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What do inflammatory bowel disorders, Chronic Fatigue Disorder, Parkinsons and Alzheimers have in common?
Chronic Fatigue Syndrome
Alzheimers
The basal ganglia, specifically the substantia nigra is known as the motivating factor in the reward pathway of the human brain. The substantia nigra is implicated in many degenerative diseases, in Parkinson's it will show as tremors, decreased motor function and severe depression, in chronic fatigye this means ceaseless fatigue, pain, depression, anxiety and muscle weakness.
In alzheimers it gets advanced neurologically of course to completely losing ones memories and brain function over time.
"Regional neuronal loss in the substantia nigra (SN) was studied in relation to extrapyramidal symptoms and dementia in 27 patients with Alzheimer's disease (AD), 12 patients with idiopathic Parkinson's disease (PD) and 18 controls. Four areas of the right SN were investigated at the level of the caudal red nucleus. In AD the number of neurons were reduced to 97%, 79%, 83% and 78% of the control values from the medial to lateral SN respectively.
https://www.ncbi.nlm.nih.gov/pubmed/2602422
Moreover, activation of microglia in the SNpc and striatum is profound in various types of PD animal models [15–17]. Further biochemical analysis reveals higher levels of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interferon-gamma (IFN-γ) in the midbrain of PD patients. These data strongly suggest the involvement of immune components in PD pathogenesis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603346/#!po=7.77778
The basal ganglia has also been highlighted in Chronic Fatigue syndrome.
"The findings show that patients with chronic fatigue syndrome have decreased activation of an area of the brain known as the basal ganglia in response to reward. Additionally, the extent of this lowered activation was associated with each patient's measured level of fatigue."
"The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers. When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patient's fatigue was tightly tied with the change in brain activity between winning and losing. Those with the most fatigue had the smallest change."
"Dr. Unger says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue."
https://www.sciencedaily.com/releases/2012/04/120424142109.htm
The observation was incredibly fortuitous but was given very little consideration. The basal ganglia does become damaged over time in those with CFS, and other conditions. Not in a similar manner to interferon treatment (in my opinion) but exactly as one would undergoing longterm, indefinite low dose interferon treatment.
Our source for this ceaseless interferon treatment? The gut.
"IFN-γ gene, its transcription factor T-bet, IFN-γ protein expression, and its release are increased in the colonic mucosa of patients with IBS and downregulate SERT gene expression in vitro. These results suggest that IFN-γ downregulates SERT expression, hence likely playing a role in altered serotonin metabolism of patients with IBS."
https://www.ncbi.nlm.nih.gov/pubmed/26744473
Why is this an issue? Sure low serotonin could bring mood down, but how does that explain feeling as though I have the flu 24/7 365 days a year?
Well, Tryptophan is a lot more complex than people realize.
It isn't just the serotonin precursor, in fact very little Tryptophan is used to make serotonin. What were concerned with is the other side of Tryptophan metabolism.
The kynurenine pathway.
Kynurenine is produced from Tryptophan via IDO Indoleamine 2,3 Dioxygenase. Kynurenine along with several or its metabolites are incredibly damaging to our bodies, and must be regulated. When we get sick, interferon gamma is released, when interferon gamma is released, IDO is stimulated to overutilize Tryptophan to manufacture kynurenine, when the infection is gone and Tryptophan has been used up, our gut begins to repair, the biome starts to replenish to regulate Tryptophan as a fuel source to lower inflammation.
But what happens when the inflammation doesn't stop? What if we lose too much of our good bacteria, are overcome by inflammatory and interferon stimulating bacteria and eventually lose our anti inflammatory Tryptophan processing bacteria? All of our food contains antibiotics right? Those will help to kill the intruders, well no, not without also killing many factors greater the good guys.
IDO activity stays high in response to low levels of a constant stream of IF-y from intestinal inflammation, Tryptophan becomes inflammatory rather than incredibly antiinflammatory as a bacterial food source, kynurenine stays at the same level causing more oxidative and inflammatory stress, further increasing IF-y production, the antibiotics you're eating continue wiping out your good bacteria, and eventually there is nothing left to suppress IDO activity, kynurenine gets the emphasis, serotonin synthesis is in decline, interferon-y is slowly destroying your health and every bit of stress you put yourself through makes the inflammatory issues worse.
IF-y eventually begins to destroy the substantia nigra, and you begin to lose your motivation, first it was energy now it's the will to have energy. Next you start losing your memory, you forget which pills are your morning pills, and which are the afternoon. What protocol am I on again?
The gut inflammation increases, nutrient absorption goes down, you are now symptomatic for a thousand conditions. The good bacteria has declined heavily, unable to process toxins, nutrients or help you in any way but keep you going.
Eventually your immune system fails to the point where it can barely damage you anymore, your blood tests all come back fine now, and you feel okay. You can't remember what feeling actually okay meant, but if you catch a glimpse it terrifies you, maybe this is 20 years on, now your IF-y reads normal, you've hardly got enough biotic cultures left to show up high anywhere on immune function.
At this point it's got to be in your head right? You can't really be this sick if no one believes you are.
Well, I'll tell you who believes you. The 100 trillion symbiotes living inside you having a much tougher time than you ever have. Well no, that's in a healthy person, let's say 50 to be safe.
Well healthy people have interferon responses as well, they just also have probiotics in their bodies, and can handle getting sick without hospitalization.
What can you do about the damage?
Well L.Reuteri (not commonly found in humans, is severely limited and tied up/destroyed by fructose or high fructose corn syrup depending on your diet) combined with Tryptophan has been shown to do a great job at treating intestinal inflammation, lowering IDO activity, increasing serotonin and Tryptophan (weird coincidence huh?)
https://www.sciencedaily.com/releases/2017/08/170803141045.htm
Berberine is a powerful inhibitor of Tryptophan to Kynurenine, and lowers IF-y, also protects against substantia nigra damage (another coincidence I suppose)
Jiaogulan or gynostemma works very strongly to repair the entire basal ganglia, and had shown great promise in all related disorders. It also lowers IF-y, suppresses gut inflammation and increases serotonin.
Rosmarinic Acid is an IDO inhibitor.
Probiotics must be used in at least several hundred billion CFUs to be considered therapeutic. Nothing short of 100 billion is going to put a drop in the bucket.
So when I look around around and see some of the main research into CFS focusing on IF-y, gut inflammation, resultant dopaminergic dysfunction, kynurenine/tryptophan and nobody seems to be trying the most powerful substances relating to those connections I have to scratch my head.
I think one person on here has mentioned trying gynostemma, they posted once and never came back.
I don't see anyone taking reparative dosages of probiotics, Reuteri specifically with Tryptophan.
Berberine is always hit or miss, well it's an antibiotic so if you're not using it with probiotics that's kind of antagonizing the underlying issue a bit.
Rosmarinic acid I believe was mentioned once as a skin lotion.
TL;DR
There is a lot of research into CFS you may find promising.
Some Google possibilities.
Tryptophan/Kynurenine CFS
Kynurenine CFS
IDO CFS
Interferon gamma CFS
IBD Kynurenine
Substantia Nigra CFS
Basal Ganglia CFS
Jiaogulan
Gynostemma
Berbeine
Rosmarinic Acid IDO
Chronic Fatigue Syndrome
- Fatigue
- Loss of memory or concentration
- Sore throat
- Enlarged lymph nodes in your neck or armpits
- Unexplained muscle pain
- Pain that moves from one joint to another without swelling or redness
- Headache of a new type, pattern or severity
- Unrefreshing sleep
- Extreme exhaustion lasting more than 24 hours after physical or mental exercise
Alzheimers
- Memory loss
- Poor judgment leading to bad decisions
- Loss of spontaneity and sense of initiative
- Taking longer to complete normal daily tasks
- Repeating questions
- Trouble handling money and paying bills
- Wandering and getting lost
- Losing things or misplacing them in odd places
- Mood and personality changes
- Increased anxiety and/or aggression
- Tremor.
- Slowed movement (bradykinesia).
- Rigid muscles.
- Impaired posture and balance.
- Loss of automatic movements.
- Speech changes.
- Writing changes.
The basal ganglia, specifically the substantia nigra is known as the motivating factor in the reward pathway of the human brain. The substantia nigra is implicated in many degenerative diseases, in Parkinson's it will show as tremors, decreased motor function and severe depression, in chronic fatigye this means ceaseless fatigue, pain, depression, anxiety and muscle weakness.
In alzheimers it gets advanced neurologically of course to completely losing ones memories and brain function over time.
"Regional neuronal loss in the substantia nigra (SN) was studied in relation to extrapyramidal symptoms and dementia in 27 patients with Alzheimer's disease (AD), 12 patients with idiopathic Parkinson's disease (PD) and 18 controls. Four areas of the right SN were investigated at the level of the caudal red nucleus. In AD the number of neurons were reduced to 97%, 79%, 83% and 78% of the control values from the medial to lateral SN respectively.
https://www.ncbi.nlm.nih.gov/pubmed/2602422
Moreover, activation of microglia in the SNpc and striatum is profound in various types of PD animal models [15–17]. Further biochemical analysis reveals higher levels of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interferon-gamma (IFN-γ) in the midbrain of PD patients. These data strongly suggest the involvement of immune components in PD pathogenesis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603346/#!po=7.77778
The basal ganglia has also been highlighted in Chronic Fatigue syndrome.
"The findings show that patients with chronic fatigue syndrome have decreased activation of an area of the brain known as the basal ganglia in response to reward. Additionally, the extent of this lowered activation was associated with each patient's measured level of fatigue."
"The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers. When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patient's fatigue was tightly tied with the change in brain activity between winning and losing. Those with the most fatigue had the smallest change."
"Dr. Unger says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue."
https://www.sciencedaily.com/releases/2012/04/120424142109.htm
The observation was incredibly fortuitous but was given very little consideration. The basal ganglia does become damaged over time in those with CFS, and other conditions. Not in a similar manner to interferon treatment (in my opinion) but exactly as one would undergoing longterm, indefinite low dose interferon treatment.
Our source for this ceaseless interferon treatment? The gut.
"IFN-γ gene, its transcription factor T-bet, IFN-γ protein expression, and its release are increased in the colonic mucosa of patients with IBS and downregulate SERT gene expression in vitro. These results suggest that IFN-γ downregulates SERT expression, hence likely playing a role in altered serotonin metabolism of patients with IBS."
https://www.ncbi.nlm.nih.gov/pubmed/26744473
Why is this an issue? Sure low serotonin could bring mood down, but how does that explain feeling as though I have the flu 24/7 365 days a year?
Well, Tryptophan is a lot more complex than people realize.
It isn't just the serotonin precursor, in fact very little Tryptophan is used to make serotonin. What were concerned with is the other side of Tryptophan metabolism.
The kynurenine pathway.
Kynurenine is produced from Tryptophan via IDO Indoleamine 2,3 Dioxygenase. Kynurenine along with several or its metabolites are incredibly damaging to our bodies, and must be regulated. When we get sick, interferon gamma is released, when interferon gamma is released, IDO is stimulated to overutilize Tryptophan to manufacture kynurenine, when the infection is gone and Tryptophan has been used up, our gut begins to repair, the biome starts to replenish to regulate Tryptophan as a fuel source to lower inflammation.
But what happens when the inflammation doesn't stop? What if we lose too much of our good bacteria, are overcome by inflammatory and interferon stimulating bacteria and eventually lose our anti inflammatory Tryptophan processing bacteria? All of our food contains antibiotics right? Those will help to kill the intruders, well no, not without also killing many factors greater the good guys.
IDO activity stays high in response to low levels of a constant stream of IF-y from intestinal inflammation, Tryptophan becomes inflammatory rather than incredibly antiinflammatory as a bacterial food source, kynurenine stays at the same level causing more oxidative and inflammatory stress, further increasing IF-y production, the antibiotics you're eating continue wiping out your good bacteria, and eventually there is nothing left to suppress IDO activity, kynurenine gets the emphasis, serotonin synthesis is in decline, interferon-y is slowly destroying your health and every bit of stress you put yourself through makes the inflammatory issues worse.
IF-y eventually begins to destroy the substantia nigra, and you begin to lose your motivation, first it was energy now it's the will to have energy. Next you start losing your memory, you forget which pills are your morning pills, and which are the afternoon. What protocol am I on again?
The gut inflammation increases, nutrient absorption goes down, you are now symptomatic for a thousand conditions. The good bacteria has declined heavily, unable to process toxins, nutrients or help you in any way but keep you going.
Eventually your immune system fails to the point where it can barely damage you anymore, your blood tests all come back fine now, and you feel okay. You can't remember what feeling actually okay meant, but if you catch a glimpse it terrifies you, maybe this is 20 years on, now your IF-y reads normal, you've hardly got enough biotic cultures left to show up high anywhere on immune function.
At this point it's got to be in your head right? You can't really be this sick if no one believes you are.
Well, I'll tell you who believes you. The 100 trillion symbiotes living inside you having a much tougher time than you ever have. Well no, that's in a healthy person, let's say 50 to be safe.
Well healthy people have interferon responses as well, they just also have probiotics in their bodies, and can handle getting sick without hospitalization.
What can you do about the damage?
Well L.Reuteri (not commonly found in humans, is severely limited and tied up/destroyed by fructose or high fructose corn syrup depending on your diet) combined with Tryptophan has been shown to do a great job at treating intestinal inflammation, lowering IDO activity, increasing serotonin and Tryptophan (weird coincidence huh?)
https://www.sciencedaily.com/releases/2017/08/170803141045.htm
Berberine is a powerful inhibitor of Tryptophan to Kynurenine, and lowers IF-y, also protects against substantia nigra damage (another coincidence I suppose)
Jiaogulan or gynostemma works very strongly to repair the entire basal ganglia, and had shown great promise in all related disorders. It also lowers IF-y, suppresses gut inflammation and increases serotonin.
Rosmarinic Acid is an IDO inhibitor.
Probiotics must be used in at least several hundred billion CFUs to be considered therapeutic. Nothing short of 100 billion is going to put a drop in the bucket.
So when I look around around and see some of the main research into CFS focusing on IF-y, gut inflammation, resultant dopaminergic dysfunction, kynurenine/tryptophan and nobody seems to be trying the most powerful substances relating to those connections I have to scratch my head.
I think one person on here has mentioned trying gynostemma, they posted once and never came back.
I don't see anyone taking reparative dosages of probiotics, Reuteri specifically with Tryptophan.
Berberine is always hit or miss, well it's an antibiotic so if you're not using it with probiotics that's kind of antagonizing the underlying issue a bit.
Rosmarinic acid I believe was mentioned once as a skin lotion.
TL;DR
There is a lot of research into CFS you may find promising.
Some Google possibilities.
Tryptophan/Kynurenine CFS
Kynurenine CFS
IDO CFS
Interferon gamma CFS
IBD Kynurenine
Substantia Nigra CFS
Basal Ganglia CFS
Jiaogulan
Gynostemma
Berbeine
Rosmarinic Acid IDO