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I want to discuss the Tryptophan pathway as it is related to CFS and see if there's any interest. I'll keep this fairly short.
Fructose.
I want to first discuss the role of fructose in the Tryptophan pathway as it relates to those with CFS. An estimated 25-30% of the general population have issues with fructose malabsorption, estimates of 45-70% in those with CFS. You will need to take this with a grain of salt as I have, these appear to be claims. But in IBS and Crohns it is a certainty you will experience issues metabolizing fructose. The best idea here is to ask yourself how you do with fruit I suppose.
A common thread between those with CFS is a high prevalence of digestive issues, either earlier on in their condition or ongoing.
In those with Fructose Malabsorption, fructose (especially in high fructose corn syrup) won't digest properly in the gut, and will ferment. This has a significant impact on gut health.
Why it's relevant to CFS?
"Fructose malabsorption (breath DH2 production>20 ppm) was detected in 35 of 50 individuals (70%). Subjects with fructose malabsorption showed signifcantly lower plasma tryptophan concentrations and significantly higher scores in the Beck depression inventory compared to those with normal fructose absorption. Conclusions: Fructose malabsorption is associated"
In these studies, Tryptophan was found to be significantly decreased in serum, and depression was noted indicating impaired Tryptophan to Serotonin conversion.
But Kynurenine was unchanged.
Tryptophan metabolism follows two pathways, both equally important.
1. TRYPTOPHAN>5-Hydroxy-tryptophan>5-Hydroxy-tryptamine (serotonin)>Melatonin
2. TRYPTOPHAN>N-formyl-kynurenine>kynurenine>2,amino,3(3-oxoprop-enyl)-fumaric acid>quinolinate>niacin
Indoleamine 2,3-dioxygenase.
IDO along with tryptophan,2,3-deoxygenase are responsible for the conversion of Tryptophan to n-formyl-kynurenine.
IDO & TDO are the rate limiting steps for conversion.
"Generating mice deficient for tryptophan 2,3-dioxygenase and comparing them to the wild type, the group found that the tryptophan 2,3-dioxygenase-deficient mice showed increased plasma levels not only of tryptophan, but also of serotonin and 5-HIAA in the hippocampus and midbrain."
Overactive IDO enzyme activity has been heavily implicated in chronic fatigue syndrome. During times of increased immune function and resultant interferon-y release, IDO becomes overactive, putting a great deal more emphasis on kynurenine synthesis. This is how our body protects itself during acute illness, but research has shown chronic illness to keep IDO active. This is important for two reasons.
1. Patients with elevated kynurenine, and overactive IDO function (Huntingtons, alzheimers, parkinsons, lyme, mononucleosis etc.) Adopt identical symptoms to those of us with CFS. During treatments with interferon-a, patients also develop what is usually temporary CFS symptoms (they claim it's horrible, yet laugh at us and call us malingerers not realizing it's a life sentence for us).
2. Through constant up regulation of IDO by interferon, this enzyme will eventually remain elevated, regardless of viral status.
The body will respond to an upregulation of IDO by releasing more interferon, this will cause further inflammation.
When the gut becomes inflamed, there is a drastic change in our microbiome.
L.Reuteri is only found in 9-30% of people, 30% being now antiquated. The administration of therapeutic dosages of Reuteri were shown very effective in mitigating liver damage in high fructose fed rats. Reuteri has not been investigated much in its role on fructose metabolism, but may well coincide with fructose intolerance given the estimated prevalence.
What reuteri is also able to do, is increase serotonin and normalize faulty kynurenine processing, these are in therapeutically relevant doses. 5-100 Billion CFU strain probiotics are not therapeutic, 50-100 could be fine for the average Joe. But actual treatment is in the 500 billion-3.6 trillion daily dosage. I haven't been able to find anyone on here who has maintained a week of this standard.
Another relevant compound I see nothing about is the IDO inhibitor rosmarinic acid taken in therapeutically relevant doses. I find this interesting as it points to a lack of trial and error on a large scale with treating IDO up regulation or kynurenine, I also see very little KYN testing going on.
This is something for people to look into I believe, and take very seriously.
Fructose.
I want to first discuss the role of fructose in the Tryptophan pathway as it relates to those with CFS. An estimated 25-30% of the general population have issues with fructose malabsorption, estimates of 45-70% in those with CFS. You will need to take this with a grain of salt as I have, these appear to be claims. But in IBS and Crohns it is a certainty you will experience issues metabolizing fructose. The best idea here is to ask yourself how you do with fruit I suppose.
A common thread between those with CFS is a high prevalence of digestive issues, either earlier on in their condition or ongoing.
In those with Fructose Malabsorption, fructose (especially in high fructose corn syrup) won't digest properly in the gut, and will ferment. This has a significant impact on gut health.
Why it's relevant to CFS?
"Fructose malabsorption (breath DH2 production>20 ppm) was detected in 35 of 50 individuals (70%). Subjects with fructose malabsorption showed signifcantly lower plasma tryptophan concentrations and significantly higher scores in the Beck depression inventory compared to those with normal fructose absorption. Conclusions: Fructose malabsorption is associated"
In these studies, Tryptophan was found to be significantly decreased in serum, and depression was noted indicating impaired Tryptophan to Serotonin conversion.
But Kynurenine was unchanged.
Tryptophan metabolism follows two pathways, both equally important.
1. TRYPTOPHAN>5-Hydroxy-tryptophan>5-Hydroxy-tryptamine (serotonin)>Melatonin
2. TRYPTOPHAN>N-formyl-kynurenine>kynurenine>2,amino,3(3-oxoprop-enyl)-fumaric acid>quinolinate>niacin
Indoleamine 2,3-dioxygenase.
IDO along with tryptophan,2,3-deoxygenase are responsible for the conversion of Tryptophan to n-formyl-kynurenine.
IDO & TDO are the rate limiting steps for conversion.
"Generating mice deficient for tryptophan 2,3-dioxygenase and comparing them to the wild type, the group found that the tryptophan 2,3-dioxygenase-deficient mice showed increased plasma levels not only of tryptophan, but also of serotonin and 5-HIAA in the hippocampus and midbrain."
Overactive IDO enzyme activity has been heavily implicated in chronic fatigue syndrome. During times of increased immune function and resultant interferon-y release, IDO becomes overactive, putting a great deal more emphasis on kynurenine synthesis. This is how our body protects itself during acute illness, but research has shown chronic illness to keep IDO active. This is important for two reasons.
1. Patients with elevated kynurenine, and overactive IDO function (Huntingtons, alzheimers, parkinsons, lyme, mononucleosis etc.) Adopt identical symptoms to those of us with CFS. During treatments with interferon-a, patients also develop what is usually temporary CFS symptoms (they claim it's horrible, yet laugh at us and call us malingerers not realizing it's a life sentence for us).
2. Through constant up regulation of IDO by interferon, this enzyme will eventually remain elevated, regardless of viral status.
The body will respond to an upregulation of IDO by releasing more interferon, this will cause further inflammation.
When the gut becomes inflamed, there is a drastic change in our microbiome.
L.Reuteri is only found in 9-30% of people, 30% being now antiquated. The administration of therapeutic dosages of Reuteri were shown very effective in mitigating liver damage in high fructose fed rats. Reuteri has not been investigated much in its role on fructose metabolism, but may well coincide with fructose intolerance given the estimated prevalence.
What reuteri is also able to do, is increase serotonin and normalize faulty kynurenine processing, these are in therapeutically relevant doses. 5-100 Billion CFU strain probiotics are not therapeutic, 50-100 could be fine for the average Joe. But actual treatment is in the 500 billion-3.6 trillion daily dosage. I haven't been able to find anyone on here who has maintained a week of this standard.
Another relevant compound I see nothing about is the IDO inhibitor rosmarinic acid taken in therapeutically relevant doses. I find this interesting as it points to a lack of trial and error on a large scale with treating IDO up regulation or kynurenine, I also see very little KYN testing going on.
This is something for people to look into I believe, and take very seriously.
