1. Patients launch a $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Leptin
Andrew Gladman reflects upon the recent IACFS/ME conference and the buzz surrounding a small molecule, leptin.
Discuss the article on the Forums.

Glutathione depletion blocks conversion of OH-B12 to methyl-B12: new evidence

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by richvank, Aug 9, 2011.

  1. hixxy

    hixxy Woof woof

    Messages:
    724
    Likes:
    106
    Russell Island, Australia


    Thanks determined. For me any worsening of MCS of any level is just an unacceptable side effect. I'm just too bad! I can tolerate almost any other kind of worsening -- just not that!
  2. determined

    determined Senior Member

    Messages:
    293
    Likes:
    47
    USA: Deep South
    I totally understand. Hopefully you will find something to help soon.
  3. aquariusgirl

    aquariusgirl Senior Member

    Messages:
    944
    Likes:
    91
    Hi, not sure if this is the best place for this, but given this paper..I am wondering if a person could still overdrive their methylation cycle by taking too much methyl B12?
    I guess I am wondering if as little as 15mg of methyl a day could be detrimental?
    Thanks.


    QUOTE=richvank;256843]Hi, hixxy.

    Yes, a recent paper from Korean researchers has reported that glutathione increases the affinity of the CblC complementation group for cobalamin by a factor of over 100. The CblC complementation group is part of the intracellular B12 processing pathway. When glutathione becomes depleted, its affinity for cobalamin drops, and that inhibits the flow of B12 through the processing pathway to make both methyl B12 and adenosyl B12.

    No, I don't have a quantitative value for the cutoff, but if you find that you need methyl B12 to get a good effect, I think that you need it. You wrote that it is a bit horrible because of your COMT SNPs. Do you mean that you experience neurotransmitter-related symptoms when you use methyl B12? Please explain.

    Best regards,

    Rich[/QUOTE]
  4. hixxy

    hixxy Woof woof

    Messages:
    724
    Likes:
    106
    Russell Island, Australia
    As little as 15mg MethylB12?? Do many people on here actually take that much MethylB12 on a daily basis?
  5. nanonug

    nanonug Senior Member

    Messages:
    1,248
    Likes:
    380
    Virginia, USA
    I currently take 6mg/day but I haven taken as much as 15mg. The intent was indeed (and still is) to overdrive the methylation cycle. I don't think this needs to be done by everybody, though.
  6. aquariusgirl

    aquariusgirl Senior Member

    Messages:
    944
    Likes:
    91
    Argh. Did not mean to say as little as 15 mg methyl.

    I just kind of wonder what rich thinks the optimal dosage of B12 is? I know it varies case to case .. but I am really confused about this overdriving the methylation cycle thing...Is it only a risk where a person is taking high dosages of METHYL B12 & METHYLTETRAHYDROFOLATE?
  7. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    737
    Hi, AQ.

    I don't have lab data from people taking high-dose methylfolate together with high-dose hydroxocobalamin, so I can't say for sure, but I don't think this would overdrive the methylation cycle, because the cells would still have to do the conversion from hydroxo to methylcobalamin, and that rate would be limited because of the low affinity of the CblC complementation group for cobalamin, given the glutathione depletion.

    I do have data from a few people who took high-dose methylfolate with high-dose methylcobalamin (methylation pathways panel together with amino acids panel), as in Freddd's protocol, and I think the data are very clear that the methylation cycle is being overdriven in that case, and glutathione is then hindered from coming up, because the homocysteine is rapidly converted back to methionine, and there is not enough available to go into the transsulfuration pathway in order to make cysteine for glutathione synthesis. I suspect that the potassium deficit will be more of an issue in that case, too, because cell division will likely be ramped up faster because of the concomitant rise in 5,10 methylene tetrahydrofolate when the methylation cycle is driven hard. 5,10 methylene tetrahydrofolate can be used to make thymidine, and it can also be converted to 10-formyl tetrahydrofolate, which is needed to make purines. Purines and thymidine are used to make new DNA and RNA, and they allow more rapid cell division, to make new cells. The new cells need potassium, because it is the main positive ion inside all cells.

    I think that when methylcobalamin is taken in high dosage, either sublingually or by injection, the concentration in the blood goes high enough that there is significant diffusion through the cell membranes into the cells, bypassing the usual B12 transport system and the usual B12 intracellular processing pathway. Thus, giving high-dose methylcobalamin together with high-dose methylfolate takes control of the rate of the methionine synthase reaction away from the cells themselves, and overdrives it.

    So there are a couple of reasons why I don't favor taking high-dose methylcobalamin together with high-dose methylfolate. I think that Freddd has to do that himself because of what I suspect are his inherited polymorphisms (not characterized). I think he has polymorphisms in the CblC complementation group (MMACHC gene) and the MTHFS gene (not to be confused with MTHFR). But I still think that these polymorphisms must be rare.

    As to what the optimum dosage of hydroxoB12 should be, I don't know. I suspect that the lower glutathione is, the higher it would need to be, because the affinity of the CblC complementation group for cobalamin would go lower as glutathione went lower. That's probably one reason why some people need more, in addition to the things that Amy Yasko has pointed out about SNPs in MTR and MTRR causing a greater need for B12. Sorry I can't do better than that at this point.

    Best regards,

    Rich
  8. nanonug

    nanonug Senior Member

    Messages:
    1,248
    Likes:
    380
    Virginia, USA
    Rich has already essentially provided the answer. I just want to explain why I am overdriving methylation: basically, to get rid of as much histamine as possible via the histamine N-methyltransferase pathway. Obviously, one only needs to do this in cases of histamine overload. However, I am also supplementing with acetyl-glutathione and methionine to address the potential problems Rich mentioned in his answer.
  9. Freddd

    Freddd Senior Member

    Messages:
    4,539
    Likes:
    864
    Salt Lake City
    HI Rich,

    As I have been gathering a variety of information from people to see where the balance of mb12 and methylfolate is and let's throw in potassium while we are at it.

    First, there is virtually NO proportionality evidenced between methylb12 and methylfolate as would have to be evident if they linked together to drive the methylation into the hypothetical "overmethylation".


    First, here are 4 specific people illustrating a range of quantities.
    person 1 - 40,000mgs/day absorbed mb12/adb12, 15000mcg Metafolin, 2000-3000mg potassium
    person 2 - 2000mcgs/day absorbed mb12/ADB12, 800mcg Metafolin, 99mg potassium
    person 3 - 50-250mcg/day absorbed mb12/adb12, 1600-2400mcg Metafolin, 2100-2800mg potassium (updated when copied)
    person 4 - 200mcg/day absorbed mb12, 3200mcg Metafolin, 2400+mg potassium

    Range of b12 doses that have turned on healing evidenced by sudden increase in potassium and Metafolin needed

    methylb12 dose 15mcg absorbed estimated to 180mg injected daily
    adenosylb12 dose - 15mcg absorbed to 10mg absorbed

    Methylfolate - person without b12 deficiency, no B12 startup, no methylation startup, no ATP startup - 800mcg
    Methylfolate - person with b12 deficiency, b12 startup, methylation startup, ATP startup - 1600-4000mcg
    Methylfolate - person with b12 deficiency, methylation startup, ATP startup, paradoxical folate deficiency with folic acid, 6000-8000mcg
    Methylfolate - person with b12 deficiency, b12 startup, ATP startup, paradoxical folate deficiency with folic acid and folinic acid-veggie-folate, 12mg - 30mg

    Potassium - with b12 deficiency, B12 startup, methylation startup, ATP startup - 1600mg- 3000mg
    Potassium - no deficiency, no cfs, no fms, no methylation startup, no ATP startup, no B12 startup, - 99mg

    You have suggested that there is some proportionality in healing start-up and I maintained it turned on suddenly. You said that was because of the large doses of mb12. With healing able to "turn on" as low as 15-50mcg absorbed (1/10-1/4 of a 1mg sublingual) mb12 and 200mcg of Metafolin, and then to have the healing so triggered not stop with folate insufficiency symptoms until the doses reached the range above determined NOT by mb12 and/or adb12 dose, but rather by how the person reacts to folic/folinic acid it would appear, and for the potassium to go to that same range in a single sudden jump and sometimes needing relatively minor adjustment in certain predictable circumstances.

    Higher doses of mb12 increases greatly the extent, especially CNS and peripheral nerves, and slightly the speed of healing. As many researchers say "B12 allows the body to seek to normal". To relieve the neurological deficiency of adb12 in these people I have recently identified, and hydroxycbl doesn't work and mb12 often doesn't work, and l-carnitine fumarate plus adenosylb12 are both usually needed, mb12 often becoming effective only AFTER the adb12 and l-carnitine, and effective doses of l-carnitine fumarate around 0.5mg before they have absolutely intolerable anxiety, panic etcfrom ATP startup if they have had the adenosylb12 first, otherwise if the have the LCF first then the adb12 has to be micro-titrated from 10mcg or less.. So the person has to titrate slowly along with 200mcg of Metafolin (which causes no particular effects) from < 10mcg of mb12 and < 10mcg of adb12, increasing by like amounts daily until healing turns on. Then the person titrates rapidly on potassium by effect, every couple of hours will do between doses, usually to between 1600 and 2400mg of potassium. Then the person titrates Metafolin by effect every 90 minutes until the folate insufficiency symptoms start decreasing or 3200mcg is reached. Continue the next day if the symptoms continue. Level of folate is determined by type and degree of paradoxical folate deficiency.

See more popular forum discussions.

Share This Page