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Lessons from ME/CFS: Finding Meaning in the Suffering
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How to lower norepinephrine

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by ktred, Mar 26, 2013.

  1. dbkita

    dbkita Senior Member

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    Because my brother had one for another reason and there was a complication and he developed viral meningitis and almost died from it (at which point they had to do btw additional spinal taps).
  2. invisiblejungle

    invisiblejungle Senior Member

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    For those of you who are interested in the connection between norepinephrine and adrenal dysfunction:

    http://www.definitivemind.com/forums/showthread.php?t=560


    WoolPippi, heapsreal and adreno like this.
  3. adreno

    adreno 3% neanderthal

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    Dr. Mariano really knows his stuff about HPA axis dysfunction.
  4. adreno

    adreno 3% neanderthal

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    dbkita

    Since we agree that the immune system is the major controller of the ANS and HPA, why can't we simply use anti-inflammatories (AIs) to treat this? Getting the inflammation under control should theoretically calm down the ANS and allow the HPA to recover. Is is because AIs are not potent enough? Do not target the right cytokines? Do not cross the BBB? Do you have any ideas about this? Since the immune system is central to our problems, it would make the most sense to target the treatment there. And yes I know steroids can do the job, but I don't see why AIs can't work?
  5. dbkita

    dbkita Senior Member

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    For InvisibleJungle:

    The one thing I would add is that for many chronic stress alone is not the culprit. That can lead to adrenal fatigue but is recoverable. But for some it is the immune system. Think about. What hormone does more to impede the work of the immune system? Answer: cortisol, among of course other hormones like DHEA, the sex hormones, etc. But really ... cortisol.

    For example did you know which system is necessary to grow muscle fibers? The immune system. Why do you think that athletes doing weight training take high levels of certain electrolytes and other substances? Answer to prevent the cortisol stress response from exercise. Why was the cortisol secreted with exercise? To dampen inflammation. The athlete intentionally wants to lower reactive cortisol to give more time for muscle fibers to be laid down post exertion. If they supplement nothing the cortisol actual makes them temporarily susceptible to viruses and such. You can read all about it on the muscle building forums. Someone like me on high glucocorticoids to control an autoimmune disease will find it virtually impossible to go into an anabolic state.

    Now back on track ...

    The immune system if over-active due to infection or autoimmune disease wants you in a low metabolic low energy fatigued state laying in bed so it can do it work. Fine for an acute illness. But not for a chronic problem that last years. The controls for NE are anti-inflammatory generally or positive neurotransmitters like dopamine and serotonin, and of course GABA. NE runs along with inflammation. Why? NE modulo direct fear / stress response is intertwined with immune system activation. So imagine the immune system is throttling the HPA axis to get cortisol down so it can "do its job". But as cortisol drops and the chains come chronically off the NE "beast" then the sympathetic nervous system is activated. Inflammation is increased. There is now a vicious cycle the loser being the adrenals. Eventually ALL hormones from the HPA axis become dysregulated and vanish.

    Such was my story when I was at the brink four years ago. The endocrinologist who saved my life did so by putting me on glucocorticoids (note I am NOT advocating them for most people because standard adrenal fatigue is solvable without them in principle). It took two more years to find the cause and then direct further treatment to achieve improved results. I still needed hormone replacement in many other parts of the HPA (and HPT) axis, i.e. testosterone, DHEA, etc. The final big pieces were florinef and cytomel (since otherwise my body converted t4 to reverse T3).

    There is a big difference between standard secondary adrenal fatigue and a full out adrenal collapse brought on by immune system +NE chronic hyperactivation. So while stress is often discussed as a source factor, stress from inflammation can be the main player. i.e. changing your sleep, diet and lifestyle habits have little consequence if you have a fire in your kitchen due to say an autoimmune disease or a Lyme's infection or a mercury overload.

    I am probably not explaining this very well, but I have learned the hard way that some of the conventional wisdom about adrenal fatigue (a la Wilson et al) misses (for some people) the really big picture. The missing piece I learned after working with my neuroendocrinologist and in subsequent research is the immune system. Many of those who chronically suffer, need to at least differentially diagnose the possibility of immune dysregulation before they assume standard secondary adrenal fatigue. I am very lucky I stumbled after years into a neuroendocrinologist that understood this.
    ttt and voner like this.
  6. dbkita

    dbkita Senior Member

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    HAHAHA.

    Guess who is my neuroendocrinologist. Dr Romeo Mariano in Monterey, CA. Sigh such a small world. Took me 10 years to find him. Off the record, he has stated I am not the worst case but the most complicated case he has ever seen. Such is life. He has done wonders for me.

    Btw I don't think my earlier post is in conflict with what InvisibleJungle pasted, I simply was trying to stress the nasty variant that can come with immune system overload where the body itself provides the "stress".
  7. adreno

    adreno 3% neanderthal

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    LOL. I've known about him for a few years, but didn't know this was your doctor. Yeah, it's a small world. Or there are just very few good doctors around.
    Victronix likes this.
  8. dbkita

    dbkita Senior Member

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    You should use AIs to help. In a sense that is what I have been 'preaching'. That is a better regimen imo than trying to directly block NE unless the person is in dire straits and needs immediate intervention.

    I would not be in favor of the NSAIDs those will hit COX and really whack your stomach lining. Believe me when I experimented with 2-3 baby aspirin a day on my own on top of my other stuff, it did help. But then it started to carve my gut since aspirin somehow prevents the stomach from healing the damage induced by prednisone. Not good. Quercetin can work but it is a COMT inhibitor and while at first a cyp3a4 inhibitor it later become an inducer which means faster break down of my glucocorticoids (uggh, been there). Things that block. Curcumin is an option. It simply rips my colon apart. No idea why. There are lots of anti-inflammatories. Prostaglandins series 1 and 3 for example. Ironically sea salt is anti-inflammatory. Vitamin D3 is inflammatory in the gut, but its downstream product 25OH is AI and very important. We could take some time I suppose to formulate a list.

    Glucocorticoids are not to be used unless working with a doctor to supervise. My brother uses physiological levels of medrol and does great. He is in the best physical shape of his life. But HRT of any type is very tricky and finding doctors who can and will administer it correctly even harder. My mother recovered in her late 60s after many years of issues and electrolyte problems with right support.

    Another piece to the puzzle is the gut. Any gut dysbiosis can really mess up inflammation. I would not be surprised that a large section of people on these forums would see substantial gain just with healing relevant gut dysbioses. So much of your immune system is in your gut.

    Also better Krebs cycle activity means less NE, means less inflammatory signaling and so on. Low energy, bad methylation, etc. are terrible stresses on the body. Just like anemia, infections, toxic overload, etc.

    The question is how much AI control do you need, does it need to be 24 hour, how does it affect the HPA axis and steroidgenesis, can you bootstrap yourself later on, etc? These are all important questions.
    voner likes this.
  9. dbkita

    dbkita Senior Member

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    My brother is the one who went to see him first. Took me five more years to make it to him only because I was stubborn. Very bad decision on my part. What was special in his case is when I was on the brink (don't want to relive those memories) he was suitably aggressive in taking action. Still it took two more years to get the right diagnosis. Then things really started to change. So yeah guess who I was referring to about wanting me on Florinef well before I started taking it? Not only due to my labs and symptoms but because it hugely helped my brother with his dysautonomia. Shared genetics :)
  10. invisiblejungle

    invisiblejungle Senior Member

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    Oh man... When I first read some of your posts, I actually had a feeling that you were seeing him because you use a lot of the same language that he uses. I stayed in Carmel when I flew out there. The beaches here in Chicago simply don't compare...

    Mariano was the first one to describe how excessive norepinephrine could be causing my symptoms. I tried various meds, including guanfacine and escitalopram, but nothing had the desired effect. The one thing that he wanted me to try that I didn't want to at the time was T4. My free T3 and free T4 were good, but my total T4 was on the low end of the range. He thought that the sub-optimal total T4 could be the main culprit, but I just wasn't sold because my free's were in a good place. Yeah, I probably should've just tried it. I had nothing to lose...

    I actually ordered some Synthroid a couple weeks ago, so we'll see if he was right. If it turns out that I spent all that time spinning my wheels... Oh well, at least I've learned a lot. :cool:
  11. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Does dr mariano also directly treat cfs/me with infection/immune type treatments like antivirals and immune mods or just sticks to hormones and neurotransmitter balancing??
  12. dbkita

    dbkita Senior Member

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    Yeah guanfacine and clonidine did not work out for me for several reasons. But in hindsight the reason was obvious. My autoimmune disease was not going to get better by simply treating with NE antagonists. For some of us, there is no substitute for corticoid control.
  13. Lotus97

    Lotus97 Senior Member

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    This might seem like a dumb question, but I've read that taking SAMe increases norepinephrine. If we produce SAMe through methylation does that have the same effect?
  14. adreno

    adreno 3% neanderthal

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    Methylation in general will do this. But it will also increase other neurotransmitters, such as 5-HT. Remember it's all about balance, there are no good or bad NTs. Both under- and overmethylation can be a problem in this regard.
    Lotus97 likes this.
  15. Emootje

    Emootje Senior Member

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    Superoxide scavengers in the brainstem may also lower norepinephrine.
    O2 reacts with and inactivates NO and thereby modulates its bioavailability.
    Low NO bioavailability suppresses NO-mediated GABAergic inhibition in the RVLM (pressor center).
    O2−↑ > NO↓ > GABA↓> SNS↑

    1-s2.0-S0006899308026279-gr8.jpg

    https://www.jstage.jst.go.jp/article/circj/76/12/76_CJ-12-0399/_pdf
    Lotus97 likes this.
  16. Lotus97

    Lotus97 Senior Member

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    I definitely get a mood boost from taking B12 sometimes, but it also makes me very wired and/or overstimulated sometimes. I didn't realize methylation itself affected neurotransmitters though.
  17. dbkita

    dbkita Senior Member

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    Methylation is both the gateway to the production and the catabolism of many neurotransmitters. Certainly serotonin and the catecholamines. Remember though it must seem like I rail against NE, you need some NE to function and feel good, else you would just be depressed.

    The problem is when it gets out of balance and hyperstimulates the SNS. You don't want sympathetic nervous overload. That is a beast of an issue and very destructive if chronic. NE also factors into the immune system and inflammation. Heck I just saw my neuroendocrinologist today and he was reminding me that my pain increase when I increase certain supplements if from increased inflammation tied into higher NE. Sigh.
  18. Asklipia

    Asklipia Senior Member

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    Has anyone used TRH to regulate the immune system?
  19. adreno

    adreno 3% neanderthal

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    How would we do that?
  20. invisiblejungle

    invisiblejungle Senior Member

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