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ADENOSYLCOBALAMIN, THE VERY LARGE GORILLA IN THE ROOM

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Freddd, Nov 6, 2012.

  1. dbkita

    dbkita Senior Member

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    BH4 can be depleted by ammonia which could be a by-product of upregulation of the trans-sulfuration pathway. If the BHMT pathway is down-regulated and / or the cystathione beta synthase gene is defective (up-regulated) then too much of homocysteine may be directed to make ammonia and alpha keto-glutarate which leads to glutamate often. On the other hand heavily driving the methylation cycle may still result in increased trans-sulfuration activity (depends on other factors I wager) on its own.

    Also people with COMT -/- may often have less catecholamines due to more effective cleanup, which is almost guaranteed if SAMe is present which is one of inherent goals of methylation support. I am MTHFR A1298c +/- but also COMT +/- and VDR -/- so methyl cleanup is a problem for me.

    Lastly if I may ask what sort of neurological defects? The reason I ask is many people associate neurological symptoms with dopamine and serotonin (both of which are affected by BH4 of course). But only some symptoms fit into that category.

    If anything far more neurological symptoms (including pain, seizures, insomnia, over-stimulation of nerves, etc.) are due to glutamate-GABA imbalances and over-activation of NMDA receptors. I know this one all too well since my auto-immune disease is Stiff Person Syndrome which means my body seeks to destroy glutamic acid decarboxylase enzymes in my CNS (and pancreas) hence my high levels of corticosteroids.

    Ironically high methylation support can stimulate glutamate imbalances by virtue of the efficient conversion histidine into glutamate using THF as a cofactor for the last step in the process. This leads to low histamine but higher glutamate.
     
  2. adreno

    adreno 3% neanderthal

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    Maybe my symptoms fit more into the NMDA category in that case. They are mostly pain, burning, twitching, and paresthesia/tingling. And then there are the autonomic issues, POTS aso.

    I am COMT +/-, MAO A +/-, and VDR +/+ so I'm easy to overstimulate. I also have the CBS and BHMT defects that you mention.

    It seems difficult to balance methylation. Like you I have been overdriven my cycle for a while, but I do not get any improvement from high doses. OTOH, without methylfolate I get quickly depressed, and unable to focus.

    Right now I'm taking 1250mcg MB12, 800mcg methylfolate, 25mg P5P, 50mg R5P, 500mg TMG and CDP-choline. I'm doing ok, but not great. I also take NAC.

    What do you do to modulate NMDA? I have tried the drug memantine (NMDA antagonist), and while I feel calm on it, it also causes extreme brain fog, to the point that simple task become impossible. Other drugs, like piracetam, can make me hypomanic. Again, it seems very hard to balance the stimulation of the NMDA receptors. Maybe it is some sort of channelopathy. Of course, there is lithium - did you have any success with that?
     
  3. dbkita

    dbkita Senior Member

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    I too get depressed if I lower methylfolate too much, but for me 400 mcg of FolaPro taken away from any vitamin C on an empty stomach seems to be about right. But I don't have your C667T mutation. I just have the A1298c in MTHFR. For me 500 mg TMG was too much, causes way more norepinephrine preferentially over dopamine which is not a good thing for an autoimmune disease since norepinephrine ramps the immune system in a vicious cycle. But then again I take supra-physiological levels of corticosteroids so I don't spend my time curled up in the fetal position with every muscle curling up on itself (not fun -- spent nearly two years that way).

    I would also be careful not to increase the amount of R5p you ingest since that is the final rate limiting cofactor for 5MTHF production (P5p is for the intermediate step, but also shows up of course all over the place). I only mention this since the regular version of B-2 linearly saturates at 30 mg absorption per dose, above that you are not going to get much. But ... the sodium salted version of R5p has no such restriction to my knowledge. Still 50 mg is probably a fair target.

    Ok let me see what I can suggest regarding NMDA receptors.These are not necessarily in order of priority. Just off the top of my head.

    I am by no means an authority but since I have Stiff Person Syndrome regulating NMDA receptors activity is one of the most important things I have to do in my life every day. That is the curse of Stiff Person Syndrome.

    1) Glorious magnesium glycinate (Albion chelated version); large dosages (i.e. 1000-1200 mg /day beyond diet or to bowel tolerance). Magnesium is an allosteric modulator of NMDA glutamate receptors. So is glycine. Ironically I used large dose glycine to knock me out at night along with some melatonin and 5HTP but that may just be me. But if you take 1000 mg of Mg-glycinate you will get lik3 2.5 (?) grams of glycine spread out through the day. Glycine is also an inhibitory neurotransmitter like GABA (though GABA is supposed to be the big boy on the block for inhibition).

    2) Zinc ... it not only helps insulin and GABA production but also affects NMDA receptor activity not to mention a ton of other processes. But let's stay on topic. Molybdenum is a caretaker of the zinc-copper balance btw in favor of zinc. So if you are low copper then you need to be careful of course.

    In my case though copper excretion over 24 hours is in normal bounds, when I take 2 mg of copper, I feel like garbage? Why? Copper inhibits the glutamic acid decarboxylase enzyme activity which I have been working so hard to allow to function with my corticosteroids. Meanwhile copper affect MAO-A and also is involved in converting dopamine to norepinephrine.

    3) Taurine. Like GABA and glycine it too is an inhibitory neurotransmitter. But ... if you have CBS mutation this may cause redirection down the sulfite-sulfate path and burden the trans-sulfuration pathway. I use 2 grams per day as magnesium taurate. But results may differ. Take with food to avoid reflux.

    4) Don't over-methylate! The more you methylate the more you stop histamine but the more you convert histidine into glutamate.Balance is key.

    5) And these are generally obvious, no gluten, MSG, etc. They will all affect your glutamate / GABA balance and overload your body's machinery to process things into safe glutamine (which is BBBP) to glutamate which is not.

    6) Try to make sure the Krebs cycle is not blocked. Mine was in lock down at the AKG stage with really high AKG intra-converting to glutamate and back. Meanwhile with insufficient ATP, I could not make glutathione. RIch Vank (bless his soul) identified that while I had one of the lowest glutathione levels he has ever seen, the methylation cycle was at best a minor player in that. He suggested working on the Krebs cycle and high dose vitamin C a la Dr Robert Cathcart and bam my glutathione tripled in six months.

    As a side note: before talking to Rich, I had doctors who fruitlessly gave me glutathione IVs (hellaciously expensive but I didn't know any better since my body was in full revolt with SPS) that made my symptoms worse. Why? The darn glutathione breaks down into glutamate, cysteine and glycine anyways and if you can't make your own you get jacked with glutamate.

    I agree with Freddd btw that people pushing glutathione injections or other forms as the end-all to everything should be carefully re-considered. The point is you are far better making your own end point chemical than supplementing directly imho. Then again I think the similar logic applies to SAMe but I know that will likely cause an argument with some people on the forum so I won't mention anything more about that one.

    7) Take melatonin at night. Methylation is generally going to oppose the melatonin production spike at night. Melatonin will damp down NMDA receptor activity indirectly at night when you need to fall sleep. Then again maybe you make enough on your own. My melatonin 24 hour profile was essentially constant even before methylation support.I use melatonin and 5htp to fall asleep and glycine (high dose) at bed to throttle muscle pain in bed as best I can.

    8) N-acetyl-cysteine. This one is tricky. NAC will drain glutamate in both brain and periphery (it is BBBP) by providing fuel to make glutathione. If you can make glutathione ok then so be it. But some people overdo it. Moreover the pharmacokinetics of typical NAC will mean you will have a transient spike in serum that will lead to transient dips in glutamate (assuming no GCL block) but that may not be what you want. If you hammer glutamate too much you will become tired and defocused with brain fog. So many people on these forums think the effect of high NAC is a detox reaction. Ummmm nope. It is what happens for most people when glutamate drops rapidly. Again balance.

    Personally I have dabbled with NAC from time to time and it certainly forces a drain of glutamate, but even using a time release version (like from Jarrows) my reflux gets worse. My guess is the spike in glutathione production in the stomach kicks the parietal cells into HCL production. Not fun. And the last thing in the world I need is proton pump inhibitors - gah! I only mention NAC as an option but like I said personally I have some undesirable side effects that make me put it back in the cupboard (and no they are not detox events that get used to explain every negative effect sometimes).

    9) CoQ10 regulates glutamate production. I forget the mechanism how. I used to take high dose at night to sleep and overcome glutamate excitotoxic effects (like a hypothalamus that is so amped it can hear a flea fart on the back of a dog three miles away when trying to sleep). Again though it creates reflux so I have to rely on small maintenance does during the day with food.

    10) You can try to take supplements to augment GABA. Zinc and P5p are already in your mix I presume. Some people like theanine, that one is tricky since tolerance is often an inevitable result. Sadly I get a weird bounce back effect from theanine since it alters glutamate receptor transport at the synapses which would be great if my GAD enzyme containing glial cells were at full strength. But my immune system will never let that happen. There are other GABA promoters but for me I guess the situation is complicated so they don't seem to help that much over time.

    Some people swear by pyncogenol and grapeseed extract. They never did anything for me. Valerian root caused me insomnia.

    A cup of coffee is death to me since it releases massive amounts of glutamate into the extracellular space which is why people drink it to perk up. Kiss your neurology good by if your balance is off and you drink lots of caffeine.

    Understand with SPS, I also take Baclofen 20-30 mg at bedtime (hate the neuro effects during the day) for GABA-B stimulation. Fortunately Baclofen is non-tolerant. I used to take 60 mg a day back before I found a real doctor to treat my SPS, get me off gluten and put me on HRT.

    Moreover, I am still digging out of a long period of overmethylation that landed me on Klonopin which I have only recently been able to reduce by 50% by dialing back the methylation (histidine to glutamate). This is important to me since most SPS patients end up on massive doses of baclofen and benzos. So far I have beaten the odds. Knock on wood.

    Summary:

    I guess my main point would be that a lot of people on these forums focus on dopamine, serotonin, norepinephrine, etc. and rightly so.

    But ... the big boy neurotransmitters for basic neurology (pain, sleep, relaxation, irritability, memory, etc.) are to my knowledge glutamate and GABA. If those are messed up, no amount of methylation support is going to fix that on its own. Their are other cycles that are of key importance (like the Krebs cycle) as well. And in fact over-methylation will distort the balance further in some cases.

    Hope this helps give you some food for thought.

    P.S. Memantine is the one drug way back before my diagnosis that abated my pain somewhat. But it gave me weird headaches and made me feel like I could not think at all. That was suppression of glutamate if one goes to far. But note suppression of glutamate is not entirely the same as increased GABA. The two have to be in balance with one another but also at a dynamic equilibrium with a large pool of brain glutamine. (note don't infer this means you should take glutamine supplements, some of the glutamine may convert to glutamate in the body, depends on the person).
     
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  4. adreno

    adreno 3% neanderthal

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    dbkita, thanks a lot, this was a very nice walkthrough of options :)

    Glycine is tricky, I have understood it to actually partially activate the NMDA (glycine and glutamate together activate the receptor). Using it free form has caused a severe flare in nerve related pain for me. I take magnesium glycinate before bed (along with melatonin and gaba), and it really helps me sleep. I will try taking it during the daytime also. Supposedly, magnesium threonate should be even more effective, did you try it?

    NAC seems to make me feel better, and more clear headed. I take 500mg twice daily. Vitamin C I take 4g daily, but I might try to increase the dose. Zinc, I'm at 60mg a day.

    What do you think about aspartic and glutamic acid? My R5P product from Thorne is aspartic acid based. As I understand it, those amino acids are only excitatory when taken isolated, free form. They are in many foods in high dosages, but when mixed with other amino acids they do not cause excitotoxicity (I presume because they compete for absorption). That's why I have also not been convinced about the MSG debate, although I do try to avoid it, if possible.

    Some other options to consider for excitotoxicity would be pregnenolone, vitamin K (MK-4), theanine, and lithium. Paradoxically, methylcobalamin had actually been shown in studies to protect from excitotoxicity.

    I might also do some experiments with ashwagandha and lions mane for neuroprotection. After 40 years of hammering my neurons, I need to salvage what I can.
     
  5. Crux

    Crux Senior Member

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    Hi Adreno;
    I wonder if the amount of methylcobalamin taken is enough. The symptoms listed : paresthesia, POTS, along with pain, burning are associated with B12 def.

    I seem to remember that you have taken higher dosages... maybe there were side-effects?

    I've found that I've had to reduce any supplement that was stimulating, to allow for the stimulating effects of the B12. I now consider it to be my foremost supplement for healing.

    (I remember feeling overstimulated by TMG and choline.)
     
  6. adreno

    adreno 3% neanderthal

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    Hi Crux, I would like to go higher on the MB12 (for the nerve healing), but for now I think I have to keep it at a relatively lowish dose. The main problem when I take high doses is that my need for potassium increases insanely. At some point when I was doing high doses (5-10mg) of MB12 and MF I needed 10 grams of potassium daily. Maybe the key to tolerating more MB12 is to get the glutamate/gaba balance under control, or maybe it is simply just too many methyl groups for me to handle.
     
  7. Crux

    Crux Senior Member

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    Hi Adreno;
    I agree about the excess methyl groups...they're in alot of foods. Caffeine is loaded.
    I also have to increase potassium when I increase MB12, or else.
    I read a report about potassium's effect on glutamate, but I haven't been able to retrieve it.
    There's also some info about MB12's effect on glutamate.
    ( I've become an information hoarder, and my filing skills are atrocious.)
     
  8. adreno

    adreno 3% neanderthal

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    I recommend Mendeley.
     
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  9. Crux

    Crux Senior Member

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    I've been trying to add adenosylcobalamin these last couple of years, and was unable to tolerate it. (I had increased nerve pain, anxiety, insomnia.)

    But now that my nerves are healing, I'm better able to tolerate it, still in small doses of 1-2 mg weekly.

    Both the Country Life brand, and Source Naturals brand caused alot of nerve pain in my mouth.

    Recently, I've been taking the Anabol Naturals brand, and I agree it's very effective, and I have no negative neuro side effects. ( I still am having to be careful about the dosage.)

    I believe the 200 mcg. of boron in each capsule has been added as a buffer/ stabilizer. It's often used in the chemical industry for that reason. Since AdoB12 is naturally unstable, perhaps the boron prevents the breakdown of AdoB12.
     
  10. dbkita

    dbkita Senior Member

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    Hi Adreno,

    Long post incoming. I apologize ahead of time.

    Glycine is indeed very tricky. It is a co-agonist of NMDA but at the same time it is an inhibitory neurotransmitter of the CNS / spinal cord only surpassed by GABA. Again my use of the free form is maybe specific to me due to my SPS affliction. So I don't recommend that necessarily for anyone. Some people swear by it for sleep, others cannot tolerate it. I use large doses at night to knock me out. Go figure.

    On the other hand, many people with fibro and neurological pain, swear by magnesium glycinate and as you yourself said it helps you to sleep at night. Maybe having a highly bioavailable form means the Mg is well enough absorbed that it is the bigger antagonistic factor. Other people like magnesium malate or magnesium taurate.They may all have their place.

    My understanding is that recent research shows that the glycine binding site (NR1) acts as a primer for the NMDA receptor to be able to get ready for the Ca+influx but the glutamate (NR2 site) is the one that provides the impulse. Also glycine concentrations at the NR1 site are not saturated at baseline and carefully controlled by the local control of spatial-temporal distributions of neuronal states on the same dendritic branch, i.e. control of the glycine site occupancy is highly regulated based on local neuronal firing (at least in the hippocampus). Then again high enough exogenous glycine may be able to override some of that. High enough doses probably do and that supports the glutamate hypothesis of schizophrenia where patients may take 30 g or more of free glycine a day ...

    Still remember that the body makes like 100 g of glycine per day, some of it via SHMT which is catalyzed by P5p. SHMT as I am sure you are aware is a critical to the folate cycle. If you supplement with methylfolate then you will have to have SHMT turn the crank to convert THF after methyl donation to B12 to get back to 5,10 methyleneTHF. I suppose supplementation with folinic acid bypasses SHMT but that is another discussion. My point is that the body makes a heck of a lot of its own glycine in a day and part of that is tied to the folate cycle (though I do not know what fraction sorry).

    NAC is an efficient way to drop glutamate in both the brain and periphery. I just wish it didn't make me reflux. It is so efficient that 2 grams a day spread out can actually overdo things for me sometimes (meaning on top of everything else I take, I become too 'doped' or relaxed). It is also nullifies the ringing in my ears, which sometimes is associated with glutamate over-stimulation.

    You have plenty of supplemental zinc. I personally can't tolerate that large a dose but maybe that depends on diet intake as well.

    Taking GABA supplements can only help you sleep IF and ONLY IF you have leaky blood brain barrier btw. Which is its own problem btw that can lead to overstimulation and inflammation in the brain. If you get tired on 500 mg of pharmaceutical grade GABA and sleepy on 1000 mg of the same then your BBB is not intact. Sorry. I tend to avoid GABA personally as the GABA receptors in the brain are notorious for developing tolerance and desensitization.

    Vitamin C is unbelievably important to me as I mentioned in my previous post. I don't think though it has a direct link to glutamate in the brain, but it certainly can help with reducing the demands placed on glutathione levels.

    I would not touch aspartic acid since it is a (weaker) NR2 agonist than glutamate but an agonist nonetheless. But I contacted Thorne about that supplement and they said there is very little aspartic acid in it (i.e. trace amounts).

    Glutamate is just the carboxylated anion of glutamic acid. Glutamic acid is the last thing I would supplement. At the very least you place load on your body to convert glutamates into glutamine. MSG destroys me with my SPS. Then again I have Celiac's (as 50% of all SPS patients do) so that means my glutamate processing machinery in the gut is handicapped. On the other hand I eat a LOT of protein. So yeah I know I get glutamic acid in my diet and I concur that it is far less devastating (at least to me) than free form. I won't touch free form glutamic acid ever again.

    I would even watch out how much glutamine supplements you ingest for say helping your GI tract and don't take it at night. Your body makes a lot of glutamine during the day. Glutamine can be made from glutamate via glutamine synthase with cofactors of biotin (?) and ATP + Mg in a two step process. But then again it can hydrolyze right back into glutamate + ammonia. Then again there are glial cells that can do a two step internal conversion to GABA. It is a tricky equilibrium.

    My results with L-theanine seemed encouraging at first and then got less and less positive effect. Again it affects glutamate transport and relies on GAD to do its job. But GABA receptors can desensitize ... so yeah mixed results for some of us.

    How does vitamin K factor into the picture, I was not aware of that link.

    I don't take pregnenolone but I do take DHEA and on HRT my progesterone is high normal. I also take aldosterone and supra-physiological levels of corticosteroids so I have what I need for the sex hormones and pretty much everything els.

    I forgot about lithium ... do you remember the connection? I think it is at the glutamic acid decarboxylase enzyme but I cannot remember.

    Ashwanghanda made me an insomniac in the past. Turmeric rips my gut. Quercetin gives me total insomnia after three days of intake. So I tend to fear herbs sorry.

    Mb12 is protective (not as strong as taurine though) and I take 2500 mcg a day with my methylfolate. But I don't have a C667 mutation and 5000 mcg can complicate sleep for me. But protective doesn't mean it will stop the NMDA signalling.

    I think what people forget is you need glutamate in your brain and CNS to live. But .. you need a balance with GABA that can be very tricky. Think of them as two large pillars in an ocean of brain glutamine. If one pillar is much higher than the other ... you will have problems one way or another.

    When I was a kid in high school (I am not kidding btw) I remembered pi to 5000 digits to win $100. I couldn't do that without glutamate. But later in life I wish I could dampen things enough to lower pain.

    Like I said before in the other post if memantine calms you or reduces your pain (where say opiods do not, which the case for me for many years) then you have a NMDA glutamate problem.

    My suggestions for now:

    1) Stick with the NAC,
    2) Put one of the three aforementioned forms of magnesium in to play during the day (don't be afraid of 1200-1400 mg total intake by suppelements); maybe try Mg-glycinate first ?
    3) Don't over do calcium (it can be be real villain here),
    4) Stay away from free form glycine but maybe don't fear it so much in Mg-glycinate (provided is it Albion brand)
    5) Feel free to try L-theanine but don't expect a miracle
    6) Seriously consider magnesium taurate for taurine (beware though CBS mutations),
    7) Don't supplement free form glutamic acid
    8) Control free form glutamine intake (depends on how you react)

    You might also increase vitamin C to see if helps other things.

    You take plenty of p5p for GAD enzyme operation and plenty of riboflavin for mental energy and the methylfolate synthesis step in the folate cycle.

    Oh and before I forget, maybe watch how much Mn you get. Some people on these forums have suggested Mn is a cofactor for GAD but every source I can directly find says otherwise.

    To that point you might find this article interesting:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950338/

    That doesn't not seem to bode well for glutamate but then again it is a cell study so who knows ...

    Good luck!
     
  11. dbkita

    dbkita Senior Member

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    This following abstract is interesting maybe (sorry nothing more recent):

    (from http://www.ncbi.nlm.nih.gov/pubmed/2472189)

    "The N-methyl-d-aspartate (NMDA) subtype of glutamate receptor appears to play a pivotal role in enabling glutamate to express its neurotoxic potential in a variety of neurological disorders. Our result show that the transition of glutamate from neurotransmitter to neurotoxin is facilitated when cellular energy is limited in cultured cerebellar neurons. Omission of glucose, exclusion of oxygen, or inclusion of inhibitors of oxidative phosphorylation or the sodium/potassium pump, enables the excitatory amino acids glutamate or NMDA to express their neurotoxic potential. We interpret these results as demonstrating that glucose metabolism, ATP production, and functioning Na+, K+-ATPases are necessary to generate a resting potential sufficient to maintain the voltage-dependent Mg2+ block of the NMDA receptor channel; relief of the Mg2+ block enables the excitatory amino acids to act persistently at the NMDA receptor, resulting in the opening of ion channels and subsequent neuronal damage. These findings are discussed in the context fo perturbations or abnormalities which lead to decreased availability or utilization of glucose and oxygen in the brain which may trigger endogenous excitatory amino acids to become neurotoxic by this mechanism."

    This suggests low ATP production or impaired ATP pumps (like with low T3, low aldosterone (yes it does not only affect renal tubule cells) are important for the Mg blockade of the NMDA receptors ...
     
  12. dbkita

    dbkita Senior Member

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    Sorry what doses do you take now of adb12? Do you mean 1-2 mg per week (one dose) or daily?

    Does that still hold true with the Anabol brand?

    Do you take it like Freddd, by putting it along the gumline?
     
  13. dbkita

    dbkita Senior Member

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    Yeah at 800 mcg Folapro, 800 mcg folinic acid, 5000 mcg Jarrows mb12 sublingual, 50-75 mg P5p, 100mg of B2 (50% r5p sodium, and 600 mg TMG, I crashed into mild hypokalemia even taking 10 grams a day of potassium (7 g in food, 3 g as extended release KCL) ... that was nuts in my opinion. That was before I realized I was over-methylating.

    I am wondering though by taking like 2.5 mg of adb12 (Source Naturals) in two doses every day, if I am still over-driving some things ... hmmm I wonder...

    Also remember if you are COMT+ methyl groups can pile up. Also A1298c for mthfr means you don't have feedback inhibition regulation work as well as SAMe levels rise. So it is tricky.
     
  14. adreno

    adreno 3% neanderthal

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    Thanks again for your generous reply. I like long posts :)

    I just looked up SPS. Very rare, one in a million. Guess you were really lucky there...

    I do not understand biochemistry at the level of being able to explain exact mechanisms for you. I know some neuroscience, but that's about it. I'm just a patient trying to cope. I study broad principles, but don't understand all the details. Are you a researcher? You seem to have a very clear understanding of things.

    Vitamin K, I guess it works because it regulates calcium. It also protect neurons from oxidative stress. And it has been proposed as a treatment for Parkinson's. I would guess that vitamin K would be extremely important for your condition. I take 15mg MK-4 daily.

    Novel role of vitamin k in preventing oxidative injury to developing oligodendrocytes and neurons
    Vitamin K prevents oxidative cell death by inhibiting activation of 12-lipoxygenase in developing oligodendrocytes
    Vitamin K2: New Hope for Parkinson's Patients?

    Regarding lithium, there are numerous studies showing it protects from excitoxicity. Again, I do not know the exact mechanism. Here are a few studies that might get you started:

    Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it be used to treat neurodegenerative diseases?
    Lithium neuroprotection: molecular mechanisms and clinical implications

    It should be noted that lithium can have a negative effect on the thyroid, as well as many other side effects at pharmacological doses. I'm thinking about using 5mg in supplemental form. I have seen one study estimating RDA of lithium to be 1mg, so 5mg should be sufficient I would guess. Yasko talks a lot about lithium, she has a lecture on it:

    http://www.dramyyasko.com/resources/webisodes/lithium-connection-webisode/

    I haven't watched it in full, as I don't understand what she is saying anyway, but I understand it is supposed to be needed for the transport of B12, among many other functions.

    I see the problem with manganese, do you suggest not to supplement at all, or just a low dose (say, 2.5mg)?
     
  15. Crux

    Crux Senior Member

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    Hi dbkita,

    Currently, I'm only taking one dose of adb12 once weekly. I estimate the dosage to be 1-2 mgs. because I just empty a portion from the capsule into my mouth and hold it there for a time. ( estimated 15 minutes).

    This is a small dosage, and I do have a strong increase in energy from it , but I still have sleep delay the night of that dosage. ( I take it in the morning.)

    Yes, it's the Anabol Naturals brand that I'm taking now in these small amounts,1-2 mgs weekly, but I'm glad I'm able to tolerate it now. ( I couldn't tolerate the other brands at all, even when I tried to swallow them, bypassing the sublingual method. )
     
  16. adreno

    adreno 3% neanderthal

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    CDP-choline does exactly that:

    Citicoline: pharmacological and clinical review, 2006 update

    Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport
     
  17. Christmas

    Christmas

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    Hi my question is I only have one injection a week of hydro. I decided to try county life dibencozide it has made me really ill. Disturbed my vision I feel sick weak etc. Is this normal three days on I will feel so I'll. I feel very very worried and very scared. I live in UK the docs over here haven't even heard of it. So I feel very alone. Can someone please advise.
     
  18. Phred

    Phred Senior Member

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    If it's 3 days in, it definitely sounds like hypokalemia (low potassium). Have your doctors looked at your potassium levels? Fred talks about this after three days of introducing active b12's. Maybe read a little on his protocol at the top of the forum. At the very least increase your potassium rich food intake. You may find that alone makes you feel better.
     
  19. dbkita

    dbkita Senior Member

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    Yeah I have all the luck :)

    In truth a doctor at Mayo said the real incidence rate is probably like 1 in 250 K but since it takes 8-12 years to show symptoms and many get it when they are later in life, many cases are undiagnosed. It was kind of a shot in the dark when a different doctor test for the antibodies, diagnosed the Celiac's and then passed me on to another specialist since my clinical history was a mess and then the real diagnosis. It took almost 10 years of doctor visits for find the core problem. Fortunately I have one of the best neuroendocrinologists on the West Coast to handle my care. He managed to keep me alive even before the diagnosis came down.

    Yes I am a researcher. Was an astrophysicist a lifetime ago. Been in biotech, genomics, and bioinformatics for a long time now. Although I think I spend far too much time managing my own healtcare ... sigh.

    I think you are right the vitamin K is probably due to its action on calcium. I know in the past I had some issues with slightly abnormal fibrin panel tests, but yeah I think I need to look into low dose of vitamin K.

    Isn't 15 mg of K-2 a big dose btw? They use 45 mg per day for bone fracture studies of osteoporosis which is 1000x food intake amount on average. Maybe the typical Japanese citizen gets 1.5 mg per day eating their diet.

    I will check out the lithium and CDP links. I knew some about lithium, apparently it potentiates GABA production to some degree and Dr Yasko mentions both iodine and lithium are often depleted in people with COMT+/(+/-) and VDR-/-. I certainly was depleted in iodine for a long time. So I will check out lithium again, I think 120 mg of lithium orotate will give you about 4.6 mg elemental lithium and is pretty bioavailable. The CDP link is news to me. I will have to check that out.

    I tend to have a pretty restricted but paleolithic diet now, so eating nuts and some other sources I get a pretty good amount of manganese plus other minerals in my diet. So yeah personally I don't supplement manganese. I only supplement 15-25 mg of zinc since I get 50-60 mg in my diet (though granted it is only 30% absorbed). I don't touch copper. Too many bad experiences. Jury is still out for me on chromium. Not sure what the dietary biovavailablity is.Molybdenum 2-3x of 75 mcg /day turned out to be very useful for me (sulfites?).

    I tend not to supplement anything unless I understand what is its biological effect AND what is its oral bioavailability in diet and other supplemental forms.

    Thanks for the tips.
     
  20. dbkita

    dbkita Senior Member

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    @ Adreno:

    P.S. I bet the link of Na/ATPase pump activity and the Mg2+ blockade of the NMDA receptor is in part why supplements like creatine pyruvate and D-ribose are very useful to me.
     

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