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Why would B12+folate cause GABA to reverse its effect?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by zanolachino, Mar 20, 2014.

  1. stevesayshi


    It may be moot by now, but this sounds like potassium deficiency. When GABA is taken up by a neuron, ammonia is released. Ammonia contributes to excitotoxicity, and potassium is one method by which it is transported from the brain. It's really hard to keep potassium up when you jump into a high dosage of folate/b12.

    I think. I'm a newbie.
  2. zanolachino



    Thank you for your many contributions to this thread. Sorry for my delay in responding!

    I wish I knew what to say about histamine. No question, it became a big problem after I got sick -- but so did other things, such as tyramine, purine, and, above all, glutamate. I suddenly became severely carbohydrate intolerant, too. At various times I have focused on each of these issues only to conclude that something deeper is at root of all of them.

    Regarding Ben Lynch's comments on 5-MTHF and Parkinsonian symptoms: I am familiar with this post and wish that he would say more. Basically, he recommends stopping 5-MTHF, supplementing B6 and Mg instead, and reintroducing 5-MTHF down the line. But I have been supplementing B6 and Mg for a long time; in the case of Mg, I try to get as much into my system as possible. With this in mind and with the results of my methylation panel, I thought that I was ready to move forward with 5-MTHF.

    (All of that said, I remain confused about B6. Based on my research, it seems appropriate for me, perhaps crucial, but there are dissenting arguments. I know that @Radio, who is healed, believes in the importance of limiting B6.)


    Thank you for your thoughts. I do not supplement Mn due to concerns about neurotoxicity: excess Mn appears to increase dramatically the risk of Parkinson's, and symptoms of Mn poisoning are Parkinsonian. This is why I was curious to know why @Vegas recommended supplementing Mn (I still am, if you are reading!).

    Mn aside, I find it hard to believe that I am not replete in the other nutrients you mention, as I have supplemented every one of them for years now. Moreover, I eat a very nutrient-dense diet, with lots of oysters, organ meats, egg yolks, and so on.

    I could be mistaken, but I must admit that I have lost hope that this is just a matter of finding the nutrient or nutrients that I am deficient in.


    Thank you for responding. I strongly doubt potassium deficiency, as I supplement about 2 grams of elemental potassium daily (usually in bicarbonate form, sometimes gluconate).

    I must stress that I studied @Freddd's posts exhaustively before beginning my B12 + folate trial. I found his arguments appealing and really wanted to believe that potassium deficiency and donut holes could explain the bad reactions. Ultimately I was forced to conclude that something else was going on.
  3. Violeta

    Violeta Senior Member

    @zanolachine, here's another possibility. B2 deficiency which is causing incorrect use in the body of copper(maybe iron, too.) In the B2 I love your thread, it's explained how taking the other B's causes a B2 deficiency. Copper not being carried correctly, especially when there's a lot in the diet, I've seen it related to problems in the brain. I've been thinking too much today so everything is too messed up in my mind, but thought I would mention this as it's a simple cause that can cause a lot of problems. I have to admit that I don't know much, but it won't take long for you to check this out and see what you think.

    Even if the B2 idea doesn't seem to be the cause, in the article you'll see that B9 and B12 manufacture by the body in the gut is dependent on B2, and if you can handle B2 it may help increase your folate levels without taking folate. When it's done by the body in this manner, repercussions I would think are nonexistent.

    B2 paper: http://ajcn.nutrition.org/content/77/6/1352.full

    The article is not very comprehensive, and at one point it even states that not much research has been done on the effects off B2 on humans!

    PS: about the B2 I love you thread, dogperson recommended taking mn, too, but later changed that recommendation.
    Last edited: Apr 22, 2014
  4. zanolachino



    This is a compelling idea -- and my best guess at present, too!

    My plan, when I get up the nerve to try m-B12 + 5-MTHF again, is to take larger daily doses of the other Bs, especially B2. The first time around, I kept dosages very low, mainly because of claims by @Freddd that anything more than small amounts of B2 and the other Bs would cause problems in folate usage.
  5. Vegas

    Vegas Senior Member

    @Vegas recommended supplementing Mn (I still am, if you are reading!).

    Mn aside, I find it hard to believe that I am not replete in the other nutrients you mention, as I have supplemented every one of them for years now. Moreover, I eat a very nutrient-dense diet, with lots of oysters, organ meats, egg yolks, and so on.


    Mn can substitute in many of the reactions that Mg participates since they can both have +2 charges, but at an enzymatic level, there is always a preference for one of these co-factors and typically Mg is more versatile. i.e. it can be incorporated into many more reactions. These cofactors are both involved in the glutamate-glutamine cycle, but if you had to have one or the other, you would want Mg, because yes, it is possible to accumulate Mn, albeit very unlikely at 10 mg. This can happen though, if you have a particular neurological condition or liver failure, and I think this certainly could be a problem with moderate to severe ME/CFS, which is marked by dysfunction of the nitrogen metabolism, intracellular mg depletion, and liver dysfunction.

    Glutamine Synthetase catalyzes the reaction that condenses ammonia and glutamate to yield glutamine, and it has a singular manganese co-factor. The condensation of glutamate/ammonia to glutamine will lower glutamate in the brain (and liver) but you can run into trouble if ATP and intracellular magnesium is low because ADP is a product of this reaction. There is cycling of ADP and ATP, which will be inhibited by intracellular magnesium deficiency, a low energy state/inhibited phosphorylation.

    You do need to look at the bigger picture though. Mn is nothing. You have fundamental problems with getting energy from food. This is likely a consequence of an overgrowth of the wrong organisms in both the small and large intestines. The other compounds you cite follow this. I also see you have benefited from some of the co-factors involved in pyruvate dehydrogenase complex, and this is something that can be caused by an accumulation of lactate. This reflects your inefficiency in deriving energy via glycolysis. The co-factors or derivatives thereof include lipoic acid, riboflavin, thiamine, and niacin, and to a lesser extent B5. Supplementing these can help (and sometimes hurt).

    So forget about the Mn, you don't need any more worries. Since you do well with Mg, try to get more in the cells, I think oral supplementation of Mg Glycinate plus taurine (provided you don't otherwise using a bunch of Sulfur) plus epsom salt baths works very well. Regardless, it must be understood that the micronutrients are, as you implied, not going to fix the problem. You likely need to correct the GIT dysfunction.

    You need species that favorably impact the host nitrogen cycle in the lower GIT, although as I noted, decreasing those species in the small intestines that contribute to lactate accumulation can be helpful. You want species that don't produce urea and also are not obligative homofermenters, something like L. mesenteroides is good. In the lower intestinal tract you will benefit from enhanced SCFA biosynthesis, which will participate in correcting the intestinal permeability while simultaneously acidifying the lower bowel to enhance the conversion of ammonia into ammonium. Ammonium is not readily absorbed like ammonia. You can also block the action of the bacteria that liberate ammonia from the proteins you eat with certain plant compounds. The right pre and probiotics should be helpful in an effort to rebalance things. Also, take a look at your diet as it sounds like it is very high in nitrogen/cysteine. Less animal protein and limited high-nitrogen vegetables (particularly when raw) may be more tolerable.
    Last edited: Apr 23, 2014
    Sidereal likes this.
  6. Victronix

    Victronix Senior Member

    FYI, I ran into B6 toxicity after taking too much and not realizing it. I would recommend getting your levels checked if you are unsure because for me the symptoms mimicked many of my side effects with methylation, but when I stopped taking it, my symptoms dropped in half, and eventually went away. So I quickly got a B6 test and it was at 30, with the range being around 3-30 mcg/L. A few months later it was around half of that level.
  7. Helen

    Helen Senior Member

    Victronix, what kind of B6 did you take? The bioactive P5P or pyridoxine? May I ask about your dose and for how long time you had taken it - just to get an idea of what could cause intoxication for someone. Is a labtest for B6 really valid? Does it include an analyze in red blood cells? Good to here that you found out about the toxicity and got rid of it.
  8. Freddd

    Freddd Senior Member

    Salt Lake City

    Sounds for the right timing and looks like the symptoms of low potassium and donut hole paradoxical folate deficiency.

    Version 1.2 12/08/2013

    Group 1 – Hypokalemia onset. Symptoms may appear with serum potassium as high as 4.3. May become dangerous if ignored. Considered “rare” with CyCbl (Cyanocobalamin) it is very common with MeCbl (methylcobalamin) and AdoCbl (adenosylcobalamin) and less so with HyCbl (Hydroxycobalamin).

    There does not appear to be a clear order of onset. The order of onset varies widely from person to person but many appear consistent for each episode for any given person. There tend to be more and more intense symptoms as it gets worse. Some people have ended up in the ER because of not recognizing the symptoms.

    IBS – Steady constipation, Nausea, Vomiting, Paralyzed Ileum,

    Hard knots of muscle, Sudden muscle spasms when relaxed, Sudden muscle spasms when stretching , Sudden muscle spasms when kneeling, Sudden muscle spasms when reaching , Sudden muscle spasms when turning upper body to side, Tightening of muscles, spasms and excruciating pain in neck muscles, waking up screaming in pain from muscle spasms in legs. Muscle weakness

    Abnormal heart rhythms (dysrhythmias), increased pulse rate, increased blood pressure

    Emotional changes and/or instability, dermal or sub-dermal Itching, and if not treated potentially paralysis and death.

    Group 2a - Both

    IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation

    Group 2b – Either or both

    Headache, Increased malaise, Fatigue

    Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency

    These symptoms appear in 2 forms generally, the milder symptoms that start with partial methylation block and the more severe symptoms that come on as partial methylation block gets worse or very quickly with methyltrap onset.

    Edema - An additional thing I would like to mention. I would never have found it without 5 years of watching the onset of paradoxical folate insufficiency and trying to catch it earlier and earlier and to figure out what was causing it and to reverse it. For me the onset order goes back to the day of onset now with edema and a sudden increase of weight. I noticed that within 2 hours of taking sufficient Metafolin I would have an increase in urine output.

    Old symptoms returning


    Angular Cheilitis, Canker sores,

    Skin rashes, increased acne, Skin peeling around fingernails, Skin cracking and peeling at fingertips,

    Increased hypersensitive responses, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms

    IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract,

    Coated tongue, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Increase irritability, Heart palpitations,

    Longer term, very serious

    Loss of reflexes, Fevers, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, bleeding easily

    Group 4 - HyCbl onset, degraded MeCbl onset, MeCbl after photolytic breakdown onset.

    Itchy bumps generally on scalp or face that develops to acne like lesions in a few days from start.
  9. Freddd

    Freddd Senior Member

    Salt Lake City
    Paradoxical folate deficiency causes hyper responses, inflammation, immune problems, demyelination of nerves. The Parkinson symptoms happen typically in people who have low CSF cobalamin, elevated CSF homocysteine and MMA, damage to limbic system and when MeCbl, AdoCbl and/or LCF are taken (LCF will often cause hyper responses) and only way to bring it back up is a very low titration start, like 100mcg (NOT MG) per day. All of the deadlock quartet can increase dopamine by increasing ATP production which was limiting dopamine production before and it all is irritating as all get out to already damaged neurons from ATP starvation for about 20 years (estimate made by researchers of the MMA, etc involvement in Parkinson's). Folks with CSF/ME/FMS symptoms plus anxiety (up to full "Parkinson's personality) tend to have these limbic reactions getting methylation-ATP going. Some people have had reversal of these symptoms on the way to taking a full ordinary LCF dose. Also, people in early pre-diagnosis stages of (Progressive) Supra Nuclear Palsy may have the same responses to the nutrients and may not have distinguishing symptoms yet.

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