A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016
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Hi serum b12 and HIgh MMA

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by sk123, Jul 17, 2017.

  1. sk123

    sk123

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    I am wondering if anyone can shed some light as to why a person would have high serum B12 levels (>2000 ) but urinary MMA is high at around 8 whereas the reference range says it should be less than 2.1?

    I understand MMA can be brought down by using adenosyl b12 but that wouldnt help with methylation correct?Methylcobalamin is need for that I suppose. My folate levels were also high on serum test >20 but low on a spectracell micronutrient test. Not sure what the folate marker is on the GREAT PLAINS OATS test.

    I had been taking Mega foods B complex along with Thorne basic B complex. I wonder if the megs foods basic B is active levels of Bs ( I assumed so since it was food based B complex).

    So having a high serum level means I have plenty of b12 but still a functional deficiency exists. Lithium on hair test was high normal but cobalt was almost nonexistent. So what could be causing this functional deficiency? ANyone have any ideas? I have been taking tocotrienols of vit E so vit E levels are good. MCV is about 90..so other signs of b12 def show on blood work besides a lowish hemoglobin but high iron saturation and serum iron but low ferritin.
    Thank you!
     
  2. alicec

    alicec Senior Member

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    High serum levels of cobalamin along with signs of functional deficiency (ie elevated MMA and homocysteine) is not uncommon. See for example this review.

    It indicates there is some problem getting B12 into cells or with its internal trafficking.

    Note that there are some serious illnesses where this can occur, as the review discusses, however there would usually be other indications of these conditions.

    You should take sufficient B12 to overcome the functional deficiency and not place too much emphasis on standard tests for serum cobalamin. These can be misleading since they measure B12 bound to haptocorrin and transcobalamin. The latter carries B12 into cells but is only a minor fraction of total bound B12. With a standard test you have no idea what proportion of B12 is in the form which can be taken into cells.

    The enzyme which results in accumulation of MMA does use adenosylB12 as cofactor, but this doesn't mean that adenosylB12 is the only form which can replenish the enzyme.

    The cobalamins are subjected to complex processing within cells which removes the upper axial ligand (ie the methyl, adenosyl, hydroxy etc group) and shuttles them to the appropriate enzymes where methyl or adenosyl groups are added, depending on cellular requirements.

    Such a high MMA means that you are just not getting enough B12 into cells. You should be aiming to increase supplementation significantly with whatever form(s) you can best tolerate.

    A similar situation can exist for folate - ie high serum levels but functional deficiency. The solution is the same - increase folate supplementation, but be aware that folic acid can exacerbate problems for some people. It would be wise to start with methylfolate.

    The folate markers on the GPL OAT are uracil and thymine.
     
    Learner1 likes this.
  3. sk123

    sk123

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    Thank you so much for your response! I read the link with great interest. :)

    So the high serum b12 along with low MMA is only when they are suspecting tumors etc ? If its a high MMA and high serum b12 then its more of a internal trafficking issue ? I couldnt open the table where it actually gave guidelines on how to correct unfortunately.

    What tests could be ran to figure out where the issue is with B12 not getting into cells?

    I have the following SNPS so I am wondering how much B12 I should increase up to? I do have the hetero SNP for TCN1 for b12 transport. How is this bypassed please? What wold be a feasible amount of B!2 to take daily in the form of the active methyl cobalamin? In the past when I took 2000 mcg of B12, my homocysteine dipped form a 7 to a 5. I wasn't on any molybdenum at that time. I am currently taking 50 mcg times 3 daily of molybdenum. So the homocysteine decreasing at that time when I wasnt taking molybdenun would mean what exactly? Increased churning of the trans sulferation pathway sucking down homocystein or decreased methionine as BHMT not recycling homocysteine back to methionine as well so no methionine made to go towards SAH and then back to homocysteine? How does one support the CBS SNPS besides with molybdenum?

    At what point do I add in folate as I am deficient in folate more so than b12 according to spectracell micronutrient testing. I understand b12 has to be added in first to avoid methyl trapping. Currently I am taking I am taking 2000 mcg of methy b12 along with 10 mg of dibencozide (adenosyl) daily. I am having a lot of hair fall out which has been happening for a few years now and lately its bad again since last 2 months.

    homozygous for AGT
    homozygous for 2 out of 3 PEMT SNPS
    homozygous for DHFR
    homozygous for NDUFS7 3 out of 7 SNPS
    homozygous for NAT 2 G590A
    homozygous for SOD2 and SOD2 A16V
    homozygous for IL13, CD14, Rad50, GSTM3
    ofcourse homozygous for HLADQA2
    Hozygous for MTC03P1 (not sure what this is)

    Hetero for 1298 C
    There are 4 other generic MTHFR that I am hetero for
    hetero for BHMT 08 and BHMT R239Q
    hetero for all CBS SNPS
    hetero for COMT
    hetero for COMT -61 P199 P
    Hetero for COMT H62H
    hetero for COMT V158M
    hetero for MTR a 2756G and MTRR
    hetro for TCN1 (what does this mean for b12 transport..how to bypass this?)
    Hetero for SHMT2

    hetero for NOS 3 4 SNPS
    hetero for all FUT2 SNPS
    hetero for most GAD1 SNPS except 2
    hetero for MAO A r297R
    hetero for 3 MTHFD1 SNPS

    Thank you!
     
    seethatlake likes this.
  4. alicec

    alicec Senior Member

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    It's a pity those figures won't open - I think they once did when I first found the paper.

    In any case MMA may or may not be elevated with tumours or other pathological conditions, it depends entirely on the particulars of the condition. One might expect other indications of these serious conditions to be present.

    High serum B12, elevated MMA and the absence of any reason to suspect these other conditions does suggest there is some blockage in uptake and/or internal trafficking. That's as far as we can speculate I think. There aren't any tests that I know of that can pin things down further.

    It then becomes an empirical trial of B12 (plus related nutrients) supplementation to try to normalise MMA. Quite high doses might be needed to drive whatever is sluggish in B12 processing. The ultimate test is does it make a difference to how you feel?

    How much B12 to use is a very individual thing.

    I don't know which particular SNPs are being flagged by whoever has analysed your 23andme results, but I suspect that almost all of them are pretty irrelevant.

    Just because a variant is identified doesn't mean that there is any consequence. Most of the SNPs that people get excited about in internet chatter do nothing - some do have an effect but usually this is small. Many of these SNPs are very common and are not the cause of people's health problems. A few may be making a contribution.

    You need to look more closely at what is known about individual SNPs to determine if they are likely to have any consequence for you.

    As an example, while you don't say which SNP on TCN1 has been flagged for you, I imagine it might be this one flagged by SNPedia. The SNP has been identified in a genome wide association study as being associated with lower B12 concentration in serum.

    That doesn't really mean much and is not particular surprising since TCN1 codes for haptocorrin, the major B12 binding protein in blood. This is not the form that is taken up into cells and individuals have been described who can't make haptocorrin at all. Here is the OMIM entry for the condition. It is described as clinically benign. (One individual did have serious problems but it was found to be the result of a combination of genetic defects, not just the TCN1 defect).

    Individuals without haptocorrin had low serum B12 because they lacked this major B12 binding protein. However they had the other binding protein, transcobalamin 2 (TCN2), which is responsible for taking B12 into cells, so their functional B12 status was ok.

    There's no reason to think that your TCN1 SNP has any consequence for you at all.

    There are some genetic defects in TCN2 which have serious consequences. These are inborn errors of metabolism which are described in the OMIM entry for TCN2. I'm not aware of other SNPs which might have a less serious effect but perhaps might be relevant to this phenomenon of high serum B12 combined with functional deficiency, nor do I know how extensivley the genetic connection has been pursued.
     
    Last edited: Jul 18, 2017
  5. Eastman

    Eastman Senior Member

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    I've posted this excerpt of an article by Dr Derrick Lonsdale in several other threads, let me re-post here in case it is useful.

    Again from a B1 angle, an excerpt from an article by Dr Chandler Marrs:

     
  6. sk123

    sk123

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  7. sk123

    sk123

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    Thank you AliceC for the detailed explanation.
     
  8. Eastman

    Eastman Senior Member

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    I am not familiar with how Spectracell tests for thiamine. This is what Dr Derrick Lonsdale wrote about the standard thiamine blood test:

    The article goes into detail on the test he recommends while this paper describes a newer test.
     

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