Wildly swinging Krebs Cycle labs -- Can someone help?

Jesse2233

Senior Member
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Southern California
Wondering if anyone can help me make sense of what my different Krebs Cycle labs mean.
  • My pyruvate and isocitric levels seemed to have more or less normalized, and cis-aconitate has improved

  • My succinic and malic levels have gone from too low to too high.

  • What's additionally confusing is that even though both labs are from Genova, the CardioION and NutraEval have different reference ranges, so I can't exactly compare apples to apples.

  • And then to make things even more confusing, there's a UCLA lab done shortly after the NutraEval still showing high pyruvate.
So it's unclear if my cellular metabolism is moving in the right direction or if these labs are just noise.

Symptomatically I am better than I was during the initial labs, but not well.

During the time between Genova labs I added:
  • Colostrum
  • MitoQ
  • Complete Mineral Complex
  • IVIG
  • Low Dose Naltrexone
  • CoEnzyme Q10
  • Equilibrant
  • Milk Thistle
Back in February my Genova CardioION showed the following:
upload_2017-8-4_12-31-40.png


This is from a NutraEval in June

upload_2017-8-4_12-36-37.png


And this is from a lab at UCLA also in June

upload_2017-8-4_12-35-23.png


Thanks!
 

ljimbo423

Senior Member
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Location
United States, New Hampshire
Hey Jesse- I think oxidative stress plays a big role in cfs in general and impairing many enzymes as well. I wonder if varying levels of oxidative stress, that everyone experiences, people with cfs probably much more than the norm, are causing much of the differences you see in your labs.

The varying levels of OS might cause impairment, to varying degrees, of enzymes needed to keep the krebs cycle functioning smoothly. Additionally, the supps. that you are taking most likely are having some effects on the enzymes, oxidative stress levels and krebs cycle in general.

If you feel better, that seems to suggest that you are moving in the right direction, whatever the labs say.:)
 

*GG*

senior member
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6,396
Location
Concord, NH
I am more interested in this stuff now. I lost 20lbs last summer from exercise, this year the weight is not coming off, I think it has something to do with my metabolism :(

GG
 

rodgergrummidge

Senior Member
Messages
124
There are alot of companies that provide metabolic and nutrient testing, but often the results are impossible to interpret and virtually meaningless. It is essential that blood tests are standardized and accredited so that i) the results can be compared between labs and regions and ii) that the readouts are interpreted in the context of evidence-based scientific 'normal' ranges. Many companies claim that they can provide accurate testing and provide clearly defined normal ranges, but in reality, the levels of metabolites vary considerably depending on the method used and there is often no scientific basis for their 'normal ranges' given in their reports. As you can see, the levels between these companies and even their proposed normal ranges differ considerably. For example, Genova CardioION doesnt even allow measurement of the lactate:pyruvate (L:p) ratio which is a widely used measure of mitochondrial function which can be abnormal in CFS.

I am assuming that UCLA data was generated by using standardized and accredited methods because the ranges indicated seem to be in line with the international standards (as opposed to the Genova CardioION levels) . If so, your high pyruvate combined with a slightly elevated lactate (giving a low-ish L:p ratio) might indicate a mitochondrial deficit. A low L:p ratio (disproportionately elevated pyruvic acid) may indicate a defect in pyruvate metabolism. Severe defects of the pyruvate dehydrogenase complex result in L:p ratios <10. Clinically, defects in Pyruvate Dehydrogenase may result in the reduced production of AcetylCoA for your Krebs Cycle to function optimally and so may result in reduced mitochondrial energy production.

However, such results really depend on whether you were fasting or not fasting, had physically exerted yourself or not physically exerted yourself before the test (even a walk up several flights of stairs could confound the readings), and whether the path lab obtained the blood sample correctly with the minimal use of a touriquet and the use of specific fluoride collection tubes........

..........such factors are often not considered in slickly-marketed metabolic/nutrient testing labs that now litter the internet.

Rodger
 

rodgergrummidge

Senior Member
Messages
124
Wondering if anyone can help me make sense of what my different Krebs Cycle labs mean.
  • My pyruvate and isocitric levels seemed to have more or less normalized, and cis-aconitate has improved

  • My succinic and malic levels have gone from too low to too high.

  • What's additionally confusing is that even though both labs are from Genova, the CardioION and NutraEval have different reference ranges, so I can't exactly compare apples to apples.

  • And then to make things even more confusing, there's a UCLA lab done shortly after the NutraEval still showing high pyruvate.
ks!

Hi @Jesse2233, i came across this paper where metabolic signatures were described in CFS that may be helpful in interpretting your profile (Scientific Reports | 6:34990 | DOI: 10.1038/srep34).

they found Pyruvate to be higher in CFS patients (others have also shown this) while the concentrations of citrate and isocitrate in the first steps of the TCA cycle related to the energy metabolism in CFS patients were reduced relative to those in healthy controls. Meanwhile, the concentration of succinate, which follows these metabolites in the TCA cycle, did not differ significantly between CFS patients and healthy controls.

As for the urea cycle, the concentration of ornithine in CFS patients was significantly higher than in healthy controls, while that of citrulline was significantly lower in CFS patients than in healthy controls.

The metabolites in glutamine metabolism and the BCAAs did not show significant differences between the CFS patients and the healthy controls.

there is some similarities with your profile and what the authors found in this paper

Data pasted below.

hopefully you find it helpful

rodger

upload_2017-9-1_14-24-20.png
 

pattismith

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rodgergrummidge

Senior Member
Messages
124
@Jesse2233
@rodgergrummidge

are we sure about succinate levels?

This slide was shared by @Murph , from the conference in Sweden, ( Jonas Blomberg), it states that Succinate may be one of the potential biomarker, although we don't know what study he is refering to.

Succinate is also used for Mitochondrial disorder.
I myself started Tocopheryl succinate 400 UI some days ago.

View attachment 24749

http://forums.phoenixrising.me/index.php?threads/rme-conferences-in-stockholm-and-malmö-october-2017.55213/page-2#post-926966
my understanding of Tocopheryl succinate is that it is not a 'succinate supplement'. Succinate is often used by chemists to attach to drugs to increase their solubility and bioavailability. Thus, in order to increase the solubility of Tocopheryl (not very soluble in aqueous solutions), it has been attached to succinate. So i think you might have been taking Tocopheryl succinate as a vitamin E supplement, not a succinate supplement.

cheers

Rodger
 

pattismith

Senior Member
Messages
3,988
you didn't answer to my concern about succinate as a potential biologic marker for CFS/ME, do you know why Blomberg quoted it? Is it low or high?

my understanding of Tocopheryl succinate is that it is not a 'succinate supplement'. Succinate is often used by chemists to attach to drugs to increase their solubility and bioavailability. Thus, in order to increase the solubility of Tocopheryl (not very soluble in aqueous solutions), it has been attached to succinate. So i think you might have been taking Tocopheryl succinate as a vitamin E supplement, not a succinate supplement.

cheers

Rodger

Yes you are right, thank you for making me aware, Tocopheryl-succinate doesn't give succinate to the Krebs cycle, as I too quickly assumed.

In fact it doesn't seem to even bring Vitamine E to the body. It is a very special compound that has both anti-inflammatory and anti-cancerous activity (this later by increasing oxydation/ROS)!...

So it doesn't bring succinate, but it doesn't bring vitamine E either!(edit: this very ennoying as it is sold as an anti-oxydant supplement, otherwise it is an oxydant)

Actually, I don't find any succinate available anywhere as such...Only Iron succinate here in my country, but I don't want to supplement with iron...
 
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