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B12 working but can't sleep.....

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by joe davison, Dec 19, 2012.

  1. Dreambirdie

    Dreambirdie work in progress

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    dbkita

    I definitely feel more over stimulated today than I did three days ago, and my sleep was worse again. I took no TMG yesterday, so it's probably the lingering after-effects from the 2 days prior, during which I took 650 mg each day.

    I am currently taking only 500 mcg of methyl B, very irregularly... sometimes only once/week, sometimes 3X/week. I do okay with the methylB as long as I do not take it every day. I do not take any form of folic acid, because I have not figured out yet which is the least problematic for me.

    I tried Rich's simplified methylation protocol back in 2010, (with the Yasko hydorxyB and the methylmate), but after about 6 weeks I began to feel so much worse, that I couldn't handle any more of it. The severe agitated depression was not something I was willing to endure and push through. I have been there and done that far too many times, and it always ends up being destructive to my overall health. I do not have energy for intense detox that is triggered in that process.

    I tend to have a lot of excito-toxicity symptoms due to a heavy metal burden that has given me long term problems with agitation and insomnia. When I do get some decent sleep, I feel like a completely different person. I can function quite well, compared to my usual wired/tired self.

    Awaiting 23&ME to see what's up with all the snps.
  2. kelly138

    kelly138

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    TMG is available easily in bulk form. I bought some Jarrow brand from iherb. A slightly rounded 1/32 teaspoon (0.15 ml scoop) weighed in for me at 100 mg. I started there. There is also the advantage of no fillers.
  3. dbkita

    dbkita Senior Member

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    Dreambirdie:

    I would indeed wait for the SNP results. You may be dealing with something else entirely than simply methylation cycle defects. It is hard to imagine you are over-methylating taking 500 mcg of methyl B12 three times a week and with no methylfolate. Even a severe CBS / BHMT combo of defects seems unlikely to explain that. I also do not know why Rich Vank's protocol would cause depression except if you were using phosphoserine and your cortisol was dropping. Again though I would wait for the SNP results before tinkering.

    I can't speak much about heavy metal toxicity since that was falsely used as an excuse for my own health problems and had nothing to do with it. I also do not trust in lab tests that use a DMPS or other chelating agent to test for heavy metal burden.So sorry I can't be of help there. Heavy metal tox is a real issue but I also think some on these boards and many in the alternative health community really over-emphasize it. But that is just me with my own experiences talking so take it with a grain of salt. For example while having amalgams will increase mercury load, people will only focus on that while ignoring their gut dysfunctions which can really wreak havoc imo.

    Btw have you had your hormones checked? What are you inflammation levels like? Are your symptoms more about pain, or CNS over stimulation, stress issues, or fatigue / depression, etc?
  4. Dreambirdie

    Dreambirdie work in progress

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    dbkita I know people here who have taken just 1/64th of a dose of the methylation supps, in order to not over-methylate. That's how sensitive some people are.

    Every heavy metal test I have had has been positive for various metals, some at high levels. I do think they are a problem for me.

    I haven't had my hormones checked lately, but plan to some time in the next month or so. Never checked inflammation, but know it's a problem, so I don't want to waste the money.

    My symptoms are mostly about being too wired to sleep and therefore never feeling rested, and I also get rather severe PEM if I overdo. And I have the MCS, which keeps me mostly at home.
  5. dbkita

    dbkita Senior Member

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    I understand the anecdotes about sensitivity to mb12 but 1/64th of a sublingual 5000 is < 100 mcg. Of which at most 20-25% would be absorbed. Something isn't right there. I fear too often things we do not fully understand are chalked up to Herxheimer reactions, start up effects and detox. I am not saying those things don't exist, I am just saying they get called into play far too often when something else is actually going on. At least for my part that is what I was told erroneously for about a decade and I just don't like to see people suffer having suffered a lot myself.

    If the heavy metals are a problem for you then they need to be removed as much as possible. They are ground zero for people with significantly high levels. Sadly the majority of people with high test results on a Doctor's Data tox panel provoked by DMPS are not necessarily even having the right ones identified as the troublemakers. My background in bioinformatics and biopharmaceuticals has given me some insight into understanding how some of those tests work or don't work. My only suggestion there is to be cautious and work with a skilled medical practitioner you can trust.

    You seem to suffer from CNS overstimulation. There are a couple of possibilities that may only be linked to methylation peripherally. Generally inflammation causes fatigue. However, if a person's adrenals are shot, cortisol and other critical hormones depleted, the immune system over-inflammtion can drive the body into a meta-stable state where you are both wired and exhausted at the same time by upsetting the balance of norepinephrine in the body.

    PEM can also result from disruption of Krebs cycle and / or thyroid deficiency. B12 is important but not as high a priority by itself to the Krebs cycle as some on these forums focus on. If you reach a point that your body is so energy deprived, your body resorts to surviving on norepinephrine alone. However, if a person reaches that point beyond being wired and tired, they will experience often significant (and I stress significant pain). I experienced a lot of pain for more than a decade (still do from time to time) but when things got really bad my pain was unspeakable for about 2 years and opiate drugs did zilch (it was NMDA regulated pain as it turns out). That being said I was lucky enough to find one of the top neuroendocrinologists on the West Coast who basically saved my life when other doctors sat on their hands. It still took another two years to get an accurate diagnosis of Stiff Person Syndrome.

    Which brings me to the last hypothesis. Wired can often mean a glutamate - GABA imbalance. Glutamate if overly high can really affect the basic neurology of a person, over-exciting their neurons and in particular their NMDA glutamate receptors. Over mehtylation can in principle amplify this by increasing levels of both alpha-keto-glutarate and glutamate itself by over-processing of histidine. But the latter would have to involve methyfolate at some level. But glutamate can be out of whack for a variety of reasons. Their is another thread where Adreno and I discuss glutamate effects on the CNS if you are interested: http://forums.phoenixrising.me/inde...e-very-large-gorilla-in-the-room.20229/page-4

    Some inflammatory markers can be ordered by a doctor for cheap provided you have insurance. Your hormone levels will also go hand in hand with inflammation. If inflammation is present one needs to really ask why? Is it infection, is it autoimmune disorder, severe allergies, gut dysbiosis, what? There has to be an answer. Methylation without understanding the cause and amount of inflammation can cause its own issues (like increased inflammation if not balanced right).

    Anyways hopefully you will learn more when you get the 23andme results. But you may also need other tests to understand your current physical state better. We only understand genetics at a somewhat still innocent / naive level sadly. Fortunately your test results will not change, but human knowledge will improve over time. So it certainly has its value...

    As far as MCS goes, my Mom was crippled by that for years. She dug out of it by a) removing sulfites, b) hormone replacement as her adrenals were shot, c) balancing her electrolytes (long story), d) paleolithic-type organic diet, e) a lot of anti-oxidant support, f) treating sulfite processing with molybdenum and g) some minor methylation support. She is in a completely different place than she was 8-10 years ago. Of course each person is an individual case study but my intent was to provide some hope.

    Good luck and God bless you in your quest to find answers.
    brenda, Dreambirdie and adreno like this.
  6. adreno

    adreno 3% neanderthal

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    dbkita, I am less than convinced about the idea of "adrenals being shot". I believe truly malfunctioning adrenal glands are rare. I do believe there is often in our case a hypothalamic problem though - or at least some sort of HPAA hypofunction. I think it is a signaling problem, rather than a functional one.

    Personally I have tested low on cortisol on several saliva tests. ACTH provocation test came out normal though, which would indicate that (my) glands are functioning, but are not receiving the signals necessary to produce optimum amounts of adrenal hormones.

    I didn't do well with supplemental cortisol, which caused a lot of side effects in me. Adrenal extracts were one of the worst things I ever did. I developed quite severe POTS by using them for about 8 weeks, and haven't ever gotten over it (though I have improved). OTOH, pregnenolone (50mg) and DHEA (10mg) have been some of the most effective supplements to help my condition. I might even increase the DHEA dose further, because I just feel so darn good on it. DHEA can really calm down an overactive immune system.

    With regards to glut/gaba balance, I find this a hard nut to crack. I tried increasing mag glycinate per our discussion in another thread, but I must say I feel horrid on the glycine. It helps me sleep, but (and I am only guessing here) it inhibits signalling in my spinal cord, causing fatigue, weakness and problems with standing, besides more pain and tingling. I have switched to citrate and do better on that, but still. It seems I am able to be anxious and wired (overstimulated) and depressed and with brain fog (understimulated) at the same time. I fear there is no way out of this (as of now), since I suspect a regional problem. I'm hypothesizing that I might need the extra glutamate in some regions (spinal cord, brain stem, frontal cortex) but have too high levels in other regions (amygdala, thalamus, striatum), thereby causing gluatamate hypo- and hyperfunction simultaneously. Or maybe my NMDA receptors are shot. My problems did start with a seizure-like excitotoxic reaction to some supplements I took. After that everything was f*ck'd.

    Yesterday a teaspoon of soy sauce on my lunch seemed to cause extreme anxiety (at least I could find no other explanation), but a cup of coffee (which is a glutamate reuptake inhibitor) doesn't have this negative effect on me, and in fact improves cognition and mood. Does this make any sense? Of course, coffee also increases dopamine and cortisol levels at the same time, maybe this is a factor.
  7. dbkita

    dbkita Senior Member

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    "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.
    helen1 and freshveggies like this.
  8. adreno

    adreno 3% neanderthal

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    dbkita

    I took two supplements about 4 years ago that totally messed me up. One was 5-HTP, 100mg, which I took for about 1 week. The other was "Memory Support", a mix of mainly cholinergic compounds. I think I took it for 2 days.

    I cannot entirely remember what happened because I went into a confused, near psychotic, cognitive-impaired, panic-like state. It's hard to explain, but suffice to say I was on my bed for 2 days, wondering whether I would survive or not. My muscles were fasciculating, sweating, couldn't sleep or eat, hard to breathe, couldn't think, and with the most violent images and thoughts flashing through my head (usually of me splattered all over the road; I drove a motorcycle at the time). Also tingling and paresthesia all over. I should have gone to the ER! I didn't. I am the kind of guy who thinks I can take of everything by myself (wrong).

    After about 2 days it started to calm down, but I was still severely cognitively impaired, anxious, depressed, had paresthesias and weakness, fasciculations and many other symptoms. Suddenly I couldn't tolerate coffee or alcohol at all, without feeling deathly sick. I was stumped. I had no idea why this had happened. The doctors I saw were clueless as to what was going on.

    It wasn't until this year that I finally think I have figured out what happened. This is just my own hypothesis though. After doing a 23andme test I found out I have a mutation on the PON1 enzyme which breaks down organophosphates. When I took the supplements I had just come back from about 9 months of travel in southeast asia. I had noticed some weird symptoms like tingling, headache, nausea and the like a few times over there, but never found any explanation for them. I now know that foods are heavily sprayed with pesticides, sometimes amounting to 100x the allowed limit. Bingo.

    I believe the combination of the high pesticide exposure, my PON1 mutation and the cholinergic supplements caused acetylcholine poisoning. All the symptoms seem to fit. Also I read that alcohol and Omega-3 acids reduce PON activity even further, and I was of course drinking alcohol and eating fish on a near constant basis. TMG was the first supplement to help me improve, and I later learned that TMG induce PON1.

    From an article I just found, basically a laundry list of my symptoms:

    Does this seem a likely hypothesis to you?
    brenda and Skyline like this.
  9. dbkita

    dbkita Senior Member

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    I am sorry to hear about that incident.

    I find the idea that 5HTP could be to in way to blame, really, really unlikely. It sounded like you explosively reacted to something in the Memory support pill.

    Organophosphate poisoning is not impossible and over a million people worldwide suffer from it. Is your PON1 mutation heterozygote or homozygote? Are there more than one SNP tested?

    Not to sound heartless but the fasciculating, parathesia, insomnia, anxierty, and depression while awful for sure could come from multiple sources. But what I find most telling is the mental collapse in terms of cognitive impairment and the psychotic 'episodes' / ideations. Also the sweating and hard to breathe are very telling (though the sweating could be norepinephrine overload; been there). I assume you never had problems breathing before right? Was it air hunger or actual problems breathing mechanically? Did you hyperventilate?

    Without knowing for more, it sounds like you were very likely poisoned (I hate to use that word). The psychotic responses are very hard to explain any other way. Again the 5htp is a baby dose that you took for a week. I have been on 200-300 mg for 2 years and regardless of what people will claim there is little to no tolerance effects for most people (a helluva lot easier to alter than say benzodiazepenes if you ask me).

    But that Memory support pill has a number of ingredients, particularly the DMAE bitartrate, bacopa, vincopetine, etc.
    The actual dose of phosphatidylserine is low. The glutamine and N-acetyl-carnitine are tiny. Even the dose of gingko is really tiny. All the doses are small but the first three I listed are a big trickier to just toss away.l

    Here are a simple list of symptoms of acetylcholine poisoning that organophophate poisoning would induce by shutting down acetylcholinesterase:

    "Depending on the duration of exposure, route of ingestion and other factors, organophosphates can cause varying degrees of acetylcholine poisoning. Mild symptoms like runny nose, sweating and nausea might be misidentified as other common ailments, while severe poisoning can lead to death if not promptly treated. Neuroscience for Kids lists muscle twitching, reduced vision, drooling, paralysis and respiratory failure as possible symptoms of acetylcholine poisoning."
    Here is from Wikipedia:
    "The health effects associated with organophosphate poisoning are a result of excess acetylcholine (ACh) present at different nerves and receptors in the body because acetyocholinesterase is blocked. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are tachycardia, hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur"
    I think other effects include seizures and comas if bad enough.
    As you can see it can hit MANY body systems.
    Note the bacopa is an acetylcholinesterase inhibitor. DMAE is not able to normally enter the brain, but can me methylated to ACh and has been implicated (possibly) as another acetylcholine esterase inhibitor. Certainly the manufacturers of the supplement think it would be since the deigned to put it in the pill for memory support (i.e. they are not interested in increasing ACh in the body). Vincopetine seems less terrifying to me personally. However, it is essentially a drug so who knows.
    Anyways the organophosphate poisoning could have set you up for an ACh buildup over time by compromising AChE and then the Memory Support pills did you in ...
    I am very sorry this happened to you.
    What sort of effects have you had as a result since then that have been ongoing?
  10. adreno

    adreno 3% neanderthal

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    dbkita

    http://www.academypublish.org/papers/pdf/437.pdf
    L55M (rs854560) is not on chip, but my Q192R (rs662) is +/+. A 40-fold variation in detoxing capability is quite a lot, especially when paired with a (perhaps) 100-fold increase in pesticide exposure. Sucks.

    I can't remember all the symptoms I had, it was a while ago and my cognition weren't working, plus I was in panic. I think I had some chest pressure, but I probably weren't in any mortal danger of stopping breathing. Still, it might not only have been ACh, maybe other neurotransmitters were involved and I just overloaded.

    I must admit I did not know what I was messing with at the time. I was depressed and had seen horror stories on SSRIs, so after reading about 5-HTP decided to try that. Also I was feeling slightly cognitive impaired, and thought a round of nootropics might do me some good. Boy, was I wrong. Still I was stumped. Go to Longecity and you will find people stuffing themselves with nootropics, at much higher doses. Some experience some discomfort, but I have never read an account of someone experiencing what I did.

    At first I thought it was the 5-HTP. It has been linked with an impurity, Peak X, also found in tryptophan, which has apparently caused a syndrome called Eosinophilia Myalgia Syndrome in a few people. Eosinophilia levels were normal though, so that was ruled out.

    I also noticed I had an outbreak (reactivation) of a shingles rash on my abdomen. I initially had the infection as a kid. I started reading up on serotonin and the HPA axis, and how high cortisol levels can reactive a virus. So that was my next theory. I also have herpes, so maybe this was reactivated as well.

    I had a saliva cortisol test done. Cortisol low across the board. So was DHEA. I read Wilsons book on adrenal fatigue, and found the symptoms very fitting. He recommended adrenal extracts and I thought that "natural" approach would be safer than messing with steroids. Wrong again.

    I felt wonderful in the beginning on the extracts. Admittedly, there were signs of overstimulation in the beginning, but that calmed down after a week or so. The extracts almost obliterated all my symptoms. I felt quite normal. I was standing up the entire day on my job, and felt okay, though there were some fatigue from time to time. Then one day, like turning on a switch, I starting feeling terrible. Tachycardia, tingling, burning, pain, weakness, dizziness, nausea, cold extremities. I couldn't stand up anymore. I was mostly bedbound for a year or so after that.

    Again I was stumped. What had happened? I went back to the hypothesis of the high cortisol and viral reactivation. Researching more I found my symptoms matched something called POTS. Sure enough, orthostatic intolerance and tachycardia upon standing confirmed (to myself) that I had POTS. Was it still adrenal fatigue?

    I tried cortisol. Another bad experience. While I felt great in the beginning, I would crash very badly as soon as the dose wore off. I usually took 15-20mg daily, but sometimes would crash badly and needed to double my dose. I had wild mood swings and crying spells. I felt like I was either too low, or too high on cortisol all the time, could never get it right. I got skin atrophy, my skin under the arms got extremely thin to the point of breaking, also on my palms. Eventually my penis started hurting from the skin thinning. That's when I plugged the plug. I was on it for about 2 months. I tried tapering several times, but each time I would crash badly. Eventually I just went cold turkey. Back to bed for another year, lol.

    Flash forward another 2 years, and I'm doing much better compared to back then. I'm on an SSRI now, and a load of supps. Methylation and B vitamins has helped tremendously, so has pregnenolone and DHEA, and drinking electrolytes. Also, at this point in time cholinergics seems to help greatly. I'm doing a shotgun approach, trying to improve everything I can, focusing on nerve health.

    Still, there are problems. I can stand without tachycardia, but only for about 30 mins at a time. Compared to the couple of mins I could stand two years ago, this is very much improved. My POTS is not cured, but it is controllable. Then there are paresthesia in the extremities, sometimes cold limbs, brain fog, attention/working memory problems, fatigue, a few fasciculations, anxiety, mood swings, muscle and nerve pain, palpitations, electrolyte dysregulation.

    There is a type of POTS called neuropathic, where the autonomic ganglia aren't working the way they should. Also viruses can create autoantibodies that disturb autonomic ganglia. I think my problem lies somewhere in there, autobodies or not. Like I said before, the glycine causes problems, weakening the signaling in the spinal cord. It's like the signaling from the spinal cord down into the legs are is not strong enough, causing weakness in the legs. Arms seem to be okay, as long as I don't raise them over my head. Also, bending forward in my spine greatly increases the tingling in the extremities. Also what lead me to this conclusion is that bupropion, a nicotinic receptor antagonist, greatly worsens my POTS and leg pain/weakness.

    A strong cup of coffee can pull me out of POTS crash, even though it also can cause anxiety, tachycardia, cold extremities and shaking. Still, a NRI (reboxetine) didn't seem to help much with POTS. On the other hand, Mirtazapine (alpha-2 antagonist) abolished my POTS. By releasing NE? I do not know. It made me near psychotic, to the point I was fantasizing about killing people, so I stopped it. In the beginning of taking Mirtazapine, I felt a kind of restless legs syndrome, with painful tingling and activity in legs, like the nerves were getting "activated". After a few days the tingling stopped and I felt much stronger in the legs. I have not been able to replicate this effect with other drugs. Could it be glutamate?

    I should mention that there were some problems before the incident, namely fatigue, depression (I suspect bipolar tendencies), repetitive strain injury (including some autonomic involvement), allergies, repetitive bouts of pneumonia, attention problems, sometimes blackout on standing. Yeah, I've been lucky too, sigh.

    Sorry for the long post, and thank you for any comments you may have. It's good to have someone with your knowledge and background around. In the last couple of years I've had a crash course in neuroscience and biochemistry, but there are many details I don't understand. At first I believed I could figure everything out, but once the complexity of this stuff starts dawning on you, the endless possible combinations of interchangeable factors, it is mind boggling. Everyone refers to rocket science when talking about complexity, but I believe it fades in comparison with biochemistry. Besides the complexity, there is the lack of data. It's like trying to solve an extremely complex equation with only a fraction of the factors at your disposal, lol.
  11. dbkita

    dbkita Senior Member

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    @ Adreno:

    I will have to take in what you said and process it a bit. I am in the middle of nasty head cold right now courtesy of my teenage daughter (such a nice holiday gift)!

    I will say three things real quick:

    a) if an SSRI is tolerated by you then the 5htp had zero to do with your "episode" referred in your other post. That is only an opinion of course and I am not an M.D. but I see one of the top neuroendocrinologists on the West Coast and he has no issue with me taking 5HTP except that at high doses it will always make more serotonin in the periphery and gut than he would desire and that can show up as GI motility issues, higher BP and some increased heart rate. But ... he won't give me an SSRI since there is no such thing as a "clean" SSRI that only hits one target, they all hit multiple enzymes and can effect dopamine which I was tragically low in when he first saw me.

    b) if pregnenolone, DHEA help you now and in the past you felt better for brief periods of time on cortisol though the seesaw was terrible, then yeah you almost certainly have some sort of adrenal fatigue. I have no idea about why Wilson pushes those damn extracts. They are massively unpredictable. People with secondary adrenal fatigue who cannot handle hydrocortisone have an underlying problem either with their HPA axis or with their immune system. This is confirmed by being woefully low on other adrenal hormones.

    Intervention in those cases depending on clinical severity = medrol or prednisone. Period. Though many endocrinologists would disagree they are usually morons anyways (sorry spent nearly a decade fighting with many of them). In the mean time while supporting the adrenals, then the doctor and patient need to figure out what is the underlying cause: 1) infection, 2) autoimmune, 3) pituitary or hypothalmic problems, etc. If you have autoimmune like I do, then you are stuck with the corticosteroids and have to live with them for the rest of your life. Self administering hormones is a dangerous game. HRT requires regular lab tests as variation is inevitable and balance is hard to maintain.

    The only supplement I know of that can actually help reboot adrenals that are not shot but recoverable (meaning no nasty underlying motivator) would be high dose of the active form of pantothenic acid. But again that will do zilch if you are being eroded from underneath.

    c) POTS and in general dysautonomia's are really hard to get a handle on sometimes.

    Viruses like EBV and CMV can cause this (I know this personally since my worst dysautonomia symptoms did not start until after I had both infections simultaneously in 2003). Do you have IBS or gut issues? problems with blood pressure drops depending on position? What is your parasympathetic response like?

    I (and my brother) have both had issues with standing since we were teenagers or young adults. For my brother the KEY was Florinef. Period. In my case it was only in the last year I went on Florinef. Florinef combined with sea salt helped my posture problems a lot but I may have discovered this combination too late, whereas my brother is in almost complete remission. Then again my rare as *bleep* autoimmune disease doesn't help either. My brother and I still have gut issues. In my case I eat 4000 calories a day of a paleolithic diet with 200+ grams of protein and 150+ grams of fat each and every day and I can't get my weight above 155 lbs though I am almost 6' 3".

    Overdoing the sea salt combined with being on corticosteroids that inhibit the action of 11-beta-HSD(1 or 2?) can lead however to low potassium, not to mention florinef increases potassium excretion, meaning I have to consume 8-10 grams of K+ a day to stay out of hypokalemia.

    I apologize for any typos, I feel like dirt tonight and need to stumble off to bed.

    Peace.
  12. Lotus97

    Lotus97 Senior Member

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    Phosphatidylserine can cause depression?
  13. dbkita

    dbkita Senior Member

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    Phosphoserine reduces cortisol signaling. This can be a problem for some chronic sufferers.
    People react differently to low cortisol. One side effects is higher NE in many. But another is
    the dreaded cortisol "dips" which often bring fatigue and depression. But to get to actual depression
    the suppression of the cortisol production has to be really strong. Not sure what doses of PS
    are needed to achieve such an effect. I suspect is different for different people.
    Lotus97 likes this.
  14. dannybex

    dannybex Senior Member

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    Oy vey is right! This is so incredibly complicated. I'm hoping you (and anyone) can help me out (again).

    As stated earlier in this thread, I've been taking TMG and folinic twice, and on some days, three times a day. It seemed to definitely help -- especially with sleep, but also allowed me to walk a few steps further, or stand a little bit longer. I also take 400mcgs methylfolate and a small amount of methyl-b12 and ad-b12, but not every day.

    Now I'm wondering if taking TMG (and perhaps the folinic) has in the long term has as you say above, slowed down the flow around the full methylation cycle, diverted things from the transsulfuration pathway, the methionine synthase pathway, etc..

    Note, that I also take (and have to take) betaine HCL, and have been taking that for years. If I don't, then food just stays in my stomach. I strongly suspect an overall thiamine deficiency -- long term -- and perhaps repleting that, and other acid-producing nutrients, will help correct the hypochlorydia I've had for almost 13 years now (not to mention the muscle wasting in my feet (ouch!) and arms, with paradoxical edema in my ankles. Lots of classical beri-beri symptoms.)

    Plus, I thought that betaine HCL and the betaine in the TMG were two completely different things (so much conflicting info online), but after re-reading some posts here, I guess I was wrong. Anyway...

    Rich talked about DMG for overstimulated BHMT on another thread:

    "Adding DMG would have the effect of slowing down the flow through the alternate BHMT pathway that is present in the liver and kidneys. Since you already had plenty of folate and B12 in your cells from your supplementation, the result likely would have been to shift the flow of homocysteine more to the methionine synthase reaction and the transsulfuration pathway.

    Use of DMG is part of the full Yasko treatment, from which I extracted the Simplified Treatment Approach. Dr. Yasko recommends building up the supports for the methylation cycle, and then adding DMG if needed to shift the flow from the BHMT pathway to the methionine synthase pathway, which is desirable."

    Would you agree with that -- do you think DMG might help? Along with perhaps cutting back on the TMG and folinic?

    I should add that in the last 2-3 weeks I started small doses of a Thorne 'B-Complex #12', so that I could get some of the other 'b's. I haven't been able to tolerate b6 and/or niacinamide very well at all, so have had to avoid b-complex vitamins, but I know I need a balance as well, so have been taking one capsule, divided into three doses, a day, plus a little extra B2 (which seems to help me handle the b6).

    From what I've read, in some ways I seem to be the opposite of you (dbkita) -- niacinamide makes me feel very doomy and gloomy and uncomfortable, and SAMe -- which I haven't taken for months, until I took 2 earlier this afternoon -- always in the past has made me feel better, as long as I don't take too much. Back in 2000, 1600 mgs a day brought me back from feeling like death, to a renewed sense of hope and energy.

    Any suggestions would be deeply appreciated. :)

    Thanks in advance!

    p.s. Should add that I'm under HUGE stress right now as I'm getting ready to move in 10 days...have been on my feet waaaaay too much, etc......so that could be playing into some of this 'downturn' as well.
  15. dbkita

    dbkita Senior Member

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    Replying from phone atm so short reply.

    Betaine is betaine. So tmg is in both your tmg supplement and your betaine hcl. About 80% of your betaine hcl is tmg.

    You do have as cbs upregulation and several heterozygotes in bhmt. So some bhmt stimulation is needed to prevent overflow down the transsulfuration pathway. But it may be question of amounts. Usibg dmg with a cbs mutation would seem ill advised. But overstimulation will ramp ne relative to da so be careful. P5p / b6 can really up the cbs flow so watch out for that also.

    I would suggest using urine sulfate strips to see where your transsulfuration flow is at.
    dannybex likes this.
  16. dannybex

    dannybex Senior Member

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    Thanks for the speedy reply -- I really appreciate it. I can wait for more info...I've been on the computer too long today...eyes are shot.

    Just wanted to also ask if you or someone could explain in layman's terms, about the methionine synthase pathway?

    Again, another quote from RIch: "The Teitelbaum supplement contains too much TMG as I recall, which can prevent the methionine synthase reaction from coming up."

    MANY THANKS!
  17. dbkita

    dbkita Senior Member

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    There is no absolute. Yes too much BHMT could stifle some of the main thoroughfare. But setting an absolute amount is not possible since it depends on the person's health status and genes. I think the NE increase from overstimulation is a stricter earlier constraint than lowering the methionine synthase activity. But if you are CBS +/+ and have BHMT issues I think you have to do something. Increased methionine synthase activity will simply drain down the trans-sulfuration pathway. Making you worse off. So there is a balance.
    dannybex likes this.
  18. dannybex

    dannybex Senior Member

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    Does one need a doctor for the urine sulfate strips? I have a feeling my sulfate is very low, as I stopped gluc/chond sulfate July 2012, and have just restarted (stopped as I thought the manganese in the formula might be giving me problems, but not so sure now.)

    The b6/p5p gives me almost instant 'stocking and glove' neuropathy, but adding b2 helps. I think I'll cut back on the b-complex for a couple of days and then restart.

    And why or how would DMG affect the CBS issue?

    Thanks in advance Dbkita!
  19. dannybex

    dannybex Senior Member

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    I understand. We're all different in so many ways...

    2 questions:

    You said 'increased methionine synthase activity will simply drain down the trans-sulfuration pathway". This is a silly question perhaps, but drain what down the pathway?

    2nd question:

    The trans-sulfuration pathway -- is that the same thing as the sulfation pathway?

    I ask this because I definitely have salicylate intolerance problems, and have had conflicting advice on which pathway or compound helps detox sals/phenols. Rich said glycine helps detoxify them, and yes, it does seem to help. Then other sites suggest calcium d-glucarate helps "glucuronidation" detox sals.

    Have also read the following on several sites:

    "Impaired sulfation leads to sensitvity to phenols and salycilates...

    "These foods (high in salicylates/phenols) should be avoided if you are low in sulfates, because they require sulfates to process them."

    That last sentence is why I believe I'm low in sulfates.

    ???
  20. dbkita

    dbkita Senior Member

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    No just search for Quantofix sulfate strips CTL scientific on google.

    DMG inhibits BHMT which means more homocysteine for CBS means more ammonia, sulfites and sulfates.
    dannybex likes this.

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