's for EBV.

Prusty and Naviaux have shown HHV-6 causes mito dysfunction as well.

EBV and HHV-6 are two of the most (if not THE two most) viruses associated w/ ME/CFS.

I don't understand why people still question whether mitochondrial dysfunction plays a role in CFS..

My worry is that taking nucleoside analogs (a class of antivirals, such a Valtrex, Famvir, Valcyte) in and of themselves cause mitochondrial dysfunction and toxicity.

 

[sometexan84]

My worry is that taking nucleoside analogs (a class of antivirals, such a Valtrex, Famvir, Valcyte) in and of themselves cause mitochondrial dysfunction and toxicity.

Why

 

[leokitten]

Why

I actually did Famvir and Valcyte together for 3 years or more after my ME diagnosis. I had (and maybe still do) very high EBV, CMV, and HHV-6 IgG and also very high EBV EA-D titers.

I didn’t notice that they helped at all, but that being said during that time I was still working mostly full-time (with partial telework), overexerting to the max, and crashing once a week or more. Maybe that’s the reason I don’t know.

One thing specifically about Valcyte is that it made my wired but tired, brain overstimulated, and super uncomfortable body symptoms at night much worse. It made sleep even more difficult and these symptoms improved back to my baseline ME the moment I would stop it.

To specifically answer your question, if, as multiple ME research labs found, there are metabolic issues at the cellular level that could be driving ME symptoms, I’m not sure I want to add a medication that inhibits or is slightly toxic to mitochondria because that would compound the problem?

 

[sometexan84]

I’m not sure I want to add a medication that inhibits or is slightly toxic to mitochondria because that would compound the problem?

If you've found any recent studies suggesting this, please share, as I would love to check those out.

From what I'm seeing, the cases of toxicity and mito alterations from Valacyclovir seem to be related to overdosing. Plus, multiple mentions of "renal function" impairments in these cases.

Like, they all seem to have been on 3 grams/day. Not that I'm saying 3g/day is overdosing... I think Dr Lerner used this dose.

I'm on 500mg, 3x/day Valtrex.

I do see a recent study on Impact of pharmacological agents on mitochondrial function: a growing opportunity? that mentions Acyclovir...

Summary of drugs with associated mitochondrial toxicity.

• Zidovudine (AZT) (black box warning)
• Acyclovir (ACV)
• Ganciclovir (GCV)
• Zalcitabine (ddC)
• Saquinavir (black box warning)
• Tetracycline
• Ciprofloxacin (black box warning)
• Cisplatin (black box warning)
• Cyclophosphamide
• Clozapine (black box warning)
• Sodium valporate (black box warning)
• Sertraline
• Fluoxetine (black box warning)

 

[leokitten]

If you've found any recent studies suggesting this, please share, as I would love to check those out.

From what I'm seeing, the cases of toxicity and mito alterations from Valacyclovir seem to be related to overdosing. Plus, multiple mentions of "renal function" impairments in these cases.

Like, they all seem to have been on 3 grams/day. Not that I'm saying 3g/day is overdosing... I think Dr Lerner used this dose.

I'm on 500mg, 3x/day Valtrex.

I do see a recent study on Impact of pharmacological agents on mitochondrial function: a growing opportunity? that mentions Acyclovir...

Summary of drugs with associated mitochondrial toxicity.

• Zidovudine (AZT) (black box warning)
• Acyclovir (ACV)
• Ganciclovir (GCV)
• Zalcitabine (ddC)
• Saquinavir (black box warning)
• Tetracycline
• Ciprofloxacin (black box warning)
• Cisplatin (black box warning)
• Cyclophosphamide
• Clozapine (black box warning)
• Sodium valporate (black box warning)
• Sertraline
• Fluoxetine (black box warning)

I will search for additional papers but it’s just a fundamental way in which nucleoside analogues work. They are far from perfect at inserting only into viral DNA, so they also insert at a lower rate into our DNA and our mitochondrial DNA, thus causing mitochondrial toxicity and reducing mitochondrial DNA generation.

Btw, valacyclovir (Valtrex) is a higher bioavailability pro-drug for acyclovir, so in your body it gets completely converted into acyclovir and this is the molecule that has activity. So you can see even Valtrex has some mitochondrial toxicity.

 

[sometexan84]

Btw, valacyclovir (Valtrex) is a higher bioavailability pro-drug for acyclovir, so in your body it gets completely converted into acyclovir and this is the molecule that has activity. So you can see even Valtrex has some mitochondrial toxicity.

I'm not sure. But Cyclophosphamide is a pro-drug as well, and they mentioned it specifically. I assumed they were listing specific medications.

According to this article, it sounds like only patients w/ impaired renal function should be concerned:

Patients with impaired renal function are vulnerable to drug toxicity due to their compromised ability to eliminate the unchanged acyclovir through the urine

 

[leokitten]

I'm not sure.

@sometexan84 yes it is. Read the pharmacology section on the Wikipedia page https://en.m.wikipedia.org/wiki/Valaciclovir or any general paper about valacyclovir on pubmed. Valacyclovir isn’t the active drug, it is a pro-drug converted to acyclovir which is the active drug.

All nucleoside analogues by mechanism of action will inhibit some mitochondrial DNA synthesis and are therefore somewhat toxic to mitochondria. They work by inserting themselves into the DNA and stopping DNA synthesis. They are supposed to always insert into viral DNA thus stopping viral replication, but the process is far from perfect and they do insert into host DNA.

 

[leokitten]

According to this article, it sounds like only patients w/ impaired renal function should be concerned:

This is a separate issue regarding valacyclovir and acyclovir. You need to have good renal function especially when taking higher daily dosages because excretion of these drugs highly depends on your kidneys and the drug can form renal crystals that build up and can cause renal failure.

 

[sometexan84]

@sometexan84 yes it is. Read the pharmacology section on the Wikipedia page https://en.m.wikipedia.org/wiki/Valaciclovir or any general paper about valacyclovir on pubmed. Valacyclovir isn’t the active drug, it is a pro-drug converted to acyclovir which is the active drug.

Right. Yes, I'm aware. I meant "I'm not sure" regarding how exactly they created that list of medications. Like, I don't know what the researchers of that study would say if you asked them about the toxicity they found in acyclovir vs valacyclovir.

Anyway, I haven't seen much to be concerned about. If you find anything, I'd certainly like to see.

 

[leokitten]

This thread is about Abilify, no ???

We’ve pretty much gone through the currently avail info related to Abilify, so to fill the temp void started veering off into related combos and treatments as well as mitochondrial protection and toxicity.