T3 intracellular calcium and caffeine

[frozenborderline]

Ray Peat is an interesting guy but to my knowledge he did not have ME/CFS or POTS so his experience would not be relevant to my own. This is why I have nothing to debate with him - he and I do not have the same condition. I suspect that he was probably treating himself for depression with high doses of thyroid. People with depression generally tend to respond well to high doses of T3 while people while people with severe CFS do not. There is a blog from a guy in Australia who went from having moderate CFS to not being able to leave his bed for the last ten years after taking T3 for a couple weeks.

It's also my impression that Ray Peat no longer believes most of what he said a long time ago, which is why he removed all his books and has tried to distance himself from the disciples who developed protocols based on his ideas since he's against any "protocols" and mainly tried to teach people to make intuitive connections about their bodies, his "perceive. think. act" mantra.

I'm not sure what peat had (I think it sounds like somewhat severe thyroid dysfunction) but despite finding the theory interesting, Im somehwat interested b/c I know of a few people with severe, disabling fatigue that benefited from his work. It's tricky to know if they had ME/CFS because they didn't go to specialists and were in europe in a country that has BPS model so I doubt they would have gotten good treatment even if going to a doctor.

There are people that are diagnosed with CFS on the ray peat forum (which is mostly a cesspool), some of whom have made full recoveries apparently through various medications and food, and some who havent



But I agree in prioritizing anecdotal evidence of people specifically diagnosed with CFS, even tho I think broader metabolic dysfunction may underlie several disease states. This is why, if doing the dosing protocol that peat/roddy recommends doesn't work, I'll add lithium, and also try the blanchard protocol next.

As for the bolded part, I'm really not sure. I honestly thought his books just went out of print because they didn't sell much. I think there are a couple of things that he may have changed based on experiment and experience.
The one on soviet neuroscience is really good read from a philosophy of science perspective and doesn't really have much in the way of practical recommendations but is cool if one is interested in exploring the differing epistemologies of two differing kinds of "materialism".

Imo I just find the stuff that gets labelled "vitalism" very interesting. It's not really vitalism in the crude sense, but I feel like if one could really understand life or living systems as a whole that it could yield relevant results for many disease states. I do kind of buy the idea that aging and fatigue and several sickness states share physiochemical properties... i think Naviaux does too

 

[Gingergrrl]

You can try doing it without stopping, just don't take Armour until after the test. It might not be accurate but still worth a try.

That is good to know and when I test other things, I have to do it in the morning while fasting and before I have taken Armour or Cortef.

I am still confused though, do you know how the results of an ion calcium test would change someone's treatment (or would they be more academic and not for treatment purposes)?

It's a recently discovered protein transporter that uptakes calcium into mitochondria. The channels you are talking about are in the cellular membranes but I suppose that if you have something that blocks Ca entrance into cells it will lead to low intracellular calcium and therefore low mitochondrial calcium, which in turn leads to mitochondrial dysfunction.

That makes sense and if the calcium is being blocked from going into the cells, it would in theory be blocked from entering the mitochondria. Is MCU a medication or treatment (or just in the experimental stages right now)?

 

[frozenborderline]

Dandelion Root Extract Induces Intracellular Ca2+Increases in HEK293 Cells
http://www.mdpi.com/1422-0067/19/4/1112

Perhaps dandelion tea with milk as an alternative to coffee?[/QUOTE]

Interesting, it's a little late in the season but could probably get some of these. I don't trust all herbal medicine but the fact that dandelion tea is thought so ubiquitous as a tonic could count for something

 

[Wishful]

I did try dandelion root coffee a few years ago, and it did seem to provide an improvement, but then stopped working. I tried it because I had the same improvement from lettuce (which also stopped working), and dandelion had the same active compound that I thought was responsible (Lactucin).

 

[pattismith]

You know i'm into the ray peat thing, but it's interesting as he is not into super high doses and says that the doses he recommends are physiological! but he's talking more in the 3-5 mcg range

I will eventually look more into this

One thing peat says tho is that T3 with a meal should be slow release essentially

We are supposed to produce about 29 mcg of T3 per day...(both from thyroid and from T4 deiodination)

If you have deiodination issue like I do (down regulated D1 and upregulated D3), you are more likely to produce maybe only half this dose...

So I could take 5 mcg x three times per day to raise my T3 level and still stay in a physiologic level....

The strange thing is that I can only take 6.25 mcg in the morning and no more....

 

[frozenborderline]

We are supposed to produce about 29 mcg of T3 per day...(both from thyroid and from T4 deiodination)

If you have deiodination issue like I do (down regulated D1 and upregulated D3), you are more likely to produce maybe only half this dose...

So I could take 5 mcg x three times per day to raise my T3 level and still stay in a physiologic level....

The strange thing is that I can only take 6.25 mcg in the morning and no more....

I really would have to do trial and error to figure all this out, I have next to no hope of being able to figure out and test for any of the transporter related stuff or intracellular calcium atm

 

[Iritu1021]

That is good to know and when I test other things, I have to do it in the morning while fasting and before I have taken Armour or Cortef.

I am still confused though, do you know how the results of an ion calcium test would change someone's treatment (or would they be more academic and not for treatment purposes)?



That makes sense and if the calcium is being blocked from going into the cells, it would in theory be blocked from entering the mitochondria. Is MCU a medication or treatment (or just in the experimental stages right now)?

MCU stands for mitochondrial calcium uniporter. We do not yet know enough about how to regulate it.

The main utility in checking ionized calcium would be to see if you are getting enough calcium. Another useful test is 24 hour urine calcium that can detect excessive urinary calcium loss. I would also include PTH (parathyroid hormone) and activated vitamin D (calcitriol), which is different than the usual vitamin D2 that people usually test.

These tests would be indicated if you have symptoms of hypocalcemia (muscle spasms, paresthesias, GI issues, depression, dry hair, brittle nails, severe PMS).

 

[Iritu1021]

I'm not sure what peat had (I think it sounds like somewhat severe thyroid dysfunction) but despite finding the theory interesting, Im somehwat interested b/c I know of a few people with severe, disabling fatigue that benefited from his work. It's tricky to know if they had ME/CFS because they didn't go to specialists and were in europe in a country that has BPS model so I doubt they would have gotten good treatment even if going to a doctor.

There are people that are diagnosed with CFS on the ray peat forum (which is mostly a cesspool), some of whom have made full recoveries apparently through various medications and food, and some who havent



But I agree in prioritizing anecdotal evidence of people specifically diagnosed with CFS, even tho I think broader metabolic dysfunction may underlie several disease states. This is why, if doing the dosing protocol that peat/roddy recommends doesn't work, I'll add lithium, and also try the blanchard protocol next.

As for the bolded part, I'm really not sure. I honestly thought his books just went out of print because they didn't sell much. I think there are a couple of things that he may have changed based on experiment and experience.
The one on soviet neuroscience is really good read from a philosophy of science perspective and doesn't really have much in the way of practical recommendations but is cool if one is interested in exploring the differing epistemologies of two differing kinds of "materialism".

Imo I just find the stuff that gets labelled "vitalism" very interesting. It's not really vitalism in the crude sense, but I feel like if one could really understand life or living systems as a whole that it could yield relevant results for many disease states. I do kind of buy the idea that aging and fatigue and several sickness states share physiochemical properties... i think Naviaux does too

Of course that would be nice. But that's like wanting to know the meaning of life - pretty ambitious

 

[frozenborderline]

Of course that would be nice. But that's like wanting to know the meaning of life - pretty ambitious

Well on one hand it may be overly ambitious, but on the other hand, the reductionism and eschewing of focus on what makes living systems tick might be part of why our doctors can't cure us. I don't have a scientific background but since getting sick and reading nietzsche, i have an interest in what is often called "vitalism", I believe unfairly

 

[Gingergrrl]

MCU stands for mitochondrial calcium uniporter. We do not yet know enough about how to regulate it.

I just Googled it (b/c I had thought it was some kind of med or treatment ) and learned it is the membrane that allows calcium to flow between the cellular fluid and mitochondria. Is this correct?

The main utility in checking ionized calcium would be to see if you are getting enough calcium. Another useful test is 24 hour urine calcium that can detect excessive urinary calcium loss. I would also include PTH (parathyroid hormone) and activated vitamin D (calcitriol), which is different than the usual vitamin D2 that people usually test.

My Endo who monitors my Hashimoto's Disease and my current (very slow) taper off of Cortef has definitely tested my PTH and Calcitriol in the past and both were normal. I do not supplement calcium but I do eat dairy (milk, cheese, yogurt, coffee creamer, etc).

 

[Iritu1021]

@drob31
https://www.ncbi.nlm.nih.gov/pubmed/8867923

Eur J Pharmacol. 1996 Feb 29;298(1):79-85.
Pregnenolone sulfate increases intracellular Ca2+ levels in a pituitary cell line.
Büküşoğlu C1, Sarlak F.
Author information
Abstract
We have investigated the rapid steroid effects on intracellular calcium ([Ca2+]i levels in a clonal pituitary cell line (GH3). Among the steroids tested only pregnenolone sulfate induced a rapid and transient [Ca2+]i increase within 1 min. The specificity of pregnenolone sulfate-induced [Ca2+]i increase with respect to steroid structure was pronounced. Other steroids (5-40 microM) including pregnenolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, progesterone, estradiol-17 beta, testosterone, 5 alpha-dihydrotestosterone, 5 alpha-dihydrotestosterone, 5 alpha-dihydroprogesterone, and 3 alpha,5 alpha-tetrahydroprogesterone were found to be ineffective. The [Ca2+]i increase with pregnenolone sulfate (30 microM) was completely abolished in a Ca(2+)-free medium or in the presence of La3+ (0.1 mM) and Co2+ (5 mM). The organic Ca2+ channel blockers methoxyverapamil (100 microM) and nicardipine (5 microM) both showed similar inhibitions (> 73%). The interaction between pregnenolone sulfate and voltage-gated Ca2+ channels (VGCC) was shown by coapplication of pregnenolone sulfate (10 microM) with Bay K 8644 (0.1 mM) or KCl (15 mM). Coapplication of pregnenolone sulfate with KCl increased the [Ca2+]i in an additive manner. However, with the specific agonist Bay K 8644(+/-), the pregnenolone sulfate effect was potentiated in a majority of the cells, suggesting cooperative interaction between the two. The results demonstrate that pregnenolone sulfate induces a rapid Ca2+ influx in GH3 cells. The marked nicardipine block also suggests that most of the Ca2+ influx is mediated through L-type VGCC.

 

[drob31]

Here's the full mechanism of action. Turns out it's a currently well established theory in psychopharmacology that lithium increases mitochondrial calcium.

Fig. 1. Role of mitochondria in intracellular calcium signaling.

Intracellular calcium level is maintained low, but two organelles, endoplasmic reticulum and mitochondria, have high levels of calcium. Mendelian diseases that accompany bipolar disorder are the diseases of these two organelles.

GPCR, G protein coupled receptor; PIP2, Phosphatidylinositol 4,5-bisphosphate; I-1-P, inositol 1-phosphate; IP3. Inositol triphosphate; IP3-R, inositol triphosphate receptor; Bcl-2, B-cell lymphoma 2.

I googled wolfram disease, the first thing I see is diabetes insipidus, which I seem to have a mild case of.

Interesting enough, HTCZ treats thats.

 

[drob31]

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!

Have you tried caffeine together with cortisol and calcium?

 

[drob31]

@drob31
https://www.ncbi.nlm.nih.gov/pubmed/8867923

Eur J Pharmacol. 1996 Feb 29;298(1):79-85.
Pregnenolone sulfate increases intracellular Ca2+ levels in a pituitary cell line.
Büküşoğlu C1, Sarlak F.
Author information
Abstract
We have investigated the rapid steroid effects on intracellular calcium ([Ca2+]i levels in a clonal pituitary cell line (GH3). Among the steroids tested only pregnenolone sulfate induced a rapid and transient [Ca2+]i increase within 1 min. The specificity of pregnenolone sulfate-induced [Ca2+]i increase with respect to steroid structure was pronounced. Other steroids (5-40 microM) including pregnenolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, progesterone, estradiol-17 beta, testosterone, 5 alpha-dihydrotestosterone, 5 alpha-dihydrotestosterone, 5 alpha-dihydroprogesterone, and 3 alpha,5 alpha-tetrahydroprogesterone were found to be ineffective. The [Ca2+]i increase with pregnenolone sulfate (30 microM) was completely abolished in a Ca(2+)-free medium or in the presence of La3+ (0.1 mM) and Co2+ (5 mM). The organic Ca2+ channel blockers methoxyverapamil (100 microM) and nicardipine (5 microM) both showed similar inhibitions (> 73%). The interaction between pregnenolone sulfate and voltage-gated Ca2+ channels (VGCC) was shown by coapplication of pregnenolone sulfate (10 microM) with Bay K 8644 (0.1 mM) or KCl (15 mM). Coapplication of pregnenolone sulfate with KCl increased the [Ca2+]i in an additive manner. However, with the specific agonist Bay K 8644(+/-), the pregnenolone sulfate effect was potentiated in a majority of the cells, suggesting cooperative interaction between the two. The results demonstrate that pregnenolone sulfate induces a rapid Ca2+ influx in GH3 cells. The marked nicardipine block also suggests that most of the Ca2+ influx is mediated through L-type VGCC.

Pretty interesting. pregnenelone definetly turned the lights on for me a few years back. I wonder if we could also get some Bay K 8644.


https://www.tocris.com/products/dl-bay-k-8644_1544

 

[Iritu1021]

I googled wolfram disease, the first thing I see is diabetes insipidus, which I seem to have a mild case of.

Interesting enough, HTCZ treats thats.

THIS IS IMPORTANT TO KNOW: Do not take lithium and HCTZ together, as it can create lithium toxicity!

 

[Iritu1021]

Yesterday I had a very pronounced effect from taking calcium glycinate. Calcium citrate on other hand does absolutely nothing for me. This is effect was more pronounced now that I'm on lithium then when I tried it a while back when I was not taking lithium. But calcium citrate does nothing even in combo with lithium. So there may be some truth to the claim that the forms chelated to amino acids cross into the cell better.

 

[drob31]

THIS IS IMPORTANT TO KNOW: Do not take lithium and HCTZ together, as it can create lithium toxicity!

Thanks for the advice.

Did HTCZ lower water retention at all for you?

 

[drob31]

Yesterday I had a very pronounced effect from taking calcium glycinate. Calcium citrate on other hand does absolutely nothing for me. This is effect was more pronounced now that I'm on lithium then when I tried it a while back when I was not taking lithium. But calcium citrate does nothing even in combo with lithium. So there may be some truth to the claim that the forms chelated to amino acids cross into the cell better.

How much calcium and lithium are you taking ?

 

[pattismith]

Have you tried caffeine together with cortisol and calcium?

I take calcium three times a day for years, so I don't know if other things would work without it for me.

Before I started T3, I was already taking coffee and cortisone when I had a need for a boost and to avoid PEM.

I still use corticoids but it doesn't work if I take it on a daily basis, so I spare it....

@drob31
https://www.ncbi.nlm.nih.gov/pubmed/8867923

Eur J Pharmacol. 1996 Feb 29;298(1):79-85.
Pregnenolone sulfate increases intracellular Ca2+ levels in a pituitary cell line.
Büküşoğlu C1, Sarlak F.
Author information
Abstract
We have investigated the rapid steroid effects on intracellular calcium ([Ca2+]i levels in a clonal pituitary cell line (GH3). Among the steroids tested only pregnenolone sulfate induced a rapid and transient [Ca2+]i increase within 1 min. The specificity of pregnenolone sulfate-induced [Ca2+]i increase with respect to steroid structure was pronounced. Other steroids (5-40 microM) including pregnenolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, progesterone, estradiol-17 beta, testosterone, 5 alpha-dihydrotestosterone, 5 alpha-dihydrotestosterone, 5 alpha-dihydroprogesterone, and 3 alpha,5 alpha-tetrahydroprogesterone were found to be ineffective. The [Ca2+]i increase with pregnenolone sulfate (30 microM) was completely abolished in a Ca(2+)-free medium or in the presence of La3+ (0.1 mM) and Co2+ (5 mM). The organic Ca2+ channel blockers methoxyverapamil (100 microM) and nicardipine (5 microM) both showed similar inhibitions (> 73%). The interaction between pregnenolone sulfate and voltage-gated Ca2+ channels (VGCC) was shown by coapplication of pregnenolone sulfate (10 microM) with Bay K 8644 (0.1 mM) or KCl (15 mM). Coapplication of pregnenolone sulfate with KCl increased the [Ca2+]i in an additive manner. However, with the specific agonist Bay K 8644(+/-), the pregnenolone sulfate effect was potentiated in a majority of the cells, suggesting cooperative interaction between the two. The results demonstrate that pregnenolone sulfate induces a rapid Ca2+ influx in GH3 cells. The marked nicardipine block also suggests that most of the Ca2+ influx is mediated through L-type VGCC.

Interestingly, I am low for pregnenolone, and I took it for years ...... with no effect at all...

 

[drob31]

I take calcium three times a day for years, so I don't know if other things would work without it for me.

Before I started T3, I was already taking coffee and cortisone when I had a need for a boost and to avoid PEM.

I still use corticoids but it doesn't work if I take it on a daily basis, so I spare it....


Interestingly, I am low for pregnenolone, and I took it for years ...... with no effect at all...

How much do you take when you need cortisol? I took 5 mg one time in the evening. I think it even helped my sleep.