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Dear Rich, Can you please take a look at my Urine AA?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by lampkld2, Jan 10, 2012.

  1. lampkld2

    lampkld2

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    Hi Rich. Hope you are doing well.

    Attatched is my new Urine AA 24, and kinda old organic acid for good measure. All I can tell from my vantage point is that my CBS SNP is pretty much confirmed as active, evidenced by the high Cystine, Taurine and Ammonia. I really loath the thought of cutting out meat, so hopefully you can tell me that this isn't too severe in magnitude :D Interestingly, my serum Ammonia was normal..

    I am also concerned about my High glutamic acid... How much would htis indiciate a functional excitoxicity issue?

    Anything else that jumps out at you? I also Have MTHFR, and do better on active methylfolate, which I am unofortnately unable to tolerate for too long.

    Thank you for your time.

    lamp
     

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  2. richvank

    richvank Senior Member

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    Hi, lamp.

    Can you tell me if there were significant changes in your diet or your condition between the times of these two lab tests? I'm trying to figure out if I can assume a similar diet and health condition for the two tests, which will allow me to consider them together as representing the same status. Otherwise, I will just have to consider the amino acids panel on its own. If it is valid to put them together, I think that more can be learned, but it would likely be misleading to do that if things changed a lot between the two.

    Best regards,

    Rich
     
  3. lampkld2

    lampkld2

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    Hi Rich. Thanks so for your reply.

    My diet was quite similiar when I took the UAA, maybe slightly less meat and cleaner.

    My UAA supplement regime included more magnesium and vitamin C recently.

    My health was also slightly worse around the UAA, more infflammation, fatigue etc. Adrenals may be worse. My brain definitly got whacked in the recent exacerbation of whatever is going on.

    I had a positive ANA with no titer, so I am looking down that route also

    I would say mild to slightly more than mildly worse at the time I took the UAA, but I am doing better now.

    lamp

    EDIT: I heard OKG (ornithine keto glutarate) is helpfull in dispensing of ammonia, along with citruiline or AKG by itself depending on the status of one's Urea cycle and UAA test. Should I consider these in my case?
     
  4. richvank

    richvank Senior Member

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    Hi, lampkld2.

    Have you had a measurement of the activity of your alkaline phosphatase? If so, what was the value, and what was the lab reference range? This is normally part of the standard comprehensive metabolic panel that physicians order, together with a complete blood count.

    Also, you mentioned in a post on Feb. 22, 2011 that "The B6 gave me neuropathy even in doses of no more than 200, so I stopped. My serum B6 remained elevated for a long time after that." Did you take a regular B6 supplement (i.e., not a P5P supplement)? Also what was measured in the serum? Was it the active form of vitamin B6, that is P5P?

    Thanks.

    Rich
     
  5. Nielk

    Nielk

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    Do you realize how funny the thread heading sounds?:)
     
  6. lampkld2

    lampkld2

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    Nielk-

    uhhh ye...Come on bro.. this is SRS BUSINESS :)

    Rich-

    Recent Alkaline Phosphatase levels were 56 on a scale of 39-117 U/L

    Thanks
     
  7. lampkld2

    lampkld2

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    Also attatched here is 9 pages of standard allopathic comprehensive labwork if needed.

    By the way, also have genetic COMT upregulation, homozygous.
     

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  8. richvank

    richvank Senior Member

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    Hi, lampkld2.

    Thank you for the allopathic lab test results.

    I added another question to my previous post by way of an edit, and I don't think you saw it. I would be interested to know the answer to it. I'm trying to home in on what I think is an inherited genetic mutation in your B6 metabolism that may be the key to understanding the whole picture.

    Rich
     
  9. lampkld2

    lampkld2

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    Wow... that would be great! Thank you for putting in the time to help me and even looking back at old posts! I really appreciate this.

    Regarding the B6, It was a pfiefer combination B6 and P5P, thought I also took some B6 by itself around the same time. The Serum levels just say, VITAMIN B6, PLASMA. The test is here on quest: http://www.questdiagnostics.com/hcp/testmenu/jsp/showTestMenu.jsp?fn=926.html&labCode=AMD
    ______
    Also two more items of note that be useful to you or others:

    1. I think I figured out brainfog and neuropathy that i had secondary to starting active b protocol This might be an inflammatory process ( I want to make a separate longer post on this, maybe It can help some other people.) Long story short, I realized that that some of the supplements which gave me neuropathy, (zinc, GLA for KPU, Vitamin E etc), led to more downstream arachodnic acid production either as a substrate or by upregulating delta 5 and delta 6 desautrase. I need GLA , so I tried to add some sesamin which is a potent Delta 6 desaturase inhibitor and I have not had any flareups since despite starting borage Oil again (last 3 days). I can confirm that atleast one of these last flareups was an inflammatory process, because as my muscles twitched, an old ankle injury flared up as well.

    I also realize that sometimes the methylation supplements cause start up inflammation, so that may be why they gave me neuropathy and brainfog. Perhaps then those that have unberable neuro startup effects such as Dannybex and I are undergoing an inflammatory process the may be PGE 2 and AA mediated.

    I have not had the nerve to try zinc or methylation supplements again, but the positive response to sesame lignans gives me hope. Hopefully this information is helpfull for people.

    Of course, this is all just a thought out guess.

    EDIT on 1/12 : I may have spoke too soon. Just had a another, milder episode last night and into today. It is probably more complicated than just Arachodnic Acid, which plays a roles along with immune aggrivators etc.... Again guessing I could be completely off.

    2. One more thing about B6

    I have mild - moderate Pyrolluria. As you probably know, two hallmarks of this disease are poor dream recall, inability to handle stress and low zinc. I have the last two but not the the complete absense of dream recall that is often suffered. I can't remember all the time, but probably 5 out of 7 days a week, especially if something triggers my memory I am good.
     
  10. richvank

    richvank Senior Member

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    Hi, lampkld2.

    As you requested, I studied your recent 24-hour urine amino acids test results. I interpreted the results in the light of the earlier urine organic acids test results, dated October 11, 2010. Although this test was run over a year before the amino acids test, I believe it is valid to consider them together, because it appears from your report that you are suffering from a lifelong condition. I have also taken into account information you have supplied to me earlier about your case, as well as what you have posted on the Phoenix Rising forums.

    The bottom line is that I strongly suspect that you inherited a genetic mutation in one of the enzymes involved in vitamin B6 metabolism. Im not sure which one yet.

    I will give you the reasons why I suspect this below, but I think it will be important to do some additional, more specific testing to determine whether this is in fact the case. I will suggest some tests.

    The reasons I believe that there is a problem in your B6 metabolism are as follows:

    1. There are markers suggesting low P5P function: high alpha-aminoadipic acid;
    high alpha-amino-N-butyric acid; low-normal to low cystathionine; alpha-hydroxybutyrate below the detection limit; scattered levels of other amino acids, suggesting low activity of the transaminases, which require P5P and are needed to convert one amino acid into another as well as to feed them into the Krebs cycle to be burned as fuel.

    2. You reported The B6 gave me neuropathy, even in doses of no more than 200, so
    I stopped. My serum B6 level remained elevated for a long time after that. I
    think this suggests that vitamin B6 is not being properly used in your metabolism.

    3. Your health history, symptoms and your other known biochemical abnormalities seem to involve organs or systems in which B6 is normally needed. These include the immune system (note your low white cell count, which suggests a problem with DNA synthesis, which requires B6 support of the SHMT enzyme), gluconeogenesis (note that your pyruvate was below the detection limit, which suggests a problem with maintenance of glucose), heme synthesis (note that you reported pyrroluria), the nervous system (both neurotransmitters and probably myelin are implicated, both of which require B6 for their synthesis. Motor neuropathy is especially significant.), muscles (you reported muscle atrophy, and the muscles depend a lot on B6), fatty acids metabolism (it needs B6 a lot), and zinc-related issues (zinc is needed for at least two of the enzymes involved in B6 metabolism).

    The way B6 metabolism is supposed to work is as follows: There are three forms of vitamin B6 (pyridoxine, pyridoxal, and pyridoxamine), and each can have a phosphate group attached. These various forms of B6 come in with the food or supplements. The ones that have phosphate groups attached have them removed by a phosphatase enzyme in the gut, before they are absorbed.

    After being absorbed, they are transported to the liver via the portal vein. In the liver, a majority of the ingested B6 is converted to 4-pyridoxic acid by the enzyme aldehyde oxidase (which requires molybdenum). Some of the rest is converted to P5P by the addition of a phosphate group by reactions catalyzed by pyridoxal kinase, and by conversion of the two other forms of B6 to pyridoxal by reactions catalyzed by pyridoxine phosphate oxidase (an enzyme that requires FMN, which is made from riboflavin, vitamin B2), and put out into the circulating blood, bound to albumin. Pyridoxal kinase is the enzyme that adds the phosphate group, which comes from ATP that preferentially has a zinc ion bound to it (Note that this is unusual, because magnesium is usually bound to ATP). Being bound to albumin protects the P5P in the blood.

    There are other forms of B6 normally found in the blood as well. P5P constitutes about 57%, pyridoxal represents about 23%, and there is also some pyridoxine, pyridoxamine phosphate and pyridoxamine.

    Pyridoxal and pyridoxine readily diffuse into cells. P5P must first have its phosphate group removed to reform pyridoxal, and this is done by a phosphatase attached to the external surface of the cell membrane. It is believed to be alkaline phosphatase, which is also a zinc-dependent enzyme. Inside, pyridoxal kinase again adds a phosphate group to pyridoxal to form P5P again. This prevents the P5P from leaving the cell, and it is then bound to enzymes for which it serves as a coenzyme.

    The mechanism of neuropathy caused by excessive B6 is not understood.

    In your case, perhaps the level of P5P is not being properly limited because not enough B6 is being converted to 4-pyridoxic acid. Or, perhaps not enough of the B6 is being converted to P5P, but is entering the blood without a phosphate group, and too much of it is able to diffuse into cells, producing neuropathy. Or perhaps the P5P is not able to enter cells at a normal rate because the phosphate group is not being removed at a high enough rate. Perhaps B6 is not able to stay inside the cells properly, because the phosphate group is not being put back on at a high enough rate. Which of these is going on will depend on which enzyme has a mutation.

    In order to shed some more light on what is going on in your B6 metabolism, I think it would be helpful to run some more tests. The Health Diagnostics and Research Institute offers two tests that I think would be helpful. They are the plasma B6 (P5P) test and the EGOT enzyme activity test (EGOT stands for Erythrocyte Glutamate Oxaloacetic Transaminase Test). If these are run at the same time, it should be possible to determine both whether the level of P5P in the plasma is normal, and also whether it is getting into the cells and assisting with a transamination reaction at a normal rate.

    These tests require an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinicians letterhead. Here is the contact info:

    Health Diagnostics and Research Institute
    540 Bordentown Avenue, Suite 2300
    South Amboy, NJ 08879
    USA
    Phone: (732) 721-1234
    Fax: (732) 525-3288

    Lab Director: Elizabeth Valentine, M.D.

    Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of tests by phone.


    If it turns out that not enough P5P is getting into the cells, it might be possible to put more in using a liposomal form of P5P.

    One more thing: Using 23andme.com, it might be possible to look for polymorphisms in the enzymes involved in B6 metabolism, though this might be difficult in view of the likelihood that the polymorphisms have not yet been well studied for these enzymes.

    Best regards,

    Rich
     
  11. lampkld2

    lampkld2

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    Hi Rich.

    Thank you so much for your assistance. I'm very hopefull that we might have solved another piece of the puzzle.

    Currently trying to convince my doctor to order those tests. I will continue to update.

    Lamp
     
  12. lampkld2

    lampkld2

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    what mito supps?
     
  13. aquariusgirl

    aquariusgirl Senior Member

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    the usual.....l carnitine fumarate, coq10, mag, nadh
     
  14. SJB944

    SJB944 Senior Member

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    I guess the question is whether high blood levels of P5P also causes neuropathy?
     
  15. aquariusgirl

    aquariusgirl Senior Member

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  16. SJB944

    SJB944 Senior Member

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    Rich,

    If getting P5P into the cells is a problem, would sublingual P5P be a better option?

    SJB.
     
  17. greenshots

    greenshots Senior Member

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    California

    Until the CBS & ammonia problem are under control, you shouldn't use B 6 and this isn't just a Yasko thing but also a Pfeiffer issue. But here's a Yasko quote:

    "I think that once the CBS/ammonia situation is under control then the use of P5P or a B complex with B6 makes sense. The use of B6 until you have CBS under control or if there are bacterial issues is a double edged sword. You need B6 to convert glutamate to GABA, which is an important very positive outcome for the body. You also need B6 for a number of other reactions in the body. However, B6 is also needed for CBS. In addition, when bacteria cause the breakdown of tryptophan one of the intermediates in the breakdown pathway is calming, kynunenate. However B6 will convert kynurenate to quinolinate which is an excitotoxin.

    So, once CBS/ammonia is in balance and bacterial triggering of tryptophan breakdown is less of an issue then the use of 1/2 B complex or about 1/2 to 1/4 of your current dose of B6 (or P5P) should be mostly all positives. However, if CBS up regulation and bacterial tryptophan breakdown are still issues then I expect you will find that B6 may start to backfire for you again as it did in the past.

    With love and hope,
    Dr. Amy"
     
  18. aquariusgirl

    aquariusgirl Senior Member

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    i think we might be dragging lamp2kd's thread off track..so maybe we should start another thread on B6?

    I am increasingly convinced I have B6 issues & probably KPU.

    Just looked up a blood test from 2006 & my plasma B6 was 230 ng/ml (range 3.3-23). Don't know if I was supplementing. Suspect I must have been.
    Doc didn't have a clue.. didn't think to retest to see if it was a fluke.. NOTHING.
    In 2010, a P5P test thru ELN gave a result of 16 (12-30) with no supplementation.

    In 2008, my GLA (fatty acid) was low 0.02 (0.1-0.30) (Lab ;ELN)

    but Arachidonic acid was high out of range 20.02 (14.2-19.2).. which doesn't fit the KPU model I don't think, but maybe its down to my high oxidative stress.

    In 2009, I had low activity of zinc/copper SOD on an Acumen test, which I guess could indicate lack of zinc.

    In 2011, an OAT test thru Great Plains indicated low levels of neurotransmitters poss. because of a lack of cofactors B6 & biopterin.

    I'm mostly putting this together for myself..but thought I would share & yes, I had high quinolinic acid/5 HIAA ratio...so definately excitotoxicity.. which could be aggravated by B6 supplementation if I understand correctly.

    Talk, about a roundabout.
     
  19. hixxy

    hixxy Senior Member

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    Yikes rich. Nice work. I think I might have to lump my very severe B6 problem on you one day too. I'd like to get some genetic testing done first though and possibly a UAA.

    Ever since I did treatment for pyroluria 2 1/2 years ago I developed extreme glutamate intolerance. Every time I supplement it again (any form), this intolerance and the neurological problems that come with it get worse. Upon ceasing supplementation my symptoms don't seem to abate, so it's like a continual downward spiral. It started pretty much over night.

    I have many obvious markers in pathology (I sent that spreadsheet of pathology with an interpretation of undermethylation on it a few weeks back via email -- Name is Troy).

    Ever since this collapse my neurological symptoms seem to go far beyond the norm for ME/CFS.

    I have severe MCS as well and since that very day I started having troubles with full body shaking on chemical exposures. Likewise with EMFs. It's like this particular problem drives the others now.

    hixxy




     
  20. brenda

    brenda Senior Member

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    Hi Rich

    Looking at my own organic acid profile from Metametrix 2010, the problems of low results on lampkld2`s are the opposite end on mine so the question is does this mean that I dont have a problem with B6 and can safely start the methylation protocol even though there seems to be a problem with amonia?

    Adipate 6.3 (<8.3)
    Suberate 3.2 (3.2)
    Pyruvate 4.2 (<6.4)
    L-Lactate 16 (3-46)
    Citrate >2000 (56-987)
    Cis-Aconitate 92 (18-78)
    Isocrite 172 (39-143)
    A-Ketoglutarate 30.4 (<35)
    Malate 3.0 (<3.1)
    Hydroxymethylglutarate 6.0(<5.1)
    vanilmandelate 4.0 (1.3-4.9)
    homovanilate 8.5 (1.6-10.9)
    b-Hydroxy-2-deoxyguosine 8.3 (<7.6)
    a-Hydroxybutyrate 0.8 (<0.9)
    Sulfate 744 (690-2,988)
    Formiminoglutamate 0.2 (<2.2)
    alkaline phosphatese 113 (35-104)

    sorry lampkld2 will start a new thread if you wish but thought it intertesting to compare.

    Brenda
     

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