• Phoenix Rising needs funds to operate: please consider donating to support PR

Organic Acid Test (OAT) results – do we ALL show the Warburg effect?

junkcrap50

Senior Member
Messages
841
Likes
1,627
Reporting my Lactate and Pyruvate levels. Both are low. But my pryvuate is much higher and my lactate much lower than others listed in this thread. My Citrate & Succinate are both normal, in the middle. So I do not think I show the Warburg effect, but feel free to correct me. (Units below are in mmol/mol creatinine).

When calculating my lactate: Pryvuate ratio (used to determine metabolic disorders), my ratio doesn't seem right. It's crazy low: 0.65. When abnormal is greater than 25. Does this mean I have a problem with pyruvate metabolism: "In conjunction with an elevated lactate, an L: P ratio less than 25 suggests a defect in pyruvate metabolism."

I think Genova f*cked up the units. Because other online reference ranges list lactic acid range to be 4.5-19.8 mg/dL or 0.5-2.2mmol/dL = 5-22mmol/L. I might call them.
Lactate & Pyruvate levels - Organic Acids Tests.png
 
Last edited:
Messages
60
Likes
139
@junkcrap50 thanks for posting your test results. The lactate-to-pyruvate ratio is useful but needs to be taken in context of whether pyruvate is low or high. When the ratio is under 25, more commonly it is because pyruvate is above normal because of mitochondrial impairment or PDH deficiency (conversion of pyruvate to Acetyl-COA). So low pyruvate AND lactate suggests you don't have a defect in pyruvate metabolism, instead suggests a defect in pyruvate production.

This is apparent with all these results so far, ME/CFS patients resemble a common pattern of low pyruvate and low to normal lactate. Unless we're all being starved or on an especially low-carb diet, this implies we have an impairment in glycolysis and a deficiency in pyruvate production. There's a link to McGregors research in this thread intro, he believes impaired glycolysis is at the root of ME/CFS.

Fisher's study found mitochondrial impairment in ME/CFS, in the form of complex V deficiency (under stress test). Leigh's disease, which is also a complex V deficiency, may also reveal a low lactate-to-pyruvate ratio, but that's because of an above normal pyruvate measure in the absence of high lactate or even lactic acidosis which is quite unlike PWME tests results. So, taken together PWME appear to have both impaired glycolysis and maybe impaired OXPHOS.

As far as the other metabolites, there seem to be two groups. One group with normal to high citrate and high succinate (possibly earlier in the disease?), and another group with roughly normal Krebs metabolites except commonly low cis-aconitate. I'm not sure what to make of that right now.

It has been proposed ME/CFS starts as a glycolytic impairment but with more severe patients also having mitochondrial impairment. My own experience supports this. First adapting to Keto, bypassing glycolysis I enjoyed a huge improvement from moderate to mild, only to wreck that with a short power walk and now Keto doesn't work for me anymore and I'm down to severe.

I hope pyruvate kinase is tested soon in ME/CFS to see if it is that impairing pyruvate production.
 

wastwater

Senior Member
Messages
1,161
Likes
820
Location
uk
Are the tests based on urine and is that reliable
Genetically I presume I have low Pyruvate
high a-ketoglutarate in urine
Is glutamate high or low
 
Last edited:
Messages
60
Likes
139
Are the tests based on urine and is that reliable
The tests are based on urine, and urine organic acids are a favoured substance to study in the emerging field of metabolomics. Being an emerging field though, the reference ranges between healthy and unhealthy may not yet be clearly defined. You should expect to have confirmed if you have low pyruvate though. You suspect this is genetic?

Is the idea that excessive brain glutamate causes problems
Yes, excessive glutamate is excitotoxic, and glutamate deficiency can also be problematic.
 

wastwater

Senior Member
Messages
1,161
Likes
820
Location
uk
I have a confirmed PITX2 (axenfeld Rieger syndrome) point mutation and two of its significant target genes are SLC13A3 and PDP2 among many others
 
Last edited:

junkcrap50

Senior Member
Messages
841
Likes
1,627
Unless we're all being starved or on an especially low-carb diet, this implies we have an impairment in glycolysis and a deficiency in pyruvate production. There's a link to McGregors research in this thread intro, he believes impaired glycolysis is at the root of ME/CFS.
Is there any way to test or evaluate glycolysis or fatty acid oxidation?

It has been proposed ME/CFS starts as a glycolytic impairment but with more severe patients also having mitochondrial impairment. My own experience supports this. First adapting to Keto, bypassing glycolysis I enjoyed a huge improvement from moderate to mild, only to wreck that with a short power walk and now Keto doesn't work for me anymore and I'm down to severe.
So sorry to hear that. Last year I had success with Keto: lost 30 lbs (most of excess weight) & felt overall better in terms of energy and cognition (though mild).
 
Messages
65
Likes
80
Here is mine. I don't fall into the pattern you mention, but have odd high numbers everywhere, so not sure what that may signify.

Screenshot (2).png
 
Messages
60
Likes
139
Is there any way to test or evaluate glycolysis or fatty acid oxidation?
Other than the usual diabetes checks (blood glucose and insulin) in conjunction with OAT test, I'm not aware of additional evaluation testing of glycolytic function. OAT test also reveals fatty acid metabolites and ketones, I don't know how else one could measure fatty acid oxidation. @Learner1 was having these tested by experts apparently, maybe can help answer your question how this was being done.

@sue1234 thanks your post. I'm intrigued with yours! Have you been diagnosed with ME/CFS? You're quite a departure from the typical pattern emerging so far, and you don't appear to have impaired glycolytic function. However, referencing your mitochondrial markers in the OAT guide it quotes "The Organic Acids Test detects levels of malic acid, which, when elevated simultaneously with citric, fumaric, and alpha-ketoglutaric acids, strongly suggests cytochrome C oxidase deficiency, indicating dysfunction in the mitochondrial energy pathways." You appear to fit that description!? This might be worth raising with your doctors? There are a few conditions with COX deficiency here for example and there may be other possibilities which could be receptive to treatment. Thank you so much for posting, fascinating!
 
Messages
65
Likes
80
However, referencing your mitochondrial markers in the OAT guide it quotes "The Organic Acids Test detects levels of malic acid, which, when elevated simultaneously with citric, fumaric, and alpha-ketoglutaric acids, strongly suggests cytochrome C oxidase deficiency, indicating dysfunction in the mitochondrial energy pathways." You appear to fit that description!? This might be worth raising with your doctors? There are a few conditions with COX deficiency here for example and there may be other possibilities which could be receptive to treatment. Thank you so much for posting, fascinating!
Thanks so much for pointing all this out! I appreciate that information I had done this test on my own, but had shown it to my functional medicine doctor at the time. They did not say anything about it. I am honestly not sure what kind of doctor might address this issue? I have not been formally diagnosed with ME/CFS, but have something going on for the last 14 years, with my abilities draining over those years.

I just read your link, and I see it says it mostly is a genetic thing that starts in infants, sometimes adolescents or early adulthood. I am 60 y/o right now, and all this began for me at age 45, so now I am wondering if it can not be genetic, but acquired?

Anyone know what kind of doctor might address the above issues??
 
Last edited:
Messages
78
Likes
118
Back in 2017 - similar results but I was making a lot of energy from ketones 3-Hydroxybutyric above range (paleo diet).

I have changed diet since then .. so probably need to get another test done soon.
 

Attachments

Messages
60
Likes
139
I just read your link, and I see it says it mostly is a genetic thing that starts in infants, sometimes adolescents or early adulthood. I am 60 y/o right now, and all this began for me at age 45, so now I am wondering if it can not be genetic, but acquired?

Anyone know what kind of doctor might address the above issues??
Keep in mind the test result is not diagnostic, only indicative, even if they do use the words 'strongly suggestive'! But certainly worth raising with your doctor to explore further. You're right, a genetic COX deficiency would most likely have shown symptoms long before age 45. Research suggests other factors such as high ROS or NO, may also suppress expression, so easily be associated with an immune response. Does coffee help your symptoms? This research article 'Feeding Mitochondria' suggests caffeine, vitamin E and to some extent selenium can stimulate complex IV activity. I do wish you luck exploring this further.

@Nine lives thanks your posting. Yes, I guess your low pyruvate might be due to low carb ketosis.
 
Messages
65
Likes
80
Keep in mind the test result is not diagnostic, only indicative, even if they do use the words 'strongly suggestive'! But certainly worth raising with your doctor to explore further. You're right, a genetic COX deficiency would most likely have shown symptoms long before age 45. Research suggests other factors such as high ROS or NO, may also suppress expression, so easily be associated with an immune response. Does coffee help your symptoms? This research article 'Feeding Mitochondria' suggests caffeine, vitamin E and to some extent selenium can stimulate complex IV activity. I do wish you luck exploring this further.
Thanks. I am seeing a functional medicine doctor in a month, and I was already set up to look for hidden infections. It will be interesting to see if finding and addressing that makes a difference.

And yes, coffee helps me, but I can't do as much as I like or I don't sleep, which in turn makes me feel more il
 

Learner1

Senior Member
Messages
4,621
Likes
8,246
Location
Pacific Northwest
Is there any way to test or evaluate glycolysis or fatty acid oxidation?
Other than the usual diabetes checks (blood glucose and insulin) in conjunction with OAT test, I'm not aware of additional evaluation testing of glycolytic function. OAT test also reveals fatty acid metabolites and ketones, I don't know how else one could measure fatty acid oxidation. @Learner1 was having these tested by experts apparently, maybe can help answer your question how this was being done.
After listening to Peter Attia's interview with Inigo San Millan, I sought out the type of metabolic testing he described that he does in his Colorado lab. I found a local physical therapy practicect that deals with elite athletes and was able to do their treadmill based test, which involved putting on a very uncomfortable mask for 20 minutes and laying on a table, then getting onto a treadmill and walking slowly in 2 minute increments gradually increasing the slope every 2 minutes, until I was weak limbed and collapsed. The output of the test tells you whether you're burning glucose or fat at various time points throughout the 45 to 60 minute test.

As mentioned, the Great Plains OAT test has glutaric acid and other glutaric metabolites, which if high indicate impaired fatty acid oxidation. You'd also want to check carnitine to ensure that you have enough to process the fats. And myoglobin if low is an indicator of impaired fatty acid oxidation.

I found that the reason I have aerobic exercise intolerance is that I'm not burning fat. I'm burning glucose and run through all my glycogen stores too fast. So I sure would like to know how you measure impaired glycolysis, because that's all I seem to be using.

The paper @WantedAlive posted on Feeding Mitochondria as an interesting comment on this;

"However, this response is inhibited during critical disease as the increased rate of glycolysis inhibits carnitine acyltransferase I via malonyl Co-A [25], [27].

Interestingly, this balance between energy substrates is not only disturbed during the critical stages of illness but may continue during the recovery period. For example, a recent study found that patients surviving severe burn injury showed no capacity to utilize fat for energy in the muscles months after ICU discharge, limiting exercise performance to only a few minutes"

I believe this is what I'm experiencing. I've been using strategies in Seyfried, D'Agostino and Nicolson's Mitochondrial Correction Paper, and though I have had improvements in labs and symptoms, it hasn't fixed this particular problem and I have 3 sets of labs and the metabolic test that show this. Lactate is low, though, not high, had my blood sugar, triglycerides, and HBA1C are all fairly low normal.

the OAT guide it quotes "The Organic Acids Test detects levels of malic acid, which, when elevated simultaneously with citric, fumaric, and alpha-ketoglutaric acids, strongly suggests cytochrome C oxidase deficiency, indicating dysfunction in the mitochondrial energy pathways
AKG isn't on the Great Plains OAT test.
I am wondering if it can not be genetic, but acquired?

Anyone know what kind of doctor might address the above issues??
I have acquired mito dysfunction and have a lot of interesting abnormalities I've been tracing down. I have consulted with two mito specialists, but they really showed little interest in helping me because they only deal with genetic mito issues which I don't seem to have. So the deal is to look for a mitochondria and metabolism specialist, but I haven't found one anywhere in the US that will see patients. There is a research lab at the University of Washington in this area but the only patients they see are mice.

If you find one, I sure would be interested...
Does coffee help your symptoms? This research article 'Feeding Mitochondria' suggests caffeine, vitamin E and to some extent selenium can stimulate complex IV activity. I do wish you luck exploring this further
I have a bad AMPD1 SNP that results in excess adenosine after exercise, which makes me sleepy. Caffeine, in the form of coffee, helps to dissipate this excess adenosine. So, there are multiple benefits to caffeine.

I have hyperactive complex IV activity which we believe is throwing off too much oxidative stress. I don't see anything in the paper about slowing it down. The MitoSwab folks told me that the typical pattern for ME/CFS patients that they have tested is low complex I and hyperactive complex IV.

I've attached the Seyfried article.
 

Attachments

Learner1

Senior Member
Messages
4,621
Likes
8,246
Location
Pacific Northwest
s "The Organic Acids Test detects levels of malic acid, which, when elevated simultaneously with citric, fumaric, and alpha-ketoglutaric acids, strongly suggests cytochrome C oxidase deficiency
From the Genova interpretive guide:

"elevated alpha-ketoglutaric acid also may be accompanied by elevated glyoxylate and oxalate. If there is weakness in the
decarboxylation of glyoxylate and alpha-ketoglutarate, renal stone (calcium oxalate) formation is possible. This is not a
common condition, and its diagnosis should be made from urine levels of oxalate and glyoxylate. In this case, supplements
of vitamin B6 or pyridoxal 5-phosphate may be beneficial"