Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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B-Complex without Folic Acid

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by arx, Sep 14, 2012.

  1. Lotus97

    Lotus97 Senior Member

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    I see, so you're getting benefit from B12 alone which is why you're taking the dose you are? I assume you're taking the B12 sublingually? The only reason I ask is because you mentioned the part about the gut and also because I was surprised a COMT could tolerate that much methylcobalamin. BTW, the standard B12 tests aren't very accurate at least in determining how much B12 you need. I don't remember the reason why.
    That is a tricky thing to answer since you're getting benefit from high doses of B12, but you're also COMT which means if you're taking a lot of B12 or even a low to moderate dose of B12 you're not going to be able to tolerate much folate. Maybe you can find some kind of balance where you still get benefit from B12, but are also able to take some folate because you need both. One reason Rich recommends the dosages and ratios is because he's concerned about overdriving the methylation cycle. I don't know much about SNPs, but COMT tend to be overmethylators. Have you tried lowering your dosage of methylcobalamin? Maybe try gradually lowering it until your symptoms return. Once you find the dosage of B12 you need then you can figure out how much folate you can tolerate.
    The other reason why Rich recommends those specific starting dosages are because similar dosages were used in a study he and Dr. Neil Nathan conducted on CFS patients.
    http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf
    Some people need higher doses which is why he gave instructions on increasing dosages (if necessary) when he revised his protocol last year.
    According to Rich's theory of glutathione depletion, it seems that most people here who need methylation would be depleted of gluathione causing a B12 deficiency which would then cause a folate deficiency. I don't know what your situation is though so I can't answer whether you need methylation or not, but this is what he said. The first quote is a summary of Rich's Glutathione Depletion-Methylation Cycle Block theory. The second quote explains why the need for a high dose of B12 for the people here.
    =================================​
    According to the GD-MCB hypothesis, if glutathione goes low enough, it provokes a functional B12 deficiency, which in turn leads to a partial block in methylation, followed by loss of folates and development of a stable vicious circle that makes ME/CFS chronic.

    Best regards,

    Rich
    =================================​
    Why is the dosage of vitamin B12 so high for ME/CFS treatment?


    Hi, all.

    The above question has been around for quite a few years, and we haven't had a good answer for it. I think it is now possible to answer it, based on some recent research in Korea.

    Here's some background: In the 1990's, Drs. Charles Lapp and Paul Cheney initiated treatment of their CFS patients by injection of vitamin B12, after observing that many patients had elevated homocysteine or methylmalonate in urine testing. They found that there was a threshold of response at between 2,000 and 2,500 micrograms per injection to produce an improvement in energy, stamina or wellbeing that lasted for two or three days. Lower dosages did not appear to produce improvements. This was puzzling, because the recommended daily allowance (RDA) for vitamin B12 in adults is only 2.4 micrograms per day. Why did the dosage need to be so high to produce improvement in symptoms?

    As many of you know, the sublingual hydroxocobalamin dosage in the Simplified Methylation Protocol today is comparable to the injected dosages that Drs. Lapp and Cheney found to be necessary, still very high compared to the RDA dosage, and this question has remained. (I note that high dosages of B12 are also used in autism, which shares much of the same pathophysiology with ME/CFS.)

    O.K., in 2011 a paper was published by two researchers in Korea, Jeong and Kim. The abstract is pasted below.
    The research they report was actually done on a bovine (cow) B12-processing complementation group and cyanocobalamin. However, the human complementation group is very similar, and I suspect that the results will also be similar for other forms of B12 than cyanocobalamin.

    They studied the CblC complementation group. This is part of the B12 processing pathway that is found inside all cells. When a form of B12 comes into a cell from the blood by the usual transcobalamin route, it is bound to CblC, and its beta ligand (cyano-, methyl-, or adenosyl-) is removed. Then it is sent on to be converted back to methylcobalamin or adenosylcobalamin as needed by the cell.

    In order for this processing to happen, the CblC complementation group must first bind the B12 form. The strength of binding is called the affinity (Kd), and it is measured in concentration units. The higher the affinity, the lower the Kd. It turns out that the bare CblC complex has a relatively low affinity for B12, compared to the concentration of B12 in the cells, and this would be unfavorable for the necessary binding, and would tend to lower the reaction rate.

    What these researchers found is that normally glutathione binds to CblC, and in doing so, it increases the affinity of CblC for B12. And it does so by a whopping amount--over a factor of a hundred!!

    Turning this around, if glutathione becomes depleted, as in ME/CFS and autism, the affinity of CblC for B12 is going to drop substantially. I suggest that the glutathione depletion, combined with its major effect on this affinity, is the reason the B12 dosage must be so high in treating ME/CFS and autism.

    Best regards,

    Rich


    Biochem Biophys Res Commun. 2011 Aug 26;412(2):360-5. Epub 2011 Jul 29.

    Glutathione increases the binding affinity of a bovine B?? trafficking chaperone bCblC for vitamin B??.

    Jeong J, Kim J.

    School of Biotechnology, Yeungnam University, 214-1 Dae-dong, Gyeongsan-si, Gyeongsangbuk-do 712-749, Republic of Korea.

    Abstract

    Intracellular B(12) metabolism involves a B(12) trafficking chaperone CblC that is well conserved in mammals including human. The protein CblC is known to bind cyanocobalamin (CNCbl, vitamin B(12)) inducing the base-off transition and convert it into an intermediate that can be used in enzyme cofactor synthesis. The binding affinity of human CblC for CNCbl was determined to be K(d)=?6-16 ?M, which is relatively low considering sub-micromolar B(12) concentrations (0.03-0.7 ?M) in normal cells. In the current study, we discovered that the base-off transition of CNCbl upon binding to bCblC, a bovine homolog of human CblC, is facilitated in the presence of reduced form of glutathione (GSH). In addition, GSH dramatically increases the binding affinity for CNCbl lowering the K(d) from 27.1 0.2 to 0.24 0.09 ?M. The effect of GSH is due to conformational change of bCblC upon binding with GSH, which was indicated by limited proteolysis and urea-induced equilibrium denaturation of the protein. The results of this study suggest that GSH positively modulates bCblC by increasing the binding affinity for CNCbl, which would enhance functional efficiency of the protein.

    Copyright 2011. Published by Elsevier Inc.

    PMID: 21821010
     
  2. Victronix

    Victronix Senior Member

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    Thanks. It's great that you are like a living search engine for Rich's discoveries and theories.

    Yes, I'm taking B12 sublingually. The start-up symptoms were extreme and I was forced to scale back to increasing in 500 increments and less, early on. Years later it was easy to increase by 1000 if necessary.

    Yes, the standard B12 tests aren't very accurate at least in determining how much B12 you need, but they can give a rough estimate of when you are too low. When your lower legs and feet are numb to the point of feeling like you are standing on two wooden clubs, you either have diabetes or B-12 deficiency, or something even worse, so it was pretty definitive in my case, given the low serum level. When it gets tricky is when the serum levels are close to the limits for "deficiency" or not. Some people's serum levels can be above what's considered deficient but still have a real deficiency.

    I had a spectracell test that showed my glutathione to be normal, but apparently that test may be useless according to some on here, and the methylation panel would be necessary to really know if that is depleted or not.

    Here's what spectracell test does --

    "The micronutrient tests measures how micronutrients are actually functioning within your patients’ white blood cells. . . . SpectraCell’s patented, chemically-defined control media contains the minimal amount of each essential micronutrient that is needed to support optimal lymphocyte growth or mitogenic response. The functional intracellular status of micronutrients involved in cell metabolism is evaluated by manipulation of the individual micronutrients in the media followed by mitogenic stimulation and measurement of DNA synthesis." http://www.spectracell.com/clinicians/products/mnt/
     
  3. Lotus97

    Lotus97 Senior Member

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    Have you tried benfotiamine, or is that only for diabetic neuropathy? Also, folate is used in neuropathy treatment such as in drugs like Metanx. It seems P5P (coenzymated B6) is also used for neuropathy. Have you tried a more diverse strategy such as P5P, folate, and B12 together?

    Do you think you have CFS or just a B12 deficiency? I don't know enough about either to know the difference. Phoenix Rising is a huge community made up of people with all sorts of illnesses brought together under the umbrella of CFS/ME. For myself, it seems that Lyme disease caused the onset of my symptoms. Many people here have various viruses or coinfections. While others have metal, mold, and/or chemical toxicity. We're just beginning to scratch the surface in terms of research as to the cause of our illnesses. I don't know if you need methylation or not, but I think everyone needs some folate. I would recommend to even relatively healthy people vitamins A, B, C, D, E, and K along with the basic minerals. Plus various other supplements such as carnitine and coenzyme q10/ubiquinol. Especially for people who are either ageing, have a physically demanding profession, or who engage in athletic activities.
     
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  4. Victronix

    Victronix Senior Member

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    P5P and B-12 together have been in B-Right, so I've been taking those for years, but with the addition of methylfolate, once I had it without vitamin C, I was overwhelmed by the folate effects.

    I don't think I have CFS (and don't want to end up getting it, am pretty fragile in many ways) and it's not entirely clear why I have B-12 deficiency, but my genes appear messed up enough to be the cause of several things.

    Lyme disease seems pretty horrible. I have relatives in Massachusetts, one of whom has gotten it and did a long bout of antibiotics, appears to be okay. Just walking around a campus in that state there are the signs out warning students about Lyme. I would be paranoid to be there since my immune system is so fragile.
     
  5. Lotus97

    Lotus97 Senior Member

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    I mentioned this one earlier, but it's on sale for 30% off until March 30th. It has a combination of coenzymated and non-coenzymated b vitamins and 500 mcg of folinic acid.
    http://www.myvillagegreen.com/pathway-b-complex-50.html
    Actually, everything made by Pathway (the brand that makes that b complex) is on sale for 30% off until the 30th. I'm not sure how many other things are worth buying. This has a low dose of coenzymated B1, B2, B6. It also has manganese, malic acid, magnesium, and glycine.

    http://www.wellnessresources.com/products/magnesium_muscle_mag.php
    Due to the amount of manganese, I wouldn't recommend more than one a day unless it's your only source of manganese. Even then, I'm not sure it's a good idea to go much higher without getting your minerals tested. I take a relatively high dose of certain minerals and I haven't been tested, but I certainly wouldn't recommend that to anyone else.
     
  6. Lotus97

    Lotus97 Senior Member

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    rachel
    I'm not sure if you went ahead and bought the Thorne b complex, but if you or anyone else is looking for b vitamins that are excipient free (some have fillers in the form of rice flour, but no stearate) Nutrabio is selling them. I haven't read through the description of every single one so you might want to doublecheck, but it does look like they're clean.
    http://www.nutrabio.com/category/vitamin/
    Their b complex does have folic acid, but you can take the b vitamins individually. Don't forget biotin. Inositol and PABA might also be good, but I don't know if they're necessary. I think there are some other brands that sell R5P and P5P without fillers so you might want to consider those instead of B2 and B6, but too much of either will increase methylation which may or may not be desirable depending on the individual. They also sell methylcobalamin in 1000, 2000, and 5000 mcg capsules. I have no idea of the quality since it can vary a lot depending on the brand of methylcobalamin, but it's about the only option other than Thorne's if you want methylcobalamin without the additives. I know some people are concerned about taking B12 sublinguals that have sorbitol and other additives. Nutrabio also sells a lot of amino acids and some minerals.
     
  7. Whit

    Whit Senior Member

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    This is pretty frustrating trying to figure all this out. Every time I try to read this thread and figure out how to get some B vitamins, I just get exhausted and have to stop.

    Where are the doctors that should be helping us through this? WTF
     
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  8. Lotus97

    Lotus97 Senior Member

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    Was there something specific you had a question about? Sometimes I don't feel like reading all the way through a thread either to get answers. I have a bunch of links to threads I plan to read saved in a text document.
     
  9. Unim

    Unim

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    Snowdrop likes this.
  10. Snowdrop

    Snowdrop Rebel without a biscuit

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    Looks good although rather pricey.
     
  11. Freddd

    Freddd Senior Member

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    Hi Snowdrop,

    It is usually easier to find that kind of low dose basic B-complex with CyCbl or folic acid in a supermarket or drugs store. Twice a day is needed for some factors. To much B1, B2 and/or b3 causes way too much potassium and methylfolate to be needed and cuts down healing. The one I buy at a drugstore in town here is US$6/100.

    One needs to be careful as paradoxical folate deficiency form folic acid or folinic acid looks just like donut hole paradoxical folate insufficiency. These symptoms are relieved by usually somewhere between 1600mcg and 30,000mcg of Metafolin. The testing for Deplin says so much. "Deplin (pure Metafolin) is generally well tolerated and has side effects similar to placebo". Cerefolin with NAC on the other hand has all the usual Nac-Glutathione "detox" symptoms of paradoxical folate deficiency.

    The normal side effects of methylfolate is low potassium, also generally called "detox".
     
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  12. Snowdrop

    Snowdrop Rebel without a biscuit

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    @Freddd

    Hi Fred,

    Thanks for posting your thoughts to me regarding the B vitamins and folate.

    Although I have been posting here and there I have not had anything scientific to add to any of these discussions.
    But what I wanted to convey re my posting is that although I might string a few words together that (hopefully) make sense I have a great deal of problem at the moment with understanding what others write especially when it comes to discussing how to go about following a vitamin protocol. I didn't use to have so much trouble but there you go.

    I have read some of your posts elsewhere and again more recently as I just purchased some 5-MTHF.
    I want to post more (elsewhere) at some point regarding this.

    On the subject of what you wrote above: I have spent endless hours scouring the web looking for a low dose vitamin B complex that did not include CyanoB12 and folic acid. Are you suggesting that taking these would be OK because they are low dose and/or because one is supplementing with the 'real' thing?
    SD
     
  13. Freddd

    Freddd Senior Member

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    No
    Hi Snowdrop,

    Are you suggesting that taking these would be OK because they are low dose and/or because one is supplementing with the 'real' thing?

    No. I am suggesting low dose b-complex so as not to have too much B1, B2 AND/OR B3 when taking 2 a day. Folic acid might be ok for some people. However one will never find out without stopping all folic acid.
     
  14. ahmo

    ahmo Senior Member

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    @Snowdrop, Swanson makes a low-dose B complex w/ all the right forms (ie MFolate, P5P...). It's what would be called a 25 mg B complex, w/ 25mg B1,2,5,6; 50mg B3. I'd been dividing the caps into 2 doses. Yesterday I used my little capsule filling device, and within 1/2 hour had created 50 caps of 12 mg B complex (1/2 the original dose), so I can now easily take low dose B twice a day. (Is that coherent??) cheers, ahmo

    https://www.swansonvitamins.com/swanson-ultra-activated-b-complex-high-bioavailability-60-veg-caps
    http://emptycaps.com/fillers.html
     
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  15. Snowdrop

    Snowdrop Rebel without a biscuit

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    Thank you for the suggestion. I just had a look at the link, it just might be useful.
    SD
     
  16. Adlyfrost

    Adlyfrost Senior Member

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  17. uyb101

    uyb101

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    I had 3 lots of Vitamin B12 shots in Bali at the end of last year, however it didn't seem to have that greater effect.

    I also tried making my own, I got a cheap one, the quality wasn't the best but it did the job alright. The issue I have is getting the dosage correct. Also I find the extract ratios of the powders kinda confusing. I wish companies were a little more straight forward with that information. It is definitely frustrating trying to figure this all out especially when my minds struggling!
     
    Last edited by a moderator: Sep 28, 2017
  18. Freddd

    Freddd Senior Member

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    Hi uyb101,

    I'm not sure what you are saying. It sounds like you are asking about concentrations of solutions.

    Let's keep it simple. If you are mixing an MeCbl or other crystal-powder different mixes have different problems, If one mixes 50 ml (50 grams of sterile saline) mixed with 1 gram of powdered B12, that approximates a 20 mg/ml concentration. If it is all put in at once it can solidify instead of dissolving. That is a preferred concentration for injecting but is inconvenient for an oral or nasal spray. B12 solution forms hydrates and the whole bottle can solidify but melts with warm water. For oral or nasal spray I use approximately 10mg/ml. That doesn't clog the sprayer with hydrate crystals. That requires 100 ml of sterile saline (100 grams, 1 deciliter). The concentration is not exactly 10mg/ml or 20 mg/ml but very slightly less. If you are talking about mixing various vitamin powders for a custom solution, you need a recipe and an adequately accurate scale. Mixing these solution yourself is like fresh foods, they don't have preservatives and need to be refrigerated and some things will break down quickly. One of the solutions people make also is Carnitine freebase. If a person has to microtitrate they need to make a very weak solution like 100 mcg per ml. It's the very low dose and slow increment that lets one do that. So depending upon the concentration started with a person might dilute 1 drop to 100 drops and use 3 drops for instance. It's a matter of being precise. Good puck.
     
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  19. Athene*

    Athene* Senior Member

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    Hi @Freddd If you get time, can you say how much Methyl B12 you use daily these days? Last time I saw your intake I think it was 3 x 10mg injected plus sublinguals (30mg?) daily. Do you use the nasal/oral spray as well as the injections or as a substitute for injections? Do you still use sublinguals as well?

    I am asking this because I had most of the symptoms and all of the responses as you had to your regime of supplements (many thanks to you for posting details over the years) and also have multiple genetic polymorphisms that interfere with B12 & folate intake & recycling (& pernicious anaemia, undiagnosed for decades) and I have same responses as you have had to folinic acid, vegetable folate and whey, also to excessive b1, b2, b3.

    I inject daily (from a reliable lab) and try to get as near as possible to a CNS penetrating dose (decades of deficiency leading to neuro issues) but can't procure (or afford!) the doses you use. Have you had to increase your intake to more than 30mg injected daily for CNS protection?
     
  20. Freddd

    Freddd Senior Member

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    HI Athene,

    I'll tell you about the series of injections a number of us tried. The Japanese were experimenting with 50mg doses of various kinds and managed to turn on CNS healing. We duplicated the results with sublingual tablets ranging from 30 to 50mg. When we went to injections, all of us trying it had no CNS effect at 6mg subcutaneous and we all had CNS effectiveness at 7.5mg SC. Then to maintain it for 24 hours we tried various things. I was able to maintain it at 4x 7.5mg a day or 3x 10 mg per day. A couple of people were able to go to 2x 15mg SC. All 3 of those were 30mg/day. That appears to largely depend upon individual absorption rate and excretion rate.

    I find that a plain sterile saline with MeCbl is absorbed well as a nasal spray at 10 mg/ml in a metered sprayer giving 1/10th ml per spray.. One spray in each nostril about each half hour works well. It gets up to and maintains the CNS level. First one appears to get 3-4% direct, near immediate absorption. Putting so much in at a time that it runs down the throat is a waste. It all ends up going down the throat in any case, works better slowly. A thin film absorbs just as well as one that runs off. Then it slowly is moved towards the throat, 12-24 hours perhaps and then the stomach. So one has the 4% or so absorbing in the nose and sinuses appearing to get to the brain very rapidly. Then there is several more percent absorbed from the absorption on the way to the throat. Once it starts down the throat, how much is absorbed depends in part how well your TC1, IF and TC2 are working. If they are working you might absorb another 10-20 mcg a day. Then as passive absorption in the gut as a whole, that is another 1%. However, it does introduce a time release effect. You get a trickle of absorption 24 hours a day after several days.


    I have found that the nasal spray can be an acceptable substitute for the injections at perhaps 20+ mg a day, the way I absorb MeCbl. You may have different absorption through the olfactory nerve interface. You may find that 5mg/ml works equally well. I don't know. I haven't explored that too well yet. I buy crystal and mix my own nasal spray and refrigerate it like a fresh food.. I'm experimenting with 1 injection a day, and then maintenance of level with the more direct nasal spray. as more appears to get into the CNS. I don't use the sublingual tablets right now. I do use at the same time as nasal, I use the same fine spray in the mouth, roof, cheeks, both sides of tongue, perhaps 4 sprays twice a day. Again, only the B12 in contact with skin gets absorbed, a thin coat is as good as a thick one as all the excess runs off. So I spray in mouth, and keep my mouth open for some while until I have to swallow. I can feel the effects of the trans nasal quickly, like I used to be able to feel the sublingual.

    I haven't changed the B12 dose particularly. I have finally reached a reasonably stable place with 45 mg of l0-methylfolate a day, phosphatidylcholine, 10mg sublingual of AdoCbl daily, 1200 mg SAM-e, and TMG. This helps the ATP methylation branch. The other methylation branch is from MeCbl- mfolate branch reprocessing HCY to methionine. It's reducing inflammation..

    After these things work for a while then trace minerals usually become a problems. I'll send you the newest version with the trace minerals as far as I can.

    Version 2.3 10/20/2017 A work in process, incomplete, limited testing, people come in many variations, use at your own risk.
    INDUCED DEFICIENCY SYMPTOMS FROM REFEEDING SYNDROME. This can follow 5 days of food deprivation, anorexia, or sort of a pinpoint starvation via vitamin or mineral or amino acid deficiencies. Whatever the “most needed” item is will often cause a strong response. The first usual notable symptoms occur on typically the third day of starting a previously insufficient nutrient. For instance it was noted in the 50s with injections of B12 with potassium deficiency (hypokalemia) as a side effect. It is dangerous and can be unpredictably fatal if not corrected and the cause is continued. When they say people are dying in Syria after they have been starved and given food, they are often sufferring REFEEDING SYNDROME. When previous symptoms return

    Group 1 – Hypokalemia onset. Often called “detox”. 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 hypokalemia and l-methylfolate deficiency
    IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation

    Group 2b – Either or both hypokalemia and l-methylfolate deficiency
    Headache, 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”. Can be caused by folic acid, folinic acid and for some people, like me and quite a few others, excess vegetable folates. Further excess B1, B2, B3 and/or inositol can increase methylfolate deficiency symptoms. Methylfolate, MeCbl and just about anythjing else that starts healing can cause the folate deficiency symptoms.

    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 in a general sense, a person may have had onset of these hundreds of time if they are on the borderline
    Edema
    Angular Cheilitis, Canker sores,
    Skin rashes, increased acne, Increased itchy acne on scalp and face, Skin peeling around fingernails, Skin cracking and peeling at fingertips, painful cracks in the skin at the corner of fingernails at approximate right angles to nails, can take months to occur and it may be only non mood or neurological symptoms.
    IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation
    Headache, Increased malaise, Fatigue
    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.

    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.

    Demyelination of nerves similar to Sub Acute Combined Degeneration except that methylation and ATP startup has occurred, and copper deficiency favors damage to the upper motor neurons with perceived muscle weakness. Brittle nails. Sleep disorders. Mood (especially depression perhaps) and personality changes. Connective tissue breakdown. Spider veins. Varicose veins. Shrinking gums. Gum disease not responsive to usual measures. Unstoppable tooth decay on exposed areas without enamel. Low testosterone

    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 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.
    Arthritis swelling and pain, can be reduced by Boron
    Contribution to fatigue, neurological effects.
    Runaway tooth decay
    Loss of calcium in bones and teeth

    https://www.organicfacts.net/health-benefits/minerals/boron.html

    Although all of the deficiency symptoms of boron are not fully understood, it is known that boron deficiency might result in the abnormal metabolism of calcium and magnesium. Some of the other symptoms include hyperthyroidism, sex hormone imbalance, osteoporosis, arthritis and neural malfunction.

    Group 9 - Vanadium insufficiency
    Deficiency of vanadium is poorly known or recognized. It affects tissue permeabilty like insulin.

    Group 10 - Lithium insufficiency Non ionizing forms, small micronutrient doses

    Lithium allows better permiability of B12 in nervous system memeberanes

    Group 11 - Iodine insufficiency, especially needed for those who don't eat iodized table salt and/or seafood.
     

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