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.