@Gail C: "But the paper does not really explain why we have too much NE."
I may have a potential answer to that: Norepinephrine is a needed precursor to Epinephrine, the fight-or-flight hormone.
Epinephrine has, according to my completely unproven opinion, some very potent beneficial properties beyond the fight-or-flight response and anaphylaxis it almost solely is linked to.
Mast cells have a very strong link to allergies and the dangerous anaphylaxis (potential deadly allergic reaction): https://en.wikipedia.org/wiki/Mast_cell
And the worldwide number 1 medicine against it is (very) high dose epinephrine: https://en.wikipedia.org/wiki/Anaphylaxis
So far, this is common accepted science.
Now, would this "medicine" called epinephrine not be possible used as a body made medicine? Let's see some arguments:
* MCAS, a mast cell disorder. According to your post, it goes hand in hand with high levels of NE.
* POTS or other OI: According to many sources, it goes hand in hand with high levels of NE.
* Dysautonomia: According to many sources, it goes hand in hand with high levels of NE.
=> In fact, there are subtypes called adrenal POTS and adrenal dysautonomia; they show even up as suggestions in search engines if you enter adrenal PO or adrenal dy.
* 2 out of 3 NIH approved fibromyalgia drugs are SNRI where NRI stands for Norepinephrene Reuptake Inhibitor or medicine that raises Norepinephrene levels in the body a lot.
* Near ALL ME/CFS patients are said to be of the "fight-or-flight" type patients; this fact is often abused to call ME/CFS patients afraid; afraid to move (Wesley and co.); sick because of anxiety thus psychological; obsessive compulsive disorder... and order excuses not to help them...
Now, let me turn cause and effect upside down:
At the start of my university studies I was REALLY stress tolerant. Even after failing a major course and being near guaranteed to have to redo a list of examinations on the second chance thing we have got, I remained calm and continued calmly to finish the two remaining examinations of two other courses that were among the most difficult of the year. When my health went done a lot a few years ago, my mother remembered me that at that time she asked how stressed I was about it and I replied: "What is stress? I don't think I really have got that". I remembered than that I actually said that a few times during university time and I actually felt that way.
Just to say that before I was ill, I had above average stress resilience.
Several years after I have had mononucleosis, haven taken no time to properly recover from it and pushing my body very hard I became nearly the most stressed-up person I did ever met. As the years passed more and more symptoms came up. Doctors attributed all symptoms to me having to much stress.
I did agree my stress levels were much to high. During the following 10 years I put a lot of time in managing my stress and emotions and improved a lot in managing them. I ended up to the point I more and more had stress but failed to find any reasonable explanation as to why I had stress at that moment.
So: does high anxiety makes us sick? I start to doubt so. It does cost plenty of energy and can make us more sick (starting a vicious circle once it gets to high), but it is likely not the cause with many patients. The high anxiety was likely one of the first SYMPTOMS of ME/CFS. Epinephrene has following good properties for us:
* It is likely the best Mast Cell Inhibitor known to mankind.
* Research has indicated that Epinephrene may actually boost immune system: https://www.sciencedaily.com/releases/2012/06/120621223525.htm and https://www.ncbi.nlm.nih.gov/pubmed/6458557/
* The research needs to be repeated, but if correct it works on the T-cells in particular. It "strenghtens" those cells and those are white bloodcells in the bloodstream.
* In comment 23 of http://www.healthrising.org/forums/threads/mella-finds-hypometabolic-state-in-chronic-fatigue-syndrome-plus-rituximab-and-new-drug-for-me-cfs.5004/page-2 I make a hypothetical case that the weakened white blood cells and overactivated mast cells may be a problematic feedback loop keeping Dauer lasting/locked in. Epinephrene reduces both mast cell activation very strongly and may, according to above research, increase white blood cell strength. That may add up to be a perfect anti Dauer medicin in above hypothesis IF IT WERE NOT HAVING THAT EPIC SIDE EFFECTS.
* As an extra, it also redirects blood flow to the core organs, what I see as a plus.
So my hypothesis: our bodies try and find an ideal mix between potentially very beneficial positives of epinehrene and potentially even more devastating side effects.
p.s.: I'll have some more stuff I will add in the future to that other post further trying to strengthen the case for problematic Dauering of white blood cells and how that could possibly explain the different starts of ME/CFS under that hypothesis. My aim is to provide a first "bigger" picture that makes many links and see if others can correct and improve upon it. Having a first model that *could* explain that our disease is theoretical possible would be a big boon to our community I believe. Very unlikely it will be useful, but with enough help it could grow to be so. If value is seen in it, all help would be welcome. I am still quite exhausted.
added: forgot to mention that one of the reason few is known about long term high epinephrine elevated levels (as in "fight-or-flight people" we are called) is likely that it is very hard and expensive to measure it continuously over long periods.
Comprehensive pedigree analysis of 16 families (39 individuals with orthostatic intolerance, and 40 individuals suspected of having orthostatic intolerance), demonstrated dominant transmission of autonomic dysfunction with incomplete penetrance. Affected individuals were predominantly female (71.8%, 28/39; F:M::2.5:1). Male-to-male transmission, though less common, was observed and demonstrated to transmit through unaffected males with an affected parent. Similar to sporadic orthostatic intolerance, probands report a range of symptoms across multiple organ systems, with headaches and neuromuscular features being most common.
Familial occurrence and vertical transmission of autonomic dysfunction in 16 families suggests a novel genetic syndrome with dominant transmission, incomplete penetrance, and skewing of the sex ratio. Elucidation of potential genetic contributions to orthostatic intolerance may inform therapeutic management and identification of individuals at risk. Adolescent evaluation should include identification and treatment of potential at-risk relatives.
We are different. My NE spikes each time I stand from sitting. There is no one spike here and one there, but each time day in and day out. I also have the high Tryptase and TGF-Beta to factor in somewhere. We may be comparing apples and oranges. But it wonderful that you have improved! I do hope that improvement continues.Is looking at it this way useful or just wasting our poor brains? Be this theory wright or wrong I learned a trick or two from it:
* I learned to use sudden spikes in adrenaline/arousal/anxiety with no obvious reason as an early warning signal that I am overexerting myself.
HI there, I'm wondering if there has been further progress / any more news re this? Many thanks.Next up for this group: developing a diagnostic test to detect alpha tryptase gene copies and finding ways to block tryptase production. For people with extra copies of this gene and who are ill the news is good indeed. Few diseases, after all, can be traced to one factor. Pharmaceutical companies are surely combing their drug databases for drugs with tryptase-inhibiting pathways.