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Novel Ideas - Strontium, Transcortin, TBG,

xks201

Senior Member
Messages
740
Please excuse my crap grammar/incompleteness of ideas. It is early in the morning, I did not sleep much, I am tired, and at this point I just want to try and help anyone I can and come to conclusions with others that may help myself. I have no financial interest here. Finally all of these supplements and drugs can have different side effects in different people which is why I recommend the oversight and if possible blessings of a doctor who can monitor you with bloodwork if you do try any supplements or anything listed here. I am not responsible for you trialing any of this or trying to obtain it illegally because I am not promoting anyone obtain anything illegal here. I am not going to provide sources on any of this via PM or here for protection of everyone (I get all of my prescriptions properly through a local doctor). I do not claim to be taking all of these at once or even claim to have taken them all. I apologize in the past if I offended anyone or was pompous about feeling better. That was not my intention. And yes I realize not everyone has the resources to constantly try new things - and my heart goes out to you all. I am in a lot of debt due to my trials with doctors and their prescriptions and supplements and I just want to thank everyone here for participating positively...

I use the word recovering and cure not lightly. Please do not take this as me saying this will cure you. These are ideas to combat my lab results and or scientific papers establishing theories for CFS. I have come to a recovery I believe - except that when I do mix various drugs (mainly progestins, some of which I use for my joy of powerlifting/bodybuilding (I am by no means at competition level, it's just a hobby), completely screw me back up and send me into fatigue. These progestins are known to lower thyroid binding globulin and raise cortisol binding globulin(also known as transcortin). For a long time I've been holding back delivering ideas to this forum, partly because I felt like I wasn't doing a service by posting "theories", and secondly because I wanted to make sure that these theories worked in myself. Well I'm realizing that the variables are different to some degree in all of us. Here are some novel ideas.

IDEAS

1) Strontium Takes Place of Calcium. There is science that strontium takes the place of calcium in the body. Several studies revealed that calcium ions are hyperactive in CFS. They referred to this as "channelopathy". SP? So I'm thinking, a calcium channel blocker will shut down the channel, but what if simply strontium was taken to take the place of excess calcium flow? I read a scientist claiming that the calcium leaks are constant in many cases of CFS, causing muscle pain, weakness, cognitive issues, etc. I have a prescription for amlodipine, but this calcium channel blocker does not penetrate the nervous system like vermapril I believe. Therefore it would be ineffective in the nervous system in comparison. There are reports of individuals recovering quite a bit with nervous system active calcium channel blockers (for lack of a better word).

2)Vitamin Mismetabolism (a new word! lol)

I notice considerable benefit from taking the altered form of B6 which I believe holds prescription status in Europe for neurological diseases called pyritinol. More knowledge of chemistry is needed for me to figure out how to modify the metabolism of this so that the sulfhydrl groups (which have been implicated in certain individuals negative reactions to this drug) do not produce a toxic reaction in myself. Ironically the pyritinol I got off the internet seems to help more than anything, yet one dose of it produces 2 days of pain in the liver and kidney region - symptoms seen in some people. I offer you all to try this drug/vitamin supplement but please discontinue immediately if you are one of the unlucky people like me who notice side effects. It claimed to have "cured" nearly 80% of people of their idiopathic vertigo (which was later proven to be a result of decreased glucose transport in brain regions responsible for balance) which it supposedly rectified. A very interesting supplement that is fairly cheap and worth a try if you have sorted out the other variables (Cortisol, thyroid, sex hormones, vasopressin, GH, etc. etc..) I am consulting currently with someone who claims to have access to B6 in various other forms we are unaware of. This might be false information from him but I will update the group if it pans out. P5P is something everyone here should trial as it is intimately involved with brain glucose transport.

3) Beta 2 Adrenergic Agonists
Including formoterol, albuterol, clenbuterol(if legal in your area), supposedly help sensitize cells to cortisol. They are anabolic by nature and activate testosterone receptors, which activate dhea receptors.

4) sublingual pregnenolone and dhea (micronized)
I use douglas labs- find smaller doses of these supplements far more effective than the oral and or non micronized versions.

5) Manipulating Choline Dominance or Insufficiency - Potential for Piracetam Supplementation
A drug I want to try is piracetam. It is anticholinergic. So much so that people take choline with it regularly due to its ability to deplete choline. A choline excess is something I am experiencing symptoms of often (whether this is a result of upregulation of receptors or supersensitivity to acetylcholine I don't know.) . This is just all speculation to some degree (then again what research does not start that way). I have tried aniracetam and receive benefits from it. Temporarily I snap out of fatigue when I am fatigued when taking it. Aniracetam is chemically related to piracetam except its half life is like 2x shorter than piracetam so I think any significant changes will be noticed on piracetam and not aniracetam. I respond with supersensitivity to huperzine and aricept which both are acetylcholine reuptake inhibitors basically (increasing acetylcholine levels). The lowest doses of these drugs leave me bed ridden for 2 days. And that is most likely due to existing choline dominance, possibly in the form of upregulation as mentioned.

6) T3 monotherapy
Whenever I take T4, armor thyroid, or any preparation containing T4 as opposed to just T3, my body temp drops and I remain in a hypothyroid state despite whatever my labs state. If I remember (have to look at the labs, my reverse T3 was in the upper quarter of the ref range. At the time I was ignorant that the ratio of T3 to rev T3 was what was important and T3 was not tested simultaneously so it remains a mystery until retested. Consider mono t3 therapy. I monitor my body temp daily which lets me know how efficiently my thyroid hormones are being used. A Degree lower than 98.6 makes me feel like crap.

7) Look at the cortisol binding globulin and thyroid binding globulin. Alterations in these globulins (if they are out of ref range) can produce symptoms of hypo or hyper thyroidism and hypo or hyper cortisolism. I have found many RX drugs manipulate these binding globulins in studies or alter sensitivity at the receptor level to these hormones which may be affecting you. My CBG was out of range high and TBG out of range low last time I checked (could be induced from my RX meds).

8) Methylene blue - I have to dig up the study but supposedly this enhances mitochondrial function and increases glucose transport in the brain (a similar concept to pyritinol possibly). I have yet to try it but most likely will soon. I believe it is legal in the US.

9) Modafinil, Low dose Fluoxetine or Sertraline, Wellbutrin
One of more of these may work for you. Doctors seem eager to prescribe the latter three in my experience. I'm not sure if modafinil is generic yet but when I attempted to fill my RX at the local pharmacy they wanted an arm and a leg for it when it was not generic (it may still not be generic).
Modafinil works on orexin and other receptors which may be understimulated in some fatigued or narcoleptic individuals. Cognitive enhancing effects have been reported.

10) You may be GH deficient. My IGF-1 was consistently under 200 (sorry do not have the units on me but I have only seen one units of this reference range used for IGF-1). An arginine stimulation test revealed almost nonexistent GH production in me. Getting an endocrinologist to RX this test can be tricky. Many do not have access to the arginine, glucagon, or other stimulating agents of GH release used in the US (fishy, right?). So that might be a hard test to come by, but very much worth it and probably indicated in my non medical non professional opinion if your igf-1 is consistently around 150 or lower like mine was. One time my igf-1 even came back at 250, though I think it was due to another RX upregulating its production possibly, but three other times it came back around 125 which was still in range but low for my age. The stimulation tests are the only way to tell for sure if you are GH deficient and most insurance companies require sometimes up to 2 stimulation tests to cover GH replacement therapy which out of pocket can be relatively expensive.

11) Partial Diabetes Insipidus,

If you frequently urinate more than you drink (or find yourself constantly thirsty), you owe it to yourself to investigate the possibility for partial diabetes insipidus. Symptoms of polyuria can be from low aldosterone, even low cortisol (as I've witnessed in my case), or low vasopressin. Initially my vasopressin was in the upper range, but the low aldosterone showing on blood tests caused frequent urination. Part of my pituitary is dysfunctional (but normal on MRI ironically(this is possible according to my endo)) and so in replacing multiple pituitary hormones I basically have hard to start replacing all of them due to atrophy of the gland or at least negative feedback inhibiting its proper function. It could have been sluggish to start.

12) Endorphin deficiency
Some studies showed people with brain disorders even relatively minor ones like ADHD may have deficiencies of beta-endorphin and other endorphins. A study showed that the majority of a group of young people who committed suicide had multiple times the amount of endorphin receptors in their brains (presumably an upregulation attempt by the brain from lack of endorphins). One study of people with CFS showed low endorphin levels, Beta endorphin is made in the pituitary. The HPA axis is known to be a center of problems in many CFS patients. In my case my pituitary is nearly useless from a head injury snowboarding a while ago (possibly a vaccine, but more likely the head injury as the vaccine thing is purely speculation and I do not have objective evidence for it myself) so my beta endorphin levels produced in the pituitary are probably low. Beta endorphin replacement to my knowledge is virtually unheard of except in studies where it showed potential to individuals with nervous system or brain disorders of varying severity. Vicodin, a stimulator of endorphin action, supposedly also causes a release of dopamine. Could many of us be endorphin deficient, potentially causing a massive downregulation of metabolism and function in the nervous system? IF you think about it, nature has designed us to experience pleasure and pain as a reward system for doing what enhances survival or what doesn't. If your body is deficient in endorphins and is constantly telling itself that you are incapable of experiencing pleasure or are to be experiencing pain, that I would think would be a reaction common in sickness - signaling the organism to slow down, to relax, and to attempt to heal. Surging endorphins beyond the timing of an injury or illness would make no sense to me as I would think they would overstimulate one and put one in reckless endangerment in nature (assuming we lived in the animal world still). Again as you can see this is a kind of serious speculation, but nonetheless an interesting topic that merits more research by us and or the scientists that dream up these experiments.

13) Flouride Toxicity - Russell Blaylock , MD, neurosurgeon, has discussed flouride toxicity (he has a great book out I believe called excitotoxicity, which talks about MSG, flouride, and other toxins which alter brain chemistry. He is anti vaccine as well (read more about it in his book - I'm not taking positions openly on that subject in this forum because I don't claim to have all the answers or evidence in front of me for either position). But flouride was used as a nervous system numbing sedative on prisoners I believe in Europe. If you think about how much flouride it would actually take to have acute effects - it probably in reality isn't much more than what would directly access your bloodstream through your gums from a dose of toothpaste containing it. That is speculation but seriously the topic is interesting. Then our water has it - which we bathe in. Filtered shower heads and certain drinking water filters I believe can get rid of a lot of it (results may vary from products). Something as potentially toxic as flouride which produces atherosclerosis in chickens fed it is not something let's just say I am excited about putting in my body in any consistent quantity. I do not use flouridated toothpaste. I brush my teeth once a day usually, and have no cavities since using non flouridated toothpaste in the last five years. Before that I used flouridated toothpaste twice daily and at least once a year developed a cavity.

14) Transdermal Magnesium
This supposedly increases magnesium levels in a matter of weeks where oral supplementation supposedly can take a lot longer (could be hearsay). Many depressed individuals are mag deficient and there may have been a study pointing to this deficiency in the RBCs of CFS patients.

15) Hematological Abnormalities
These seem to occur in CFS patients to a significant level. One scientist claimed the RBCs are shaped abnormal. My blood results personally indicate excessive destruction of RBCs, yet no anemia. The marker for variation in size was out of range, showing a large size variation average of the RBCs. WBCs normal. Dehydration possibly? Improper utilization of Vitamins and or nutrients? Vitamin metabolism abnormalities?

16) Elevated B12 - saw this on my blood test. Very weird. Active b12 makes no different even supplemented consistently. I've seen this abnormality in others.

17) Prior tendency to excessive acne - this resolved with a mix of active coenzyme b vitamins and folic acid. The acne was cystic and bad. I am assuming it was bacterial but perhaps it was due to improper metabolism from lack of nutrients.

18) Body Odor - Always have had a rotting smell that sometimes came up in belching (sorry for graphic nature or ruining your breakfast) Don't know if it is related but it comes and goes. There is a fish order disease related to improper vitamin metabolism if I recall.


19) copper, iron, and niacin destroying bacteria - these infections produce symptoms similar to CFS in cows. All of these nutrients are cofactors to neurotransmitters and some sort of plasma test is probably better than a urine test in diagnosing potential deficiency.

20) E1, E2, and E3 estrogen imbalance in both men and women. When the interconversion of these estrogens gets blocked a lot of derangements can happen. I personally had extremely high e1, with low e2 and nonexistent e3 last time I checked. Iodine (can be bought in the 50 mg doses) according to one doctor was beneficial in increasing estrogen detoxing and interconversion.


I put the numbers up there so you guys could reference the topics/paragraphs in your replies if you choose to add something. I don't care what you add. I'm not claiming any of this as gospel or recommending any of it per se. This is just where I am at in my journey. I have done the nutri eval urine test which revealed next to nothing. Some krebs cycle metabolites/intermediates appeared on the lower level of normal and there was a recommendation for supplementation of b6, b12, zinc, and magnesium.

I am especially interested in methylene blue, piracetam, strontium, endorphin replacement, and modulation of the thyroid and cortisol binding proteins. I may continue adding b12. I for example found in one study that alcohol freed up some bound cortisol from the cortisol binding globulin. Then I pondered...possibly alcoholics have lower free cortisol and in addition to alcohol increasing their beta endorphin levels(as shown in some studies), possibly it is increasing their free cortisol(as shown in one study). If they are potentially deficient in free cortisol, the antidepressant effect or stimulating effect of alcohol then makes sense in that context. Why many CFS patients complain of alcohol intolerance is probably due to a multitude of factors that are individualized and there most likely is not one reason that applies to everyone. (at least I do not believe so as we are so biologically diverse with so many influencing factors like genes, environment, diet, existing state of the endocrine system, existing fitness level, etc. I also stumbled upon several scientific articles talking about the potential for cortisol deficiency from alterations in the cortisol binding globulin level despite NORMAL serum cortisol levels. This is a possibility in any of us experiencing cortisol deficiency or potentially excess problems. Most docs I have dealt with will not test these parameters. Private lab services in this regard have been my godsend.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
I think you have a lot of very valid points! I've been exploring down many of these roads myself.

I would add phosphatidylserine which is meant to resensitize the neurons of the hypothalamus to cortisol and increase dopamine production as well. This is meant to be appropriate for both low and high cortisol states, though it is much more commonly referenced in the latter. I have not been able to find any references that show it lowers cortisol below normal.

I would also add nicotine to this list. If it were a drug, I think it would be a first line treatment for many of our issues. Nicotine increases cortisol, norepinephrine, dopamine, vasopressin, thyroid function...

LDN may also be indicated for endorphin deficiency along with DPA/DLPA.

Ema
 

Sushi

Moderation Resource Albuquerque
Messages
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Location
Albuquerque
I think you have a lot of very valid points! I've been exploring down many of these roads myself....

I would also add nicotine to this list. If it were a drug, I think it would be a first line treatment for many of our issues. Nicotine increases cortisol, norepinephrine, dopamine, vasopressin, thyroid function...

LDN may also be indicated for endorphin deficiency along with DPA/DLPA.

Ema

Has anyone experimented with nicotine patches? I've considered it too.

Sushi
 

xks201

Senior Member
Messages
740
I have tried the nicotine gum but did not notice benefits. I also am finding from a Nutri-Eval that my metabolism appears to have shifted anaerobically (this is most likely the reason for the metabolites and intermediates of the Krebs cycle being low). I do not do cardio, just low rep weight lifting so this could be one reason if indeed that is what has happened.
 

vamah

Senior Member
Messages
593
Location
Washington , DC area
Has anyone experimented with nicotine patches? I've considered it too.

Sushi

I chew nicotine gum and it helps me with brain fog and mental focus issues. I have also noticed recently that it makes me very talkative (I am generally a very quiet person). Don't know if that's a benefit or an annoyance to the people around me. :D BTW, I have never been a smoker, but started the gum about 6 mos ago.
 

rosie26

Senior Member
Messages
2,446
Location
NZ
If anyone try's nicotine patches, I would start at lowest. When I tried to give up smoking 15 years ago I tried the patches and I found the nicotine taste was coming out strong in my mouth, it was like I had a mouth full of nicotine the taste was awful. Actually made me feel quite sick.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Has anyone experimented with nicotine patches? I've considered it too.

Sushi
If by experimented you mean "spent a small fortune using them for around 8 years", then, yes, I have experimented. It did help me feel better (more energetic and satisfied) but the effects of the patch would wear off in about 4 hours so I would be inclined to rip that patch off and apply a new one for a fresh fix. If I overdid this, then I would get shaky and nauseous in what I suspect was a mild overdose. I tried augmenting the patches with gum but hated how it numbed my throat.

If I went back to it, I would try the ecigs instead. But it was so hard to stop that I'm not exactly rushing back either even though I think nicotine did help. I am going to try galantamine instead which is supposed to work on some of the same brain receptors.

Ema
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
If anyone try's nicotine patches, I would start at lowest. When I tried to give up smoking 15 years ago I tried the patches and I found the nicotine taste was coming out strong in my mouth, it was like I had a mouth full of nicotine the taste was awful. Actually made me feel quite sick.
I found that it really does matter which brand you buy. The generics were worthless for me and the ones with the metal backing also caused me issues. Only the very most ruinously expensive clear Nicoderm patches worked for me.

Ema
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
I found that it really does matter which brand you buy. The generics were worthless for me and the ones with the metal backing also caused me issues. Only the very most ruinously expensive clear Nicoderm patches worked for me.

Ema


They are prescription I guess?

Sushi
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
They are prescription I guess?

Sushi
No, OTC. About 50 bucks for a box of 14 which is meant to last two weeks but I could only get about 5 days out of...max. I could easily go through 3-5 a day.

ETA they are only 29 bucks on Amazon! Scary how this conversation has made me want a box even after all these years...
Ema
 

rosie26

Senior Member
Messages
2,446
Location
NZ
Ema - it was the metal backing patch that I tried. I think the nicotine e-cigarettes you mentioned would be better to try too.
 

nandixon

Senior Member
Messages
1,092
5) Manipulating Choline Dominance or Insufficiency - Potential for Piracetam Supplementation

A drug I want to try is piracetam. It is anticholinergic. So much so that people take choline with it regularly due to its ability to deplete choline. A choline excess is something I am experiencing symptoms of often (whether this is a result of upregulation of receptors or supersensitivity to acetylcholine I don't know.) . This is just all speculation to some degree (then again what research does not start that way).

I have tried aniracetam and receive benefits from it. Temporarily I snap out of fatigue when I am fatigued when taking it. Aniracetam is chemically related to piracetam except its half life is like 2x shorter than piracetam so I think any significant changes will be noticed on piracetam and not aniracetam.

I respond with supersensitivity to huperzine and aricept which both are acetylcholine reuptake inhibitors basically (increasing acetylcholine levels). The lowest doses of these drugs leave me bed ridden for 2 days. And that is most likely due to existing choline dominance, possibly in the form of upregulation as mentioned.
@xks201 (I broke up the above part of your original post a bit.) Just wondering if you ever tried the piracetam and how it compared to aniracetam?

I think I've possibly had an ongoing problem with excess acetylcholine, too. My "Cholinesterase RBC" (aka Acetylcholinesterase) tested low several years ago at:
9706 U/L (ref 10000-20000)

Like you, Huperzine A (an acetylcholinesterase inhibitor) severely exacerbates my fatigue. (All the members of the nightshade family also exacerbate both fatigue and inflammation for me as well.)

Thanks!
 
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Crux

Senior Member
Messages
1,441
Location
USA
Choline intolerance could be genetic or secondary.

The genetic cause would be some defect in the FMO3 gene. This would result in trimethylaminuria, or TMAU. The most noticable symptom would be a fishy body odor.

A secondary cause would be from gut dysbiosis. It's treated with antibiotics, although this article brings up the use of charcoal.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052392/
 
Messages
40
Hello everbody,

I am new to this forum and this is my first post. I got diagnosed with hypothyroidism two years ago in 2013. Since then my condition improved a lot but the incredible tiredness is something I couldn't overcome yet. Googling for nicotine and thyroid binding globuline (TGB) brought me to this forum :) I am smoking again since 2007 after I was abstinent for 6 years.

Ever since I want to quit again, but even with thyroid hormone supplementation this proves to be very difficult, although I really dislike smoking. So from my perspective I can only advise you not to try to play with nicotine since the changes it induces in the endocrine system are deep and partially lasting. Each time I tried to quit smoking my symptoms became worse and after starting to smoke again it takes weeks to months to arrive at the "well-being" status before quitting. I don't think that it should be used as a therapy.

However one may look at the underlying mechanism of nicotine's actions on the endocrine system, such as boosting cortisol levels and dopamine, as well as somehow increasing the blood values of free thyroid hormones and decreasing TSH. However, how this increase in thyroid hormones exactly happens is not clear. E.g. thyroid hormones are measured by using competitive immunoassays, the mechanism is more or less to measure the free sites at the TGB and then from that estimate the amount of free thyroid hormones.

Now e.g. nicotine also binds to Thyroid Beta Receptors which probably in addition to the rise in cortisol explains the learning and or concentration and or brain fog lifting effect nicotine has. The information pdf about the Chiron Diagnostics ACS 180 thyroid test states that anything that alters the TGB levels and or competes with T3 T4 binding sites will alter the test results. Therefore the results of many studies may probably only give a hint on certain directions.

It may however also explain why the results of studies are contradictory with respect to the fact that some observe an increase in thyroid hormones while others report an decrease in thyroid hormones in smokers compared to non-smokers. Without knowing exactly what kind of test kits have been used and also without knowing the TGB levels it is very difficult to interpret the results of these tests. However, something in cigarettes "works" for some people. However again, nicotine patchs alone didn't work in my case and probably the effects of cigarettes are not only explained by the effects of nicotine but by an interference of some other components.

With respect to xks201 point no. 1 I wanted to add, that the NMDA receptor which is e.g. responsible for opening calcium channels to allow calcium to flood the cell, that they are activated/deactivated by magnesium. If magnesium is lacking/absent, calcium channels will remain open. Therefore instead of strontium one could simply test which effect high doses magnesium have.

One of the differential diagnosis of CFS is hypercalcemia. In the case of a lack of magnesium - which sadly is with current methods difficult to test - one doesn't need to be hyper in calcium in order to experience symptoms of someone being hyper in calcium, since a lack of magnesium will because of the open calcium channels produce similar effects to those that result from a too much of calcium.

Moreover, since magnesium is needed in order to render the ATP molecule biologically active a lack of magnesium will also result in a lack of biologically active ATP which could be one possible piece in the puzzle of understanding how "fatigue" can/could be explained by a lack in a certain nutritional element. Nicotine, caffeine, alcohol, they all by different mechanisms alter magnesium homoeostasis in the body. It is not an explanation of everything, but it can be one piece and thus one more step into the direction of recovery.
 
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Messages
40
In the last weeks I was playing with Vitamin C and it definitely provided an energy boost... The article below describes how Vitamin C influences the production of catecholamines. The highest concentrations of Vit C are found in the brain and in the adrenal glands. For those who want to play as well, it is recommended to start with 500-1000 mg a day and then go up to around 3 g in smaller steps. If you stop taking it it is also recommended of gradually decreasing the dose such that the body can adapt to it. Vitamin C also is needed for steroid hormone production such as cortisol.

http://www.sciencedirect.com/science/article/pii/0301008294900523

It took two weeks until I could feel an improvement and since few days I don't want to smoke in the mornings anymore and it is much easier to wake up in the morning and most important :) I feel refreshed after sleeping. In the last years I always felt worse after sleeping and guessed that it was due to low cortisol production. The first cigarette in the morning felt like "life-saving" now I don't "need" them. I still didn't quit, since I felt so bad last time... Sorry, for the sloppy writing style today... I am very tired and should actually sleep, but I wanted to share nevertheless.