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New protocol thanks to Freddd--going off hydroxy B12, starting methyl B12

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by grapes, Apr 6, 2017.

  1. grapes

    grapes Senior Member

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    Freddd has given me excellent info in another post that started out about glutathione, and I want to start a new post and string specifically about what I'm doing, and keep reporting back.

    But first to explain... I found myself with rising B12 six months ago---1500 (top of range 900), as well as rising iron, which at that time was only 116, but that was above optimal for me. I had been taking methyl B12, but not iron. Methyl issues!! I have only one copy of MTHFR 1298, but also realized I needed to pay attention to my other mutations which affect methylation...COMT, MOA-A, MOA-B, four GAD ++ mutations, MTRR, and a few more.

    So I switched to a combo of Hydroxy and Adenosyl....and voila, after testing 1 1/2 month ago, found my B12 "over 2000" with clear symptoms of deficiency (numb little fingers, numbness if I sat down on the floor in legs) and iron at 160. Clearly I couldn't tolerate the Adenosyl either....and the rising iron was a concern--methylation issue....

    So I switched to Hydroxy only...which helped get rid of final symptoms I was having of B12 not getting to my cells.

    BUT....after a month of detoxing (didn't plan that---it happened from my use of 10 mg lithium which I had been using to get B12 to my cells), then clearly stopping the detox....I find myself still feeling very fatigued when I shouldn't have anymore...as of two weeks ago...plus a constant headache. I am not a headache person, yet there it was, all the time. I THOUGHT it was due to having three Meyer's Cocktails that had glutathione in them...and that the glutathione was causing me to detox something else. (My glutathione had gotten low due to a major copper detox in 2015 and another one in 2016. )

    So I came on here to talk about it in another glutathione thread I found...and Freddd saw my post and SET ME STRAIGHT. How?? I am posting a summary right after this that I put together of all that Freddd stated which convinced me I needed to do something totally different here.

    So here is what I have started to do (and the next post which summarizes what Freddd stated....explains why). I plan on using the thread to update my progress. i.e. Today is my third day OFF of Hydroxy B12... and on Methyl B12 at 1000 mcg. Today is also my third day of much higher amount of l-folate--I'm on 1000 mcg as of today...multi-dosed. I HAD been on only 400 mcg...yet turns out it was VERY inadequate for me. I have already been on l-carnitine, which is important in all this. I am also going to take adenosyl B12 twice a week.

    Now I want to state that when I found out from Freddd that I just may be having that fatigue and headache from a FOLATE deficiency, (NOT a detox from the glutathione), I took an extra 200 mcg that night (to equal 600 mcg that day)---that was four days ago. AND VOILA, I woke up with no headache the next morning! BINGO. And I've haven't had that headache since.

    So....I am now starting a new protocol to get myself out of this clear methylation mess and will keep reporting back here to update. Oh, and I need to say that I'm treating a lot of other genetic issues as well as nutrition issues...but that's for another post. SEE MY SUMMARY OF WHAT FREDDD TAUGHT ME BELOW (plus more)
     
    Last edited: Apr 6, 2017
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  2. grapes

    grapes Senior Member

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    The following is a summary I created of what Freddd taught me (in another string that was actually more about glutathione). I especially fit groups 2a and 2b--not yet sure about group 1
    *************

    ABOUT FREDDD: “I cured myself of CFS, FMS, MCS, IBS, about half of my neuropathies, asthma, food sensitivities, congestive heart failure and holding my own on other things. I lost 85 pounds of water, 40+ pounds of fat and rebuilt 50 pounds of atrophied muscle, over 5 years. Healing took constant decisions of what needs to be corrected and how as the symptoms change constantly the first year or so and then slower as most of the symptoms are gone.

    DEFINITIONS: MeCbl is methylcobalamin aka Methyl B12; HyCbl is hydroxycobalamin aka Hydroxy B12; AdoCbl is adensylcobalamin

    SUMMARY OF WHAT FREDDD STATED WHICH IMPRESSED ME AND HELPED ME DECIDE TO DO THIS ALL DIFFERENTLY:
    • What one calls a “glutathione detox” (it's what I thought was causing my fatigue and headaches) is actually acute MeCbl deficiency which causes methyltrap which causes acute methylfolate deficiencies

    • (I am adding this from another source) Methyl trapping or Folate trap is a situation in which folate becomes trapped and unusable by the body. It is defined as a functional folate deficiency that alters homocysteine metabolism such that folate–dependent resynthesis of methionine is compromised. http://datapunk.net/opus23blog/2016/02/20/dont-fall-into-the-methyl-trap/

    • MeCbl is involved in over 600 chemical reactions including the making of enzymes and the making of ATP. It’s an important B12.

    • In the healing process with methyl B12, there can be INDUCED DEFICIENCY SYMPTOMS FROM REFEEDING SYNDROME i.e giving someone a nutrient they have been lacking of, similar to giving someone food who has been starving. There will be a strong response, and usually by the 3rd day. For example, injections of B12 can cause low potassium.

    • When one has bad reactions, they will usually fall into one of the following groups:
    GROUP 1: hypokalemia. i.e. LOW POTASSIUM. And that can happen even as high as 4.3. Constipation is a symptom, as is fatigue and feel bads, increased heart rate, increased blood pressure. Can also occur when trying to give oneself the nutrients one needs

    GROUP 2a: Both hypokalemia and l-methylfolate deficiency Symptoms tend to be diarrhea alternating with constipation, IBS or normal alternating with constipation (I had this for several evenings)

    GROUP 2b: Either or both hypokalemia and l-methylfolate deficiency Headache (Definitely had this) , Increased malaise, Fatigue

    GROUP 3: Induced and/or Paradoxical Folate deficiency or insufficiency, partial methylation block to methyltrap on 1 or more internal triage levels. Frequently called “NAC DETOX” or “GLUTATHIONE DETOX” by people, but it not. Can be caused by folic acid, folinic acid and for some people, like Freddd and quite a few others, excess vegetable folates. Further excess B1, B2, B3 and/or inositol Can increase methylfolate deficiency symptoms. Edema can happen….Freddd noticed that within 2 hours of taking sufficient Metafolin (a brand of folate), he would have an increase in urine output.

    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.

    GROUP 5: Copper deficiency after methylation startup has been achieved which often starts refeeding syndrome. 50mg or more of zinc has been indicated as a possible cause. 200-400 mg of zinc has been linked to copper deficiency. Excess supplemental or environmental manganese is linked to copper deficiency. Any or all symptoms can occur at “low normal range” copper tests.

    GROUP 6: Excess P-5-P, an active form of B6 that appears to drive hematocrit. High hematocrit. The blood thickens and doesn’t pump as easily. Deep vein thrombosis can result. Other suspected circulatory hazards. Sometimes linked to high testosterone when lowering P-5-P might reduce it.

    GROUP 7: Excess B-vitamins affecting methylation When taking the active B12/folate deadlock quartet (AdoCbl, MeCbl, Metafolin, L-methylfolate) Excess B1 - Thiamin, Excess B2 – Riboflavin, Excess B3 – Niacin and/or Excess Inositol (I may have done this to myself) can all produce an excess need for potassium to deal with Groups 1, 2a and 2b symptoms and/or produce an excess need for l-methylfolate to reduce groups 2a, 2b and 3 symptoms. A person might not be able to correct by taking potassium or folate and may need to reduce B1 <= 15mg/day, B2<= 10.2mg/day, B3 <=50mg, and inositol below an unknown quantity.

    GROUP 8 – Boron insufficiency https://www.organicfacts.net/health-benefits/minerals/boron.html Freddd had this.
    • Hydroxycobalamin is perhaps as much as 1% as effective MeCbl and AdoCbl, and the latter raise the cobalamin levels more. They both are the human active and effective kinds. AdoCbl sits in the mitochondria and the MeCbl circulates until used or excreted. Methylfolate increases the serum half-life of MeCbl.

    • Methytrap and folate deficiency symptoms happens when MeCbl is NOT being in the cell when it is needed for cell division, then the methylfolate is dumped out of the cell and the "fail" symptoms are folate. HyCbl causes methyltrap becasue it is NOT putting enough MeCbl in the cell when needed. All the symptoms respond to MeCbl/AdoCbl. Some of them may respond with HyCbl for some people. The cobalamin/B12 numbers are worse than useless except for telling you the house is already burned down. The folate deficiency symptom free range is likely between 7.5mg and 30mg with MeCbl/AdoCbl. HyCbl likely won't do that.
    • Because raising folate/healing can cause potassium deficiency symptoms, Fredd notes he can have with them a potassium level at 4.3 or below. He says he can’t move it out of tissue into serum fast enough to meet need and it appears pretty common. It also is the number one most common potentially fatal side effect of healing.You can't possibly respond fast enough to save your life going by numbers. Go by symptoms and have the potassium at hand. I know people who ended up in the ER

    • A lot of people respond even better to Metafolin as the methyl B12 to use. https://www.iherb.com/r/solgar-folate-as-metafolin-800-mcg-100-tablets/13961/?p=1 and https://smile.amazon.com/dp/B001LR2RVQ?sa-no-redirect=1

    • The big four: MeCbl, AdoCbl, Metafolin and L-Carnitine-fumerate

    • Don’t take different cobalamins at the same time--they can compete with each other for cell use. Methyl B12 needs to be in the cells for use, not the others.

    • Why hydroxy is the worst B12 to take: No matter what the size of the HyCbl you take, about 10 mcg a day gets converted to Methyl and Adenosyl...but only if everything is working right...each conversion needing an enzyme and ATP to convert and which ALSO require MeCbl, AdoCbl, L-methylfolate and the right carnitine for your body. HyCbl consumes both MeCbl & L-methylfolate products and ATP in converting the HyCbl to MeCbl.

    • Why hydroxy is the worst B12 to take: As long as you continue the HyCbl, it makes the methylfolate less useful.

    • Healing with MeCbl does best with over 100mcg absorbed MeCbl into the serum which a 1000mcg tablet will likely do. HyCbl is worse than useless. After you get healing going well and get rid of the symptoms, then try the HyCbl if you want to and see if the healing reverses and the symptoms come back.

    • The serum half life of cobalamins means that 98 to 99% are excreted by the kidney within 24 hours, 99% plus at 2 days. A serum level of 2000pg/ml means that your 5 liters of blood have 10mcg total in circulation. That is what is left after all the excretion typically. Right after taking it or even while absorbing it the serum half life is 20-50 minutes. At 12 hours in the serum half life is 4-5 hours. For the next 48 hours the serum half life averages 12+ hours. When you absorb 100 mcg from a sublingual MeCbl it is at about 20,000pg/ml for less than an hour. During that time it diffuses into most all the cells that need it. Having the high serum level for a little while aids penetration of the cells in all the body's tissues.

    • Generally MeCbl heals you better all by itself because it is the active form that is absorbed and doesn't require the same set of deadlock nutrients to convert HyCbl and folic acid to the active forms.

    • More methylfolate doesn't overcome the problem with using HyCbl.

    • Why Hydroxy is the worst B12 to take: Yes, when taking HyCbl, it will convert to MeCBl by reclaiming broken down MeCbl. So you USE methyl to convert to methyl. You also use adensyl and more folate to break hydroxy down to methy. In studies by the way HyClb only works on about 2/3s of the people being studies. It doesn't work for the other third of people. That has been speculated to be for all sorts of reasons.

    • Why Hydroxy is the worst B12 to take: In converting HyCbl to MeCbl, first the methylfolate or MeCbl donate a methyl group or is routed via SAM-e but still originates or is handed on by MeCbl/methylfolate. It takes the methyl group from one MeCbl to convert HyCbl, plus ATP, plus enzyme to push the uphill energy reaction to MeCbl. It costs more than one MeCbl to convert each HyCbl. It sort of eats it. So it is really quite funny in a very sad way. HyCbl is another competitor for that methyl group that makes the MeCbl so special and is needed to convert HyCbl to MeCbl and then to AdoCbl which makes that very expensive, a second round of enzyme and ATP to convert the MeCbl to AdoCbl. And a lot of people do that poorly.

    • Said Freddd: In my experience almost everybody who reacts to MeCbl also reacts similarly to AdoCbl indicating that converting leaves a lot of hole for many people and that means poorly working mitochondria.. So if a person doesn't have what it takes to convert the HyCbl, it can't work and causes faulty cellular reproduction and/or faulty cell growth. My muscles were the last things that grew/recovered after everything else was fixed.

    • The worsening symptoms when trying to heal are the ones caused by refeeding syndrome, i.e. induced deficiencies of the body trying to heal and not have the exact item needed. B12 and folate works in the body in such a way that some "compartments" are healing at the same time as other compartments are in deficiency with worsening symptoms. That is a flag of healing saying "Give me more of the right nutrients. That's what groups 1-8 above are about. That is a roadmap to induced deficiencies, what you get when you take active B12s and active folate…like low potassium. Healing can be dangerous.

    • HOW TO CORRECT ALL THIS--Freddd states: I would start the MeCbl immediately. If you have a brand that makes noticeable differences before it is even done absorbing that would be a good starting place. 1mg/ 1000mcg with a real noticeable effect is good. On the days you take AdoCbl, once or twice a week is usually good, take it about 6 hours after the MeCbl. That avoids most interference between them and will allow for the best takeup. Get the MeCbl working. I found better results at a given daily dose with l-methylfolate with taking it 3 to 4 times a day because of short serum half life. Many people have a dramatic difference based on type of l-carnitine. My experience is that about 90% of people do well with the L-carnitine fumarate , the actual kind of carnitine that transports the fats to the mitochondria. Some have no effect from LCF. About 10% have great results with ALCAR. It's one or the other. There is another form that might work well. Jarrow has a liquid freebase carnitine in a bottle, great if you have to titrate, or capsules. That often works for both groups of people. I needed 2 doses a day of the freebase carnitine instead of one dose for LCF, again something to do with serum half life.

    • Freddd states: A caution, some people, when they get the all these nutrients working well, have their blood pressure shoot up with CoQ10. I take it now and can't feel a thing from it. When I first started MeCbl and took CoQ10 my BP went up to 190/90 from about 135/70, in 2 hours. So be careful. I had rapid improvement each time I increased methylfolate.but also my potassium need went up (healing flag, cell making). Correct the potassium and know it is indicating healing. Low potassium makes one feel miserable with the symptom on the lists. I have had to take between 1200 mg to 3000 mg of potassium for the past 14 years. Healing can need more folate than 800 mcg, by the way

    • Another thing to try is an active form of B6, P5P. Also pantethine is an active form of pantothenate. It might be more effective, less conversions. But before trying to different forms, you need to get the basic 4 going, the MeCbl, AdoCbl, methylfolate and carnitine..

    • Freddd increased manganese, boron, selenium and molybdenum when he was still having trace mineral problems and got a decrease of symptoms and increase in healing flagged by potassium, 300mg a day increase but don't know which. They often come together because of depleted soils don't have it for the growing foods.

    • This is complicated but just plugging along adding one thing at a time. It is combinations. When people have this refeeding syndrome a characteristic is they have a whole lot of induced deficiencies, and over time all the trace minerals usually show up more slowly than the methylation/ATP influencing nutrients. Once you get going on these things and symptoms are changing it works well to look at the induced symptoms. Some b-complex components can drive the need for folate and potassium too high. Again, that is a later thing after you have all these things working and stable. Then it becomes fine tuning. Some symptoms changing are the effects of them healing. Some are induced by healing and causing deficiencies. It's important to recognize which is which. I hope this helps to explain. One thing to remember, some things have a genuine maximum and others are only a statistical statement like B12.

    • The methylfolate is the only folate, in my experience, to cause MeCbl to have a little longer serum half life.

    • Now lets see you get rid of those symptoms and see what is left. That is how things get chased down. Once you have the healing solidly going the new symptoms will generally fit the pattern on the refeeding syndrome pattern. It gets easier as you go on. Having groups 1, 2 and 3 symptoms pop up when using MeCbl/AdoCbl and Methylfolate happens and are deficiencies of potassium and methylfolate. So one increase doses until the symptoms start fading which can happen and be noticed in hours. Folate can be healing and deficient on different parts of the body at the same time until you get the folate symptom free dose.

    • It is methylfolate deficiencies and/or potassium deficiencies which can be dangerous. Seriously. One way to get some (not enough) is "NoSalt" (potassium chloride) sold in supermarkets as a substitute for salt. Potassium gluconate comes in bulk packages and tablets. I take about 700mg (4 teaspoons, 20 ml) of potassium in each 15 ounce glass of water, 2-3 a day and I take 800mg of tablets with each meal (2). It has little taste, unlike the chloride. And the chloride has a lot more potassium per 1/2 teaspoon and can be added to food. I can barely keep my potassium under control, much more difficult than most people.. "Unstable electrolytes" are normal with some genes I have which is fortunately rare. I also have the usual folate problems and need LCF instead of ALCAR.

    • And an important distinction: The symptoms that change the same day or next are usually healing symptoms. Suddenly worsening or appearing symptoms on the third day or so after a change are refeeding syndrome symptoms and need to be corrected and will respond starting in hours to enough of the right nutrient.. Heal well.

    • Hydroxycobalamin is perhaps as much as 1% as effective MeCbl and AdoCbl. Of course, they raise the cobalamin level more. They are the Human active and effective kinds, the AdoCbl sits in the mitochondria and the MeCbl circulates until used or excreted. Methylfolate increases the serum halflife of MeCbl. Last time my Cbl was tested it was > 220,000pg/ml. I Inject 10,mg 3 times a day to maintain my nervous system along with 30mg of methylfolate.
    • The folate deficiency symptoms with methyltrap is caused by MeCbl NOT being in the cell when it is needed for cell division, then the methylfolate is dumped out of the cell and the "fail" symptoms are folate. HyCbl can cause methyltrap too becasue it is NOT MeCbl in the cell when needed depending upon all sorts of things. All the symptoms on the list below respond to MeCbl/AdoCbl. Some of them may respond with HyCbl for some people. The Cbl numbers are worse than useless except for telling you the house is already burned down. The folate deficiency symptom free range is likely between 7.5mg and 30mg with MeCbl/AdoCbl. HyCbl likely won't do that.
    • From Freddd: My problems with potassium start at about 4.3 and below. I can't move it out of tissue into serum fast enough to meet need. It appears pretty common. It also is the number one most common potentially fatal side effect of healing.You can't possible respond fast enough to save your life going by numbers. Go by symptoms and have the potassium at hand. I know people who ended up in the ER
    ON ANOTHER PAGE EXPLAINING “METHYL TRAP”:

    In the body, Tetrahydrofuran (THF) is formed into methylfolate. Methylfolate needs to get rid of its methyl groups to become THF again.

    THF is used for several things, whereas Methylfolate is being used for one thing: to work together with B12 and form methionine out of homocysteine. While doing that methylfolate loses its methyl groups to become THF again.

    If there's no B12, methylfolate can not be turned into THF again, because it can not get rid of its methyl groups. So there's no nice circle anymore, but a dead end. The methylfolate starts building up. It's trapped. When it's trapped it starts going from the cells to the blood plasma.

    Continue to take folates and no B12 and simply more folates are turned into methylfolate while none is turned back into THF, so serum folate rises while the intracellular folate concentration is going down.

    i.e. Folate works with B12: B12 works with folate. So if one goes up, the other wasn't enough.....

    Freddd states: There is not enough MeCbl for the methyl. Basically the "methyltrap" (hypothesis for 30 years or so) occurs when folate in the cell to complete its function (which happens when hydroxy is taken) and it is kicked out of the cell, causing distinctive folate deficiency symptoms instead of the MeCbl deficiency symptoms that would be expected. It is a more severe level of methylation block than the partial methylation block.

    To heal you need the l-methylfolate and MeCbl hitting the cells at the same time. If you take the folate 30-60 minutes before a sublingual, absorption and retention appears better, usually a small improvement, but then that’s what I have done for 10 years, after the big ones are in place. It became a matter of gaining another few percentage points of improvement over and over again.

    Swallow a l-methylfolate and put the MeCbl AND AdoCbl under you lips.

    METHYL VS ADENOSYL

    Adenosylcobalamin acts as a coenzyme in the mitochondrial methylmalonate pathway, which feeds certain substances into the Krebs cycle to be used as fuel for making ATP. These substances are isoleucine, valine, threonine, methionine, the side-chain of cholesterol, and odd-chain fatty acids.

    Methylcobalamin acts in the cytosol as a coenzyme for the methionine synthase reaction, which links the methylation cycle with the folate metabolism and also helps to govern the flow into the transsulfuration pathway, which feeds the synthesis of glutathione, among other reactions.

    The effect of lowering adenosylcobalamin is to decrease the fuel supply to the Krebs cycle and hence to lower the rate of production of ATP.

    The effect of lowering methylcobalamin (from being on hydroxy B12) is to partially block the methionine synthase reaction, lowering the methylation capacity, and draining the methylation cycle and disrupting the sulfur metabolism in general. The methyl trap mechanism then continues to convert other forms of folate into methylfolate, and this is partly catabolized by reaction with peroxynitrite which forms as a result of the glutathione depletion. The folates thus become depleted, and a chronic vicious circle mechanism is set up.

    And a lot more here: http://forums.phoenixrising.me/index.php?threads/what-is-methyl-trapping.22007/
     
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  3. Freddd

    Freddd Senior Member

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    Salt Lake City
    Hi Grapes,

    Gathering in those more technical descriptions are good to have in there. It's important in this to distinguish partial methylation block from methyl trap. Good health to you.
     
  4. grapes

    grapes Senior Member

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    Ah, then let me send everyone to where your more technical descriptions to me started. Go down NINE comments to where you see my picture....then below that are Fredd's more extensive comments...and from which I got the above summary for ease of understanding to those new to this. Then when you finish reading it all, please come back here and comment or ask questions---you'll see that I posted the link back to here. http://forums.phoenixrising.me/inde...s-initial-detox-last.15381/page-2#post-832898

    I will also continue to post on this string with my journey using Fredd's protocol....for example, I'm curious what a full week of 1000 mcg methyl B12 and 1000 mcg Folate will show in this beginning journey. I definitely feel better even the 3rd day in with higher folate..and hope to see all this improve my newly-acquired poor methylation as of last Fall.

    By the way, I am also working to raise my B6, B5 and biotin, since all were shown to be borderline inadequate on the Spectracell test...same with chromium and manganese. And what SHOCKED me is my Coq10 was shown to be functionally deficient...yet I'm on 1000 mg ubiquinol liquid daily (if I go lower, I become breathless), another approx 400-600 ubiquinol in gel caps. Just added in apprx 500-600 ubiquinone. I probably have mito damage from mold inhalation plus high copper in the past...plus my inadequate B6 is not helping my mito.
     
  5. maz

    maz

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    Hi, thanks so much for all the information Fredd and Grapes. I am having trouble getting my foggy head round it, so could I just clarify - do I take the adB12 and MB12 together or not. I am very muddled and can't figure out which of the statements below is right for escaping methyltrap:
    Near the end of your long post it says, "Swallow a l-methylfolate and put the MeCbl AND AdoCbl under you lips."
    but further up the page it says..
    "Don’t take different cobalamins at the same time--they can compete with each other for cell use. Methyl B12 needs to be in the cells for use, not the others."
    I am grateful for any advice you can give me.
     
    Last edited: Apr 8, 2017
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  6. grapes

    grapes Senior Member

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    Maz, Freddd feels that should be taken apart. As I understand it, you are doing this so that the cells have available methyl B12 and not have the other versions introduced to the cells first.
     
  7. grapes

    grapes Senior Member

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    Oh and I am only taking adenosyl once or twice as week, also as recommended by Freddd, but apart from the methyl B12. I'm on Day 5 of taking methyl B12 with a higher dose of l-folate...in fact, both are at 1000 mcg now. I do notice that my headache tries to come back, probably from inadequate folate levels, but never succeeds.
     
  8. maz

    maz

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    Thanks Grapes, I was doing really well for a month on around 1000mcg mb12, 850mcg adb12 and 200 mcg calcium folinate and 400mcg methylfolate plus potassium and various other supps then, around 10 days ago, I took 2 phosphatidylserine capsules at night (probably unrelated) woke up feeling horrible the next day and the day after that I suddenly got the anxiety feelings people talk about. Thinking It could be a paradoxical folate deficiency, I tloaded up with a lot more methylfolate and mb12 but ended up with pins and needles on the top of my head and restless leg syndrome! I carried on trying to push through but I have today come to the conclusion that I am experiencing excitotocity from excessive glutamate (which I have now learned is attached to all forms of folate). I guess I don't have enough glutathione yet to clear it so I've taken some NAC today and that seems to be calming things down. When I start making enough of my own glutathione, presumably I won't feel the excitotoxicity of the glutamate and can stop taking NAC before getting too much glutathione and depleting my B12. Im aware of Fredd's warning about NAC but I think I needed to do something as I want to protect my brain cells so I still have enough of them alive for when the fog finally clears! I think I will have a day off methylfolate tomorrow and then go back the same as you. I think I may have had too much green veg before so I have cut that out now. It's so hard to figure out what's happening as there are many individual responses to methylation supplements and its not easy to know what each reaction means, ie is it too much, not enough or something else entirely missing.
     
  9. grapes

    grapes Senior Member

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    Maz, that is interesting that taking NAC may have calmed things down. My three Meyer's Cocktails in March with Glutathione (my level went too low due to copper detoxing in 2015 and 2016, so I know I needed to raise it) are what revealed, or lowered, my folate levels.

    Like you, I also have had too high levels of glutamate, which I figured out in 2016, causing excitotoxicity and word recall problems last year. My brain was inflamed--the organic acids test proved that in July of 2016:
    HIGH Quinolinic / 5-HIAA Ratio 2.2 (0.42 - 2.0 ) but I didn't put 2and2 together until September. But in my case, I had two causes---the possibility of mold still in me from a 2013 massive exposure, and four GAD homozygous mutations which equal excess glutamate in the brain.

    Let me tell you what will help you: Rg3 spray. I called a doctor I know to put me on it, and it made a huge difference in a few weeks. I'm STILL on it until I correct this mess. Austin Compounding is the one who makes it and sends it to me. This is the page where I first found out about it: https://www.holisticprimarycare.net...t/1617-is-neuro-regeneration-a-reality-2.html
     
  10. grapes

    grapes Senior Member

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    Time for an update in my journey...as I've hit a potassium-need hell.

    On my 6th day of increased folate, now at 1000 mcg, plus the same with methyl B12, I started to notice a bit of physical fatigue. I took 200 mg of potassium. On my 7th day, BAMM....much more pronounced physical fatigue. I took 400 mcg potassium which relieved it, but it returned that afternoon, so another 400 mcg...except that was too much and I got diarrhea that evening plus some heart palps.

    i.e. clearly my body's need for potassium has increased due to raising the folate...plus have also slightly raised my Biotin, B5 and B6, as Spectracell showed them borderline low. I regret I didn't start on more potassium from day one....

    So today, the 8th day since I raised, I bought and drank a large glass of low sodium V8, and will be supplementing with potassium supps spread out or more V8 throughout the day. I'll do a slightly lower amount of folate today but work on saturating myself with more potassium in several small doses throughout the day.

    I've read that magnesium-need occurs with potassium need when upping B-vitamins, but luckily, my levels are good plus I take 400 mcg magnesium daily anyway. If I take more, diarrhea.

    I love Rich's explanation of all this, as I hadn't yet figured out WHY we need more potassium as we up folate: Now, enter a methylation protocol, which incorporates at least B12 and methylfolate. The effect of this will be to increase the rate of the methionine synthase reaction. One of the effects of this will be to convert methylfolate into tetrahydrofolate more rapidly, and the latter is then converted to other forms of folate, including those needed to make purines and thymidine, which are necessary for making new DNA.

    All of a sudden, the cells now have enough DNA to overcome the arrest of the cell cycle, and their rate of cell division goes up, making new cells more rapidly. These new cells require potassium, and their membrane pumps start pumping it in from the blood plasma. Unfortunately, since the existing cells, which contain 95% of the body's potassium inventory, are already low in potassium, there is no cushion or buffer for the blood plasma potassium level, and if it is not augmented by increased potassium intake from the diet or supplements, the PWC's blood plasma potassium level drops, resulting in hypokalemia. This is hazardous, because it can have detrimental effects on the heartbeat and on other vital processes in the body, such as the use of muscles for breathing.
    http://forums.phoenixrising.me/inde...entation-needed-in-methylation-treatmt.18670/

     
  11. grapes

    grapes Senior Member

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    Also, I need to figure out something. On the same page (link posted above after posting what Rich said), someone states this: I think a simpler explanation for the need for increased potassium in individuals using very large doses (greater than 2mg) of methylcobalamin (MeCbl, MeB12) and/or L-methylfolate (5-MTHF, Metafolin) is that, by overdriving the Methionine (methylation) Cycle, a large amount of S-adenosylmethionine (SAMe) is being produced that has an aldosterone-related effect via increased methylation capacity as explained in the article below. I think this is actually a better fit for your GD-MCB hypothesis as well.

    If I am now creating more SAMe, which increasing need for potassium, I wonder if I need to get off the amount of SAMe I'm on, which is 400 mg.
     
  12. maz

    maz

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    Thanks for the link for RG3 Grapes. I may give it a go later if what I am doing now doesn't work out. Although I am rather wary of Panax Ginseng, which RG3 appears to be derived from, after a bad experience with it last year - 2 days no reaction, 1 day on top of my game, 7 days massive crash!

    I'm feeling pretty good today (9/10). After a few days of MB12 without folate and still feeling function-stopping anxiety and brain fog, I decided the day before yesterday to try nicotinic acid instead of the NAC. Unfortunately, in my fogginess I didn't read up on how much B3 I should take, which turns out to be 50mg every half hour until symptoms subside, and swallowed a 500mg capsule. That resulted in the worst day I have had for symptoms for many years, I felt so weak. However, yesterday I woke up feeling really good! Yesterday I only took an active B-complex (500mcg MB12 and 400mcg methylfolate plus other Bs) without any sublingual B12, and one NAC to smooth the slight edginess that I got and carried on feeling good all day. I feel like I am making progress again. I think I will probably benefit from the 23andme test to get a better understanding of what's going on, so I may go for that after next pay day!

    Have you tried reducing the SAMe to see if you feel better/worse since that last post? I haven't tried SAMe yet. I think I read what you posted, about taking high amounts of MB12 and methylfolate resulting in a lot of SAMe, somwhere before so decided not to.
     
    Last edited: Apr 18, 2017
  13. grapes

    grapes Senior Member

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    My understanding from Freddd's information is that taking 50 mg or more of B3 is going to lead to methylfolate deficiency symptoms, but glad you did feel better and making progress.

    No, haven't stopped the SAMe yet. Still trying to figure out if I should or not.

    Not sure why you cut out the folate?? We badly need it. I have personally moved my methyl B12 up to 1500 mcg and my folate up to 1600 mcg--and will up the folate more as I started having evening headaches a few evenings ago.
     
    Last edited: Apr 23, 2017
  14. grapes

    grapes Senior Member

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    A happy update in this process of improving my methylation: Tested my iron two days ago and it's down from the high 160's to low 130's...the latter still high for a woman, but clearly on its way down to there it should be right above 100.

    But...my B12 has not improved....or at least, I can't see the improvement yet. In January, it was "over 2000" and here three months later, it's still "over 2000". Maybe it went down from 1400 to 1250. lol. Sure hate those "more than" or "less than" ranges.

    But...I know things are improving, because as Freddd has mentioned before, when you start taking the right supps (methyl B12 with higher levels of folate...I was already on L-Carnitine), you'll know the "repair", increased cell division and improved methylation is going on due to the increased need for potassium by the third day...mine was by the 5th day.

    I've gotten increasingly more tired this week, but that could be because I went without potassium for over two days. On my second day back on potassium, so we'll see. Moving my methyl B12 up to 2000 today and folate is around 1600.
     
  15. maz

    maz

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    Great you're doing well now, Grapes. I got tired from lack of potassium after 3 days when I first started with MB12 and methylfolate (1 March 17). A few bananas plus potassium supps sorted that out and I was great on most days for a month after that. Then at the end of March, the wired and foggy feelings started and I've been trying to find my way back ever since. I cut the folate for a few days to see if that was the cause of the wiredness, but the MB12 alone made me wired too. I couldn't function at work like that, hence the B3 to stop it. However, I understand B3 also blocks methylation so it's not a long-term solution.

    The night before last I read Caledonia's documements, "Start low and go slow" and, "Road blocks to successful methylation" and, as a result, yesterday I took smaller amounts - I have gone down to 500mcg MB12 and 200mcg methylfolate, a ratio of 5:2, beween the 5:1 and 5:3 recommended in "Roadblocks". I still got a little wired and resolved it with I x 600 NAC, (no B3). If I can cope with that amount for a while, I can always increase later.
    I've picked up a throat infection so it much harder to know which is fatigue symptoms from that and which is ME/CFS. I megadosed with ascorbic acid, which has stopped the sore throat to some extent, but hasn't completely cured it, which is unusual in my experience.

    I also found research that resveratrol increases glutamate uptake and I was taking that during that month of feeling great. I ran out, not sure exactly when, but didn't bother to order more as I didn't attribute my wellness to it - I have ordered it now and I'm waiting for it to arrive. It probably won't be the panacea I am hoping for, but its definitely worth a shot! I'm also waiting for lithium orotate which may help with the wiredness.

    I also my 23andme test a couple of days ago. So much advice seems to be specific to various genetic factors. I am hoping it will at least give me an idea of what it more likely to work best. I'm in England so it will likely take a while to get results.

    Are you taking phospholipids for cell repair?
     
  16. grapes

    grapes Senior Member

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    Hi Maz. Luckily I've been taking phospholipids for over a year now after I read it can help my mito issue. It's one of those things that I have no noticeable improvement from, but I do have a genetic mutation that says I need it, as well, so I'll stay committed.

    Hoping I figure out what went wrong this week with the progressive fatigue. Was it going without the V8 juice/potassium those two days? It my guess. But this is day 3 back on the V8 and I'm surprised I'm still physically tired. I'll have to see how I do tomorrow, I guess.

    One thing I've noticed is I seem to have an increase in lactic acid this week, too. That is always a mito issue for me.
     
  17. grapes

    grapes Senior Member

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    You know, I've noticed something very clearly this week--my lactic acid levels have increased to the same degree that my fatigue has increased...and this seems to clearly correspond with increased cell division/methylation since I started on rising levels of folate, plus went back to methyl B12, nearly 18 days ago...

    So it all makes me wonder---has this improved methylation added much more stress to my already-compromised mitochondria?? I am thinking so.


    I know I have some form of mitochondrial dysfunction. My Organic Acids Test proved that. I also require quite high amounts of liquid CoQ10 (ubiquinol) to function--gel caps do practically nothing for me, thus the need for liquid. And those with mito dysfunction, which can mean those with CFS/ME, can easily switch to anaerobic form of energy which causes rising levels of lactic acid. And I have definitely noticed more lactic acid being produced this week at the same time my fatigue has increased.

    Myhill states that the body is using glucose to make the conversion into lactic acid. So that can mean I need d-ribose more acutely right now, which I have started tonite.

    She also states: When mitochondria function well, as the person rests following exertion, lactic acid is quickly converted back to glucose (via-pyruvate) and the lactic burn disappears. But this is an energy requiring process! Glucose to lactic acid produces two molecules of ATP for the body to use, but the reverse process requires six molecules of ATP. If there is no ATP available, and this is of course what happens as mitochondria fail, then the lactic acid may persist for many minutes, or indeed hours causing great pain. (for the biochemists, this reverse process takes place in the liver and is called the Cori cycle). (from http://drmyhill.co.uk/wiki/CFS_-_The_Central_Cause:_Mitochondrial_Failure--a page I love)

    Bottom line, I am strongly surmising that improving my methylation with higher doses of folate and methyl B12 is now stressing my already-stressed mito...so all I know to do is take d-ribose while going through this (bottle says 1 1/2 tsp a day) and I may need to increase my already-high liquid Coq10. Yes, I already take all sorts of mito supplements like PQQ and more, but they haven't changed this mito problem I have. I may have a biosynthesis problem.

    P.S. I'm pretty sure that my mito problem is due to mold inhalation a few years ago, following by high copper and lead, both which I have since lowered. I also have high cadmium which I have never been able to lower---chem trails)
     
  18. grapes

    grapes Senior Member

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    Whoops. Got a dropped screw in the escalator here.

    My Nutrahacker report suggests that because of three particular COMT genes I have, i.e. rs165722 (++), rs6269 (++) and rs5993882 (+-), Methyl B12 should be avoided and Hydroxy B12 favored. This probably means those are all three "slower COMTs", meaning I may not be using up methyl groups vert quickly, and might need to be careful about adding more methyl donors like methyl B12 to my body. (Also mentioned here: http://forums.phoenixrising.me/index.php?threads/interesting-comt-variations.24672/)

    I did find a discussion about these COMT mutations here with methyl B12 (bolding is mine for emphasis):

    Since COMT +/+ mutations slow the activity of the COMT enzyme, this variant slows dopamine metabolic activity, allowing dopamine levels to build. As a result, these higher levels then feed back and inhibit additional dopamine synthesis. For this reason, individuals who are COMT +/+ seem to have a reduced tolerance for methyl donors.

    So what is the best approach to B12 use for those who are COMT +/+ as compared to those who are COMT-/-? According to published work by Dr. James Neubrander, no toxic doses of B12 have been found, and this medical finding is supported by my clinical experience. Parents report back that “the more B12, the better.” In some cases, elevated doses of B12 (50 milligrams and above) have helped to stimulate speech in formerly apraxic children.

    However, those who are COMT + often cannot tolerate high doses of any methylating agents. For this reason, I tend to focus more on the use of hydroxylcobalamin B12, dibencozide (adenosyl) B12, and cyanocobalamin B12 for those who are COMT +/+ and to use methylcobalamin B12 along with these other forms of B12 for those who are COMT-/-."

    Freddd says people like us should stop any form of carnitine for a few days till it fades from the system then use a combination of MB12 and ADB12 for example starting on 10 mcg and slowly titrate up to 100 mcg daily.

    Knowing your COMT status is not enough by the way. Do you also have no mutations on VDR? Because it makes things worse.I have none for VDR.
    http://forums.phoenixrising.me/index.php?threads/comt.20337/

    I'm on 2000 mcg Methyl right now...and I don't know what they mean about "not tolerating it". Is my current physical fatigue and increased lactic acid an example of "not tolerating it?" Or is it simply a sign of healing? I see others with this questioning....

    And I wonder if I need to move over to the recommended hydroxyy/adenosyl/Cyano?? Yet I see Freddd stating to stick with Methyl and Adenosyl but in low doses...but will a LOWER amount of methyl and adenosyl give me good B12 levels??

    And why is it recommended to stop carnitine before starting on methyl and adenosyl?? I didn't do that. I've been on carnitine for 1 1/2 years. And if you read the last statements above about VDR, I have two +- VDR mutations.

    Then you see alicec stating this (but for the time being, I'm believing what I quoted above):

    It is a myth that COMT +/+ means you cannot tolerate methyl groups (and) The VDR SNPs have little effect.

    Now I love what Freddd explained here (4th comment down) from 2010 in a string started about having too many methyl groups (which would be a possibility if one has slow COMT mutations):

    Finally consider that no body is actually deficient of hycbl or cycbl (and he then explains that it CAN be deficient in methyl and adenosyl...) He also states that "hycbl demonstrates that it is NEVER sufficient. It never fills the b12 needs of the body to the point that there is nothing left to demonstrate startup responses for either mb12 or adb12." A lot more here: http://forums.phoenixrising.me/index.php?threads/too-many-free-methyl-groups.5983/
    For my situation as having had had high copper and lead in 2015, and high copper again in 2016, this was interesting from Joopiter76 and if true, underscores that I probably still need Adenosyl B12, which Freddd said to take twice a week:

    A-B12 [Adenosyl B12] works in the mitochondria and if you have massive oxidative or nitrosative stress inside them, A-B12 will become depleted faster than it can be generated from M-B12 or Oh-B12. http://forums.phoenixrising.me/index.php?threads/too-many-free-methyl-groups.5983/

    But Rich stated the following, and my MMA was NOT elevated upon testing this year...so who knows:

    an elevated MMA usually indicates that the cells do not have enough adenosylcobalamin.

    THEN finally comes Rich's comment about overdriving the methylation (which could happen with COMT issues plus higher doses of methyl B12):

    My concerns about overdriving the methylation cycle are first that if methionine synthase is driven too fast by high levels of 5-methyl THF and methylcobalamin, too much of the homocysteine is converted rapidly back to methionine, so that not enough is available to go down the transsulfuration pathway to form glutathione. I've seen results of organic acids and amino acids testing on people who were taking high dosages of methylcobalamin, and I think this concern was born out. I think this will slow the progress of recovery, and slow the detox of stored toxins. Second, I'm concerned about the possible effects of overmethylating the DNA. I don't know what the effects of this might be. DNA methylation controls gene expression, and the methylation capacity is normally tightly controlled in the body. Taking high dosages of methylcobalamin might override this normal control, and I think we should be cautious about doing that.
    But on page two, Freddd states this, which I like (which could imply that my increased physical fatigue this week is not about too many methyl groups with my COMTs, but about the healing process, which I believe is the same as his term "startups"):

    Telling somebody to avoid methylb12 because of it's meager quantity of methyl groups in light of the quantities of methyl groups from other sources, it ought to be clear the startup effects of mb12 are about all sorts of other things but very little attributable to the methyl groups it brings into the body per se. Mb12 isn't magic. It's donatable methyl groups are not magically 1000 times more powerful than the methyl groups from other sources. Since it clearly isn't based on the quantity of methyl groups brought into the body by mb12 it has to be the qualities of the complete methylcobalamin itself, and there are several forms of mb12 with somewhat different effects and effectiveness that has nothing whatsoever to do with the methyl group itself. http://forums.phoenixrising.me/index.php?threads/too-many-free-methyl-groups.5983/page-2

    And more from Rich about "startups", which possibly is what my fatigue is about since I started back on methyl B12 with high doses of folate:

    As the startup responses are the sum of a whole lot of stalled and broken processes, they are perceived as a worsening and/or shifting of symptoms requiring some days to months to diminish, change and improve.

    And I very much like what Freddd stated to Joopiter considering I have clear mito issues as revealed on two different OAT tests and my symptoms:

    In my experience very few people actually fullfill the practical need for adb12 by taking cycbl, Hycbl or mb12. Taking adb12 directly after 6-12 months on any other form of b12 will cause an immediate startup effect as the mitochondria start working better. Adb12 goes into the mitochondria and stays for the life of the cell as far as I know. In practical terms, body level (muscles mostly) turn over only at cell death. B12 dosn't normally "oxidize". However, cyanide will convert it to a plus 3 oxidation state as cyanocobalmin if the cyanide can get at it. Nitrous oxide does the same, oxidzie it permanently. As adb12 is locked up in mitochiondria it does not appear to be available as vulnerable to all the problems mb12 is vulnerable to. It takes me about 3 weeks without adb12 to develop enough unmet demand that I notice a dose at all. If it was only for my body I would take a single 3mg sublingual once a week. As I also have a CNS level deficiency as demonstrated by a sudden startup response to a 51mg sublinguial dose. However, that can be duplicated by 18mg taken as a single dose once a week 1 hour folowing an injection of mb12. One person I know requires 15mg/day or so to keep brainfog at bay.

    I'm ready to take a break from looking all this up, so will stop for now. My current conclusion is to continue with Methyl B12 daily, but probably not any higher than 2000 mcg for the time being, taking the Adenosyl twice a week as well, and perhaps adding in a little Hydroxy a few times a week at a separate time from the Methyl. And l-folate will continue to be a MUST, especially since I have mutations that make it inadequate....I'm at 1600 mcg right now. ANdddddd, I will have to accept this physical fatigue sadly...for the time being....
     
  19. Valentijn

    Valentijn Senior Member

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    @alicec is correct - the recommendations for methylB12 versus hydroxoB12 are based purely on speculation. In reality, people have to try them to see what works for them.

    And it's very unlikely that VDR Bsm has anywhere near the impact attributed to it. In studies, the effects of it on gene function are very small. VDR Taq should not be taken into consideration at all because 1) it's in very strong linkag disequilibruim with VDR BSM, so has no cumulative impact on top of BSM, and 2) Yasko reports it backwards so that literally everyone will have a supposed VDR problem.
     
  20. sregan

    sregan Senior Member

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    That's interesting! Wonder if just boosting the thyroid might lead to MFolate deficiency or it's specifically related to T3?
     

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