@ Adreno:
I have a 4-year old organic acid test, back from when this crap started. It says I have very high pyruvate levels. I have had problems with kidney stones and high creatinine, also."
Understood about the pyruate you are all set there then. Just make sure you get enough biotin, B1, carnitine, etc. to make use of it well.
I am more suggesting, than claiming anything. I am very confused about all this. I suspect I have cyclothymia, although I have never been diagnosed. I have always had mood cycling, and many substances can make me hypomanic. This includes too much TMG, alcohol, and many others. I think there is a problem with ion channels involved in bipolar disorders, this probably means my glutamate is unstable, perhaps fluctuating. This is just a guess though. To be fair, I've taken NAC so long I can't remember how I felt without it. Maybe it's time to give it a break.
Again I re-iterate that one of the major effects of NAC if it calms you down may be that it clobbers glutamate pretty efficiently. Clearly over sulfuration is not a big problem for you or you would get nasty effects (NAC makes me reflux pretty hard for example). That is a NMDA link for sure.
I have been thinking along these lines, too. I am not sure I understand how you suggest I achieve this?
My suggestion with glutamine synthetase is to get the bad boy working better. That would mean biotin, Mg and (maybe) Mn. At least make sure you are not Mn deplete. If you add any Mn start with baby dose like 2.5 mg or so.
Potassium helps the tachycardia. Sometimes sodium is needed also. But you are right, NE is a problem. I often have cold limbs, anxiety, tachycardia. When I take a bath my skin wrinkles very easily. ALCAR also reduce my tachycardia, so it leads me back to thinking about neuropathic autonomic (nicotinic) ganglia.
Norepinephrine can be a problem for a whole host of reasons, HPA, adrenals, low cortisol and the most likely candidate which is immune system dysregulation (including gut dysbiosis).
If ALCAR is helping your tachycardia it might be because it helps you get more effective use of your Krebs cycle and thus your body turns less to back up energy sources of which norepinephrine signaling is meant to be the last resort (of course that is often not the case in today's modern society).
If you think instead it is beneficial at a CNS level you could test this by taking regular L-carnitine or L-carnitine fumarate (don't take the tartrate that stuff is BAD news since it kills the malate shuffle). The other two won't cross the BBB while ALCAR does. That way you could differentiate your hypothesis.
I just looked at a 3 year old blood test. The doctor told me my aldosterone was normal, but I can see that it is in fact low. There are 2 results, with 8 mins between. Not sure why this is. The first result is 0.18 nmol/L, second 0.23. The reference is 0.19–0.83 nmol/L. Looks like I should have another test. I believe angiotensin is low. Angiotensin II antagonists and ACE inhibitors makes me worse. Coffee helps (though I get some SNS overstimulation), probably by stimulating angiotensin. Seems like a double edged sword. I need to "stim" to get the angiotensin up, but at the same time overload other systems. Please stop me if I'm babbling, lol.
I must say that I'm not willing to go on a steroid again at this point. Like I said, at physiological doses or HC, the skin was atrophying like crazy. I have also seen steroids kill my mother. She had Crohns and was on steroids for 15-20 years. She died at 60, about the size of a Golden Retriever. Just getting down on her knees was enough to cause a hip fracture. Not to talk about bleeding skin, infections that wouldn't heal aso. Can't I just take more pregnenolone or something, lol? There must be a reason why the aldosterone is low. It makes more sense to fix the cause of it, rather than taking steroids the rest of my life. I know this is easier said than done, lol.
Beyond easier said than done. Hormones are very complicated. Unless you are working with a good physician I have no clue to predict what more pregnenolone will do for you. It is the mother hormone one step removed from cholesterol. It could do just about anything in the steroid space.
If HC was making your skin atrophy then I would suspect there is another player involved. Either you don't metabolize it well or the half-life is too long or you have defective 11 beta HSD enzymes or you have an immune function antagonist (i.e. infection or other condition). Not trying to spook you but 24-30 mg HC should not do that.
Considering what your mom went through you may have a genetic factor no one understands and yeah I would stay the heck away from glucocorticoids.
But ... don't necessarily lump aldosterone in that mix. Hear me out.
Most doctors don't know how to assess aldosterone level correctly. My Mom had several readings of 5-7 (scale 0-30) but she was borderline hyponatremic and really low potassium, but the doctors said normal. I finally convinced her, when she had bad arrhythmias, was blacking out, tachycardia and extreme emotional disturbances with terrible norepinephrine surges, to go to the hospital and ask for Na IVs and extended KCL tablets, she completely came back. She would go home and the cycle repeated. I told her to bring up Florinef with the doctors since if her salt is low and her aldosterone is low something is clearly screwed up and they of course refused. Finally I got her, after the third cycle,. to go to another doctor and he gave her Florinef in a small escalating dose + some extended release KCL and her heart is solid as a rock now. Her NE surges dropped, she sleep 7-8 hours of night on using only a bit of tryptophan and her mood is generally excellent. She has osteoporosis and the doctor is not concerned with the florinef impact since she takes 0.1 mg. She jokes that doctors would have to pry Florinef out her cold dead hands before she gave it up.
I do take sea salt. Quite a lot. 1/2 teaspoon per liter, plus I salt my food heavily. I think I'd be dead without the salt, I need it that bad, lol.
What are your electrolytes like? If you take 1/2 tspn sea salt per liter and assuming 400-500 mg per 1/4 tspn and say 2-3 liters of water a day, that is a LOT of salt. That will certainly amp your CV system and can shift your sleep quality. Your aldosterone could be low since your salt intake is so high. I would be interested in what your recent Comp Metabolic panel results are for Na, K, Cl, etc. That being said if you think the salt is key that is a clear sign of dysautonomia.
I understand your aversion to steroids but Florinef and HC have completely different pharmacological behavior. Florinef is a methylated version of HC that has almost no glucorticoid effects while enhanced mineralcorticoid effects. I don't have time in a post like this to go into all the biology of the different relevant receptors and how they relate to 11 beta HSD1 and the kidney and electrolytes, etc. It can could fill an entire thread practically.
But I will stress that at usual doses of 0.1 mg, florinef has about as much chance of making osteoporosis as taking aspirin (I jest some but only slightly). That is no way to belittle the suffering your mother endured and I am very sorry to hear that. I will also say that if you research dysautonomia (there is a national society for it), florinef is almost always step #1 in treatment followed by the appropriate amount of salt.
In my own case salt saved my life along with Medrol in 2009. My neuroendocrinologist wanted me on Florinef in Spring 2010 and I was reluctant because I did not want another steroid, even though it helped my younger brother greatly. When my Mom needed it in Winter 2012, I caved in an started taking it. I can not describe how much it improved things. It is hard to relate to to others who don't live in my body.
Suddenly I could take sea salt once in the morning only and get by the rest of the day, I went from 2 tspns per day of salt to eventually 1/2 - 3/4 of sea salt after titrating up the Florinef. My potassium suddenly revived (there is a complicated misunderstood relationship there) from near hypokalemic to 4.0+ in the day without altering diet or supplementation and I stopped urinating 12 times or more a day. My BP came down and my heart rate while not awesome came down out of the high 90s and low 100s to say the mid 80s. Also I had MUCH more muscle strength (which gets me into trouble when I think I can do something in say the bedroom (*wink*) or around the house that I should not be attempting these days anyways.
Excess ACh will cause excitotoxicity through NMDA. This is well known. Yes, I do have pain. I get pain from typing, for example. I've had very serious RSI, where my hands turned purple, freezing cold, and I couldn't move my fingers, plus tremendous pain. I'm better now, but yeah I have some pain. I just suck it up, I guess. It's not screaming pain, though.
Maybe I am being dumb here but I don't know about that connection. I know that NMDA glutamate activity has control actions on ACh release in many parts of the brain but I have never heard of the reverse. Anyway I can't seem to find anything and you seem to have amassed a wonderful treasure trove of articles. Can you link something regarding ACh and NMDA? I am always learning new things
That being said if you are high on ACh, due to lets say reduced ACHe presumably (right?) how much choline and B5 do you take? Those might be double edged swords for you ...
Ok so pain is a clear issue (I have too many bad memories of the screaming variety). So yeah NMDA is certainly a likely culprit especially since a lot of your pain seems nerve related.
How much elemental magnesium do you get a day? That stuff is maybe really key for you since it is your main allosteric switch to down regulate NMDA without using NAC to effectively chelate it. I bet you are ramping GAD activity via your high p5p (I am jealous with my SPS). You might want to check if you are low in lithium, for some that has a huge effect on the glutamate - gaba balance and I think Dr Yasko stated that people with A1298c mutations are at risk for low iodine and lithium. I have not checked my lithium yet but my iodine was dead for until I started Iodoral a year or so ago.
However, a bad vicious norepinephrine / inflammatory cycle can do that too since eventually the muscles' request for laying down new fibers in a catabolic state (been there) is ironically vetoed by a hyper immune system and the signals eventually get translated as pain ... through the NMDA receptors. So see how you can end up at the same place for different reasons. It can be hard to disentangle them.
I only bring this up since I would guess 50% or more of the people on these boards essentially ignore the immune system component when it might be their 800 lb gorilla in the room. And when I mean immune system I mean not simply glutathione, I mean norepinephrine signaling, gut problems, autoimmune, infections, etc. Methylation alone won't make much of dent in the gorilla if those are a problem. It is a pet beef of mine how people ignore the immune system which beyond the workings of the brain is one of the most complicated and vulnerable systems in our body for dysregulation.
The thing is, it's very easy for me to gain weight. Not muscle though, this is hard. But gaining fat is very easy for me.
If you gain weight then you are not catabolic ... .which is great! The process for gaining fat can be so complicated and multi-factorial I won't touch that conversation with a 10 foot pole. People will foist all sorts of ideas ... I toss my hands up on that one unless someone is say clearly hypothyroid or something.
There are many reasons why someone cannot gain muscle. I am in the midst of that in spades right now and I don't have any answer yet. And my testosterone / DHEA on HRT is better than when I was teenager. My catabolism is probably a combination of gut dysbiosis and my lovely lottery ticket autoimmune disease. Meh. 4000 calories it is!
I use this one:
I will check that out, I just wish I did not only get like 50 mg per pill. Sigh. That means for me it can be at best an adjunct and not a replacement. How much do you take of the Mg-threonate do you take per day?
I will definitely check out the zinc carnosine
Ciao.