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This is false.
We need to be specific otherwise people will misunderstand the disease.
We need to be specific otherwise people will misunderstand the disease.
IDO Metabolic Trap Hypothesis Published Today
- Thread starter Ben H
- Start date
I don't think you understood my previous post. Have a look at it again.
Prof Paul Ewald posits that most chronic diseases of currently unknown etiology will turn out to be caused by infectious pathogens. This includes diseases such as multiple sclerosis, Parkinson's, heart disease, diabetes, cancers, etc. In the case of MS, we know this is linked to EBV, and in particular, to specific genetic subtypes of EBV.
Thus those diseases are also communicable in a certain sense.
What is that certain sense? If you read my previous post, I point out that if you catch a pathogen from someone with one of these diseases, you may not get the same disease as the person you caught it from has.
For example, you may catch EBV from someone with MS, but in you, the EBV may trigger a different disease such as nasopharyngeal cancer (which EBV is known to cause). Or the virus may cause you no problems at all.
If Prof Ewald is proven right (and suspect he will be), most chronic diseases will turn out to be caused by infectious pathogens that are in common circulation.
So this aspect of communicability applies not only to ME/CFS patients, but MS, Parkinson's, diabetes, etc patients. And also to healthy people, who carry lots of disease-causing infections but are not ill themselves — we are all Typhoid Marys.
Prof Paul Ewald posits that most chronic diseases of currently unknown etiology will turn out to be caused by infectious pathogens. This includes diseases such as multiple sclerosis, Parkinson's, heart disease, diabetes, cancers, etc. In the case of MS, we know this is linked to EBV, and in particular, to specific genetic subtypes of EBV.
Thus those diseases are also communicable in a certain sense.
What is that certain sense? If you read my previous post, I point out that if you catch a pathogen from someone with one of these diseases, you may not get the same disease as the person you caught it from has.
For example, you may catch EBV from someone with MS, but in you, the EBV may trigger a different disease such as nasopharyngeal cancer (which EBV is known to cause). Or the virus may cause you no problems at all.
If Prof Ewald is proven right (and suspect he will be), most chronic diseases will turn out to be caused by infectious pathogens that are in common circulation.
So this aspect of communicability applies not only to ME/CFS patients, but MS, Parkinson's, diabetes, etc patients. And also to healthy people, who carry lots of disease-causing infections but are not ill themselves — we are all Typhoid Marys.
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This is a very subtle point. There will be disagreement until we agree on the definitions of our terms. To me, there is an important difference between the trigger of the disease and the cause of the disease. If a viral infection is the cause of ME/CFS then: 1) it's very difficult to explain all the cases of ME/CFS that do not begin with an infection - the ones beginning with trauma, or surgery, or overtraining, 2) we should be able to find an active infection with the causal virus, not just antibodies to some past infection, or 3) we have to explain why the immune system can successfully clear the viral infection and yet the patient is still sicker than they have ever been in their lives.
I am not saying Prof Ewald is wrong. I have heard other scientists argue that if the disease is chronic then its cause must be chronically present. Metabolic traps are just an alternative hypothesis. Traps are interesting because they do not require a chronic cause. A transient trigger is all you need.
Prof Ewald could be right, or Dr. Naviaux's failure of the healing cycle could be right, or some version of a bistable metabolic trap could be right, or any of the hypotheses in the literature, or something yet unthought could be right. All of these have in common the need for experimental tests.
If Prof Ewald means that chronic diseases of unknown etiology will be found to be triggered by infectious pathogens, then I would have no argument, but if he means that these diseases are caused by a chronic infection with these pathogens, then it's difficult to explain why someone has not isolated non-human RNA or DNA from ME/CFS patients who have been sick for years. Of course, absence of evidence is not evidence of absence, so if tomorrow someone isolates a causal RNA or DNA virus from ME/CFS patients who have been sick for decades, stimulates the immune system to clear it, and cures this horrific disease, I'm going to celebrate along with everyone else. But techniques for isolating hon-human RNA and DNA are now extremely powerful and there is as yet no candidate virus to be followed up.
I think @Cam Newton has made these points as clearly as I could (and also much more succinctly). We are, I think, both saying that ME/CFS is not infectious. You can meet and marry someone who has ME/CFS and not fear contracting this illness. Of course, if you are convinced by my argument that predisposing mutations must be common to explain epidemics, then you could still be at risk for encountering a complex of triggers and becoming ill through no fault of your partner.
I hear you when you say that if EBV is the trigger/cause and you can catch EBV from an ME/CFS patient, then you might not develop ME/CFS but instead develop some other chronic disease or even just defeat the infection. In this scenario, I think you are saying EBV could still be the cause of ME/CFS. But then you have to answer Dr. Naviaux's pointed question: Why does the body fail to heal - fail to cure itself - how did a person make it through childhood and often through young adulthood and suddenly encounter an infection the immune system cannot handle? And if the immune system is defeated, then why can we not detect the victorious virus in the body?
I am not saying Prof Ewald is wrong. I have heard other scientists argue that if the disease is chronic then its cause must be chronically present. Metabolic traps are just an alternative hypothesis. Traps are interesting because they do not require a chronic cause. A transient trigger is all you need.
Prof Ewald could be right, or Dr. Naviaux's failure of the healing cycle could be right, or some version of a bistable metabolic trap could be right, or any of the hypotheses in the literature, or something yet unthought could be right. All of these have in common the need for experimental tests.
If Prof Ewald means that chronic diseases of unknown etiology will be found to be triggered by infectious pathogens, then I would have no argument, but if he means that these diseases are caused by a chronic infection with these pathogens, then it's difficult to explain why someone has not isolated non-human RNA or DNA from ME/CFS patients who have been sick for years. Of course, absence of evidence is not evidence of absence, so if tomorrow someone isolates a causal RNA or DNA virus from ME/CFS patients who have been sick for decades, stimulates the immune system to clear it, and cures this horrific disease, I'm going to celebrate along with everyone else. But techniques for isolating hon-human RNA and DNA are now extremely powerful and there is as yet no candidate virus to be followed up.
I think @Cam Newton has made these points as clearly as I could (and also much more succinctly). We are, I think, both saying that ME/CFS is not infectious. You can meet and marry someone who has ME/CFS and not fear contracting this illness. Of course, if you are convinced by my argument that predisposing mutations must be common to explain epidemics, then you could still be at risk for encountering a complex of triggers and becoming ill through no fault of your partner.
I hear you when you say that if EBV is the trigger/cause and you can catch EBV from an ME/CFS patient, then you might not develop ME/CFS but instead develop some other chronic disease or even just defeat the infection. In this scenario, I think you are saying EBV could still be the cause of ME/CFS. But then you have to answer Dr. Naviaux's pointed question: Why does the body fail to heal - fail to cure itself - how did a person make it through childhood and often through young adulthood and suddenly encounter an infection the immune system cannot handle? And if the immune system is defeated, then why can we not detect the victorious virus in the body?
It is certainly important to consider all angles to a mysterious disease like ME/CFS, and to its great to see ideas like your metabolic trap hypothesis being explored. I did mathematics and physics as my first degree, so can relate to concepts like the metabolic trap, involving system equilibrium points and non-linear effects.
When I was exploring IDO a bit some years ago, I came across several studies showing that IDO activation may be involved in the brain fog of post-stroke and meningitis conditions:
Though of course the IDO metabolic trap hypothesis posits that IDO is underactive, rather than overactive.
Yes agreed, that is an important distinction.
In the light of the newly-discovered link between ME/CFS and craniocervical instability (CCI), I am guessing that ME/CFS triggered by physical trauma could be explained in terms of physical damage to the craniocervical junction, leading to CCI.
Some people claim that their ME/CFS had no apparent trigger, but it's worth bearing in mind that you can also catch all the ME/CFS-associated viruses asymptomatically with no acute symptoms; so it's possible to acquire such a virus without knowing it. This may explain the ME/CFS cases with no apparent trigger.
Chances are that if you marry someone with ME/CFS you will not contract this illness yourself, I agree. But according to a paper I mentioned earlier, spouses/partners and children of ME/CFS patients are in the order of 10 times more likely to have ME/CFS than the general population.
Now that higher prevalence in spouses and children might be due to sharing a home environment that may predispose to ME/CFS (eg, a moldy home, which Dr Brewer found is linked to ME/CFS), and/or it might arise because of the higher chances of viral transmission when a person lives in close social contact with another.
In the case of enterovirus, its RNA is is now routinely found in ME/CFS patients, thanks to Dr Chia.
Originally British researchers used to perform muscle biopsies on ME/CFS patients (these British studies are listed here), and detect the RNA in the muscle tissues. But Dr John Chia realized that it was easier to take a stomach tissue biopsy, as enterovirus usually inhabits the GI tract too. So Dr Chia now routinely tests stomach tissues in his clinical practice, and finds enterovirus RNA, dsRNA and enterovirus VP1 capsid protein in these tissues.
You do also find (at a much lesser prevalence) enterovirus infections in the muscle and stomach of healthy people too, so these muscle and stomach infections cannot explain ME/CFS just on their own. Furthermore, these chronic enterovirus infections are low-level infections, so you need to explain why a low-level infection can produce such strong symptoms.
As for herpesviruses, I only know of one study which detected EBV DNA in the muscle tissues of ME/CFS patients, but apart from that study, I am not aware of any research where someone has actually tried to detect herpesviruses in the tissues of ME/CFS patients. I am not sure why such studies have not been conducted.
The most simple answer to this question might be the strength of the immune system at the time of catching the virus.
It's known that ME/CFS is associated with periods of chronic major stress in the year before ME/CFS first appeared. Chronic stress down-regulates antiviral immunity, so if you were unfortunate enough to catch a nasty virus during a time of major stress, that virus may be given the opportunity to insinuate itself more deeply into the body's organs (like the brain) which it would not otherwise have been able to do.
Toxic exposures might also weaken the immune system, making it easier for viruses to gain a hold in the body. So perhaps ME/CFS is only triggered in dual-factor circumstances: the first factor is the virus, and the second is some immune weakening factor.
When I was exploring IDO a bit some years ago, I came across several studies showing that IDO activation may be involved in the brain fog of post-stroke and meningitis conditions:
- The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment
- Inhibition of indoleamine 2,3-dioxygenase prevented cognitive impairment in adult Wistar rats subjected to pneumococcal meningitis
- Genetic and hormonal regulation of tryptophan kynurenine metabolism: implications for vascular cognitive impairment, major depressive disorder, and aging
Though of course the IDO metabolic trap hypothesis posits that IDO is underactive, rather than overactive.
Yes agreed, that is an important distinction.
In the light of the newly-discovered link between ME/CFS and craniocervical instability (CCI), I am guessing that ME/CFS triggered by physical trauma could be explained in terms of physical damage to the craniocervical junction, leading to CCI.
Some people claim that their ME/CFS had no apparent trigger, but it's worth bearing in mind that you can also catch all the ME/CFS-associated viruses asymptomatically with no acute symptoms; so it's possible to acquire such a virus without knowing it. This may explain the ME/CFS cases with no apparent trigger.
Chances are that if you marry someone with ME/CFS you will not contract this illness yourself, I agree. But according to a paper I mentioned earlier, spouses/partners and children of ME/CFS patients are in the order of 10 times more likely to have ME/CFS than the general population.
Now that higher prevalence in spouses and children might be due to sharing a home environment that may predispose to ME/CFS (eg, a moldy home, which Dr Brewer found is linked to ME/CFS), and/or it might arise because of the higher chances of viral transmission when a person lives in close social contact with another.
In the case of enterovirus, its RNA is is now routinely found in ME/CFS patients, thanks to Dr Chia.
Originally British researchers used to perform muscle biopsies on ME/CFS patients (these British studies are listed here), and detect the RNA in the muscle tissues. But Dr John Chia realized that it was easier to take a stomach tissue biopsy, as enterovirus usually inhabits the GI tract too. So Dr Chia now routinely tests stomach tissues in his clinical practice, and finds enterovirus RNA, dsRNA and enterovirus VP1 capsid protein in these tissues.
You do also find (at a much lesser prevalence) enterovirus infections in the muscle and stomach of healthy people too, so these muscle and stomach infections cannot explain ME/CFS just on their own. Furthermore, these chronic enterovirus infections are low-level infections, so you need to explain why a low-level infection can produce such strong symptoms.
As for herpesviruses, I only know of one study which detected EBV DNA in the muscle tissues of ME/CFS patients, but apart from that study, I am not aware of any research where someone has actually tried to detect herpesviruses in the tissues of ME/CFS patients. I am not sure why such studies have not been conducted.
The most simple answer to this question might be the strength of the immune system at the time of catching the virus.
It's known that ME/CFS is associated with periods of chronic major stress in the year before ME/CFS first appeared. Chronic stress down-regulates antiviral immunity, so if you were unfortunate enough to catch a nasty virus during a time of major stress, that virus may be given the opportunity to insinuate itself more deeply into the body's organs (like the brain) which it would not otherwise have been able to do.
Toxic exposures might also weaken the immune system, making it easier for viruses to gain a hold in the body. So perhaps ME/CFS is only triggered in dual-factor circumstances: the first factor is the virus, and the second is some immune weakening factor.
I'd like to see the agent(s) in exosomes, which appear to trigger a reversible change in cellular energy production, identified. Possibly the high resolution mass spectrometry instrument you are using could help to identify those signalling compounds (in the exosomes) and/or the "parent" cells which are shedding the exosomes. Even if these signalling compound(s) are in exosomes, if they were foreign RNA (pathogen) then I presume enough would still be detectable in plasma/blood.
On the plus side the tools (such as mass spectrometry) are getting better and the scientists are leading researchers -- just leaves the funding (Government and other).
There's a petition calling on the European Commission to fund ME research -- they funded Lyme disease (33.9 million Euros/roughly 37 million US dollars, in the last 10 years) - ME got zero. European Community citizens can sign the petition - Petition No 0204/2019 [https://petiport.secure.europarl.europa.eu/petitions/en/petition/content/0204%2F2019/html/Petition-No-0204%2F2019-by-Evelien-Van-Den-Brink-%28Dutch%29-on-a-request-for-funding-for-biomedical-research-on-Myalgic-Encephalomyelitis]
Thanks for all you are doing @HTester
On the plus side the tools (such as mass spectrometry) are getting better and the scientists are leading researchers -- just leaves the funding (Government and other).
There's a petition calling on the European Commission to fund ME research -- they funded Lyme disease (33.9 million Euros/roughly 37 million US dollars, in the last 10 years) - ME got zero. European Community citizens can sign the petition - Petition No 0204/2019 [https://petiport.secure.europarl.europa.eu/petitions/en/petition/content/0204%2F2019/html/Petition-No-0204%2F2019-by-Evelien-Van-Den-Brink-%28Dutch%29-on-a-request-for-funding-for-biomedical-research-on-Myalgic-Encephalomyelitis]
Thanks for all you are doing @HTester
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@HTester
Hi Dr Phair.
I have severe M.E and I hope you do not mind me asking a question about your research.
One thing that I find very puzzling is the presence of sensory problems (very severe) in severe / very severe M.E/CFS patients. Sensory problems relating to light, noise, touch, sound, taste, movement/vibration.. all of which actually make patients other symptoms a lot worse as well as increase the sensitivities further. It’s a very strange symptom as I have not heard of it much in other conditions (except autism - which I also have (aspergers), but even then my sensory issues with aspergers was only about 1/100th of what they are now with M.E!):
So I was wondering what does the OMF and what do you think about why we have such sensory processing issues? And could they be explained by the metabolic trap hypothesis - if so, how? Thank you so much , I am very hopeful of all the research you and the OMF are doing.
Hi Dr Phair.
I have severe M.E and I hope you do not mind me asking a question about your research.
One thing that I find very puzzling is the presence of sensory problems (very severe) in severe / very severe M.E/CFS patients. Sensory problems relating to light, noise, touch, sound, taste, movement/vibration.. all of which actually make patients other symptoms a lot worse as well as increase the sensitivities further. It’s a very strange symptom as I have not heard of it much in other conditions (except autism - which I also have (aspergers), but even then my sensory issues with aspergers was only about 1/100th of what they are now with M.E!):
So I was wondering what does the OMF and what do you think about why we have such sensory processing issues? And could they be explained by the metabolic trap hypothesis - if so, how? Thank you so much , I am very hopeful of all the research you and the OMF are doing.
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does anyone know what happens to serotonin and melatonin as a result of this trytophan based metabolic trap (as opposed to the tyrosine one)....?
could anyone link me to any relevant discussion? Thank you.
could anyone link me to any relevant discussion? Thank you.
According to the speculative schematic in the paper, the excess L-tryptophan would lead to more being converted into serotonin/melatonin.
https://www.mdpi.com/diagnostics/di...html/images/diagnostics-09-00082-g002-550.jpg
The manuscript states:
https://www.mdpi.com/diagnostics/di...html/images/diagnostics-09-00082-g002-550.jpg
The manuscript states:
@Snow Leopard answers this question with a quote from our paper that's right on target. I would just add that these are predictions are based on enzyme kinetic theory, not on experimental data.
Also, the dependence on cell type has consequences for testing the IDO trap hypothesis. If one cell type is in the IDO metabolic trap, this does not prove that all cell types are in the trap. Conversely, if one cell type is not in the trap, we can't conclude that all cell types are "trapless."
Also, the dependence on cell type has consequences for testing the IDO trap hypothesis. If one cell type is in the IDO metabolic trap, this does not prove that all cell types are in the trap. Conversely, if one cell type is not in the trap, we can't conclude that all cell types are "trapless."
Best drug for me when I'm floating down **** creek is Ativan as a rescue drug. Second best drug was Elavil 25mg. It gave me about 3 years worth of a good life running at about 80%. I could lift weights without a lot of PEM, ride motocross, mountain bike, snow ski, etc.
My pea brain understands it works with serotonin which I've seen mentioned in this thread, maybe I was on to something there for a little while.
When I started noticing the side effects of Elavil going away around the 3 year mark, I started noticing I was going down hill. Now I'm housebound/bed bound. Something about that Elavil though...
I'm classic POTS with PEM at around 36-48hr mark.
My pea brain understands it works with serotonin which I've seen mentioned in this thread, maybe I was on to something there for a little while.
When I started noticing the side effects of Elavil going away around the 3 year mark, I started noticing I was going down hill. Now I'm housebound/bed bound. Something about that Elavil though...
I'm classic POTS with PEM at around 36-48hr mark.
this is weird, I actually have low serotonin as measured in the platelets... platelets are know to collect serotonin from the blood across the whole body and store it inside themselves. Could a serotonin overload actually disrupt the ability of said platelets to collect serotonin causing an opossite effect to what would be expected in this case?
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I believe I read that the trap, if true, could cause higher serotonin in some places, and lower in others.
I’m assuming this explains why an SNRI removes 95% of my chronic pain. That is, the SNRI increases serotonin in my area of need.
Just a guess...
I’m assuming this explains why an SNRI removes 95% of my chronic pain. That is, the SNRI increases serotonin in my area of need.
Just a guess...
thanks for the info! do you remember where could you have read that? on a side note, clomipramina, that also acts increasing serotonin concentration in the synaptic cleft, relieves my pain from disc herniations (I've got 4 of them)
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A poster on a facebook forum posted this study showing the old drug Disulfiram has an effect on tryptophan. Significance?
https://www.ncbi.nlm.nih.gov/pubmed...VS_60RFb8Ywf2l16XGvyjfdVVQt-c65CaDLAtCqlXWftA
Effect of disulfiram administration on brain tryptophan, serotonin and peripheral tryptophan content.
Nagendra SN1, Shetty KT, Subhash MN, Udaya HB, Pradhan N.
Author information
1Department of Neurochemistry, Psychopharmacology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Abstract
The prophylactic deterrent effect of disulfiram (DS) has been attributed to its ability to exacerbate sympathetic function. Though there are reports to indicate that DS administration could as well affect the neurotransmitter metabolism, few reports implicate the possibility of central nervous system (CNS) mediated anticraving effect of the drug. The present study involving the oral administration of DS to rats for 45 days has clearly shown a significant increase in 5-HT (815.4 +/- 74.7 ng/g, P < 0.01) and 5-HIAA (506.1 +/- 86.3 ng/g, P < 0.02) contents in brain when compared to control rats. The observed increase in 5-HT and 5-HIAA content was found to correlate (zeta = 0.89) with the concomitant increase in brain tryptophan content (4.15 +/- 1.05 nmol/g, P < 0.001) following DS administration. Further, the study on peripheral tryptophan content has shown an increase in both total and free fraction (ultrafiltrate) of plasma, which in turn was found to have an inverse relationship (zeta = -0.94, P < 0.05) with the decrease in liver tryptophan content following DS administration. Thus the observed increase in brain 5-HT level is attributed to the ability of DS to mobilise peripheral tryptophan for 5-HT synthesis in CNS. As there are reports to imply the hyposerotonergic function as responsible for craving, the present findings, that DS could enhance the 5-HT metabolism in brain, may partially explain the CNS mediated anticraving effect of DS.
https://www.ncbi.nlm.nih.gov/pubmed...VS_60RFb8Ywf2l16XGvyjfdVVQt-c65CaDLAtCqlXWftA
Effect of disulfiram administration on brain tryptophan, serotonin and peripheral tryptophan content.
Nagendra SN1, Shetty KT, Subhash MN, Udaya HB, Pradhan N.
Author information
1Department of Neurochemistry, Psychopharmacology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Abstract
The prophylactic deterrent effect of disulfiram (DS) has been attributed to its ability to exacerbate sympathetic function. Though there are reports to indicate that DS administration could as well affect the neurotransmitter metabolism, few reports implicate the possibility of central nervous system (CNS) mediated anticraving effect of the drug. The present study involving the oral administration of DS to rats for 45 days has clearly shown a significant increase in 5-HT (815.4 +/- 74.7 ng/g, P < 0.01) and 5-HIAA (506.1 +/- 86.3 ng/g, P < 0.02) contents in brain when compared to control rats. The observed increase in 5-HT and 5-HIAA content was found to correlate (zeta = 0.89) with the concomitant increase in brain tryptophan content (4.15 +/- 1.05 nmol/g, P < 0.001) following DS administration. Further, the study on peripheral tryptophan content has shown an increase in both total and free fraction (ultrafiltrate) of plasma, which in turn was found to have an inverse relationship (zeta = -0.94, P < 0.05) with the decrease in liver tryptophan content following DS administration. Thus the observed increase in brain 5-HT level is attributed to the ability of DS to mobilise peripheral tryptophan for 5-HT synthesis in CNS. As there are reports to imply the hyposerotonergic function as responsible for craving, the present findings, that DS could enhance the 5-HT metabolism in brain, may partially explain the CNS mediated anticraving effect of DS.
As I understand, this drug increases tryptophan content on the brain while releasing it from storage on the liver... It seems to be something that could be useful for ocd, depression, etc, but I don't see how it could help with this metabolic trap. What do you think?
Hi everybody,
Hi Dr. Phair (@HTester)
This is my first post on this forum though I am a member of the forum since 2011.
Sorry for my English, I'm not a native speaker.
I really liked your metabolic trap hypothesis, I've watched the conference talks and read the newly published paper. I'm not a scientist but as other persons with ME/CFS I'm really interested in ME/CFS science and its outcomes.
When I googled articles to find out more about kynurenine pathway, all I get is articles that link the kynurenine pathway and its metabolites to neurodegenerative diseases and to my surprise more commonly its overactive state. Also IDO2 is linked more with its proinflammatory role in some autoimmune diseases in several papers.
The kynurenine pathway and neurodegenerative disease.
https://www.ncbi.nlm.nih.gov/pubmed/25773161
IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119657/
IDO2 in immunomodulation and autoimmune disease
https://www.frontiersin.org/articles/10.3389/fimmu.2014.00585/full
On the other side there are papers stating that inhibition of kynurenine pathway or modulating it could be therapeutic in some neurogical diseases:
Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection
https://febs.onlinelibrary.wiley.com/doi/full/10.1111/j.1742-4658.2012.08487.x
Inhibiting the kynurenine pathway in spinal cord injury: multiple therapeutic potentials?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199950/
Inhibitors of the kynurenine pathway
https://www.frontiersin.org/articles/10.3389/fmolb.2019.00003/full
So my question is: Is it possible that if the theory of metabolic trap is correct, that the trap is not only pathological state but also protective state that acts as emergency brake to not cause bigger damage? But if that is correct, then it is not a good idea to try to open the kynurenine pathway if the chronic trigger is still present.
And my second question and the thing I was missing in the paper: How precisely nonfunctional kynurenine pathway explains ME/CFS symptoms or what is the main possible reason that this pathway is cause of ME/CFS symptoms specifically?
Thank you for your time.
Hi Dr. Phair (@HTester)
This is my first post on this forum though I am a member of the forum since 2011.
Sorry for my English, I'm not a native speaker.
I really liked your metabolic trap hypothesis, I've watched the conference talks and read the newly published paper. I'm not a scientist but as other persons with ME/CFS I'm really interested in ME/CFS science and its outcomes.
When I googled articles to find out more about kynurenine pathway, all I get is articles that link the kynurenine pathway and its metabolites to neurodegenerative diseases and to my surprise more commonly its overactive state. Also IDO2 is linked more with its proinflammatory role in some autoimmune diseases in several papers.
The kynurenine pathway and neurodegenerative disease.
https://www.ncbi.nlm.nih.gov/pubmed/25773161
IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119657/
IDO2 in immunomodulation and autoimmune disease
https://www.frontiersin.org/articles/10.3389/fimmu.2014.00585/full
On the other side there are papers stating that inhibition of kynurenine pathway or modulating it could be therapeutic in some neurogical diseases:
Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection
https://febs.onlinelibrary.wiley.com/doi/full/10.1111/j.1742-4658.2012.08487.x
Inhibiting the kynurenine pathway in spinal cord injury: multiple therapeutic potentials?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199950/
Inhibitors of the kynurenine pathway
https://www.frontiersin.org/articles/10.3389/fmolb.2019.00003/full
So my question is: Is it possible that if the theory of metabolic trap is correct, that the trap is not only pathological state but also protective state that acts as emergency brake to not cause bigger damage? But if that is correct, then it is not a good idea to try to open the kynurenine pathway if the chronic trigger is still present.
And my second question and the thing I was missing in the paper: How precisely nonfunctional kynurenine pathway explains ME/CFS symptoms or what is the main possible reason that this pathway is cause of ME/CFS symptoms specifically?
Thank you for your time.
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