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
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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/