The 12th Invest in ME Conference, Part 1
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Methylation Panel Questions? What does this all mean? Rick

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by nipsic, Apr 17, 2012.

  1. nipsic

    nipsic

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    Hi Everyone,

    I have had a methylation panel done and just trying to figure out which supplements to take.

    MY VALUES REFERENCE RANGE
    Aminoacids in plasma
    Glutathione (oxidized) .41 .16- .50
    Glutathione (reduced) 3.1 L 3.8- 5.5
    Derivates
    S-Adenosylmehtionine (RBC) 250 221- 256
    S-Adenosylhomocysteine (RBC) 32.8 L 38.0 49.0
    Folic Acid Derivates
    5-CH3-THF 11.9 8.4- 72.6
    10-Formyl-THF 2.9 1.5- 8.2
    THF 0.72 0.6 6.80
    Folic Acid 10.5 8.9 24.6
    Folinic Acid (WB) 9.3 9.0 35.5
    Folic Acid, Active (RBC) 339 L 400 1500
    Nucleoside
    Adenosine 16.7 L 16.8 31.4
     
  2. richvank

    richvank Senior Member

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    Hi, nipsic.

    Thanks for posting your results.

    They are unusual. I haven't seen a set like this before, and I've probably seen a couple of hundred by now.

    The thing that's unusual is that you have high-normal SAMe with low SAH. That would speed up your methyltransferase reactions and make you truly "overmethylated."

    Normally, this is prevented by the glycine N-methyltransferase reaction, which acts as sort of a pressure-relief valve to keep the SAMe to SAH ratio from getting too high. It takes methyl groups from SAMe and gives them to glycine, converting it to sarcosine, and then sarcosine gives them to THF to make more 5,10 methylene THF, and then the MTHFR reaction converts that to 5-CH3-THF, which then reacts with homocysteine via the methionine synthase reaction, to produce methionine. Methionine reacts with ATP to make SAMe again, and it goes 'round and 'round. So the SAMe to SAH ratio is limited, but the methyl groups are recycled, not wasted.

    Since your reduced glutathione is also low, and glycine is one of the amino acids needed to make glutathione, I'm wondering if you are low in glycine. It would take a plasma amino acids test to find out, such as the Metametrix 40 plasma amino acids test, or one of its competitors. I think Life Extension offers a test through LabCorp that is less expensive. Anyway, it would be interesting to know what your glycine level is.

    I would also be interested to know what your symptoms are like. I have encountered many people who have low methylation capacity, some very low, but I haven't encountered someone with a high SAMe to SAH ratio of 7.6. The mean normal SAME to SAH ratio is 5.48, and PWMEs usually have a value less than this. Is that 250 number a typographical error, or is it for real?

    Best regards,

    Rich

    P.S. I see that you posted once before, on Jan. 29. I'm sorry that I didn't see that one then, but I just read it now. That's a pretty high MCV. I'd be interested to know if you have other abnormal lab test results (of any kind). If your SAMe is indeed at 250 and your SAH is low, I would recommend trying to sort out what's going on before pushing your methylation cycle any harder.

    Rich
     
  3. nipsic

    nipsic

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    Hi Rick,

    I can send you the lab results if you would like. The 250 number isnt a typo it is my SAMe number.

    My symptoms arent that complex compared to the vast majority of chronic fatigue people. I have baseline low energy that gets significantly worse with too much stress. Also, certain activities just drain my energy--for example, eating and showering. For generally for 2 to 3 hours after eating I am fairly useless (my baseline line low energy gets worse). I dont pass out anymore from eating but it still pulls my energy lower. My only other mentionable symptoms are frequent daily headaches, lost the ability to sweat, dizziness, a mental-like fog (difficult to concentrate or process information), and fluid retention. I am very susceptible to nutrients: magnesium, Fish Oil, and Potassium and seem to make me worse. I have been getting better but still not where I would like to be.

    My lab values that are commonly outliers are MCV always high sometimes out of range. My RBC and WB low sometime out of range. Ironic and perplexing considering my folic acid, B12, iron, and ferritin are in normal range. I do have reactive hypoglycemia that isnt insulin resistance produced the endocrinologist suggests it might because of borderline low cortisol functioning as mine in low to out of range low at times. But the irony when I supplemented with cortisol there was no improvement in my symptomology so it was ruled that probably wasnt the reason for my profound fatigue after eating. I personally believe it is just some dysautonomia but I carry a diagnosis of chronic fatigue syndrome.

    Other than the above, I have normal lab values for most everything else from thyroid to sleep apnea and back. I even had my amino acids check and glycine is normal in both the blood and the urine. I can get it re-assess though. It will not hurt to add it to the blood. It would be interesting if it was off though.

    My interpretations of the labs were that I was riboflavin deficit (despite supplementation). My thoughts were based on the most sensitive indicator of riboflavin deficit is high oxidized glutathione and low reduced glutathione. But that was more of a guess than a sure thing. But that is just a guess and probably circumstantial.

    Thank you for your assistance/reply. I will take to my doctor about adding the glycine test.
     
  4. nanonug

    nanonug Senior Member

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    I believe this condition is called macrocytic anemia. Wikipedia list several possibilities as causes.
     
  5. richvank

    richvank Senior Member

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    Hi, nipsic.

    Thanks for the information. O.K., if those SAMe and SAH numbers are correct, and your glycine is normal, then there must be something wrong with the glycine N-methyl transferase enzyme, either a genetic polymorphism that lowers its activity, or low gene expression of this enzyme. I'm guessing that you haven't been ill all your life, so that would suggest that it isn't genetic. Another possibility might be that the gene that codes for this enzyme or perhaps a gene that controls its expression has become overmethylated, lowering the gene expression of glycine N-methyltransferase. Maybe it got "stuck" into a positive feedback situation, forming a vicious circle, so that the enzyme activity stays low, and methylation stays high.

    If you are indeed "overmethylated," that could be lowering the expression of a lot of genes by overmethylating the DNA, which would lower the synthesis of many proteins, which in turn would have lots of effects on the overall metabolism.

    Fluid retention is the opposite of what happens in most people who have ME/CFS. They have diabetes insipidus (not to be confused with diabetes mellitus) and they are not able to retain enough water, so they are usually hypovolemic.

    I would like to see the results of a urine organic acids test on you, such as the Genova Diagnostics Metabolic Analysis Profile, or the Metametrix Organix Profile, or the Great Plains Lab OAT. If your gene expression is generally low, I think it will show up as low values for some of the organic acids in the urine, because the whole metabolism would likely be running more slowly. The Genova Diagnostics and Metametrix tests are available without a doctor's order from www.directlabs.com, if it isn't possible to get one of these tests through your doctor.

    I have encountered a case in which the glycine N-methyltransferase had too high an activity, but yours is the first I've seen in which it seems to be too low. In that other case, I think it was caused by the drug Accutane, which is known to raise the expression of the gene for this enzyme.

    I find your case very interesting. If you can run a urine organic acids test, I would like very much to see the results.

    Best regards,

    Rich
     
  6. nipsic

    nipsic

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    Thank you for the information. True, I am macrocytic anemic at times The real question is why? I no deficiency in b12 or folic acid. I have no known abnormality of the liver or spleen. Ff you can locate something that cause macrocytic anemia with unremarkable liver and spleen function and histology with normal b12 and folic acid levels I am all ears. In all the years, and all the doctor's I have seen no one has give me a straight answer. I would like to correct this aspect but have yet to have a direction to do so.
     
  7. nipsic

    nipsic

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    I am been sick the majority of my life so it probably wasn't genetic. I can probably scan it and send it over. My doctor had all my amino acids tested when she was thinking that I might have had an inborn error. I can do them through an additional lab. I will have my glycine lab done in the near future.

    Thanks again for looking at this Rick.
     
  8. richvank

    richvank Senior Member

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    Hi, nipsic.

    You're welcome. Please note that I would be interested in both your amino acids and a urine organic acids test, if that's feasible for you to get.

    You wrote that you have been sick the majority of your life. At what age did it first occur? If it was early in your life, it could still be a genetic issue. And some of them don't show up until adulthood.

    I really do think that this high SAMe, low SAH combination is something that should be pursued. It could be the key to your illness.

    Best regards,

    Rich
     
  9. nanonug

    nanonug Senior Member

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    Rich, given that SAM is within the specified normal range, why do you say it's high? Thanks!
     
  10. richvank

    richvank Senior Member

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    Hi, nanonug.

    Sorry, I meant to say high-normal, as I did in my first response to nipsic.

    Best regards,

    Rich
     
  11. nanonug

    nanonug Senior Member

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    I am going to guess a cause: all of your tetrahydrofolates are actually lowish, not to mention that red blood cells "Folic Acid, Active" (whatever that means) is actually low. Have you tried supplementing with methylfolate to see what happens?
     

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