This post is very much just trying to crystallize my ideas of the last few months and get some feedback, sorry for the length. I know what I'm saying is not new and maybe others have connected the dots as well. Even though this is a long post I cannot cover everything I've learned which has led me to this conclusion but I can add details if asked.
Just to give some background again about myself, I fell ill in January 2013 with what appeared to be a sudden onset flu-like illness and the subsequent downward spiral of classic ME/CFS symptoms and continually worsening condition. As the disease initiated and symptoms appeared I noticed that in truth it wasn't exactly sudden onset, that I had gradual appearance of low-grade symptoms over the years that I just attributed to "getting older" which were in fact likely the beginnings of this disease and the sudden onset at the end was just the final tipping point that started a serious chain of events.
In March 2013 when I came to terms that this "flu" I was having and worsening condition wasn't going to resolve itself I started going to doctors and doing all kinds of tests and trying to measure and figure things out on my own. Of all the insane and severe symptoms I was having only one test they did showed something amiss, a 24-hr Holter monitor showed I was having ~800 PVCs/day and of course like many of you from almost the moment I got sick I started having severe heart issues.
During this time I started all kinds of vitamins and supplements, severe diet changes, yoga and other exercises, etc. in a desperate attempt to figure out what might be wrong and fix it. None of these things made any difference whatsoever and I only got worse.
It wasn't until September 2013 after seeing my PCP, cardiologists, neurologists, endocrinologists, urologists, gastroenterologists, etc. and all the MRIs, CTs, echos, holters, lab work, other tests, etc. that other diseases were ruled out and everything pointed to ME/CFS.
After this confirmation I found an ME/CFS doctor and proceeded to do a mountain of ME/CFS-specific lab work for things that can be treated. At that time I found I had very high antibody titers to HHV-6, CMV, EBV and Mycoplasma pneumoniae. I started effective treatment against all these infections right away with high dose Valcyte, Famvir, antibiotics and Lovenox.
When I started treatment in September 2013 I would say I had a very "clean" version of this disease because I caught it fairly early and did not yet acquire any of the downstream problems many other people with ME/CFS get after having the disease for a long time without treatment, e.g. no HPA axis or other hormone deficiencies (yet), no other infections, no MCS, no autoimmunity, etc.
My health and symptoms only got worse from the moment I got sick until approx. two months after starting hard core treatment with pharmaceuticals. At first the downward spiral stopped and I stabilized and then slowly certain symptoms started to improve. In addition I started filling any gaps I had in supplementation and covered all the possible bases, i.e. mitochondrial, methylation/glutathione, autonomic dysfunction, hypercoagulation, immune, liver/detox, leaky gut, you name it I'm taking it.
One important thing I noticed was that with all this treatment only a portion of symptoms were improving, I definitely felt that parts of this disease were continuing to evolve and doing damage and getting worse. So I kept researching and doing new tests.
The next tests that shed light on continuing symptoms where some 24-hr urine and other tests. As is typical with ME/CFS, I found that I have polyuria (approx 5 L/day but somewhat intermitent), high plasma catecholamine levels, periods of highly elevated cortisol followed by normal-to-low cortisol (like my adrenals are fatigued following a period of high cortisol production), and zero antidiuretic hormone (ADH or vasopressin). Also I used to have normal aldosterone levels earlier in the disease and then later as it has unfolded more and more they became very low.
After measuring 24-hr urine volume and seeing this was way too much water loss I immediately realized I've been peeing this much and more at least since I became ill if not earlier. This chronic mild-to-moderate diabetes insipidus and blood volume loss is definitely something extremely important.
Also since the moment I got ill one thing I continually measured was my blood pressure and heart rate. I started having POTS and OI within weeks of getting ill, right around the same time the heart symptoms started. What confused me at first is that this disease made me go from normal low blood pressure and heart rate to constant slightly high blood pressure and an abnormally very low heart rate with periods of tachycardia, generally when I stood up or lied down or sometimes out of nowhere. My heart rate is usually 50-55 bpm and during the 24-hr Holter monitor I did early in this disease which showed the PVCs it also showed that my average heart rate during sleep was only approx 40 bpm.
So knowing this and seeing the high 24-hr urine catecholamine results I started low-dose clonidine recently. Not only did it normalize my blood pressure right away, after taking it for a while it has made some serious symptoms that were not getting better with the antiviral and antibiotic treatment slowly disappear.
I can tell you for sure that some of the gradual symptoms that started appearing years before getting outright CFS were those fixed by clonidine recently. So to me for sure elevated catecholamine levels preceded onset of ME/CFS. I cannot say whether the DI and lowering of blood volume precede it but we all know that there is a connection between catecholamine levels and blood volume.
So what causes chronically elevated catecholamine levels? Biological/physiological stress. Even though I don't have proof from my own labs I would also say that cortisol levels are very high early in this disease if not for a long time before and I remember reading that other ME/CFS experts believe this. What causes high cortisol levels? Biological/physiological stress.
EDIT: Everyone I'm NOT talking about mental or psychological stress, I'm talking about physiological or biological stress which is what causes chronically high levels of catecholamines and cortisol.
The clonidine made additional symptoms improve or disappear but there are still other serious symptoms that seem to be related to chronic loss of blood volume. I am just starting desmopressin/DDAVP and IV saline. My initial belief is to try to get my body to return back to normal without the desmopressin, just clonidine plus frequent IV saline to see if after doing this for a few months my body will be able to recover and then reset itself.
If you read the NorCAPITAL trial paper by Wyller testing the hyperarousal hypothesis he didn't fail or disprove anything except that his particular protocol failed. After reading it I was upset that Wyller said clonidine isn't useful in ME/CFS. He's wrong and the reason he's wrong it like a lot of other researchers they are looking for a single magic bullet and that will never work.
If he corrected the low blood volume and polyuria in addition to the elevated catecholamines I believe he would've seen different results. Look for example at this Wikipedia text describing treatment of a more severe disease causing elevated catecholamines, pheochromocytoma:
When you take out all the infectious-related symptoms all the other symptoms of this disease seem to be explained by high catecholamine levels and low blood volume. And the intercellular infections come about due to a Th1 deficiency which is caused by chronic elevated catecholamines and biological stress.
Just to give some background again about myself, I fell ill in January 2013 with what appeared to be a sudden onset flu-like illness and the subsequent downward spiral of classic ME/CFS symptoms and continually worsening condition. As the disease initiated and symptoms appeared I noticed that in truth it wasn't exactly sudden onset, that I had gradual appearance of low-grade symptoms over the years that I just attributed to "getting older" which were in fact likely the beginnings of this disease and the sudden onset at the end was just the final tipping point that started a serious chain of events.
In March 2013 when I came to terms that this "flu" I was having and worsening condition wasn't going to resolve itself I started going to doctors and doing all kinds of tests and trying to measure and figure things out on my own. Of all the insane and severe symptoms I was having only one test they did showed something amiss, a 24-hr Holter monitor showed I was having ~800 PVCs/day and of course like many of you from almost the moment I got sick I started having severe heart issues.
During this time I started all kinds of vitamins and supplements, severe diet changes, yoga and other exercises, etc. in a desperate attempt to figure out what might be wrong and fix it. None of these things made any difference whatsoever and I only got worse.
It wasn't until September 2013 after seeing my PCP, cardiologists, neurologists, endocrinologists, urologists, gastroenterologists, etc. and all the MRIs, CTs, echos, holters, lab work, other tests, etc. that other diseases were ruled out and everything pointed to ME/CFS.
After this confirmation I found an ME/CFS doctor and proceeded to do a mountain of ME/CFS-specific lab work for things that can be treated. At that time I found I had very high antibody titers to HHV-6, CMV, EBV and Mycoplasma pneumoniae. I started effective treatment against all these infections right away with high dose Valcyte, Famvir, antibiotics and Lovenox.
When I started treatment in September 2013 I would say I had a very "clean" version of this disease because I caught it fairly early and did not yet acquire any of the downstream problems many other people with ME/CFS get after having the disease for a long time without treatment, e.g. no HPA axis or other hormone deficiencies (yet), no other infections, no MCS, no autoimmunity, etc.
My health and symptoms only got worse from the moment I got sick until approx. two months after starting hard core treatment with pharmaceuticals. At first the downward spiral stopped and I stabilized and then slowly certain symptoms started to improve. In addition I started filling any gaps I had in supplementation and covered all the possible bases, i.e. mitochondrial, methylation/glutathione, autonomic dysfunction, hypercoagulation, immune, liver/detox, leaky gut, you name it I'm taking it.
One important thing I noticed was that with all this treatment only a portion of symptoms were improving, I definitely felt that parts of this disease were continuing to evolve and doing damage and getting worse. So I kept researching and doing new tests.
The next tests that shed light on continuing symptoms where some 24-hr urine and other tests. As is typical with ME/CFS, I found that I have polyuria (approx 5 L/day but somewhat intermitent), high plasma catecholamine levels, periods of highly elevated cortisol followed by normal-to-low cortisol (like my adrenals are fatigued following a period of high cortisol production), and zero antidiuretic hormone (ADH or vasopressin). Also I used to have normal aldosterone levels earlier in the disease and then later as it has unfolded more and more they became very low.
After measuring 24-hr urine volume and seeing this was way too much water loss I immediately realized I've been peeing this much and more at least since I became ill if not earlier. This chronic mild-to-moderate diabetes insipidus and blood volume loss is definitely something extremely important.
Also since the moment I got ill one thing I continually measured was my blood pressure and heart rate. I started having POTS and OI within weeks of getting ill, right around the same time the heart symptoms started. What confused me at first is that this disease made me go from normal low blood pressure and heart rate to constant slightly high blood pressure and an abnormally very low heart rate with periods of tachycardia, generally when I stood up or lied down or sometimes out of nowhere. My heart rate is usually 50-55 bpm and during the 24-hr Holter monitor I did early in this disease which showed the PVCs it also showed that my average heart rate during sleep was only approx 40 bpm.
So knowing this and seeing the high 24-hr urine catecholamine results I started low-dose clonidine recently. Not only did it normalize my blood pressure right away, after taking it for a while it has made some serious symptoms that were not getting better with the antiviral and antibiotic treatment slowly disappear.
I can tell you for sure that some of the gradual symptoms that started appearing years before getting outright CFS were those fixed by clonidine recently. So to me for sure elevated catecholamine levels preceded onset of ME/CFS. I cannot say whether the DI and lowering of blood volume precede it but we all know that there is a connection between catecholamine levels and blood volume.
So what causes chronically elevated catecholamine levels? Biological/physiological stress. Even though I don't have proof from my own labs I would also say that cortisol levels are very high early in this disease if not for a long time before and I remember reading that other ME/CFS experts believe this. What causes high cortisol levels? Biological/physiological stress.
EDIT: Everyone I'm NOT talking about mental or psychological stress, I'm talking about physiological or biological stress which is what causes chronically high levels of catecholamines and cortisol.
The clonidine made additional symptoms improve or disappear but there are still other serious symptoms that seem to be related to chronic loss of blood volume. I am just starting desmopressin/DDAVP and IV saline. My initial belief is to try to get my body to return back to normal without the desmopressin, just clonidine plus frequent IV saline to see if after doing this for a few months my body will be able to recover and then reset itself.
If you read the NorCAPITAL trial paper by Wyller testing the hyperarousal hypothesis he didn't fail or disprove anything except that his particular protocol failed. After reading it I was upset that Wyller said clonidine isn't useful in ME/CFS. He's wrong and the reason he's wrong it like a lot of other researchers they are looking for a single magic bullet and that will never work.
If he corrected the low blood volume and polyuria in addition to the elevated catecholamines I believe he would've seen different results. Look for example at this Wikipedia text describing treatment of a more severe disease causing elevated catecholamines, pheochromocytoma:
The patient with pheochromocytoma is invariably volume depleted. In other words, the chronically elevated adrenergic state characteristic of an untreated pheochromocytoma leads to near-total inhibition of renin-angiotensin activity, resulting in excessive fluid loss in the urine and thus reduced blood volume. Hence, once the pheochromocytoma has been resected, thereby removing the major source of circulating catecholamines, a situation arises where there is both very low sympathetic activity and volume depletion. This can result in profound hypotension. Therefore, it is usually advised to "salt load" pheochromocytoma patients before their surgery. This may consist of simple interventions such as consumption of high salt food pre-operatively, direct salt replacement or through the administration of intravenous saline solution.
When you take out all the infectious-related symptoms all the other symptoms of this disease seem to be explained by high catecholamine levels and low blood volume. And the intercellular infections come about due to a Th1 deficiency which is caused by chronic elevated catecholamines and biological stress.
Last edited: