In the case the combination ischemia and the body producing it's own acetaldehyde would be a major source of symptoms then this allopurinol drug might be helpful.
So I looked into that. https://www.drugs.com/allopurinol.html
"Allopurinol reduces the production of uric acid in your body. Uric acid buildup can lead to gout or kidney stones."
=> Dang. Uric acid is a major anti-oxidant in the body and in this hypothesis we need plenty of anti-oxidant in order to fight the oxidative stress. On the other hand it could reduce one source of oxidative stress. So I looked into this further.
https://en.wikipedia.org/wiki/Xanthine_oxidase
"Most of the protein in the liver exists in a form with xanthine dehydrogenase activity, but it can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification."
=> Maybe that means that some people make more XO then others, genetically determined?
The following chemical reactions are catalyzed by xanthine oxidase:
Now let's look at the rest of the reactions it catalyzes:
=> Superoxide is really nasty and a lot worse then hydrogen peroxide, so this XO thing seems to be nasty in too high quantities.
I looked into the role of 1-methylxanthine and 1-methyluric acid:
https://pubchem.ncbi.nlm.nih.gov/compound/1-Methylxanthine:
"1-methylxanthine is the major metabolites of caffeine in the human. The oxidation of 1-methylxanthine to 1-methyluric acid occurred so rapidly that the parent compound could not be detected in plasma, and only low concentrations could be detected in brain. "
=> So this component of caffeine converts *really* well and fast into another component called 1-methyluric acid.
That chemical has many names to make it confusing. See https://pubchem.ncbi.nlm.nih.gov/compound/1-Methylxanthine#section=MeSH-Entry-Terms.
There it appears that the page on https://en.wikipedia.org/wiki/IBMX my search function delivered has the name 1-Methyl-3-(2-methylpropyl)-7H-purine-2,6-dione and that is the same as 1-Methyl-3,7-dihydro-purine-2,6-dione as the (2-methylpropyl) part is optional IMO. So that IBMX stuff is very likely 1-methyluric acid, the stuff part of caffeine is converted in very rapidly.
1-methyluric acid or very likely IBMX has properties:
IBMX (3-isobutyl-1-methylxanthine), like other methylated xanthine derivatives, is both a:
"1-Methyluric acid (1-U) is a major metabolite of caffeine and theophylline with antioxidant activity that protects molecules such as low density lipoproteins (LDL) from oxidative modifications."
=> Now that would indicate why I do well on caffeine and even use it daily in moderate quantities at night in order to sleep better. It contains a component that reduces inflammation and innate immunity (as in unspecific, against nothing in specific, immune reaction as seen in ME) and is an anti-oxidant. As a side, it uses / keeps busy part of noxious catalyst XO from producing copious amounts of oxidative stress. What's not to like? I do however understand caffeine has its downsides and I am lucky to tolerate the side effects of many stimulants very well. So that may be the breaking point where some patients fare well with stimulants and others get even more "hyper".
While I'm into it, it gets better. I described like some other ME patients before that "chocolate is a medicine and should be refunded by insurance". I did however add: half of the time it clears up my head, the other half it makes things a lot worse. The latter seems to be digestion induced.
So I did find:
"Caffeine and theobromine are the most abundant methylxanthines in cacao and their physiological effects are notable. Their health-promoting benefits are so remarkable that chocolate is explored as a functional food."
"Recent interest on these compounds derives from their antioxidant properties."
"In fact, flavonols inhibit lipid peroxidation and affect production of lipid or lipid-derived molecules regulating the immune response and, recently, dietary cacao has been shown to ameliorate obesity-related inflammation in high fat-fed mice"
"These molecules also seem to be key players in the increase of beneficial gut microbes (e.g., Lactobacilli) and the decrease of less beneficial ones (e.g., Clostridia) that follow cacao intake [3,4]. Hayek [5] has recently revisited data showing that cacao and/or chocolate modifies intestinal flora in the same way that prebiotics and probiotics do."
=> Now that may explain my dual chocloate experience:
"
Other reactions
Because XO is a superoxide-producing enzyme, with general low specificity,[9] it can be combined with other compounds and enzymes and create reactive oxidants, as well as oxidize other substrates...
...XO has also been found to produce the strong one-electron oxidant carbonate radical anion from oxidation with acetaldehyde in the presence of catalase and bicarbonate."
=> Holy crap: this XO combined with acetaldehyde creates a strong one-electron carbonate radical anion in the presence of catalase and !!!BICARBONATE!!!
=> That's wright, it can indirectly produce a seemingly really powerful oxidative stress molecule from CO2, the thing we ME patients breath out as if our life depends on it (and creating poor oxygen uptake due to the Bohr effect because of it)!!!!!!!
That's wright, add CO2 to water (blood) and you get Bicarbonate (component of sprankling water). Add acetaldehyde from alcohol consumption (many ME patients do tolerate alcohol very poorly) or from gut microbiome production and add ischemia (lack of oxygen, believed to be very common in ME) and you potentially get a storm of oxidative stress raging through our veins. If so, no wonder we "hyperventilate" or "breath like a horse" like our lives depend on it.
At night, blood flow gets worse so ischemia may increase. Now breathing at night can get *very* intense in my case.
During exercise, CO2 levels rise a lot. And all ME patients are intolerant to exercise.
It's bold, but it sounds like this may summarize a *potential* "clear, straight" biological line in my disease:
So I looked into that. https://www.drugs.com/allopurinol.html
"Allopurinol reduces the production of uric acid in your body. Uric acid buildup can lead to gout or kidney stones."
=> Dang. Uric acid is a major anti-oxidant in the body and in this hypothesis we need plenty of anti-oxidant in order to fight the oxidative stress. On the other hand it could reduce one source of oxidative stress. So I looked into this further.
https://en.wikipedia.org/wiki/Xanthine_oxidase
"Most of the protein in the liver exists in a form with xanthine dehydrogenase activity, but it can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification."
=> Maybe that means that some people make more XO then others, genetically determined?
The following chemical reactions are catalyzed by xanthine oxidase:
- hypoxanthine + H2O + O2
xanthine + H2O2
- xanthine + H2O + O2
uric acid + H2O2
Now let's look at the rest of the reactions it catalyzes:
- Xanthine oxidase can also act on certain other purines, pterins, and aldehydes. For example, it efficiently converts 1-methylxanthine (a metabolite of caffeine) to 1-methyluric acid, but has little activity on 3-methylxanthine.[8]
- Under some circumstances it can produce superoxide ion RH + H2O + 2 O2
ROH + 2 O2− + 2 H+.
=> Superoxide is really nasty and a lot worse then hydrogen peroxide, so this XO thing seems to be nasty in too high quantities.
I looked into the role of 1-methylxanthine and 1-methyluric acid:
https://pubchem.ncbi.nlm.nih.gov/compound/1-Methylxanthine:
"1-methylxanthine is the major metabolites of caffeine in the human. The oxidation of 1-methylxanthine to 1-methyluric acid occurred so rapidly that the parent compound could not be detected in plasma, and only low concentrations could be detected in brain. "
=> So this component of caffeine converts *really* well and fast into another component called 1-methyluric acid.
That chemical has many names to make it confusing. See https://pubchem.ncbi.nlm.nih.gov/compound/1-Methylxanthine#section=MeSH-Entry-Terms.
There it appears that the page on https://en.wikipedia.org/wiki/IBMX my search function delivered has the name 1-Methyl-3-(2-methylpropyl)-7H-purine-2,6-dione and that is the same as 1-Methyl-3,7-dihydro-purine-2,6-dione as the (2-methylpropyl) part is optional IMO. So that IBMX stuff is very likely 1-methyluric acid, the stuff part of caffeine is converted in very rapidly.
1-methyluric acid or very likely IBMX has properties:
IBMX (3-isobutyl-1-methylxanthine), like other methylated xanthine derivatives, is both a:
- non-competitive selective phosphodiesterase inhibitor[1] which raises intracellular cAMP, activates PKA, inhibits TNFα[2][3] and leukotriene[4] synthesis, and reduces inflammation and innate immunity,[4] and
"1-Methyluric acid (1-U) is a major metabolite of caffeine and theophylline with antioxidant activity that protects molecules such as low density lipoproteins (LDL) from oxidative modifications."
=> Now that would indicate why I do well on caffeine and even use it daily in moderate quantities at night in order to sleep better. It contains a component that reduces inflammation and innate immunity (as in unspecific, against nothing in specific, immune reaction as seen in ME) and is an anti-oxidant. As a side, it uses / keeps busy part of noxious catalyst XO from producing copious amounts of oxidative stress. What's not to like? I do however understand caffeine has its downsides and I am lucky to tolerate the side effects of many stimulants very well. So that may be the breaking point where some patients fare well with stimulants and others get even more "hyper".
While I'm into it, it gets better. I described like some other ME patients before that "chocolate is a medicine and should be refunded by insurance". I did however add: half of the time it clears up my head, the other half it makes things a lot worse. The latter seems to be digestion induced.
So I did find:
"Caffeine and theobromine are the most abundant methylxanthines in cacao and their physiological effects are notable. Their health-promoting benefits are so remarkable that chocolate is explored as a functional food."
"Recent interest on these compounds derives from their antioxidant properties."
"In fact, flavonols inhibit lipid peroxidation and affect production of lipid or lipid-derived molecules regulating the immune response and, recently, dietary cacao has been shown to ameliorate obesity-related inflammation in high fat-fed mice"
"These molecules also seem to be key players in the increase of beneficial gut microbes (e.g., Lactobacilli) and the decrease of less beneficial ones (e.g., Clostridia) that follow cacao intake [3,4]. Hayek [5] has recently revisited data showing that cacao and/or chocolate modifies intestinal flora in the same way that prebiotics and probiotics do."
=> Now that may explain my dual chocloate experience:
- a really good and powerful "clearing the head up effect" from the methylxanthines
- a potentially nasty digestion based backlash if you do very poorly on prebiotics and probiotics as they act very similar to those. Maybe in some patients they kick of acetaldehyde production by nasty gut microbes?
"
Other reactions
Because XO is a superoxide-producing enzyme, with general low specificity,[9] it can be combined with other compounds and enzymes and create reactive oxidants, as well as oxidize other substrates...
...XO has also been found to produce the strong one-electron oxidant carbonate radical anion from oxidation with acetaldehyde in the presence of catalase and bicarbonate."
=> Holy crap: this XO combined with acetaldehyde creates a strong one-electron carbonate radical anion in the presence of catalase and !!!BICARBONATE!!!
=> That's wright, it can indirectly produce a seemingly really powerful oxidative stress molecule from CO2, the thing we ME patients breath out as if our life depends on it (and creating poor oxygen uptake due to the Bohr effect because of it)!!!!!!!
That's wright, add CO2 to water (blood) and you get Bicarbonate (component of sprankling water). Add acetaldehyde from alcohol consumption (many ME patients do tolerate alcohol very poorly) or from gut microbiome production and add ischemia (lack of oxygen, believed to be very common in ME) and you potentially get a storm of oxidative stress raging through our veins. If so, no wonder we "hyperventilate" or "breath like a horse" like our lives depend on it.
At night, blood flow gets worse so ischemia may increase. Now breathing at night can get *very* intense in my case.
During exercise, CO2 levels rise a lot. And all ME patients are intolerant to exercise.
It's bold, but it sounds like this may summarize a *potential* "clear, straight" biological line in my disease:
- On mothers side of the family, there is a clear pattern of several members having severe gut issues with the potential of it being in part the gut microbiome producing acetaldehyde. This chemical aggresses the gut and poisons body and brain. If so the body may well initiate a near permanent "unspecific = hard to have a clear diagnostic marker" "carpet bombing" immune reaction to gut bacteria. Both this strong immune response blocking good digestion and the damage both acetaldehyde and the gut immune response do to the gut should make nutrient absorption pretty poor.
- On fathers side there is a chain of several generations of easy increase in uric acid even when drinking only limited amounts of alcohol and I am in at least three generations of males who developed sudden very strong leg weakness. These uric acid levels *may* be the consequence of easy/increased XO production. Note that my uric acid levels are not too high. But having ME I likely have very high levels of oxidative stress so uric acid levels should be low rather then normal if uric acid metabolism were average.
![ME/CFS lecture | Dr Nancy Klimas | 2011 [Chronic Fatigue Syndrome / SEID / New Zealand] - YouTube](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)
