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BH4 and Folate Questions - Rich? Anyone?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Sparrow, May 5, 2012.

  1. Sparrow

    Sparrow Senior Member

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    I was hoping maybe somebody could help me out in clarifying a couple of things. I'm not in great shape for researching myself these days. Any input would be most welcome and appreciated.

    In particular, I was wondering:
    1) My Yasko genetic results and some symptoms seem to indicate that my BH4 may be quite low, but the pre-fab organic acids test results (see attached) seemed to be suggesting that my tyrosine might be too high based on my level of 4-hydroxyphenyllactic acid. This seems inconsistent. Any thoughts?

    Organic Acids Results: View attachment Sparrow Organic Acids.pdf

    2) I don't have the MTHFR C677T polymorphism, which I understand to be the one that makes methylfolate critical. I do have other MTHFR polymorphisms, though (3, and A1298C). If I do not have the C677T polymorphism, do I still need to shy away from folic acid, or should they both be helpful?

    Genetic Results: Sparrow Genetic Test Results.jpg

    Any additional input on the Organic Acids in particular would be greatly appreciated. I've done my homework on the Yasko side as much as I was able to. Thanks!!
  2. richvank

    richvank Senior Member

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    Hi, Sparrow.

    Here are some comments on your organic acids panel:

    The high 3-Oxoglutaric acid and the elevated Arabinose indicate that you have an intestinal yeast overgrowth.

    The elevated 4-Hydroxyphenylacetic acid, high 4-Hydroxybenzoic acid, and elevated Hippuric acid indicate that you have intestinal bacterial dysbiosis. It would require
    a comprehensive stool analysis to determine the details of this, to decide on treatment.

    The high succinic acid could be partly due to intestinal dysbiosis, but see below.

    I dont know the significance of the high Glycolic acid in the presence of a normal Oxalic acid level.

    The low Pyruvic acid indicates low flow through the glycolysis pathway. This could be due to a low carbohydrate diet, or to low magnesium.

    Because of the low availability of Pyruvate, your cells have gone into ketosis. Fatty acids are being mobilized, but they are not being burned at a very high rate in the Krebs cycle, perhaps because of low carnitine or low B2, and some are being diverted to omega oxidation. There are several markers indicating ketosis and also omega oxidation of fatty acids.

    The drop from Aconitic acid to 2-Oxoglutaric acid could be due to aluminum toxicity or
    to a deficiency of B3, magnesium or manganese.

    The high Succinic, Fumaric and Malic acids together could be due to low coenzyme Q10,
    or to low B2 and B3 together.

    The drop from HVA to VMA is likely due to low copper, since vitamin C looks good.

    The high ratio of Uracil to Thymine indicates low folate, which would be consistent
    with a partial block of methionine synthase.

    Ive already discussed the ketone and fatty acid oxidation markers.

    The high Methylmalonic acid indicates a B12 deficiency. In view of the glutathione
    deficiency (see below), it could be a functional B12 deficiency. The B12 deficiency together with the high ratio of Uracil to Thymine suggest are consistent with a partial block in the methylation cycle at methionine synthase.

    The high Pantothenic acid suggests recent supplementation with B5.

    The high Glutaric acid indicates deficiency in B2.

    The high Ascorbic acid suggests recent supplementation with vitamin C.

    The low Methylcitric acid indicates a deficiency in biotin.

    The low Pyroglutamic acid indicates glutathione depletion.

    The low Orotic acid indicates that the urea cycle is not being challenged, which suggests a low rate of burning of amino acids. Together with the above results, this indicates
    that none of the three main fuels (carbohydrates, fats, and amino acids) are being burned at a high rate. This is consistent with fatigue.

    The first four amino acid metabolites are very low. This is likely due to low B2 and
    possibly also low B6 (these cannot be distinguished on this panel). It means that the
    branched-chain amino acids are not being fed to the Krebs cycle at a significant rate,
    and that means that the high Succinic acid is not due to amino acids burning, and
    must be due to intestinal dysbiosis.

    The elevated Mandelic acid could be due to exposure to styrene, or it could be due
    to supplementation with phenylalanine.

    The high 4-Hydroxyphenyllactic acid is likely due to gut bacterial metabolism of tyrosine.

    I dont know the significance of the somewhat elevated levels of N-Acetylaspartic acid
    or 3-Methylglutaric acid.

    The low phosphoric acid could be caused by a low phosphate intake in the diet, or to a deficiency in Vitamin D.


    You asked me specifically about your BH4 in the light of the high 4-Hydroxyphenyllactic acid. I think the latter could just be due to intestinal bacterial dysbiosis breaking down your tyrosine in the gut, before it can be absorbed. Your BH4 could indeed be low. It's difficult to say for sure from the available data, since your SNPs are such that they tend to compensate each other in terms of the formation and the breakdown of the neurotransmitters.

    I would recommend avoiding folic acid for other reasons beside whether you have the MTHFR C577T SNP. We don't know what your DHFR SNPs look like, nor do we know what your NADPH level is, and those are both important for utilization of folic acid. Methylfolate is still important for supporting BH4 as well as the methylation cycle block. You could try adding folinic acid if you would like. That would probably help to normalize your thymine/uracil ratio, which would be good for making new DNA for new cells.

    I hope this helps.

    Best regards,

    Rich
    Gloria H and Gavman like this.
  3. Sparrow

    Sparrow Senior Member

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    That is AMAZINGLY helpful. Thank you so much for your help with this!! I hope you know how truly valued you are around here. Many, many thanks again.
  4. richvank

    richvank Senior Member

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    You're welcome, Sparrow.

    Rich
  5. hixxy

    hixxy Woof woof

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    Rich,

    Seeing as you've interpreted so many of these organic acid tests now, and there seems to be a fair amount of difference between all the different labs that offer this particular kind of test.

    Which lab do you find measures the most useful organic acids?

    My last OAT was done with Metametrix, and I've looked at a fair few of these tests on the forums here, and it seems the Metametrix OAT leaves a lot to be desired.

    I'm currently consulting someone who typically uses the Genova MAP test, and may order that in the future. Is this one any good. What's your personal favourite?
  6. Sparrow

    Sparrow Senior Member

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    Thanks a ton for your comments. That was a huge help, and packed with things I hadn't heard before.

    The Mandelic is the only part that puzzles me. I don't know how I would have been exposed to styrene anywhere near the time of this test. Is that one of those things that hangs around forever? I also don't supplement with phenylalanine at all. (Which is in no way doubting your interpretation, just noting that I might be an odd case...)
  7. richvank

    richvank Senior Member

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    Hi, Sparrow.

    Apparently the general public's main exposure to styrene is by inhalation of indoor air, but some comes in from food and drink, also. Probably Styrofoam cups would be one source. I have seen elevated mandelic acid in the MAP results from quite a few PWMEs. I don't have data for people who don't have ME/CFS.

    Here is a report on styrene toxicity. I'm sorry that it is one horrendously long paragraph and is difficult to read, but toward the end there is a discussion of the metabolism of styrene, and apparently it can contribute to the depletion of glutathione:

    http://www.ncbi.nlm.nih.gov/pubmed/20737009

    Best regards,

    Rich
  8. richvank

    richvank Senior Member

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    Hi, hixxy.

    Not easy questions to answer. Great Plains, Metametrix and Genova Diagnostics each include some parameters that the others don't. All of them contain most of what's useful. I do like the ability to distinguish between deficiencies of B2 and B6, which is possible with the Great Plains OAT. They also include oxalic acid, which is important in some cases. I also like their inclusion of uracil and thymine, which gives information about the status of the folates. Their vitamin C measurement is helpful, too, as is their phosphate measurement. On the other hand, Metametrix includes figlu, xanthurenic, 8-hydroxy-2-deoxyguanosine, glucarate, sulfate and D-lactate, which are nice to know. I guess I would say that in general the Great Plains and Metametrix panels offer more useful data than the Genova Diagnostics MAP, but I can learn a lot from the MAP panel, too.

    The organic acids panels are more useful if there are also some other tests, including amino acids, toxic and essential elements and fatty acids, such as in the NutrEval or ION profiles. It's possible to narrow down the possible causes of abnormalities more if these others are available, because they complement each other.

    Best regards,

    Rich
  9. lizw118

    lizw118 Senior Member

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    Hi everyone
    I would like to try a BH4 supplement, as on my metametrix test a while back there were indications the level is low (the phenyl/tyro ratio). Are there still no supplements available in this country? I have also read that taking larger doses of folate might increase the level. But how large of a dose would that be? Also, does anyone recommend a high dose folate supp?
    Thanks
    Liz
  10. hixxy

    hixxy Woof woof

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  11. nanonug

    nanonug Senior Member

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    Huh, which country? Xenforo doesn't show where people are from...

    Yes, that's the trick used by Deplin. I currently take 5mg/day of methylfolate (Thorne 5-MTHF 5mg). I take it away from methylcobalamin as I don't want this methylfolate to end up in the methylation cycle.
  12. lizw118

    lizw118 Senior Member

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    Hi Nanonug
    Sorry I didn't include details-- I am from the U.S.
    Do you take the high dose of folate for BH4? Or methylation in general?
    Thanks
    Liz
  13. nanonug

    nanonug Senior Member

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    Yes, although I believe this trick only works with methylfolate.

    For basic nutritional and methylation support, I take Pure Encapsulations Multi t/d.
  14. lizw118

    lizw118 Senior Member

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    Have you noticed any particular symptom relief since starting the higher methylfolate dosage that you attribute to BH4 increase? If so, what symptoms?
    Thanks!
    Liz
  15. nanonug

    nanonug Senior Member

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    There were basically two reasons for why I wanted to increase BH4. The first one has to do with oxidative/nitrosative stresses. In this case, the more BH4 you have, the less peroxynitrite is produced. Given that peroxynitrite is a very nasty free radical this by itself justifies higher BH4 levels. The second reason has to do with mood support. I am convinced that anyone that is forced to endure any kind of chronic debilitating disorder will end up somewhat depressed. Therefore, being preemptive about this by increasing BH4 levels seemed like a good idea to me.

    I can tell you that in general, I feel much more cheerful, much more than before the BH4 protocol. The effects, however, are not immediate except for maybe the first week in which there is somewhat of a hypomanic state (by the way, my spell checker suggested nymphomaniac instead of hypomanic, eheheh). I also take extended-release Vitamin C as this appears to be able to recycle BH3 back into BH4.
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  16. Christopher

    Christopher Senior Member

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    Can you explain why you take your MethylB12 away from your methylfolates? Thanks.
  17. nanonug

    nanonug Senior Member

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    If you take methylfolate together with methylcobalamin, what will mostly likely happen is methylation of homocysteine. However, if a condition is created in which methylfolate cannot be readily used by methionine synthase (which requires methylcobalamin) the MTHFR enzyme is "forced" to work in reverse, converting methylfolate into methylenefolate and recycling BH2 back into BH4. It is this latter reaction we are after.
  18. Christopher

    Christopher Senior Member

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    I don't really understand any of that, but if I just take methylfolates away from methylb12, I'll be good right? :)
  19. nanonug

    nanonug Senior Member

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    Depends! Are you trying to improve methylation or improve levels of BH4?
  20. Christopher

    Christopher Senior Member

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    Well, both I guess. Is it something where I can alternate daily with taking them together and then taking them apart? Thanks.

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