Intracellular calcium and viruses

[Wonkmonk]

This study says the bioavailability of lithium carbonate (which I understand is used in psychiatry) is also high, 80-100%.

https://www.ncbi.nlm.nih.gov/pubmed/19374461

 

[Iritu1021]

This study says the bioavailability of lithium carbonate (which I understand is used in psychiatry) is also high, 80-100%.

https://www.ncbi.nlm.nih.gov/pubmed/19374461

Although this is still debated, Hans Nieper (the doctor who popularized the orotate form) claimed that organic forms are transported across the membranes better than inorganic forms.

 

[Wonkmonk]

I took 5mg yesterday and it was a bit strange, I got sleepy on the one hand, but woke up about 5 times during the night. Also my lower back pain increase. Didn't feel good actually.

But it might also be a nocebo effect or it might go away with continued use. I will still probably not use regularly for the time being.

Perhaps I'll try using just half a capsule.

 

[Iritu1021]

I took 5mg yesterday and it was a bit strange, I got sleepy on the one hand, but woke up about 5 times during the night. Also my lower back pain increase. Didn't feel good actually.

But it might also be a nocebo effect or it might go away with continued use. I will still probably not use regularly for the time being.

Perhaps I'll try using just half a capsule.

I don't think it's nocebo, it definitely made me feel very bad when I first started taking it. But at that point I already came to the conclusion that everything that produces immediate positive effect, will either stop working or make me worse later on so I was very much in "no pain, no gain" mind set.

You might try changing the time of the day when you take it and start at low doses, even quarter capsule every other day. The sleepiness is probably due to the effect on sodium channels (and should get better after a 3-5 days) and waking up and increase in pain might be due to sudden increase in T3 conversion (which may be mismatched to your cortisol production) or some viral "die off" reaction. You have to keep in mind that it decreases your intracellular calcium to starve off the virus. This is essentially an endurance battle between the virus and its host. We're are a more compicated organism so we can adapt to things better than they can but any adaptation takes time.

But keep in mind that I only have experience with orotate, not aspartate. As you can see from the picture I posted yesterday they might not be exactly the same.

 

[Wonkmonk]

In my experience, what makes me feel worse initially doesn't get better over time. Things that helped over a longer term (e.g., microdose Aciclovir plus aspirin) did start to help initially.

I will probably try miltefosine before making another trial with lithium at a lower dose. I have now got the miltefosine from the pharmacy. It's a long shot, but maybe Akt inhibition works, it should from a theoretical point of view.

But then again, I tried other things that were supposed to help against HSV-1 and they didn't, or even made me worse (e.g., licorice root, Aloe Vera juice). It seems to be complicated (or it might not be HSV-1 after all).

 

[Iritu1021]

In my experience, what makes me feel worse initially doesn't get better over time. Things that helped over a longer term (e.g., microdose Aciclovir plus aspirin) did start to help initially.

I will probably try miltefosine before making another trial with lithium at a lower dose. I have now got the miltefosine from the pharmacy. It's a long shot, but maybe Akt inhibition works, it should from a theoretical point of view.

But then again, I tried other things that were supposed to help against HSV-1 and they didn't, or even made me worse (e.g., licorice root, Aloe Vera juice). It seems to be complicated (or it might not be HSV-1 after all).

For me it always changing too. When I tried licorice several years ago during my acute crash, it made me worse while now I've started taking it again and I'm actually liking it now - I think because my fT3 is so much higher.
But my primary viral suspects (for myself) are EBV and HHV-6, not HSV-1. But it's all just guess work. There may be multiple parasites at play.

 

[Wonkmonk]

I have tested almost all usual suspects and the only one that came back elevated was HSV-1, and it was extremely high with HSV-1 IgG ">1:20,000", so if a virus is responsible, everything points to HSV-1.

But my doctor said she had another patient with HSV-1 IgG 1:18,000 with no symptoms at all and otherwise healthy. That's why she isn't sold on the HSV-1 hypothesis.

I believe in it or let's say it's definitely the best guess because there is no sign of autoimmunity or any other disease whatsoever.

 

[Wonkmonk]

In case anyone is also considering it: The adverse effects of the lithium seem to be gone after two days. Sleep was normal again last night.

It was worth a try, but I don't think it will help me.

 

[Iritu1021]

In case anyone is also considering it: The adverse effects of the lithium seem to be gone after two days. Sleep was normal again last night.

It was worth a try, but I don't think it will help me.

Yes, two days sounds about right, unless someone has a bad thyroid and not taking thyroid hormone, then it might take longer.

I think an alternative explanation of the lithium benefit for me could have to do with altering postsynaptic 5HT1A receptor function (which takes about two weeks to manifest). I think my thyroid dose sensitivity and HPA dysfunction might be related to these receptors (which in turn could have something to do with the viruses "hacking" them). It also could be the reason why I get physically worse on SSRIs and feel worse with DHEA and progesterone supplementation despite both of them being on the low side.

A recent study from U of Oregon showed that normal people can't tell any subjective difference between their doses of thyroid they are taking - which I tend to believe because it was also my clinical experience as a physician. Most people just seem to not feel their thyroid meds at all, and definitely not in a short-term like we do. There's clearly something different neurologically about people like us.

 

[pattismith]

This is very interesting because after I had thyroid surgery there is a several day waiting period before starting thyroid hormones (not sure exactly why it is needed). I didn't get much worse during that period, but I got much worse in a matter of days after starting thyroid hormone replacement and I am permanently worse (and worsening) since then.

I was always convinced that thyroid hormones played a role for my condition getting so bad. I definitely was sick before, but I could work, manage my own household, felt not too bad. After starting thyroid hormones, it all went downhill very fast.

Maybe Akt activation is the reason.

Akt is also activated via IL8 receptors, and KDM found IL8 to be a biomarker in CFS/ME.

IL8 also raises intracellular calcium, so the target you are looking for might be this cytokine.

I found that both Ambroxol and Erithromycine, (and Clarythromycine), both drugs that helped me to fight some symptoms, are IL8 inhibitors.

 

[Wonkmonk]

I found that both Ambroxol and Erithromycine, (and Clarythromycine), both drugs that helped me to fight some symptoms, are IL8 inhibitors.

Interesting, I had IV erithromycin for a few days in spring and it didn't do anything (neither good nor bad).

I have to look into Ambroxol. Maybe trying makes sense.

 

[pattismith]

Interesting, I had IV erithromycin for a few days in spring and it didn't do anything (neither good nor bad).

I have to look into Ambroxol. Maybe trying makes sense.

Ambroxol as a sodium channel blocker has secondary inhibiting effect on Voltage gated calcium channels (probably non selective effect), so it affects intracellular calcium in several ways. Ambroxol has an activity on nervous cells.


Nimodipine an inhibitor of L voltage gated calcium channels also has properties to modulate intracellular calcium and also have a complex effect with additional effect on intracellular calcium channels (sarcolemma).


I am not able to tell if the association of these two drugs can give benefits or if it is conter-productive.


I tried to associate them, but I was not very successful, so now I try to take them separately to see if it could be better.


The association of these drugs with Inosine could modulate their effect, as Inosine seems to inhibit the L calcium channels blockade!

https://www.ncbi.nlm.nih.gov/pubmed/15026152

https://www.ncbi.nlm.nih.gov/pubmed/23731236


This means that it is a very complicated matter when we try associations between drugs with intracellular calcium effect….

 

[Wonkmonk]

Okay, Inosine and Ambroxol added to my list (already have nimo, will maybe try in combination).

 

[Iritu1021]

Okay, Inosine and Ambroxol added to my list (already have nimo, will maybe try in combination).

@pattismith what is your experience so far with nimodipine?

by the way, phenibut is another drug that modulates calcium channels similar to gabapentin. In fact, it's sometimes classified as "gabapentinoid". These drugs don't block the channels but bind to them and modify their function.

 

[Iritu1021]

So it looks that Jay Goldstein did not actually think that nimodipine primary mode of action was calcium blockade but rather 5HT2, 5HT3 and NMDA blockade. Which goes well with my own latest conclusion that most of my issues were due to supersensitive serotonin receptors (with different receptor settings that varied over time) that I described in my latest blog post.

I also now believe with quite some certainty that the primary mode of lithium orotate action for me is the stabilization of the receptors. Any receptor effect takes time to achieve and unfortunately, requires getting through a rough patch at first due to a transient increase in serotonin synthesis and other cellular effects of lithium effects that the body has to adapt to (just think of it as "herxing" reaction).

I would recommend that if at all possible to tolerate, no one who suspects serotonin receptor supersensitivity should rule out lithium orotate unless they've been on it for at least a week without seeing any improvement in side effects. And for me personally it takes at least 20 mg of elemental lithium to see the improvement but your individual mileage can vary. Once I reach the right dose, there is a clear and drastic switch in my CNS function. Below the effective dose it's mostly just side effects.

I'm starting to think that intracellular calcium and viral infections/autoimmunity are probably a downstream effect of the receptor supersensitivity rather than the primary issue.

here's the link to the page from Goldstein's book "Tuning the brain" where he mentions nimodipine although doesn't link his sources:

https://books.google.com/books?id=KTuMAQAAQBAJ&pg=PT563&lpg=PT563&dq=nimodipine 5ht2 antagonism&source=bl&ots=CDU5eImb0o&sig=KjzqZUZ3B8YplKUsMOcZB8vmLeQ&hl=en&sa=X&ved=2ahUKEwjgpLLlmvjeAhVNLK0KHd39CSAQ6AEwD3oECAMQAQ#v=onepage&q=nimodipine 5ht2 antagonism&f=false

 

[Wonkmonk]

So it looks that Jay Goldstein did not actually think that nimodipine primary mode of action was calcium blockade but rather 5HT2, 5HT3 and NMDA blockade.

Dr. Mason Brown suspected that the effect might not be related to calcium at all, but rather to vasodilation, which results in viral particles and toxins being flushed out. He hypothesized that this is also why some patients experienced a herxheimer-like reaction when starting with calcium channel blockers.

 

[Iritu1021]

Dr. Mason Brown suspected that the effect might not be related to calcium at all, but rather to vasodilation, which results in viral particles and toxins being flushed out. He hypothesized that this is also why some patients experienced a herxheimer-like reaction when starting with calcium channel blockers.

It might be viral die-off or it might be receptors adapting to new settings but it seems that in many cases one has to endure a period of discomfort before things start getting better.

 

[Wonkmonk]

in many cases one has to endure a period of discomfort before things start getting better.

It was definitely that way when I started Nimo. But in the end, benefits were small only.

 

[Inara]

I think

It's also about the quality of the signal, is it oscillating, a puff or...?

 

[Inara]

But I'm concerned about any calcium-centric hypotheses that are not highly specific and testable.

It's just a single case (actually 4...), but in my case it's specifically an IP3 receptor. BUT it is extremely difficult to have its function tested. It is possible and it's done in research, but I don't get "my" receptor checked, which is needed to know if it's dysfunctional or not.

Also, my impression is ME research is not interested in calcium pathway issues, that may underlie some cases of ME.