T3 intracellular calcium and caffeine

S-VV

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That is certainly one explanation - my iodine not being used up. My 2018 test is after supplementing with lithium which is why I wasn't deficient anymore. Have you ever tried lithium orotate? Or iodine? (and by the way, don't use them together, especially in high doses - that gave me a very bad reaction!)

I found this on Wikipedia page: "ACTH, which probably controls cortisol by controlling the movement of calcium into the cortisol-secreting target cells." So if that's true than abnormality of calcium transport could be responsible for "adrenal deficiency' rather than vice versa...
Edit: In the earlier post, I meant Na/Mg ratio, not Mg/Na

I'm currently trying one drop of Iodine a day. I have not yet tried Lithium. When I start the T3 trial I may add some Li. Do you hypothesize why Li and I dont play together?

Hmm, that's interesting. Now it seems that Calcium and hormones have a bidirectional connection. Then maybe you partially fixed your abnormal calcium transport by taking T3/Li and that increased your "ACTH effectiveness".

But if it were true that ACTH partly loses it corticostimulant function in calcium abnormalities, why doesn't it rise in response?
 

pattismith

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I don't know if the boost I can feel from stress is related to T3 and cortisol peaks, but I have some doubts.

Stress makes your cortisol high, but also dopamine, epinephrine, norepinephrine.
Dopamine and cortisol have the effect to make your Thyroid hormons low.

And in my case, stress only works now if I take my T3 at the same time.

I wonder if you exhausted your deposited Ca reserves by mobilizing them with T3 and cortisol, and if adding supplemental Ca while taking both hormones could mantain remission
I don't know, I already take calcium supplements for years!
 

Iritu1021

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I believe that mitochondria are supposed to be able to stockpile calcium because calcium binds to the phosphorus molecules in the phospholipids of the mitochondrial membranes. (I would encourage you to look this up rather than take my word for it though.) I don't know if this ties into the altered phospholipid levels found in recent studies or if low phosphorus levels could be contributing to the issue? Phosphorus also helps hold calcium in the bones.

I need calcium supplements to function normally, but I have not reached a point of repletion after many months of supplementation. Serum calcium levels have always been normal. Since calcium greatly improves my energy levels, I believe it is being absorbed into the cells but the result is not sustained, and so I must take calcium periodically throughout the day. My calcium needs increase greatly when I take the fat-soluble vitamins to try to maintain bone health, as if I do not have enough calcium to maintain tissue levels and build bone. If I do not get enough calcium, I have greatly increased muscle tension/spasms (including my digestive tract), horrible cognitive function and extreme fatigue.
Your symptoms sound similar to mine. Have you checked your fasting ionized calcium? My total serum calcium is usually above 9 -totally normal, it's only the ionized calcium that's low.

My serum phoshoporus is normal and the hair test interpretation says that hair is not an accurate measure of phosphorus in the body. However, the only calcium supplement that seems to make me feel better (more energy and brain clarity) is calcium triphosphate which comes in gummy form. Maybe it's the sugar in the gummies, or maybe it's the phosphorus - or maybe it is somehow more able to reach mitochondria when it's bound to phosphate.
 

Iritu1021

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Edit: In the earlier post, I meant Na/Mg ratio, not Mg/Na

I'm currently trying one drop of Iodine a day. I have not yet tried Lithium. When I start the T3 trial I may add some Li. Do you hypothesize why Li and I dont play together?

Hmm, that's interesting. Now it seems that Calcium and hormones have a bidirectional connection. Then maybe you partially fixed your abnormal calcium transport by taking T3/Li and that increased your "ACTH effectiveness".

But if it were true that ACTH partly loses it corticostimulant function in calcium abnormalities, why doesn't it rise in response?
My cortisol was pretty high when I was taking T3, especially slow release T3. But I still felt bad. It's just many different shades of bad that are always shape shifting, some are worse than others.

As for Li and I - I remember reading about it somewhere, there's an old threat on lithium orotate here that you might be able to pull up where I remember posting a link to the explanation - but lithium inhibits iodine transport, and excess iodine also inhibits iodine transport. If you only take a tiny dose of iodine within RDA it might be ok. I was taking Iodoral at the time which is a pretty high dose.
 

drob31

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I don't know if the boost I can feel from stress is related to T3 and cortisol peaks, but I have some doubts.

Stress makes your cortisol high, but also dopamine, epinephrine, norepinephrine.
Dopamine and cortisol have the effect to make your Thyroid hormons low.

And in my case, stress only works now if I take my T3 at the same time.



I don't know, I already take calcium supplements for years!

The dopamine thyroid connection is interesting. If dopamine makes thyroid low, then that explains a lot of my pre-illness symptoms.

Namely how excessive orgasm could release dopamine and depress thyroid.
 

Iritu1021

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I should add that when I first began taking calcium phosphate, it felt a lot like when I first began taking T3, just not as pronounced. I get the feeling of blood vessels constricting in my nasal pathways and in my head, and I gain brain clarity within minutes.

Taking both T3 and lithium also initially causes me to get pain/tightness in my throat - I used to think it was due to thyroid, but now I think it might be due to parathyroid glands swelling up from stimulation.

It is interesting that nature has placed two main hormones that regulate calcium (PTH and calcitionin) right next to or inside the thyroid gland - as if the two were meant to go together.
 

S-VV

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@Iritu1021 this may be interesting

Long-term lithium carbonate therapy causes hyperparathyroidism

https://www.ncbi.nlm.nih.gov/pubmed/6810840
Twelve patients taking lithium carbonate for two to 13 years were compared with age- and sex-matched controls to determine whether long-term lithium carbonate therapy is associated with alterations in calcium metabolism. As a group and individually, patients had significantly higher levels of serum total calcium, ionized calcium, and parathyroid hormone. When compared with serum calcium levels, patients' parathyroid hormone levels were significantly more likely than those of controls to indicate hyperparathyroidism. Lithium carbonate-induced mild hyperparathyroidism appears to be more common than had previously been suspected

 

drob31

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@Iritu1021 this may be interesting

Long-term lithium carbonate therapy causes hyperparathyroidism

https://www.ncbi.nlm.nih.gov/pubmed/6810840
Twelve patients taking lithium carbonate for two to 13 years were compared with age- and sex-matched controls to determine whether long-term lithium carbonate therapy is associated with alterations in calcium metabolism. As a group and individually, patients had significantly higher levels of serum total calcium, ionized calcium, and parathyroid hormone. When compared with serum calcium levels, patients' parathyroid hormone levels were significantly more likely than those of controls to indicate hyperparathyroidism. Lithium carbonate-induced mild hyperparathyroidism appears to be more common than had previously been suspected

Maybe this why lithium was helpful even though it was detrimental to thyroid levels?
 

drob31

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My trials with T3 and cortisol have lead me to the conclusion that I have intracellular calcium flux abnormalities in my muscles and brain cells.

I only found transient but total relief of my symptoms when supplementing with T3 and prednisolone, but mostly losing the good effect when supplementing on a regular basis.

I experimented that a hugh emotional stress associated with T3 and cortisol is doing a great job to relieve my symptoms, so i have to investigate why I benefited so much from this association.

When the stress was lower, i was back to the broken doll state....So I found this article and decided to try again caffeine.

I have taken it in the past, but it made me worse, and this phenomenon was more marked with time going by.

I had to take a full cup of coffee to get the effect, while still supplementing with T3 but miracle, it worked!

So coffee and stress may have the same effect!

So caffeine, a typical activator of sarcoplasmic reticulum Ca2+-release channel, doesn't work well if cells are T3 deprived, but the association is working!


This makes me think that my main problem is a dysfunction of this sarcoplasmic reticulum Ca release channel, with a T3 insufficiency/blockage.

I still can't say why T3 alone can't do the job and my journey to recovery is far from finished, but I am now able to manage a bit more my disability, and to have more control on it, so I have hope!

How much cortisol do you use and when do you take it? Hydrocortizone better than Pred?
 

Iritu1021

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Maybe this why lithium was helpful even though it was detrimental to thyroid levels?
Yes, as I said it only works for me if I take levothyroxine, otherwise I can't handle it. When I used it with T3 I began to feel overstimulated.
 

Iritu1021

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The mitochondrial calcium uniporter (MCU) is a transmembrane protein that allows the passage of calcium ions from a cell's cytosol into mitochondria.[1] Its activity is regulated by MICU1 and MICU2, which together with the MCU make up the mitochondrial calcium uniporter complex.[2]

The MCU is one of the primary sources of mitochondria uptake of calcium, and flow is dependent on membrane potential of the inner mitochondrial membrane and the concentration of calcium in the cytosol relative to the concentration in the mitochondria. Balancing calcium concentration is necessary to increase the cell's energy supply and regulate cell death. Calcium is balanced through the MCU in conjunction with the sodium-calcium exchanger.[1]

The MCU has a very low affinity for calcium, so the cytosolic calcium concentration needs to be approximately 5-10 uM for significant transport of calcium into the mitochondria. Mitochondria are closely associated with the endoplasmic reticulum (ER), at contact sites, which contains stores of cellular calcium ions for calcium signaling. The presence of 1,4,5-triphosphate (IP3) triggers the release of calcium from these intracellular stores, which creates microdomains of high calcium concentration between the ER and the mitochondria, creating the conditions for the MCU to take up calcium
 

Iritu1021

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I have posted here a long time ago that my TSH went up after going on lithium but so did my T3 and T4 and my mood and mental energy significantly improved (before that I was a total wreck after Armour and high doses of T3). So it was if my metabolic rate got reset to a higher point, and I went from being a person with CFS who has low metabolic rate but low TSH to being more like a person with subclinical hypothyroidism.

To put it in perspective now, my current hypothesis is that lithium helped to replenish my mitochondrial calcium so the mitochondria were now signaling to my hypothalamus that they were willing to handle a higher metabolic rate. When I tried to push that higher metabolic rate on them before they were ready, it always backfired in very, very bad ways for me.

Part of what drew me to lithium in the first place was the fact that it has been shown to increase mitochondrial function.
 
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By the way, as I sit here, I watch all these fasciculations occuring in my calves. Symptoms of low calcium or sodium or potassium or magnesium, etc?
You can taste-test electrolytes. You don't have to wonder which ones are low. Your tastebuds will tell you very quickly.
 

drob31

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So I took 200 mg of caffeine + 5 mg hydrocortizone and 500 mg of calcium. I'm also on 125 mcg t4 (tapering down once i stabalize).

This combo definitely forced my brain to turn on.
 

Gingergrrl

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This is an interesting discussion.
I agree and can't believe that I some how missed this entire thread until tonight! I hope it is okay that I am late to join the calcium party...

I would love input from everyone in this thread since I have the N-type Calcium Channel Autoantibody and have been told NOT to take any meds that further block the calcium channel. I also have Hashimoto's Disease and take Armour Thyroid which contains T3 (and do very well with it). And now that my POTS is basically in remission, I can drink coffee and lattes again and do well with them (although I still usually drink decaf to be safe).

Nimodipine is blocking sarcoplasmic reticulum Ca channels, whereas drugs that have shown to help me are activators of these channels (T3 + caffeine).
Patti, do you mean that T3 and caffeine actually unblock the calcium channels (or am I misunderstanding this)?

In fact I've been able to document either borderline low or slightly below normal levels of ionized calcium several times... and who knows how low they are inside the cells. My non-ionized calcium, however, is always within the normal range
@Iritu1021 How do you test for ionized calcium levels? Is this a rare test? I don't think I have ever had this test and am not even sure what it is called. My calcium level (as part of the standard CMP) is normal but I assume this is not testing for ionized calcium?

I believe that I was also used T3 to regulate calcium channels but it's not a good way to do it since both hypo and hyperthyroidism are associated with lowered ionized calcium and there's a very narrow "sweet spot" range that's hard to maintain.
I never realized before this thread that T3 regulates calcium channels. Does this apply to someone like me who has an anti-CA+ channel autoantibody? Does this mean that taking Armour Thyroid (which has T3) is helping me in addition to helping my Hashimoto's?

That's what I've been running on for most of my life. Latte with chocolate :)
I love lattes, mocha lattes... and pretty much all lattes :mug::love: and am so happy that I can drink them again (after having a complete caffeine intolerance for several years due to POTS, MCAS and other problems).

Also what about calcium channel openers versus blockers.?
@drob31 I had no idea until this thread that there even were "calcium channel openers"! Do you know what they are called? Are they prescription medications or supplements or something else?

I get the spasms in my calves
I also get really bad cramps and spasms in my calves that wake me up at night. Does this relate to calcium? I had always thought it related to Potassium and recently bought V8 to try to increase my potassium but haven't tried it yet. I also take a prescription potassium called Klor Con which is 20 MEQ or approx 780 mg per day.
 

drob31

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@drob31 I had no idea until this thread that there even were "calcium channel openers"! Do you know what they are called? Are they prescription medications or supplements or something else?
.
I googled for calcium channel agonists and found Bay K8644, which seems to still be experimental.

How did you test for calcium channel antibodies?
 

Gingergrrl

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I googled for calcium channel agonists and found Bay K8644, which seems to still be experimental.
I just Googled this and Wikipedia says that Bay K8644 functions as a calcium channel agonist and is a "structural analog of nifedipine". It also said that it targets the L-type Calcium Channels. I don't get it since I thought nifedipine was a calcium channel blocker not an agonist?

But regardless, if we assume it is an agonist and opens the CA+ Channels, would this potentially be helpful for someone like me with CA+ channel autoantibodies?

How did you test for calcium channel antibodies?
It was part of a panel called "PAVAL" that was sent to Mayo Clinic by a Neuro that I saw in 2016. I tested positive for the N-type Calcium Channel autoantibody (and also for anti GAD65 on the same panel in case this is relevant to anything). I will very soon be re-testing both autoantibodies on a different Mayo Panel "DYS1" to see if they have changed after two years of treatment and going into remission (for lack of a better word).

* Even though it's a slightly different Mayo panel, it is testing the exact same CA+ Channel autoantibodies and a bunch of others.
 

S-VV

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Regarding the above Wikipedia paragraph about MCU and IP3 - please check out this diagram for mechanism of lithium action? If I'm connecting this the right way, then it's possible that lithium increases cytosolic calcium by blocking the action of the enzyme in the IP3 breakdown pathway.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805456/figure/fig1-2045125312471963/?report=objectonly
Yes that seems to be a possibility. If I'm reading the diagram correctly, Li inhinits IP breakdown into myo-inositol. Does that mean that IP can be converted to IP3 quicker and in a larger proportion?
 

S-VV

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I have posted here a long time ago that my TSH went up after going on lithium but so did my T3 and T4 and my mood and mental energy significantly improved (before that I was a total wreck after Armour and high doses of T3). So it was if my metabolic rate got reset to a higher point, and I went from being a person with CFS who has low metabolic rate but low TSH to being more like a person with subclinical hypothyroidism.

To put it in perspective now, my current hypothesis is that lithium helped to replenish my mitochondrial calcium so the mitochondria were now signaling to my hypothalamus that they were willing to handle a higher metabolic rate. When I tried to push that higher metabolic rate on them before they were ready, it always backfired in very, very bad ways for me.

Part of what drew me to lithium in the first place was the fact that it has been shown to increase mitochondrial function.
Calcium and metabolic rate seem to go together. For example:

Mitochondrial calcium as a key regulator of mitochondrial ATP production in mammalian cells

However, work by Denton and McCormack in the 1970s and 1980s showed that free intramitochondrial Ca2+([Ca2+]m) activated dehydrogenase enzymes in mitochondria, leading to increased NADHand hence ATP production. This leads them to propose a scheme, subsequently termed a “parallel activation model” whereby increases in energy demand, such as hormonal stimulation or increased workload in muscle, produced an increase in cytosolic [Ca2+] that was relayed by the mitochondrial Ca2+transporters into the matrix to give an increase in [Ca2+]m. This then stimulated energy production to meet the increased energy demand.