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A revolving door (or the ME-CFS stress response) - part 1

Posted May 22 2010 12:00am
I remember the automatic revolving door at the main entrance to Wanamakers, a big department store in center city Philadelphi where my grandmother took me when we came to visit.  I found the door scary at first.  I’d have to step behind the glass partition as it emerged from the side wall with a huge whoosh, and quickly pick up my pace to avoid getting hit in the back.  I feared getting caught in the cracks someplace between the outside and the inside.  But once I mastered the art, while my little sister held our grandmother’s hand, I rode around and around, from inside to outside to inside, until she pulled me safely inside. 

This memory has come up in the last two weeks because they have felt like riding through revolving doors.  One minute I am in heaven, feeling happy with my progress.  Hours later, I am in hell.  In between,  I am in limbo, but I am always moving in circles, like an endless.

Two weeks ago, when I posted “An Unexpected Blessing”, I never imagined I would walk back into the hell of relentless palpitations, insomnia and chest pain.  But it happened almost immediately.

I had a hard time falling asleep that night.   When I finally did so, I woke after two or three hours at 4:30 am, hot as hell, a burning sensation at the base of my sternum, my heart thumbing loudly.  Where were the benefits of the Trivedi blessing? I had screwed everything up by going in for acupuncture that morning.  Of that I was sure.  I’d been cold all day, then somewhat overcharged at night, now sleepless with a new set of cardiac/stress/gastric symptoms. 

Thankfully, I didn’t panic.  I chastised myself and resolved not to do any more acupuncture.  The unfolding energy of the Trivedi blessing kept me believing that everything would work itself out if I just left well enough alone.  After that I was able to meditate peacefully for over an hour; I even felt the continuing energy of the blessing as a sweet, light joy inside, puffing my cheeks into a gentle smile.   

The refrigerator had a funny smell when I opened the door to get breakfast:  it had accidently been turned off for 24 hours.  Convinced that I was now immune to the stress response that had terrorized me for the past six weeks, I set to work cleaning out potentially spoiled items, cutting up a chicken we’d defrosted overnight and putting it up to marinate, and finally throwing together a quiche with the rest of the milk and eggs.  This adventure took over 45 minutes, during which I was standing 95% of the time.  My stress hormones were going at full speed! My feet hurt, but I still believed I’d be okay.  I sat at the computer to check my e-mail, promising myself I’d return to bed before noon.  But I was still too wired to relax at noon, and we had to get ready for a symphony concert in Columbus.

I told myself I’d relax on the ride down and nap at my brother-in-law’s while David ran his errands. But I didn’t set clear boundaries, and because of some conversation in the car, I was even more wired when we arrived in town.   I lay on their guest bed for over an hour, quiet and motionless, in a dark room, but only felt a slight shift, as if I had moved from 110 mph down to 95. Then, during the concert, since I did relax during a lovely Brahm’s piano concerto, I rose from my seat at intermission.  This turned out to be a mistake, for it kicked off the palpitations, dry mouth, and uncontrolled stress reaction.  We had to leave the concert early, and even though I fell asleep in the back set on the way home, I was not able to quiet my nervous system until 11 pm.

Everyone I know with ME/CFS has similar episodes of uncontrollable stress reactions.  We meditate.  Or we do yoga, or tai chi, or qigong.  We do what we can to reduce stimulation.  Still the body goes bonkers with amazing unpredictability.  I have longed to understand what is happening, because I think if I only understood the mechanism, I’d have a better idea of how to reverse it.  So I have come up with the following theory based upon my physical reaction to very small amounts of Cortef (1/4 of a 5 mg tablet) and to a combination of Folirinse and OH B12

I am pretty sure our strange stress reaction is mediated by norepinephrine, a neurotransmitter and adrenal stress hormone, not by the stress hormone cortisol.  Norepinephrine (NE) is the precursor to epinephrine, better known as adrenaline.  The difference between the two molecules is that adrenaline has a methyl group which has been added to the norepinephrine by the process of  methylation.

If, as Rich Van Konynenberg postulates, CFS/ME patients have a compromised methylation capacity, then in times of high stress we will find ourselves lacking the ability to methylate NE.  In times of low stress, we will methylate better, but we won’t be able to do all the functions of methylation, like repairing DNA or making creatine to keep muscle cells strong.  In other words, even in periods of low stress, our methylation capacity will be limited.

Adrenaline and NE work together in the fight or flight response to speed up the heart rate, send blood to the large muscles, and pull energy away from digestion, reproduction, and cognition – activities less essential for survival when stress is perceived.  A nucleus in the brain stem  called the  locus ceruleus is the origin of most of the norepinephrine pathways in the brain.

According to labs that do neurotransmitter testing, such as Neuroscience, Inc, there are both optimal levels and an optimal ratio of NE to adrenaline.  It is the ratio that is especially significant here.  When NE is much higher than adrenaline, there are signs of stress and fatigue.  As the ratio becomes more unbalanced, there is low energy and motivation, burnout, and poor concentration.  Does this sound familiar? 

Taking a combination of one drop of Folirinse (5 gm liquid folic acid) on a sublingual tablet of OH B12 (2 gm) seems to reduce norephinephine.  I, and a few friends who have been experimenting with this magic potion according to the patented protocol of Dr. Alan Vinitsky, MD, have found it to be moderately effective at symptomatic relief.  The reasons are twofold.  First, the two B vitamins are essential for methylation, and support the process of methylating NE into adrenaline.  Methylation is also needed to break down adrenaline down so that it can be excreted. Second, folic acid alone has been found to be effective at reducing norepinephrine in the brain.  This was found in a study on hot flashes in menopausal women.

Gynecol Endocrinol. 2010 Mar 16 “Folic acid supplementation may cure hot flushes in postmenopausal women: a prospective cohort study,”Gaweesh SS, Abdel-Gawad MM, Nagaty AM, Ewies AA., Department of Obstetrics and Gynaecology, Shatby Maternity University Hospital, University of Alexandria, Egypt. PMID: 20230331
Background. Neurotransmitter norepinephrine seems to be involved in the pathophysiology of hot flushes in postmenopausal women, and folic acid was found to interact with its receptors.  Objectives.  To examine the effect of  folic acid supplementation on the occurrence of hot flushes and the plasma level of 3-methoxy 4-hydroxy phenyl glycol (MHPG, the main metabolite of brain norepinephrine). Method. Forty-six postmenopausal women were allocated (by alternation) into 2 groups (n = 23 each); Group 1 received folic acid 5mg tablets daily for 4 weeks and group 2 received placebo tablets. Four women in group 2 discontinued the study. Results. The number of women who reported improvement in hot flushes was significantly higher in the treatment group. On comparing the mean plasma levels of MHPG before and after treatment, a significant lowering was found in the treatment group (mean % change =-24.1 +/- 17.9, p < 0.001) when compared with the placebo-control group (mean % change =-5.59 +/- 16.4, p =0.10). In the treatment group, there was a significant negative correlation between improvement in hot flushes and the plasma level of MHPG (r =-0.453, p =0.03). Conclusion. Folic acid supplementation may cause subjective improvement of hot flushes by lowering the increased central noradrenergic activity.

For further discussion of the Vinitsky protocol, take a look at this thread on the Phoenix  Rising forum: http://www.forums.aboutmecfs.org/showthread.php?4587-High-dose-folic-acid-with-OH-B12

I also found taking low dose cortisol helpful.  This surprised me because cortisol usually goes up during stress, and so it seemed counter intuitive to take more of a stress hormone to lower the stress response.  But it worked this night, and it has worked in the recent past and in October 2007 when I had a relapse characterized by a similar reaction.  These experiences lead me to propose that there are optimal ratios between cortisol and NE, or cortisol and adrenaline.  I am treading on shaky ground, with have no real evidence.  But it makes sense to me in light of how other hormones and minerals function in the body.

For example, researchers at Sabre Sciences, Inc. have determined optimal ratios of estradiol to progesterone, of progesterone to testosterone, of estrogen to testosterone, where subjects feel better and function better.  As ratios depart further from optimal, problems like endometriosis and erectile dysfunction arise; and when interventions bring ratios closer to optimal, such problems tend to be reversed.  Similar, Analytical Research Labs has determined optimal ratios for most nutritional minerals, such as calcium to magnesium, sodium to potassium, copper to zinc that correspond to optimal functioning of glucose control, thyroid and adrenal function, and mood.  It stands to reason that in something as crucial to survival as the stress response, optimal ratios of the principal stress molecules would mediate a healthy, temporary response as opposed to an unhealthy, lingering, and destructive response.  The anatomy of the adrenal glands, as well the close connection between the sympathetic nervous system response and those glands gives many opportunities for carefully modulated feedback between one hormone/ NT and another.

Anatomists used to identify three distinct zones in the adrenal glands, the outside (cortex) responsible for cortisol, the inside (medulla) for the catecholamines NE and adrenaline, the intermediate area for DHEA.  But I’ve read articles showing that anatomists have now identified some overlapping or infiltration of each hormone into the other’s zone.   I have also read that, contrary to popular believe, cortisol is not purely a catabolic, destruction hormone.  It actually protects the digestive system from damage when norepinephrine levels go up, protects against inflammation everywhere, and protects the immune system from autoimmune activity.  It is only when cortisol levels get too high that the immune response is suppressed.  If I weren’t so tired, I’d try to put links to these citations.  But I had a big day today, and so, if you can’t find them on an internet search, e-mail me and I’ll look around for them.

To be continued.....
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