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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.
    Little Bluestem likes this.
  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
    Adlyfrost and juniemarie like this.
  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 Senior Member

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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".
  12. Snowdrop

    Snowdrop Senior Member

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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
    Snowdrop likes this.
  15. Snowdrop

    Snowdrop Senior Member

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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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