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Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways

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Which physician has diagnosed the patients, and which city? i cannot recognize any of the authors.
All in australia ... three are at University of Melbourne (Biochemistry and Medicine departments), one is at "CFS Discovery" in Donvale, and one is at "Bioscreen" in Yarraville.

I think Dr Lewis of CFS Discovery is pretty well known in Australia, and has a good reputation.
 

ebethc

Senior Member
Messages
1,901
@JaimeS @Gondwanaland

thanks for the info - interesting!

I've always felt that I have problems w blood sugar - but no diabetes dx or even in my family.. I have cortisol problems, and I'm not sure if the cortisol problems cause the glucose or vice versa or both are artifacts of another problem. Have high inflammation, which I think is related to both glucose & cortisol. On a separate but related note: I took a high dose of ALA tonight and felt so much better, then read that ALA helps glucose..So, #glucosetuesday
 

Sidereal

Senior Member
Messages
4,856
Rich figured this out years ago:

Cause of reactive hypogycemia according to the GD-MCB hypothesis for CFS

Hi, all.

For what it's worth, here is an explanation for reactive hypoglycemia in CFS based on the Glutathione Depletion--Methylation Cycle Block pathogenesis hypothesis for CFS:

1. Because glutathione is depleted in the mitochondrial of the skeletal muscle cells (and also some other types of cells), a partial block occurs at aconitase in the Krebs cycle, caused by oxidizing free radicals. Note that oxidative stress is probably the best documented biochemical abnormality in CFS, and glutathione depletion has also been found in many PWCs. For example, see the treatment study at www.cfsresearch.org Glutathione depletion is intimately tied to oxidative stress, which means an increase in the concentrations of oxidizing free radicals. These are known to inactivate aconitase by oxidizing one of its iron ions.

2. Because carbohydrates must enter the Krebs cycle at its "beginning" (as acetyl Co-A, produced from pyruvate, which in turn is produced from glucose in the glycolysis pathway), they (together with fatty acids, which must also enter here) are partially blocked from being utilized as fuel by the cells in CFS.

3. If a PWC consumes carbohydrates at a rate higher than they can be processed by the partially blocked Krebs cycle, the initial result is buildup of glucose in the blood. The pancreas responds by increasing its secretion of insulin, and because the skeletal muscle cells do not respond by accepting glucose at a higher rate, insulin goes high enough to push the glucose into the liver and fat cells, to be converted to fat and stored.

4. The results of this are an increase in weight (which is later very stubborn, because fats cannot be burned well as fuel by the cells either) and an overcorrection that causes a drop in blood sugar level below normal, which constitutes hypoglycemia.

5. Because glucose is normally the main source of fuel for the brain, hypoglycemia causes brain-related symptoms, such as tremor, irritability, and even seizure in some cases.

6. The above process is compounded in CFS cases in which the HPA axis is very dysfunctional, so that cortisol is not able to rise and promote an increase in glucose in the blood from stored glycogen in the liver and from processing of amino acids through the gluconeogenesis pathway in the liver.

7. According to the GD-MCB hypothesis, the dysfunction of the HPA axis in CFS is also caused by glutathione depletion, in this case occurring in the hypothalamus and pituitary, inhibiting the properly regulated secretion of CRH and ACTH, which control the secretion of cortisol.

8. This scenario explains why a low carb, high protein diet is favorable for PWCs, as reported by several people on this thread. The low-carb aspect prevents reactive hypogycemia from occurring, because there is no high compensatory secretion of insulin by the pancreas, and it also prevents weight gain. The protein supplies energy for the skeletal muscle cells, because it is broken down into amino acids. Amino acids can be interconverted by transamination reactions, and some of the resulting types of amino acids can enter the Krebs cycle beyond the partial block and thereby be used as fuels in this cycle.

9. In the longer term, this explanation indicates that restoring the glutathione levels to normal is the way to correct this tendency toward reactive hypoglycemia when carbohydrates are consumed. And we have found in recent years that it is necessary to lift the partial block in the methylation cycle to enable glutathione to come back up to normal on a permanent basis.

10. In fact, lifting this partial block, according to the GD-MCB hypothesis, will correct essentially all the other features of CFS as well.

11. There are several treatment protocols that various people are using to lift the methylation cycle block. These include the Vinitsky protocol, the DAN! approaches used in autism, the full Yasko treatment approach, the protocol advocated by freddd on this forum, and the Simplified Treatment Approach, which I extracted from the full Yasko treatment program a little over three years ago, with the help of a person on the full Yasko approach. It isn't clear at this point which approach is the best, but I think it is clear that lifting the methylation cycle block is the right goal.

Best regards,

Rich
 

Kyla

ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ
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721
Location
Canada
hmmm.
My understanding of this stuff is also close to nothing. but I have a (possibly stupid) question.

My Lactate Dehydrogenase levels have been tested a few times (presumably to check for cardiac issues ) and every time it has come back flagged as well below the reference range. I have always been told this doesn't mean anything, and it probably doesn't in the context they were checking in. (though I always wondered why it would be flagged / why there is a bottom of the range if a low result doesn't mean anything)

Lactate Dehydrogenase is used in glycolosis (or at least I think so?)

Does anyone know if this would be consistent with the broken pathway described here? maybe @JaimeS can answer this?
and if so does anyone else get this result on their blood tests?
 

JaimeS

Senior Member
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3,408
Location
Silicon Valley, CA
Which physician has diagnosed the patients, and which city? i cannot recognize any of the authors.

They don't mention the physician by name, and I'm not sure why it's important except to admit that everyone coming from the same physician implies a certain homogeneity. The researchers are all from Austrailia, though, and the two lead authors are from Melbourne.

@acer2000 - decreased alanine in the urine may imply increased alanine in the blood - I'd have to check.

@Sidereal - was the paper behind a firewall? If so, that's why I took the diagrams and direct quotations down. There are copyright issues.

@Kyla - yes, that would appear to agree with the results of the paper.... I believe.

Guys, I think I'll probably do a blog post on this one with further explanation/summary. If I do so, I'll put a link in this discussion.

-J
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
Re: Julia Newton's paper, @Bob - it also indicated raised levels of glucose in ME/CFS, so that much is supported by both papers.

However, it appears that in her paper, she did muscle biopsy (?) and subjected the cells in vitro to electrical pulses to simulate muscle contraction. Uptake of glucose did not increase, implying that there is some issue with glycolysis in the tissue itself. (On the thread Bob mentioned, someone commented, 'try calling it psychogenic now!')

This still supports the 'impaired glycolysis' hypothesis, because glycolysis occurs within every living animal cell without the need for outside signalling. (She says, partly in ignorance... if this doesn't make sense to someone, please correct me.)

-J
 

Kyla

ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ
Messages
721
Location
Canada
@Kyla, my LDH is very low. No one ever commented on it. I don't know why they measure things if they don't know or care how to interpret the results.

Interesting. Maybe this calls for a poll to see if this is common?
Or maybe it is a subgroup? Or maybe the two of us are just weirdos ;)

Fwiw this inspired me to look it up. There is a genetic disease called Lactate Dehydrogenase deficiency. It causes exercise intolerance! Though it seems like it would be apparent if you have it ( It causes brown/red urine and muscle wasting)
Maybe there is a subclinical version? Now I am just wildly speculating.
But if it fits with exercise/metabolic findings it is certainly interesting.
 

Sidereal

Senior Member
Messages
4,856
Interesting. Maybe this calls for a poll to see if this is common?
Or maybe it is a subgroup? Or maybe the two of us are just weirdos ;)

:lol:

Fwiw this inspired me to look it up. There is a genetic disease called Lactate Dehydrogenase deficiency. It causes exercise intolerance! Though it seems like it would be apparent if you have it ( It causes brown/red urine and muscle wasting)

Right, it seems unlikely since it causes actual muscle breakdown which would show up on blood and urine tests.
 

Tammy

Senior Member
Messages
2,181
Location
New Mexico
Do they comment at all on plasma Alanine? A doctor I see has done amino acid panels, and this has been elevated on occasion. I have never gotten an explanation as to why.
You might google genova diagnostics amino acids interpretation guide
 
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JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
My cholesterol is quite low, @Kyla , @Sidereal ; also triglycerides. I'd have to check the LDL.... yes, it's pretty low too:

MTP gene mutation
Formation and exocytosis of CMs at the basolateral membrane of intestinal epithelial cells is necessary for the delivery of lipids to the systemic circulation. One of the proteins required for the assembly and secretion of CMs is MTP. The gene for this protein (MTP) is mutated in patients with ABL.[10, 11]

Several mutations in the MTP gene have been described. In most patients with ABL, the mutation involves a gene encoding the 97-kd subunit of MTP. Consequently, children with ABL develop fat malabsorption and, in particular, suffer the results of vitamin E deficiency (ie, retinopathy, spinocerebellar degeneration).[12] Biochemical test results show low plasma levels of apoB, triglycerides, and cholesterol. Membrane lipid abnormalities also affect the erythrocytes, causing acanthocytosis (burr cells). Long-chain fatty acids are very poorly absorbed, and the intestinal epithelial cells become engorged with lipid droplets. Such children respond to a low-fat diet rich in medium-chain fatty acids, as well as to supplementation with high-dose, fat-soluble vitamins, especially vitamin E.[13]

Boldface mine. NOTE: they are talking about people with VERY low LDL, like in the 50s. Like a lot of things, I've seen "less than 90 is too low" and "less than 70 is too low" in different places, and mine is 81. My cholesterol, though, is in the 140s and my triglycerides are at 61mg/dL. All low or borderline-low.

Uhhhh, this seems a candidate for my family, at least. Off to my 23andme!

-J
 

Sidereal

Senior Member
Messages
4,856
My cholesterol is quite low, @Kyla , @Sidereal ; also triglycerides. I'd have to check the LDL.... yes, it's pretty low too:



Boldface mine. NOTE: they are talking about people with VERY low LDL, like in the 50s. Like a lot of things, I've seen "less than 90 is too low" and "less than 70 is too low" in different places, and mine is 81. My cholesterol, though, is in the 140s and my triglycerides are at 61mg/dL. All low or borderline-low.

Uhhhh, this seems a candidate for my family, at least. Off to my 23andme!

-J

We were referring to LDH (lactate dehydrogenase), not LDL cholesterol. ;)
 

Kyla

ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ
Messages
721
Location
Canada
My cholesterol is quite low, @Kyla , @Sidereal ; also triglycerides. I'd have to check the LDL.... yes, it's pretty low too:



Boldface mine. NOTE: they are talking about people with VERY low LDL, like in the 50s. Like a lot of things, I've seen "less than 90 is too low" and "less than 70 is too low" in different places, and mine is 81. My cholesterol, though, is in the 140s and my triglycerides are at 61mg/dL. All low or borderline-low.

Uhhhh, this seems a candidate for my family, at least. Off to my 23andme!

-J

My cholesterol has always been normal to high.
Not sure if you are mixing up LDL with LDH (Lactate Dehydrogenase)?

LDH is involved in converting lactate to pyruvate (I think? again I'm not up on the biochemistry). It is also used as a lab test to measure tissue damage. In particular it is often measured in cases where they suspect/want to rule out a cardiac event.
 
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Bob

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England (south coast)