Thanks
@godlovesatrier you seem to fit the profile.
I did Genova Diagnostics test, they use slightly different metabolites and measures to your test, who was yours done through? I might read up on their guide to compare the measures with what Genova uses (mcg/mg creatinine). While your citric wasn't high, your aconitic was low suggesting a slight 'break' in the cycle. Can I ask what severity you were when you did the test and were you a fast or slow ME/CFS onset? I'm wondering if a sudden onset might show in these results compared to a slow onset. This is all rather intriguing.
Thanks your results
@sb4 - what brand test was yours? What severity were you when you did the test? And were you a slow of sudden onset? Your pyruvate isn't
that low so I'm curious how that compares with your functionality at the time of the test.
Out of interest, I've created a rough illustration of this warburg effect showing the krebs-cycle breaks and why Citrate and succinate are elevated, and where PKM2 is and why pyruvate/lactate is likely low.
View attachment 38270
This is my OAT test from about 10 years ago, 3 years into CFS/ME.
Pyruvate and Fumarate, as well as several others, are undetectable. Lactate is on a different page but is mid-normal so no lactate elevation here.
I've been down a lot of roads over the years trying to figure out what's wrong with me and honestly, I forgot about this test. The OAT legend didn't give any indications for low Pyruvate so I just assumed at the time that it was a normal finding. All I could find on the internet at the time was the importance of NAD+ in regards to glycolysis. The problem is nearly ALL synthetic B vitamins make me feel much worse. B3/NAD supplements drive catecholamines down and add to my lethargy. I've taken high dose NAD/NMN and it's no Bueno for me.
The reason that I even found this thread on google is because I was going over my old labs and seeing if I could make a connection to Glutamine deficiency and low urine Pyruvate. Two weeks ago I got the novel idea to test my serum amino acids. I had done that years ago but it was one of those blood spot tests the results weren't very helpful. So this time I ordered it from Labcorp and low and behold, I'm very deficient in Glutamine. This can cause all manner of metabolic mayhem. I've also got some other aminos that are in range but quite low compared to normals.
I've done quite a bit of reading on the effects of Glutamine deficiency lately because of this test result and I've become convinced that this is likely the genesis of my entire disease. I wanted to post my finding here in case anyone can be helped by it. Or, at least rule it in or out of their own situation.
Generally, fasting serum levels of amino acids are under various regulatory controls so it is rare for healthy people to have any levels that fall outside of the laboratory range. Usually a serum amino acids test is ordered to look for congenital diseases in children.
Strangely, my Glutamate and GABA levels are the only ones that are somewhat higher than normals in serum, but they are still in physiological range. But even so, everything I read indicates that the brain depends on high levels of GLN in the blood for a substantial part of it's GLU and GABA metabolism. For reference, in a study that searched for normal levels of serum amino acids in healthy adults had normal GLN level at 586 +-84, mine are 275 umol/L. That's less than half of where it should be. Neither GLN or GABA pass directly from the blood into the brain.
A deficiency of GABA and GLU synthesis in the brain easily explains all of the following:
- Feeling both wired and tired at the same time.
- Loss of memory and neuroplasty
- Changes in sensory perception
- Loss of executive function
- Low monoamine neurotransmitter release
- Impaired removal of ammonia from neurons
- Just about all pathological brain conditions are linked to deranged Glutamate signaling.
My CFS symptoms came on gradually after years of ever growing levels of stress. A protracted withdrawal from Xanax however was the trigger that left me in a state of permanent disability. That was over 12 years ago so whatever has happened is the result of long-term biological changes. The Xanax is long gone.
Since my late 20s, GERD and gastritis have been the bane of my existence. I've spent many years rotating between PPIs, H2 blockers, and antacids. Chronic GI destress was my primary physical ailment in the years leading up to my fatigue and has been ever since. As it turns out, GLN is the sole source of energy used to fuel the enterocytes in the gut. It is the preferred fuel source in most rapidly dividing cells. Without enough GLN, those high turn-over tissues simply can't fully repair themselves.
So it's easy to speculate that a chronically inflamed intestinal track could eventually create such a demand for GLN that the body just can't keep up. And as a result, both GLN substrates and end-products could become compromised. My long and sorted personal history with GI dysfunction is the thing that makes me feel like GLN depletion is the causative factor that set things into motion. In my case at least, it definitely predates the disease.
Don't get me wrong, I don't think that GLN deficiency is a unified explanation for CFS/ME, it would have been discovered by now. But it may be that impaired GLN metabolism more broadly is the genetic or acquired variable that leaves people vulnerable to CFS and CFS-like conditions, the thing that renders the body unable to cope with extreme physical, biological, or mental stress. Glutamine deficiency lowers immunity substantially so it also might be the common denominator between viral and non-viral causes of the syndrome.
Here is a study where they show that chronic stress causes the downregulation of several Glutamine-Glutamate-GABA cycle genes.
Here's one that shows that a lack of Glutamine in the amygdala causes anhedonia. (Granted, I'm not an epileptic rat)
And on a positive note, here is one where GLN supplementation reversed the negative effects.
On topic with this thread is the fact that in GLN deficiency Glutaminolysis would be working at an impaired capacity, theoretically producing less pyruvate. Maybe it's possible that a with lack of available Glutamine as an energy source the body does something that is similar to the Warburg effect seen in cancer.
Honestly, all I can do is guess at what is going on. My own plan at this step is to supplement heavily with L-Glutamine and L-Arginine/Citrulline for several months. They are both considered conditionally essential. Arginine is an important end product of Glutamine metabolism and my levels are at the bottom of the range. Having low levels of Nitric Oxide all this time could help explain the loss of stamina as well as cognitive and mood problems. Both Glutamate and NO are critical regulators of neurotransmitter release all throughout the brain, especially in the cortex and striatum (reward center). Tyrosine hydroxylase levels are controlled by GLU. That's possibly why my Tyrosine levels are so close to the bottom of the range, regardless of my high protein diet.
All together there are 13 aminos in my test that are well below the levels seen in normal healthy people. My goal is to get as many of them as possible up into the middle of the range as I can. I'm already long term on a Carnivore diet so the amount of protein I consume can't get any higher. Since Glutamine is so important to protein synthesis I'm going to wait and see what supplementing GLN and ARG does to the other amino acid levels. Then I'll take it from there. I'll definitely follow up here if any major improvements happen in CFS symptoms. I've been supplementing 50g/d of GLN for about 2 weeks and fatigue is improved, but mood, attention, memory, and cognition is still just as bad. I just recently added ARG.
Anyhow, sorry for the long read. I found your post and that graphic on the Warburg effect and I really just wanted to pipe in share my situation. I wish everyone here the best of luck.
