"Adrenals may be shot" is probably a misnomer for many people, I agree.
But you have to understand while some people may have hypothalmic or pituitary signaling problems, the real functional regulator in the process is the immune system. Why? Because if the adrenal produces at normal capacity including cortisol, the the immune system is less able to do its job. This is where the sympathetic nervous system and norepinephrine enter the mix. Coupled with chronic stress which heightens norepinephrine fight or flight and caused the body to try to catch up with cortisol production you can have a problem. Chronic "acquired" adrenal fatigue (seconday, not primary) is always accompanied first by high cortisol levels before the drop / dysregulation.
So where I am going with this, if you enter a vicious cycle of norepinephrine which increases inflammatory signaling, which increases immune stimulation, which then shackles the adrenals more and more, you can get into real problems.
When I say my neuroendocrinologist in 2009, I had 180 testosterone (1/2 is made in the adrenals, btw), really, really low progesterone, pregnenlone, DHEA, my cortisol one week would test at a 30 on random morning test and next week at a 6, then at a 11, and then back to a 5, my aldosterone was low even though my sodium and potassium were low, and while my estradiol was low since the testosterone was wicked low, the ratio was off. 10+ other doctors only looked at my cortisol levels every say 3-4 months, said everything was fine before that and told me to just deal with my pain (they even suggested it was in my head). They never bothered to look at the OTHER hormones the adrenals makes.
My neuroendocrinologist, looked at the more extensive test and interverned with immediate MEDROL (forget hydrocortisone he said since I was basically operating on norepinephrine alone). Turns out we later found my C3A marker for autoimmune inflammation was 10x above the upper range even when I was only on 6 mg of Medrol. Along the way DHEA, testosterone, and thyroid meds (my reverse T3 was the highest value my doctor had ever seen, i.e. 800+ and that was on Medrol). But they did help some more. Took two years to find the actual autoimmune disease (SPS) and then of course my corticosteroids got bumped up so I could tame inflammation (I am on them for life hence the interest in MK-4
).
My point is not that someone has a dreaded autoimmune disease. Nor should they run to a doctor for corticosteroids who won't probably give them to them anyways even if they needed them (most endocrinologists are some of the poorest doctors I have ever met in terms of intellectual capacity but that is another discussion). The point is that a person should get their hormones checked across the board, to get a full clinical picture. A rampant sympathetic nervous system / norepinephrine imbalance is like a beast that has broken its chains. Cortisol is only one component. Neurotransmitters play a huge role in control as well. But hormones are also part of the picture.
Yes your adrenals will respond to an ACTH provocation, but if the immune system has its way your functionality is disrupted. Think of it this way, what does the immune system want you to do when it thinks you are sick? Stay in bed, don't move, sleep, rest, no stress. Then it kicks off inflammation and goes to work. What does cortisol do? The reverse. High cortisol in the morning gets you moving. Aberrant high cortisol at night = insomnia (though not the 'wired' stuff being discussed on here). The immune system is not smart enough for someone like me to realize it is a MAJOR part of the problem and that I couldn't lay in bed all day for the rest of my life. And btw the increase in norepinephrine means eventually you don't sleep, lose weight, can't rest, and drain your body.
I would never touch adrenal extracts, every alternative doctor who gave them to me I just refused or dumped in the garbage when I got home. I have read lots of horror stories about them. I am sad to hear about the POTS. Did you ever get your aldosterone checked along with renin / angiotensin? Florinef while powerful stuff is another thing that helped my Mom, brother, and myself with our dysautonmias.
---------------------------------------
For some people DHEA is a wonderful thing. Be careful though that it does not bleed into too much estradiol. I am lucky. I take one shot of testosterone cypionate a week and my testosterone is 1250 when the doctor said it would normally bring a person to maybe 600 (my CYP450s are slow to break it down). I take 150 mg of DHEA a day and sit at a 20 year old's level and yes I feel better on it. But ... I make very little estradiol from these hormones so I don't get the negative effects. Most people don't realize that it is not he testosterone that makes men freak out, be irritable, or aggressive ... in fact testosterone itself is calming (guess why old men are cranky) ... the problem is the estradiol. In men estradiol leads to a LOT of bad problems when it is too high. You need enough (from the adrenals usually) to have passion, drive, and mental focus, too little means stare at a wall and do nothing, too much means getting into meaningless bar fights or worse.
My doctor personally prefers to use pregnenolone and progesterone and if necessary estradiol for women and DHEA and testosterone for men. He may go with pregnenolone if needed but in my case did not since I ended up on corticosteroids anyways and there was no choice in the matter ultimately.
High zinc btw will really down regulate your NMDA receptors but upregulate other ones. Dr Yasko if I remember considers high zinc a double edged sword. I only go above 25 mg per day when I am fighting a virus or something. Otherwise I take 12.5-25 mg per day. Anything higher can muck me up in weird ways. Then again I get a lot in my diet now I wager.
--------------------------------------------------------------------
Not sure what to say about the gaba / glutamate imbalance. You get about 1.4 grams glycine btw per 200 mg Magnesium pill. So say 4-5 pills a day will be a lot of glycine. So maybe that mix is not right for you. Maybe you are better off with citrate, malate or taurate forms. Glycine is a double edged sword for some. I would stop taking it if I were you since you are reacting badly to it. Problem is citrate can wreck the GI track above a certain amount.
Ironically after out discussion on the other thread, I tried to drop free form glycine at night and slept better for one night, but then had insomnia two nights running, not fun ((. So dunno. Taurine is another option with your glutamate but you have CBS mutations, right? So dunno again what the impact would be.
What supplements caused you seizure like symptoms?
Caffeine will always improve mood and cognition and yes it is not just the glutamate. The question is can you get the glutamate to shut down and go to sleep that night. If you can then glutamate may not be your main problem. The soy sauce could me MSG or a sensitivity. I have high IgG to soy so among other things I avoid it. You would know by now I wager if MSG hits you or not. What makes MSG special is it is blood brain penetratable. Regular glutamate has turn into glutamine first which can be regulated in the brain to glutamate or gaba. The issue may not be total glutamate for you, it might be the glutamate - gaba balance. The depression sounds less like low glutamate and more like low serotonin or norepinphrine (from low dopamine processing). Low glutamate can make you feel tired, burnt out, and sluggish but depression is usually invoked with other neurotransmitters. That might fit with your A1298c mutation with BH4 since that ties into dopamine and serotonin. Maybe you need more GABA stimulation especially at night, and less reduction of glutamate?
Btw glycine is an inhibitory neurotransmitter and its prime area of functionality is not most of the brain where GABA rules, but in the spinal cord and maybe brain stem. I have never heard though of Mg-glycinate causing pain or tingling before ... usually the Mg is very efficient at blocking NMDA, since glycine concentrations are usually regulated at the co-agonist site by your neurons anyways. Unless really swamped by free form glycine I don't see how 1.4 grams a pill could exacerbate the NMDA activation. If so your memory and focus should have gone up. But they didn't. Brain fog for me is more the purview now of supplements like NAC that drains glutamate too strongly or high doses of alpha lipoic acid that probably hit my blood sugar. Or overly reducing mb12 and methylfolate. Ironically adb12 can give me brain fog also (dip due to BH4 processing of inflammation?)
------------------------------------------------------------------------------------------------------------------------------------------------
On that note the last several days I experimented with taking methylfolate alone without vitamin C at the same time as I had for years. I took usual mb12, some minor adb12, and some riboflavin and p5p as usual. I no longer take folinic acid or TMG (until I get 23 and me test results back I suppose). The point is I had a can of whoop a** opened up on me. I felt good emotionally, energy wise, and strength, better muscle action ... but .... my nervous system went bonkers, where I could hear a pin drop six miles away when I was trying to sleep (this was after the glycine reduction experiments last week so separate thing) and my ear ringing went nova. I reduced to 200 mcg of methylfolate today with 1250 mcg of methyl b12 and I am still way over stimulated, this is day 3 of this experiment (500 -> 300 -> 200 and I am not pleased).
Before I used to take 800 mcg of methylfolate with 2500-5000 mcg sublingual mb12 but I took the methyfolate with vitamin C which lowers absorption drastically apparently. So there I had a change in methylation trigger a firestorm in my nervous system. Gah! I suspect the real culprit might be the mb12 (since I have the a1298c +/- only) OR a trans-sulfuration overload and with my molybdenum supplements I started a month ago ---> increased sulfates ---> gut bacteria and voila H2S. Either that or my glutamate is way out of whack from THF reduction of histidine but that seems like a stretch based on past doses. The only way I got to sleep the last two nights was taking 300 mg of niacin to quench the methyl donors. I plan to retreat on the methylfolate with no vitamin C and rethink this operation.
Hilarious since I took 800 mcg folinic acid, 800 mcg folapro, 2500-5000 mcg mb12 sublingual, 50 mg P5p, 50 mg r5p sodium + 50 mg riboflavin, 600 mg TMG in two doses, etc. for 2 years, and while I had some signs of overmethylation that showed up when I added phosphoserine and SAMe (I am COMT +/- also btw), I had nothing like this. Had no real insomnia for two years.
Who knew vitamin C ingested at the same time made such a difference. Oy ve!
Btw if I drink coffee say 2-3 cups (last time was a decade ago) I don't sleep for 3 nights. Period. But then again I have the CYP1b1 polymorphism so who knows.