T3 intracellular calcium and caffeine

[frozenborderline]

You omitted the fact that phenibut also acts on dopamine receptors and antagonizes PEA.

Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug.
Lapin I1.
Author information

Abstract
Phenibut (beta-phenyl-gamma-aminobutyric acid HCl) is a neuropsychotropic drug that was discovered and introduced into clinical practice in Russia in the 1960s. It has anxiolytic and nootropic (cognition enhancing) effects. It acts as a GABA-mimetic, primarily at GABA(B) and, to some extent, at GABA(A) receptors. It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA), a putative endogenous anxiogenic.

yeah, I was more interested in the "hangover" than the acute effects, and this "hangover" ( i use it in quotes because it wasn't like a standard hangover) happened among other drugs with different pharmacological effects, the only commonality being gaba agonism. I gotta look again but I think GHB and Phenibut share GABA-B agonism. I would think glutamate toxicity as a kind of rebound would make sense with both of them.
I neglected to mention that i did have one experience with alcohol during this period.

I had quit drinking totally about 3 months before I got sick, and so I didn't have many experiences, but I did have one relapse with drinking while I was ill (I was at school still, so certainly not as ill as I am now, but fairly ill still). That hangover was the worst hangover I've ever experienced in my life. It was not the most I've ever drank ever, and not solely attributable to the alcohol naivety for a couple reasons I won't go into. I've had alcohol poisoning before this, and was a drinker from when I was about 18-21-and-a-half, so I've experienced hangovers before, and many different doses of alcohol.
I remember palpitations and just a very fast weak pulse the whole day after, which is not something I've ever gotten from a hangover before, and then, the kind of brain on fire storm and inability to even think a thought clearly, all of this, feeling extremely intensely weak. The only thing that relieved it at all, was again, gabapentin. Now the alcohol hangover was a little different as alcohol has a lot more dirty effects, esp. the ones on cardio system. But I still had that "brain-on-fire" part of it that I describe from these other substances.

I'm surprised I can even remember this stuff to be honest. This was awhile ago, before I had any idea I might be sick for the rest of my life lol. I definitely didn't take notes, but it just occurred to me recently when I took gabapentin and remembered this.

 

[frozenborderline]

Fact #1. Caffeine increases intracellular calcium release.
Fact #2. Caffeine makes you feel better.

How do you apply the logic test to that?

Also, if intracellular calcium is low, then the speed of neurotransmission can be greatly amplified. And if that's the case even normal levels of glutamate (or any other excitatory neurotransmitter) can become toxic.

To me, it appears far more likely that the real danger in CDR is the fact that the mitochondria are depleted in calcium and as a result of that the cells must rely mainly on the glycolysis to survive.

High intracellular calcium may be a problem for other, more common diseases.

. Well as you have pointed out elsewhere, caffeine and coffee have many, many different effects--everything from mitochondrial uncoupling, to ACh inhibition, to mast cell inhibition. It's hard to isolate just one. But I know I'm probably wrong, I had just read something to the contrary, anyway I will look more at the literature on intracellular calcium.

 

[frozenborderline]

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

 

[Inara]

Fact #1. Caffeine increases intracellular calcium release.

It opens ryanodine receptors but inhibits IP3 receptors (I hopefully remember correctly); a more "robust" inhibitor of IP3R seems to be heparin. RYRs and IP3Rs release calcium from the ER/SR, while a "pump" (that needs ATP to work) sucks calcium back into the ER.

 

[Iritu1021]

It opens ryanodine receptors but inhibits IP3 receptors (I hopefully remember correctly); a more "robust" inhibitor of IP3R seems to be heparin. RYRs and IP3Rs release calcium from the ER/SR, while a "pump" (that needs ATP to work) sucks calcium back into the ER.

I just ordered an encyclopedia on Intracellular Calcium Regulation from Amazon so once I get through that book, I will hopefully be able to piece it all together a lot better

 

[Iritu1021]

It opens ryanodine receptors but inhibits IP3 receptors (I hopefully remember correctly); a more "robust" inhibitor of IP3R seems to be heparin. RYRs and IP3Rs release calcium from the ER/SR, while a "pump" (that needs ATP to work) sucks calcium back into the ER.

. Well as you have pointed out elsewhere, caffeine and coffee have many, many different effects--everything from mitochondrial uncoupling, to ACh inhibition, to mast cell inhibition. It's hard to isolate just one. But I know I'm probably wrong, I had just read something to the contrary, anyway I will look more at the literature on intracellular calcium.

Does T3 alter your reaction to caffeine? The thread began with @pattismith noting that it changed her response.

The author of biochem corner proposes that raising ATP production may lead to initial better sequestration of calcium into the ER but can also cause intracellular calcium deficiency because the plasma ATPase will pump calcium out of the cell a lot faster.

When I abruptly lowered my thyroid hormone, I had a drop in my plasma ionized calcium which was likely due to decreased plasma ATPase activity.

 

[Inara]

I just ordered an encyclopedia on Intracellular Calcium Regulation from Amazon so once I get through that book, I will hopefully be able to piece it all together a lot better

Oh, I found that some days ago, too. Quite envious it's too expensive.

 

[Iritu1021]

Oh, I found that some days ago, too. Quite envious it's too expensive.

It sure is. I know, I splurged... It's going to be my birthday present from myself

I will make sure to sum up all the most interesting points for you!

 

[Iritu1021]

 

[Iritu1021]

Before I began taking lithium orotate, I had a very low ceiling of how much thyroid I could tolerate - it would worsen my POTS and other dysautonomic symptoms. I believe that lithium has stabilized my IP3 receptors so now I don't over-dump calcium from my ER.

 

[Iritu1021]

however... I read that orotate gets converted to uridine and uridine regulates mitochondrial metabolism and phospholipid synthesis. So I can't rule out that the positive effects I observed from lithium orotate are due to lithium alone. Uridine is also an emerging therapy for bipolar. So if I respond to uridine that it would send me back to phospholipid metabolism as my primary issue (which is what lead me to lithium in the first place).

 

[frozenborderline]

Does T3 alter your reaction to caffeine? The thread began with @pattismith noting that it changed her response.

The author of biochem corner proposes that raising ATP production may lead to initial better sequestration of calcium into the ER but can also cause intracellular calcium deficiency because the plasma ATPase will pump calcium out of the cell a lot faster.

When I abruptly lowered my thyroid hormone, I had a drop in my plasma ionized calcium which was likely due to decreased plasma ATPase activity.

T3 hasn't qualitatively altered my reaction to caffeine, as in caffeine worked before t3 and works similarly after. However thyroid (t4 and t3) did lower the amount of caffeine i needed for relief, daily. Which is what I would expect if both t3 and caffeine increased uncoupling protein

 

[frozenborderline]

I just ordered an encyclopedia on Intracellular Calcium Regulation from Amazon so once I get through that book, I will hopefully be able to piece it all together a lot better

Wow, that looks fun

 

[Iritu1021]

Wow, that looks fun

Well, I'm glad I have you guys to share my excitement about this purchase because I don't think anybody else I know would appreciate how much fun this is

 

[frozenborderline]

Well, I'm glad I have you guys to share my excitement about this purchase because I don't think anybody else I know would appreciate how much fun this is

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

 

[Iritu1021]

here's my caffeine anecdote. In 2015 I had one of the worst days of my life (and I had many bad days, but this one is right there on the top). My POTS specialist put me on Fluorinef on top of midodrine and stimulants, and it gave me cerebral edema or something terrible along the lines. My systolic blood pressure dropped below 90, my standing HR went up to 160s, and I felt like my brain was going to explode, extreme brain on fire feeling, and I was losing my ability to think by the minute. It was the worst kind of agony - and naturally, I didn't want to go to ER out of fear they would give me something that could kill me. So I didn't know what to do but somehow my intuition told me to take a caffeine pill - within 15 minutes everything began to normalize. So that was one time when caffeine saved my life.

I also felt like I needed a lot of caffeine when I was only on T4 without taking lithium.

But now it mostly just gives me a good 30 minute mental burst but then overstimulates me - almost not worth it.

 

[pattismith]

@iritu, @Inara , I am thrilled to read more about intracellular calcium homeostasis.

I am currently crashing and struggling a lot for some weeks, so can't be very helpful to anybody, but found some studies about calcium and fibromyalgia:


Role of intracellular calcium ions in the physiopathology of fibromyalgia syndrome.
2000
Abstract
Calcium ions have a key role in the physiology of muscular contraction: changes in calcium ion concentration may be involved in the pathogenesis of fibromyalgia. Although, since the plasmatic level of calcium in fibromyalgia patients is always in the normal range, it seemed interesting to evaluate the intracellular calcium concentration. The study was carried out on two groups of subjects: 70 affected by fibromyalgia and 40 healthy controls. The results obtained show that in fibromyalgia patients the intracellular calcium concentration is significantly reduced in comparison to that of healthy controls: the reduced intracellular calcium concentration seems to be a peculiar characteristic of fibromyalgia patients and may be potentially responsible for muscular hypertonus. The effective role of this anomaly in the physiopathology of fibromyalgia and the potential role of drugs active on the calcium homeostasis are still to be confirmed.


Women with Fibromyalgia Have Lower Levels of Calcium, Magnesium, Iron and Manganese in Hair Mineral Analysis

Abstract
Little is known about hair mineral status in fibromyalgia patients. This study evaluated the characteristics of hair minerals in female patients with fibromyalgia compared with a healthy reference group. Forty-four female patients diagnosed with fibromyalgia according to the American College of Rheumatology criteria were enrolled as the case group. Ageand body mass index-matched data were obtained from 122 control subjects enrolled during visit for a regular health check-up. Hair minerals were analyzed and compared between the two groups. The mean age was 43.7 yr. General characteristics were not different between the two groups. Fibromyalgia patients showed a significantly lower level of calcium (775 µg/g vs 1,093 µg/g), magnesium (52 µg/g vs 72 µg/g), iron (5.9 µg/g vs 7.1 µg/g), copper (28.3 µg/g vs 40.2 µg/g) and manganese (140 ng/g vs 190 ng/g).
Calcium, magnesium, iron, and manganese were loaded in the same factor using factor analysis; the mean of this factor was significantly lower in fibromyalgia group in multivariate analysis with adjustment for potential confounders. In conclusion, the concentrations of calcium, magnesium, iron, and manganese in the hair of female patients with fibromyalgia are lower than of controls, even after adjustment of potential confounders.

And interestingly, Pregabalin and Gabapentin, calcium channel blockers, are considered to be helpful for Fibro

 

[frozenborderline]

@iritu, @Inara , I am thrilled to read more about intracellular calcium homeostasis.

I am currently crashing and struggling a lot for some weeks, so can't be very helpful to anybody, but found some studies about calcium and fibromyalgia:


Role of intracellular calcium ions in the physiopathology of fibromyalgia syndrome.
2000
Abstract
Calcium ions have a key role in the physiology of muscular contraction: changes in calcium ion concentration may be involved in the pathogenesis of fibromyalgia. Although, since the plasmatic level of calcium in fibromyalgia patients is always in the normal range, it seemed interesting to evaluate the intracellular calcium concentration. The study was carried out on two groups of subjects: 70 affected by fibromyalgia and 40 healthy controls. The results obtained show that in fibromyalgia patients the intracellular calcium concentration is significantly reduced in comparison to that of healthy controls: the reduced intracellular calcium concentration seems to be a peculiar characteristic of fibromyalgia patients and may be potentially responsible for muscular hypertonus. The effective role of this anomaly in the physiopathology of fibromyalgia and the potential role of drugs active on the calcium homeostasis are still to be confirmed.


Women with Fibromyalgia Have Lower Levels of Calcium, Magnesium, Iron and Manganese in Hair Mineral Analysis

Abstract
Little is known about hair mineral status in fibromyalgia patients. This study evaluated the characteristics of hair minerals in female patients with fibromyalgia compared with a healthy reference group. Forty-four female patients diagnosed with fibromyalgia according to the American College of Rheumatology criteria were enrolled as the case group. Ageand body mass index-matched data were obtained from 122 control subjects enrolled during visit for a regular health check-up. Hair minerals were analyzed and compared between the two groups. The mean age was 43.7 yr. General characteristics were not different between the two groups. Fibromyalgia patients showed a significantly lower level of calcium (775 µg/g vs 1,093 µg/g), magnesium (52 µg/g vs 72 µg/g), iron (5.9 µg/g vs 7.1 µg/g), copper (28.3 µg/g vs 40.2 µg/g) and manganese (140 ng/g vs 190 ng/g).
Calcium, magnesium, iron, and manganese were loaded in the same factor using factor analysis; the mean of this factor was significantly lower in fibromyalgia group in multivariate analysis with adjustment for potential confounders. In conclusion, the concentrations of calcium, magnesium, iron, and manganese in the hair of female patients with fibromyalgia are lower than of controls, even after adjustment of potential confounders.

And interestingly, Pregabalin and Gabapentin, calcium channel blockers, are considered to be helpful for Fibro

Hmm i really wonder about my copper especially. Good sources other than shrimp or liver?

 

[S-VV]

High cacao chocolate

 

[Gingergrrl]

Well, I'm glad I have you guys to share my excitement about this purchase because I don't think anybody else I know would appreciate how much fun this is

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.