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Need Help w/ Genova CardioION Results (High Pyruvate / Low Lactic Acid)

Discussion in 'General ME/CFS Discussion' started by Jesse2233, Apr 20, 2017.

  1. Jesse2233

    Jesse2233 Senior Member

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    Hey everyone,

    A bit overwhelmed with my CardioION results from Genova. Any help would be greatly appreciated!

    Caveats: Is Genova reliable? Supplementing at the time. Snapshot in time.

    Other relevant info: ill 3 months at time of blood draw, high Coxsackie B4 titers, low ANA

    Krebs cycle problems
    • Pyruvate is off the charts = 15.9 (reference range <= 6.4)
    • L-lactic is low = 0.1 (reference range 0.6 - 16.4)
    • Also low cis-aconitate and isocitrate
    There seems to a clear block in the Krebs cycle, but if PDH is impaired (per Fluge/Mella's findings), shouldn't my pyruvate be low, and lactic acid high? Does this mean LDH is impaired?


    Pre-illness these levels were normal
    • High insulin, triglycerides

    High aminos
    • High lysine, methione, tryptophan, isoleucine, leucine, valine, phenylaline, histidine, threonine, arginine, serine
    Does this mean I'm not properly absorbing or that I'm consuming too much?


    Other abnormalities
    • Lowish zinc and copper
    • High alpha linolenic
    • High capric, lauric, and behenic

    Full results:

    upload_2017-4-20_11-1-42.png
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    upload_2017-4-20_11-3-45.png
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    upload_2017-4-20_11-5-35.png

    upload_2017-4-20_11-6-17.png
     

    Attached Files:

    Last edited: Apr 20, 2017
  2. Jesse2233

    Jesse2233 Senior Member

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    More results:

    upload_2017-4-20_11-9-57.png
    upload_2017-4-20_11-10-25.png
    upload_2017-4-20_11-11-4.png
    upload_2017-4-20_11-11-31.png
    upload_2017-4-20_11-12-5.png
    upload_2017-4-20_11-13-14.png
     
  3. JaimeS

    JaimeS Senior Member

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    .....HIGH pyruvate.

    LOW lactate?

    .....LOTS of glycolysis? NOT lots of TCA cycle?

    ....your crazy-high amino acid levels bear that out. You appear to have the OPPOSITE picture of the 'average' ME/CFSer -- if such a thing can be said.

    Do you take a protein supplement? Whey protein, eg? Do you take BCAAs as a supplement?

    ....your high fats bear this out as well.

    http://care.diabetesjournals.org/content/39/5/833

    Here is a metabolomic review of diabetics. Have you had a glucose tolerance test recently? Not diagnosing you or anything, but that is worth a read for you, IMO.

    Jaime
     
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  4. halcyon

    halcyon Senior Member

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    @Jesse2233 were you able to get insurance to cover this test? I was interested in doing it, until I saw the price tag. :eek:
     
  5. Jesse2233

    Jesse2233 Senior Member

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    Thanks Jaime I had the same take you did!!! Thought it was just my brain fog

    I wasn't in PEM state when this was done so maybe that's why lactate wasn't high (Fluge/Mella mention this in their paper), but why so low???

    The pyruvate thing is weird unless it's just building up because an enzyme (LDH??) can't process it

    Will investigate the diabetics literature
     
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  6. Jesse2233

    Jesse2233 Senior Member

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    Yes my insurance (Blue Shield PPO) paid everything except for around a hundred dollars
     
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  7. Jesse2233

    Jesse2233 Senior Member

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    Was taking a plant based protein drink at the time but nothing craaaazy
     
    JaimeS likes this.
  8. A.B.

    A.B. Senior Member

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    Pyruvate is produced by glycolysis. The Krebs cycle can then use pyruvate to produce more energy. Alternatively, if there is not enough oxygen, or there is a block in the Krebs cycle, the pyruvate would be fermented into lactic acid. I'm not an expert, but these results seem inconsistent with Krebs cycle impairment.

    I don't know why your body is running with pyruvate and various amino acids that high.
     
  9. alicec

    alicec Senior Member

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    You need to appreciate that the first part of the results is from blood, the second part (from nutrient markers onwards) from urine.

    High and low results from either source can often have almost the opposite interpretation.

    High in blood may mean the substance is not being used in the cell - the pathway involved is slow. Of course it could be that there is an excessive supply, but one can often work out which is which depending on the substance and what is known about intake.

    Low in blood could mean the substance is being used excessively. The same proviso holds that it could be lack of supply, but again this can often be worked out knowing intake.

    The opposite is the case in urine since here we are dealing with the discards of metabolic pathways. High means that the pathway has been used excessively, low that it is not being used much.

    There are some substances where high has a particular meaning. These accumulate when there is a downstream blockage. MMA is a good example, accumulating when a B12 dependant enzyme downstream is not functioning well. Nothing else leads to MMA accumulation so this is diagnostic of B12 deficiency.

    Interpretation guides with tests usually point these types of markers.

    Also in sequential pathways such as the Kreb's cycle, the pattern of high and low can point to blockages.

    Your Kreb's cycle markers could be quite consistent with Fluge and Mella's findings. They were looking at amino acids in blood. The ones that were low, that is, the ones being consumed excessively, were those that didn't enter the Kreb's cycle via PDH, suggesting that PDH was blocked and the body was forced to use other sources of fuel.

    Your Kreb's cycle metabolites are in urine. You have plenty of pyruvate so glycolysis is proceeding ok, but it's all downhill from there.

    PDH acts on pyruvate to make acetylCoA which then reacts with oxaloacetate to make citrate. You have made a bit of citrate, but not much in comparison with the amount of pyruvate. Most of it is not being used and is accumulating.

    Two enzymes are involved between pyruvate and citrate so we don't know which is at fault but, in light of Fluge and Mella's study, it is reasonable to imagine the PDH is not functioning well and that there is not much acetylCoA to make citrate.

    Then there is almost a complete blockage at the aconitase enzyme which catalyses the next two steps, leading to almost no formation of cis-aconitate and isocitrate. This is a common source of blockage in the Kreb's cycle since the iron-sulfur clusters needed for enzyme activity are readily oxidised.

    You are obviously getting a little input into the cycle beyond this point (presumably from amino acids) since it limps along a bit after this, but essentially the cycle is stuffed.

    Join the club.

    The very high blood amino acids are puzzling and are maybe saying something about your own particular metabolic problems. Possibly a combination of high intake and low use but the reason for the latter would require a lot more delving.

    The low lactate in face of high pyruvate does suggest the LD is not working well.
     
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  10. A.B.

    A.B. Senior Member

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    Acetyl-CoA can alternatively be used to make fats. Judging by the high triglycerides this might be happening.
     
  11. Jesse2233

    Jesse2233 Senior Member

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    Thanks for the feedback @alicec, really appreciate it!!

    Would supplementing acetylCoA be of any use?

    Any way to externally increase these levels or repair the enzyme?

    I'm scheduled to see a mitochondrial research doctor, might he be of use?

    Any tips on investigating this further?

    Thanks!
     
  12. alicec

    alicec Senior Member

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    Not available.

    One could consider the strategy of supplementing amino acids which bypass the PDH blockage, as considered here (there is interesting discussion in this whole thread if you are able to read it), but your high blood amino acids suggest something very strange is going on so this strategy might not help you.

    Your fatty acid oxidation markers are ok, suggesting that fats might be useful to you as an energy source.

    Address oxidative stress.

    Possibly, particularly if he is open minded and doesn't think in the black and white terms of in-born errors of metabolism leading to mitochondrial disease and normal mitochondrial function with no shades of grey in between.

    Not really.
     
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  13. Jesse2233

    Jesse2233 Senior Member

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  14. alicec

    alicec Senior Member

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    I'm not familiar with that product, but in theory it might help a bit. Sometimes when an enzyme is slow, adding large amounts of cofactors/substrates for the enzyme might stimulate it. It depends what is causing the slowness.

    This strategy is used for some of the inborn errors of metabolism and sometimes works.

    I suspect this is the reason that some of us get a boost from relatively large amounts of some vitamins and minerals.

    Which help what people is impossible to predict though tests such as yours sometimes give clues about what might be worth trying. It's largely a matter of trial and error
     
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  15. halcyon

    halcyon Senior Member

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    So in one of the coxsackie B linked ME outbreaks, elevated LDH was a common finding. Seems like increased LDH activity might explain both low lactate and elevated pyruvate.
     
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  16. halcyon

    halcyon Senior Member

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    Although I guess what they were measuring in that study was LDH level in the blood, which can increase due to infection. Doesn't necessarily mean enzyme activity is increased in cells.
     
    Jesse2233 likes this.

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