PKM2 accelerated the progression of chronic fatigue syndrome

[Violeta]

https://www.nature.com/articles/s41598-025-93313-w.pdf

Meng Sun1,5, Xinwen Zhang2,5, Xinli Feng3,4 & Lu Liang3
March 28, 2025

Researchon CFS has gradually shifted from symptom management to investigating its molecular mechanisms, withthe role of PKM2 (pyruvate kinase M2) increasingly becoming a focus.

The metabolic patterns in CFS patients have significantlychanged. Studies have found increased glycolytic activity and reduced efficiency of mitochondrial oxidativephosphorylation in CFS patients, leading to energy deficiency and the accumulation of metabolic waste, suchas lactate3.PKM2 plays a crucial role in this process.

Research suggests that abnormal activation of PKM2 in hippocampal cells may enhance glycolysis and lactateaccumulation, leading to mitochondrial dysfunction and accelerating the progression of CFS6. Furthermore, theactivation of PKM2 not only promotes glycolysis but also regulates lactate accumulation, which further alters theacidic environment within cells. This metabolic disorder is considered a crucial mechanism underlying energyproduction deficits in CFS patients.

 

[andyguitar]

abnormal activation of PKM2 in hippocampal cells may enhance glycolysis and lactateaccumulation, leading to mitochondrial dysfunction and accelerating the progression of CFS6.

Can be blocked by Metformin.

 

[Violeta]

Can be blocked by Metformin.

Yes, and other SIRT1 agonists are beneficial, too. Berberine, kelp, quercetin, Vitamin D, pau d'arco, to name a few.

The lactate can cause NAFLD, so dealing with that might be necessary, too,

 

[Violeta]

Oleuropein, a constituent of olive leaf, can inhibit the expression of PKM2.

PKM2 accelerates the progression of ME/CFS. It is the enzyme that increases formation of lactate.

This study is about PKM2 in relationship to cancer, but it is also involved in ME/CFS and COVID.

Natural products targeting glycolysis in cancer

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1036502/full

"Studies have shown that oleuropein can inhibit the expression of PKM2, a key enzyme in the glycolytic pathway, which is often upregulated in cancer cells."

 

[Violeta]

So far I have increased my intake of reishi, at least 6 X 500mg a day.

SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2​

SIRT1 interacts with and deacetylates pyruvate kinase M2 (PKM2) at K135 and K206, thus leading to reduced PKM2 enzyme activity and lactate production, which eventually results in decreased glial activation in the brain.

https://pubmed.ncbi.nlm.nih.gov/39128469/

I am waiting for spirulina for its remedial action on superoxide. If it helps with collagen production and improves the condition of my skin, or at least stops the deterioration of it, I will be extra happy.

Extracellular pyruvate kinase M2 induces cell migration through p-Tyr42 RhoA-mediated superoxide generation​

https://pubmed.ncbi.nlm.nih.gov/37722568/

The extracellular recombinant PKM2 protein not only enhanced cancer cell migration and invasion but also increased superoxide production
Spirulina is a blue-green algae that is a good source of natural antioxidants, including superoxide dismutase (SOD), an enzyme that helps break down harmful oxygen molecules, potentially preventing tissue damage.

Restoration of mitochondrial function by Spirulina polysaccharide via upregulated SOD2 in aging fibroblasts​

https://pmc.ncbi.nlm.nih.gov/articles/PMC10319841/
We demonstrated that the Spirulina polysaccharide complex (SPC) restores mitochondrial function and collagen production by scavenging superoxide.

 

[Violeta]

There is an article linked at the top of the opening page of Phoenix Rising about a young man being diagnosed with Alzheimer's.

PKM2 is involved in both Alzheimer's and Parkinson's. Is it what causes brain fog in ME/CFS?

 

[andyguitar]

PKM2 is involved in both Alzheimer's and Parkinson's. Is it what causes brain fog in ME/CFS?

Could be, if it is then Metformin should improve it.

 

[Violeta]

Could be, if it is then Metformin should improve it.

I don't like the possible side effects of Metformin, but there are SIRT1 agonists that don't have side effects.

If someone isn't prone to bad reactions from drugs, that would be an easy thing to try.

 

[Oliver3]

I don't like the possible side effects of Metformin, but there are SIRT1 agonists that don't have side effects.

If someone isn't prone to bad reactions from drugs, that would be an easy thing to try.

I've just started on good quality berberine...almost went into what felt like remission
Can feel the disease creeping back in as I gain tolerance, but felt better for sure. Waling up refreshed. No anxious. Much less dysautomnia abd fatigue

 

[Violeta]

I've just started on good quality berberine...almost went into what felt like remission
Can feel the disease creeping back in as I gain tolerance, but felt better for sure. Waling up refreshed. No anxious. Much less dysautomnia abd fatigue

That's good news! Which berberine do you take?

I wonder if reishi being a SIRT1 agonist hits the problem from a different direction.

I have had very good results for the past week taking a lot of reishi. The feeling of not being able to stay awake after 12:00 noon and needing a nap, and then still feeling like I couldn't move is lessening. Also, I have shoveled dirt for cleaning up my front yard, yesterday took the dog for the longest walk I have done in 3 or 4 years, started doing some Tibetan exercises, and other stuff, too.
Oh yeah, much less anxious, too.

I had to look up berberine + PKM2. There's a lot of hits, here's one:
https://journals.sagepub.com/doi/pdf/10.1177/1934578X1701200909

 

[Bobby Peru]

Can be blocked by Metformin.

I started taking Metformin roughly seven months ago due to the hypothesis listed at the bottom.

• It helps. Not remission by any stretch, but I have not had a significant crash since then. Normally, during the winter months, I have numerous crashes due to whatever virus I picked up.
• I did not experience any side effects.
• I am not diabetic.

Myalgic Encephalomyelitis/ChronicFatigue Syndrome (Me/Cfs) Hypothesis:Three Subtypes of NoradrenergicNeuron Dysfunction
Tamara Carnac
*
Posted Date: 19 September 2024
doi: 10.20944/

 

[Violeta]

I started taking Metformin roughly seven months ago due to the hypothesis listed at the bottom.

• It helps. Not remission by any stretch, but I have not had a significant crash since then. Normally, during the winter months, I have numerous crashes due to whatever virus I picked up.
• I did not experience any side effects.
• I am not diabetic.

Myalgic Encephalomyelitis/ChronicFatigue Syndrome (Me/Cfs) Hypothesis:Three Subtypes of NoradrenergicNeuron Dysfunction
Tamara Carnac
*
Posted Date: 19 September 2024
doi: 10.20944/

That's so great. I could post your reply on twitter in Tamara's thread, if you don't mind.

And here's the thread where those who are interested can read about Tamara's hypothesis:

https://x.com/tamararivc/status/1836799647911751996

And this is the link to her add-on about phosphatidylcholine:
https://x.com/tamararivc/status/1907454122015469756

 

[Bobby Peru]

Sure, no problem. Ol' Bobby Peru