Intracellular calcium and viruses

[Iritu1021]

A few of us had an interesting thread here going for a while titled "T3, intracellular calcium and caffeine"
That led to my delving into the subject about the connection of intracellular calcium, mitochondrial function, and viral infections and as a result, I have written this post that I wanted to share with the rest of you.

http://www.chronicfatiguediagnosis.com/2018/11/01/intracellular-calcium-and-viruses/

 

[sb4]

Very good article, thanks. I particularly liked the link between viruses and PDH Phosphatase. Makes sense how some have improvement with DCA.

 

[Learner1]

Thank you for putting the post together. It is very interesting. The link to PDH was interesting. I've known my calcium system is off for a couple of years but am not sure what to do about it and your blog post doesn't go far enough to my questions.

If we've had a bunch of herpes viruses and have tackled them with antivirals, will our calcium system revert to normal?

And yes, I am interested in how this affects our bones... my mom used to be 5'9" and is now 5'3" - her shin bones curve due to loss of bone.

Five years ago, I had a normal DEXA scan for a woman my age. I have lifted weights, take DHEA and testosterone, have adequate calcium in my diet AND take a plant based calcium with all the cofactors. Still, last year, my DEXA came back at just above osteoporosis and my doctor did some none marker lab tests which indicate I'm actively losing bone. And, my serum calcium runs low on blood tests.

I can't help but think that all of this is related. I tried going to an endo who supposedly specializes in bone health, but he just freaked out because my TSH was .006. even though my FT3 and FT4 are low mid range. I have no reason to believe my pituitary is making any hormones and would make TSH if I stopped taking T3.

Trying to figure out how to normalize this entire calcium system ...

 

[keenly]

A few of us had an interesting thread here going for a while titled "T3, intracellular calcium and caffeine"
That led to my delving into the subject about the connection of intracellular calcium, mitochondrial function, and viral infections and as a result, I have written this post that I wanted to share with the rest of you.

http://www.chronicfatiguediagnosis.com/2018/11/01/intracellular-calcium-and-viruses/

'it appears that all the roads lead to the intracellular calcium dysregulation in CFS and dysautonomia.'

Thanks for stating this my friend. I have tried stating it myself on here when talking about 5G and all nnemf.

What causes calcium to flood into mitochondria? nnemf. 5G will mean every cubic CM of the UK and eventually U.S.A will be covered with 3.5Ghz all the way up to 90Ghz artificial magnetic field.
Why would viruses reactivate? Poor redox. What causes poor redox? nnEMF.

We need to look at our environments.

 

[wigglethemouse]

And yes, I am interested in how this affects our bones... my mom used to be 5'9" and is now 5'3" - her shin bones curve due to loss of bone.

@Learner1 You might be interested in these two quotes from John Whiting on Twitter (doc in Australia)

Bone loss is not genetic but it is the single most serious complication of ME. When an 55-60 year old ME spine collapses by 6 inches, sad++

The only thing I know it is incredibly common. Maybe 60-70% of the thousand or so of the patients that I have tested for this.

I wish there was more research looking at this connection.

One thing I find interesting is that Osteoporosis has been shown to have a relationship to MCAS, and that some ME docs think a significant proportion of their patients have mast cell issues. Another option is if it is somehow related to hypometabolism (lack of essential minerals). Or perhaps both........

 

[Wonkmonk]

@Iritu1021 This is super-interesting, because I have on several separate occasions observed, that I am getting much worse if I take Vitamin D or calcium supplements or if i eat lots of high-calcium foods. It happened so consistently that it can't be a coincidence. Conversely, I am getting a bit better with low-dose calcium channel blocker.

So my hypothesis was that I might have too much intracellular calcium (as I understand your hypothesis, though, you think it is a intracellular deficiancy).

I also have massively elevated HSV-1 IgG titers (">1:20,000" in 5 tests over last 2 years, never below that). IgM were always negative.

Then I found a study that says that HSV-1 uses the Akt pathway to increase intracellular calcium and that this enables cell entry and HSV-1 replication. Did you look into that? I didn't see anything about Akt in your article.

That leads me to hypothesize that HSV-1 infection, possibly abortive/non-cytolytic, is causing my CFS and that calcium intake worsens it because it helps the virus to replicate via the Akt pathway.

Interestingly, there is a drug called miltefosine (Impavido) that can inhibit Akt, and there is one in vitro study in which it in fact had anti-HSV-1 activity. I am probably going to try it at some point.

Is there any other known way how to inhibit Akt (drugs, herbs or supplements)?

What else could I possibly do to lower intracellular calcium?

 

[drob31]

@Iritu1021 This is super-interesting, because I have on several separate occasions observed, that I am getting much worse if I take Vitamin D or calcium supplements or if i eat lots of high-calcium foods. It happened so consistently that it can't be a coincidence. Conversely, I am getting a bit better with low-dose calcium channel blocker.

So my hypothesis was that I might have too much intracellular calcium (as I understand your hypothesis, though, you think it is a intracellular deficiancy).

I also have massively elevated HSV-1 IgG titers (">1:20,000" in 5 tests over last 2 years, never below that). IgM were always negative.

Then I found a study that says that HSV-1 uses the Akt pathway to increase intracellular calcium and that this enables cell entry and HSV-1 replication. Did you look into that? I didn't see anything about Akt in your article.

That leads me to hypothesize that HSV-1 infection, possibly abortive/non-cytolytic, is causing my CFS and that calcium intake worsens it because it helps the virus to replicate via the Akt pathway.

Interestingly, there is a drug called miltefosine (Impavido) that can inhibit Akt, and there is one in vitro study in which it in fact had anti-HSV-1 activity. I am probably going to try it at some point.

Is there any other known way how to inhibit Akt (drugs, herbs or supplements)?

What else could I possibly do to lower intracellular calcium?

What calcium channel blockers are you using?

I think @Iritu1021 mentioned it could work both ways. It could either be too much or too little.

 

[wigglethemouse]

Interesting post @Iritu1021

Intracellular calcium seems to be regulated by many things. I thought this snippet on the Wikipedia for "Muscarinic acetylcholine receptor" was interesting

Like the M1 and M3 muscarinic receptor, M5 receptors are coupled with G proteins of class Gq that upregulate phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signaling pathway.

Link : https://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptor

A few folks on PR have found they are positive for antibodies to some of these M receptors using the Cell Trends POTS test.

 

[Wonkmonk]

What calcium channel blockers are you using?

I am using Nimodipine at a very low dose (7.5mg, i.e. 1/4th 30mg tablet). I also tried verapamil and nifedipine, none of which worked better, so I stick with Nimo, because it is very safe with very few adverse effects.

My hypothesis is the problem in my case is "too much", because I consistently get worse whenever I go up with my calcium intake (food, supplements or Vitamin D, all "works" that way).

The problem is you can't do it by eliminating calcium from your diet entirely or going very low on Vitamin D because once you do, parathyroid hormone goes up and the body maintains a certain level of calcium in the blood by taking it from the bones.

I am looking for other ways to reduce intracellular calcium, if anyone has suggestions, I'd appreciate it.​

 

[Learner1]

It seems we need more info to understand how our entire calcium systems work.

I was on a different calcium chsnnel blocker, amlodipine, for 2 weeks, and it almost killed me. Not joking...it gave me pancytopenia, and LabCorp sat on my test results which showed alarming destruction of red and white blood cells and platelets. And I was so tired I couldn't move.

@wigglethemouse Your point about MCAS is appreciated. They just tell us osteoporosis a symptom but no one says anything about fixing it. And my very conventional dentist earned me away from Fosamax, etc. He's seen too many jaw necroses from these drugs...

 

[Iritu1021]

It's important to realize that calcium channel blockers do not really affect intracellular calcium stores in the endoplasmic reticulum (with the possible exception of nimodipine) - these are two separate issues which are regulated in separate ways.

The same goes for taking supplemental calcium, it should not have any major effect on intracellular calcium stores assuming that the intracellular calcium homeostat is off. The only calcium that matters is ionized calcium which is in the active form and the body has a tight regulation on ionized calcium.

 

[Learner1]

Right, so where does that go?? I'd love to see some mapping of it, as I definitely have some problems, as do others. It's not on out doctor's radar screens... I keep asking...

 

[Iritu1021]

@Iritu1021 This is super-interesting, because I have on several separate occasions observed, that I am getting much worse if I take Vitamin D or calcium supplements or if i eat lots of high-calcium foods. It happened so consistently that it can't be a coincidence. Conversely, I am getting a bit better with low-dose calcium channel blocker.

So my hypothesis was that I might have too much intracellular calcium (as I understand your hypothesis, though, you think it is a intracellular deficiancy).

I also have massively elevated HSV-1 IgG titers (">1:20,000" in 5 tests over last 2 years, never below that). IgM were always negative.

Then I found a study that says that HSV-1 uses the Akt pathway to increase intracellular calcium and that this enables cell entry and HSV-1 replication. Did you look into that? I didn't see anything about Akt in your article.

That leads me to hypothesize that HSV-1 infection, possibly abortive/non-cytolytic, is causing my CFS and that calcium intake worsens it because it helps the virus to replicate via the Akt pathway.

Interestingly, there is a drug called miltefosine (Impavido) that can inhibit Akt, and there is one in vitro study in which it in fact had anti-HSV-1 activity. I am probably going to try it at some point.

Is there any other known way how to inhibit Akt (drugs, herbs or supplements)?

What else could I possibly do to lower intracellular calcium?

I have to explore Akt issue more in-depth but check out arteseminin/artesunate: https://academic.oup.com/cid/article/47/6/804/325924

 

[Iritu1021]

Interesting post @Iritu1021

Intracellular calcium seems to be regulated by many things. I thought this snippet on the Wikipedia for "Muscarinic acetylcholine receptor" was interesting

Link : https://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptor

A few folks on PR have found they are positive for antibodies to some of these M receptors using the Cell Trends POTS test.

Yes, thanks for bringing that up - the muscarinic issue actually did come up during discussion in our previous intracellular calcium thread but I forgot to mention it in the article.

 

[Iritu1021]

Right, so where does that go?? I'd love to see some mapping of it, as I definitely have some problems, as do others. It's not on out doctor's radar screens... I keep asking...

My hypothesis is shaping up like this right now:

The viruses might be sensitizing our extracellular calcium receptors to calcium and the body might be trying to lower intracellular calcium stores as a defense against them. So depending on the balance between these two processes as well as the type of viral constellation and individual genetics and also which drugs and supplements we are taking there may be multiple scenarios of abnormal regulation of extracellular calcium (affecting neurotransmission) and intracellular calcium (affecting cell signaling and bioenergetics).

Does anyone happen to have the full text of the TRPM3 study? I believe you sent it to me at one point but I might be wrong. I remember reading that they weren't able to influence the calcium flux through the receptor until they depleted the cells of calcium. Once they did that, things changed. It would be interesting to know how long they kept the cells depleted - not sure if they mention it in their M&M. I wonder if the calcium depletion decreased the expression of viral proteins on the surface.

 

[Learner1]

My hypothesis the viruses might be sensitizing our extracellular calcium receptors to calcium and the body might be trying to lower intracellular calcium stores as a defense against them. So depending on the balance between these two processes as well as the type of viral constellation and individual genetics and also which drugs and supplements we are taking there may be multiple scenarios of abnormal regulation of extracellular calcium (affecting neurotransmission) and intracellular calcium (affecting cell signaling and bioenergetics).

And bones, yes?

Does anyone happen to have the full text of the TRPM3 study? I believe you sent it to me at one point but I might be wrong. I remember reading that they weren't able to influence the calcium flux through the receptor until they depleted the cells of calcium. Once they did that, things changed. It would be interesting to know how long they kept the cells depleted - not sure if they mention it in their M&M. I wonder if the calcium depletion decreased the expression of viral proteins on the surface.

See attached.

 

[Iritu1021]

Thanks @Learner1 - it turns out that I was thinking of their previous paper from last year. I read the summary of it on Health Rising here. This is how Cort summarized it:

The only way the researchers were able to increase cytotoxic T-cell activity in the ME/CFS patients was by whacking their NK cells with a calcium depleter first and then activating them with a ion channel (TRPM3) enhancer.

To be honest, these TRP papers are extremely technical and are way over my head. But I think its interesting that these channels are regulated by pregnenolone. My pregnenolone is really low but I'm not sure now if it's a result of the viral infection or part of the adaptive response to it.

 

[Murph]

I'm very open to the idea of calcium channel deregulation.

But I'm concerned about any calcium-centric hypotheses that are not highly specific and testable. As you yourself point out, calcium is crucial in many, many bodily systems.

I've got too excited in the past by finding that certain compounds or enzymes keep popping up in my research. For me it was a kinase: AMPK. I kept seeing it everywhere. It was related to every tratment I googled, and every system I was studying, I felt like it must be central to ME/CFS. But the reality was that it is just super important in the body, so it is mentioned in every article, pretty much, no matter what they're about.

 

[Learner1]

Good point @Murph I've been told we can't taste calcium, its so ubiquitous.

To be honest, these TRP papers are extremely technical and are way over my head.

They sure are. I suspect we woukd need to read a few hundred papers to fully understand what's going on. I sure wish out doctors knew more about this...

But I think its interesting that these channels are regulated by pregnenolone. My pregnenolone is really low but I'm not sure now if it's a result of the viral infection or part of the adaptive response to it.

Low pregnenolone was one of the findings mentioned at the Symposium. My doctor put me on it, but I can only toleratate about 10mg. Any more and my estrogen goes through the roof, which is not good as I had an estrogen-driven cancer. I've heard it can promote testosterone in other patients. It's worth trying but with some care...

 

[Iritu1021]

I'm very open to the idea of calcium channel deregulation.

But I'm concerned about any calcium-centric hypotheses that are not highly specific and testable. As you yourself point out, calcium is crucial in many, many bodily systems.

I've got too excited in the past by finding that certain compounds or enzymes keep popping up in my research. For me it was a kinase: AMPK. I kept seeing it everywhere. It was related to every tratment I googled, and every system I was studying, I felt like it must be central to ME/CFS. But the reality was that it is just super important in the body, so it is mentioned in every article, pretty much, no matter what they're about.

I agree that you can't suspect something just because it pops up in your reading. I only suspect something when it pops up in my own data. I have ignored the TRPM paper until I discovered that abruptly lowering my dose of thyroid hormone causes my ionized calcium to drop below normal which was associated with all sorts of weird symptoms (inner restlessness, a feeling of abnormal electrical flow (not sure how else to describe it) muscle spasms, tachycardia, paresthesias).

But then the ionized calcium returned to normal once my thyroid hormone stabilized. The serum calcium has been always perfectly normal so it wasn't an issue of calcium deficiency (I eat a lot of dairy too).

So that made me wonder why would my body want to lower ionized calcium under the circumstance - what it was compensating for, etc and also led me to give lithium orotate another chance because I knew that lithium can shift ionized calcium curve.