T3 intracellular calcium and caffeine

[Iritu1021]

I don't think I would be up to reading something like that right now, but of course it looks great. The first thing I'm going to do when I achieve some modest improvement is find and crack open my copy of Szent-gyorgyi's "Introduction to a Sub-molecular Biology" and also all the chemistry and cell biology textbooks I have lying around that I over-ambitiously collected when i was getting ill

sub-molecular? that sounds like zooming in on a whole next level than what we're discussing here. I am still at the molecular stage.

I am excited for you @Iritu1021 for your purchase (even though I lost the ability to follow the science behind thread quite a while ago)!

I got my tests back from the Mayo Clinic of the Autoimmune Dysautonomia Panel (which includes the Calcium Channel autoantibodies) and wrote about the results in my Rituximab thread. You had asked me about them (a while back) but I was not certain if they still pertained to this thread or if the info would be helpful to you? Can you let me know and if they'd be useful, I am happy to write about it here later.

Sure, please tell us - I'm still curious about the antibodies! Did they come down after Rituximab?

 

[Iritu1021]

@pattismith, thanks for the article! sorry to hear you're crashing. Hope you get over it soon!

@S-VV I got another hair analysis done a week ago and now my calcium has come down even further compared to 2014, it's now in the mid-range (my last one was upper normal, while in 2014 was off the chart high after stimulants). I think there's either correlation with T4 or lithium or the combination of both.

My copper is borderline low. My vanadium is also really low (used to be even lower) but I read that high vanadium can induce both mania and depression.

 

[S-VV]

Fantastic news about the Calcium!!! You seem to have found your winning combination. How are your mineral ratios?

 

[frozenborderline]

sub-molecular? that sounds like zooming in on a whole next level than what we're discussing here. I am still at the molecular stage.


Sure, please tell us - I'm still curious about the antibodies! Did they come down after Rituximab?

. I'm not up to reading the whole book and/or describing all of it right now, but szent-gyorgyi is hugely influential in bioenergetics, as well as essentially discovering the kreb's cycle. Anyway as far as submolecular biology, he is really just talking about various forms of electron exchange (hence submolecular) and the ways in which that drives the living state. Redox reactions could be viewed in terms of submolecular biology. Anyway I misplaced this book and can't find it, even if I had the energy 2 read something this dense right now

 

[Iritu1021]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1189865/

I think this is saying that caffeine causes calcium release from cells? But i can't really parse it. Damn, my brain fog today

Caffeine causes release from the ER stores inside the cell. ER has projections into mitochondria. So if you release calcium from the ER you re-fuel mitochondrial stores.

There are two types of issues (see the diagram I made for my future blog article - after I read my book

Situation #1.

You have too little Ca2+ in your ER or your ER is not properly stimulated so it doesn't release calcium into the cells and mitochondria from its stores. That means your mitochondria don't have enough calcium and pyruvate dehydrogenase can't function.

Situation #2
You have too much calcium in your ER or you overstimulate IP3 or RyR receptors and they over-release it Ca2+. That can lead to calcium toxicity within mitochondria, which will cause them to swell up and get damaged.

I think that if one of this situations were to happen and persist for a long time, it can make one more susceptible to the reverse situation dut to the adaptive changes that take place.

 

[Iritu1021]

. I'm not up to reading the whole book and/or describing all of it right now, but szent-gyorgyi is hugely influential in bioenergetics, as well as essentially discovering the kreb's cycle. Anyway as far as submolecular biology, he is really just talking about various forms of electron exchange (hence submolecular) and the ways in which that drives the living state. Redox reactions could be viewed in terms of submolecular biology. Anyway I misplaced this book and can't find it, even if I had the energy 2 read something this dense right now

I'm not good with physics but I do remember his famous quote that "discovery is looking at the same thing that everyone else looked at and thinking something different".

 

[Iritu1021]

Fantastic news about the Calcium!!! You seem to have found your winning combination. How are your mineral ratios?

I think the initial high calcium also had something to do with the Vyvanse I was taking and Armour thyroid.

The current ratios are
Ca/Mg 13.6 (4-30)
Ca/P 5.33 (1-12)
Na/K 3.57 (0.5-10)
Zn/Cu 15 (4-20)

One other thing that has improved on this last test is phosphorus which was always on the low side but their interpretation guide says that it's not a marker of phosphorus but of cellular metabolism.

 

[Gingergrrl]

Sure, please tell us - I'm still curious about the antibodies! Did they come down after Rituximab?

I did the DYS1 (Mayo Autoimmune Dysautonomia Panel) and one of the autoantibodies came down since the IVIG and Rituximab and one did not.

The anti GAD65 was 1.6 in 2016 (pre-treatment) and is now 0.08. It is still positive b/c anything above 0.02 is considered positive by Mayo but it did go down quite a bit.

The N-type Calcium Channel autoantibody, however, did not go down. It was 0.05 in 2016 (pre-treatment) and it is now 0.06 (and anything above 0.02 is also positive per Mayo). The increase is so slight that it basically remained the same, however, it did not go down.

My main doctor was not sure what to make of this but all of the literature said that the severity of symptoms in LEMS (which links to the calcium autoantibodies) do not correlate to the titers. Kind of like in Hashimoto's, the level of autoantibody titers do not correlate with symptom severity (at least they don't for me).

He said that it was hard to fully understand the significance of the persistent elevation, since I am recovering so well, but that he would not change any of my current treatment plan based on this unless my overall condition changes (which I completely agree with). So I am still done with IVIG (as of July- three months ago) and my first maintenance infusion of Ritux will be in Nov or Dec (pending a few additional blood tests and my symptoms).

I e-mailed him re: my own theory on this but have not heard back yet (and had to bother him w/a couple of other issues- poor guy ). But my theory was that perhaps without the treatments, the N-type CA+ Channel autoantibody might be MUCH higher now (2.5 years later) instead of remaining virtually the same. In addition several Neuros back in 2016 said that I would go on to develop the P/Q type CA+ Channel autoantibody, yet I didn't, and maybe this is also b/c of the treatment? Also, the GAD65 autoantibody did go down and I suspect this is b/c of the treatment. Lastly, I just re-tested my Cell Trend autoantibodies today (beta-adrenergic and anti-muscarinic) and we do not yet know if these have gone down (and I was positive for 7/9 of them pre-treatment).

Do you have any thoughts about this, Iritu, (or anyone else)?

 

[Iritu1021]

I did the DYS1 (Mayo Autoimmune Dysautonomia Panel) and one of the autoantibodies came down since the IVIG and Rituximab and one did not.

The anti GAD65 was 1.6 in 2016 (pre-treatment) and is now 0.08. It is still positive b/c anything above 0.02 is considered positive by Mayo but it did go down quite a bit.

The N-type Calcium Channel autoantibody, however, did not go down. It was 0.05 in 2016 (pre-treatment) and it is now 0.06 (and anything above 0.02 is also positive per Mayo). The increase is so slight that it basically remained the same, however, it did not go down.

Do you have any thoughts about this, Iritu, (or anyone else)?

Again - really glad that you responded to Rituximab and I can definitely see why you and your doctor wouldn't want to "rock the boat" at this point.

Interesting about antibody titers. My thoughts is that we don't yet understand what autoimmunity really is. I doubt it's as simple as just antibody binding to cells and causing destruction. How would that explain the fact that there is sero-negative disease or that symptoms are often not proportional to the titers?

I prefer to think of antibodies as a marker for tissue destruction. So if a virus, let's say binds to a certain receptor to enter the cell, then, as a result, the receptor might be damaged and the fragments would enter the bloodstream and stimulate antibody production.

But would this antibody production cease if the viral infection is treated and goes into remission? Not necessarily since the immune memory is already there. People may have antibodies to childhood infections many decades after they had an acute infection, so the same may be true for self tissue.

I found that Rituximab is increasingly used in transplant patients as "a preemptive therapy for EBV viremia".

Have you seen this recent article on EBV and autoimmunity?

 

[S-VV]

I think the initial high calcium also had something to do with the Vyvanse I was taking and Armour thyroid.

The current ratios are
Ca/Mg 13.6 (4-30)
Ca/P 5.33 (1-12)
Na/K 3.57 (0.5-10)
Zn/Cu 15 (4-20)

One other thing that has improved on this last test is phosphorus which was always on the low side but their interpretation guide says that it's not a marker of phosphorus but of cellular metabolism.

These ratios look damn good. It amazes me that just Li could have such a profound effect

 

[Iritu1021]

I don't know how to explain this but I got my labs back and my fT3 is 4.0 for the first time ever after going off all T3. That is crazy for me.

Before I went on LO, it was 3.0, with selenomethionine I could get it up to 3.2.

I know that it's due to lithium orotate and to a lesser degree selenomethionine. (I am specifying the carriers because I don't know if it's just the minerals - the orotate and methionine may have a role in it too).

In the past, I used to take high doses of NDT which only worsened my POTS, and despite all the T3 I took, in the morning my fT3 would still be back to 3.1. It was like my body was absolutely determined to keep my metabolic rate below a certain point - and maybe it had some good reason for that because I certainly made myself very ill by trying to push it too far.

But now thanks to lithium, I'm converting on my own like a champ. I really don't know how to explain this phenomenon, given that according to most published studies lithium is supposed to decrease the deiodinase function. Either the studies are wrong, or Li (or orotate?) have unblocked something in my cellular function (calcium release?)

I think 4.0 is probably too high for my taste, I think I will have to back down some since the dose of LO I've been taking is pretty high (I slowly worked it up to 30 mg). There was a recent study that showed that lower levels of thyroid hormones are associated with longevity - so there can be too much of a good thing.

 

[Iritu1021]

These ratios look damn good. It amazes me that just Li could have such a profound effect

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For comparison those are my ratios from 2014 during my acute crash:

Ca/Mg 39.1 (4- 30)
Ca/P 23.3 (1- 12)
Na/K 2 (0.5- 10)
Zn/Cu 3.65 (4- 20)

 

[Inara]

Caffeine causes release from the ER stores inside the cell. ER has projections into mitochondria. So if you release calcium from the ER you re-fuel mitochondrial stores

I don't know if this is entirely correct? Will caffeine raise intracellular Ca+, if it opens the ryanodine receptors and blocks (at least partially) the IP3 receptors? (If everything works correctly.) I wonder about this for some time now.

 

[pattismith]

Maybe at some point. Right now I'm trying to optimize my lithium +T4 combo.

@drob31 , sorry, I missed the post about Ambroxol, probably my brain fog...But these past few days, the wide spread pain was worsening so much, I had a look at Fibro treatment (I was looking mainly for intracellular calcium modulation), and I saw Ambroxol was mentioned as a sodium channel blocker that may have some effect!

So I started a trial yesterday, as it is considered a safe drug with few side effects, it is worth giving a try!

 

[Gingergrrl]

Again - really glad that you responded to Rituximab and I can definitely see why you and your doctor wouldn't want to "rock the boat" at this point.

I apologize for my delayed reply @Iritu1021 and like you said, we are definitely not doing anything right now to "rock the boat" re: my treatment. The only factors that have changed are that I completely stopped IVIG back in July and I am very slowly tapering down on Cortef. I will be doing first maintenance Ritux infusion in Nov or Dec as planned.

Interesting about antibody titers. My thoughts is that we don't yet understand what autoimmunity really is. I doubt it's as simple as just antibody binding to cells and causing destruction. How would that explain the fact that there is sero-negative disease or that symptoms are often not proportional to the titers?

This topic is so interesting to me and I wish I understood why and how there are sero-negative disease and cases where the symptoms are not proportional to the titers. (I don't understand them and just thinking out loud )

I prefer to think of antibodies as a marker for tissue destruction. So if a virus, let's say binds to a certain receptor to enter the cell, then, as a result, the receptor might be damaged and the fragments would enter the bloodstream and stimulate antibody production.

But would this antibody production cease if the viral infection is treated and goes into remission? Not necessarily since the immune memory is already there. People may have antibodies to childhood infections many decades after they had an acute infection, so the same may be true for self tissue.

That makes sense.

I found that Rituximab is increasingly used in transplant patients as "a preemptive therapy for EBV viremia". Have you seen this recent article on EBV and autoimmunity?

Thank you, and I had not seen that specific article before, but both of my doctors feel strongly that the re-activation of EBV (IgM+ and EA+ for several years after having Mono) was what led to the autoimmunity in my case.

 

[Iritu1021]

@drob31 , sorry, I missed the post about Ambroxol, probably my brain fog...But these past few days, the wide spread pain was worsening so much, I had a look at Fibro treatment (I was looking mainly for intracellular calcium modulation), and I saw Ambroxol was mentioned as a sodium channel blocker that may have some effect!

So I started a trial yesterday, as it is considered a safe drug with few side effects, it is worth giving a try!

@pattismith, I've got Ambroxol too. I tried it a couple times but didn't notice much from it but I think it needs to be a long term or higher dose. I'm not as sensitive to things as I used to be so I don't notice effects as much anymore. I'm interested to see what it does for you. What about just putting one or several lidocaine patches for sodium channel blockade?

 

[Iritu1021]

I don't know if this is entirely correct? Will caffeine raise intracellular Ca+, if it opens the ryanodine receptors and blocks (at least partially) the IP3 receptors? (If everything works correctly.) I wonder about this for some time now.

I started reading calcium book and it turns out to be even more complicated because caffeine also blocks calcium voltage-gated channels. So maybe @debored13 is using it as a calcium channel blocker. Or maybe for its analgesic effect is due to adenosine.

@Inara, the book is not worth the money so don't be jealous, seventy percent of it is about plants and bacteria. There's maybe only one really useful chapter. What I'm learning right now is that the interplay of all these channels is extremely complex. It seems to me that it's theoretically possible to have too much calcium conduction flowing through the channels but also be depleted in mitochondrial calcium at the same time.

But I'm still trying to wrap my brain around how it all works.

 

[frozenborderline]

I started reading calcium book and it turns out to be even more complicated because caffeine also blocks calcium voltage-gated channels. So maybe @debored13 is using it as a calcium channel blocker. Or maybe for its analgesic effect is due to adenosine.

@Inara, the book is not worth the money so don't be jealous, seventy percent of it is about plants and bacteria. There's maybe only one really useful chapter. What I'm learning right now is that the interplay of all these channels is extremely complex. It seems to me that it's theoretically possible to have too much calcium conduction flowing through the channels but also be depleted in mitochondrial calcium at the same time.

But I'm still trying to wrap my brain around how it all works.

One thing i"m curious about in all this is Jay Goldstein's use of lidocaine/local anaesthetics but systemically. Iirc those act through either blocking calcium channels, or some kind of ion channel.

 

[Iritu1021]

One thing i"m curious about in all this is Jay Goldstein's use of lidocaine/local anaesthetics but systemically. Iirc those act through either blocking calcium channels, or some kind of ion channel.

Voltage gated sodium channels. You can't get it IV but you can approximate the effect by lidocaine oral spray or patches which you can buy online.
VGSC are important in the pain transduction.

It is remarkable that many tricyclic antidepressants, selective serotonin-reuptake inhibitors, and serotonin–norepinephrine reuptake inhibitors also block sodium channels.For instance, duloxetine is beneficial for FMS157,238 and blocks both Nav1.7 and Nav1.8. Furthermore, gabapentin, which was recommended in a data analysis by Cochrane249 also blocks Nav1.7 and pregabalin, which was also classified as beneficial, reduces paroxysmal neuropathic itch in patients with a variant of the SCN9A gene, which encodes for Nav1.7. Even ibuprofen, which is often preferred by patients,157 blocks the channel subtypes Nav1.7 and Nav1.8 after systemic and topical administration. Finally, tramadol, which is recommended as second-line treatment, also blocks sodium channels. An interesting fact in this respect is that at least peripheral analgesia with opioids is partly mediated via µ-receptors on primary afferent Nav1.8-positive neurons.

 

[Gingergrrl]

@Iritu1021 I was curious, does your new book list all of the meds that block the calcium channel?