Unfolded Protein Response and A Possible Treatment for CFS

[mariovitali]

@mariovitali , if bile acids helps so much, then you most likely can return to good health by cleaning up liver and gallbladder congestion so that your body makes it's own bile the bile is able to flow.

And on another note, do you have any information about DCYTB, a cupric reductase?
This enzyme also works in the duodenum, and if things are messed up there, copper might not be reduced, leading to copper being absorbed in it's biounavailable form, which actually causes copper deficiency. This can then lead to iron deficiency, but that's for later.

I do not know the exact mechanism of "Liver cleanse" and Gallbladder congestion Violeta. What i am hypothesising here is that dysregulation of the enterohepatic circulation of Bile acids takes place or some other issue with Bile acids which further aggravates things in a very nasty way.

I came across CCK in my research, i've never tried to boost CCK production. To me i think it is the conversion of primary Bile acids to the conjugated form that is problematic. I am not sure if a boost in bile volume would be a good idea. Then we have the people that have gallstones...that would be a problem for them too.

I do not know anything about DCYTB,i will have a look.

What you write about Copper is really interesting. For me a Key part to my success was Molybdenum (even though i did not know about the role of Cysteine Dioxygenase and how it is boosted by Molybdenum and FMN). I feel that those with CBS mutations should definitely consult with their Physicians about the possibility of supplementing with Molybdenum and FMN.

 

[Peace]

@sflorence

I will be making a new Thread as soon as i have info/evidence of complete recoveries. In a nutshell :

TUDCA/UDCA/Bile Acids from jarrows appear to be working almost equally well. I would say that the order of effectiveness appears to be the following :

1. TUDCA
2. UDCA
3. Bile Acids from Jarrows

The protocol uses :

1) UDCA or TUDCA or Bile Acids from Jarrows
2) Methylation support (especially Metafolin and P5P)
3) Molybdenum and/or Zinc and/or Manganese for Copper Level control if it is found to be high
4) Selenium


Note : It appears that this regimen requires many Months to show its effects.

Hi mariovitali,
thank you for sharing and making this thread. Very interesting and could be another key in recovering from illness.
I already have bile, choline supplements for my liver among other reasons but ordered TUDCA, choline from Jarrows. Are there any particular brands that you prefer or which has worked best? Is resveratol necessary and if so, which type/method trans capsule, liposomal, knotweed, etc?

 

[mariovitali]

@Peace There is no preferred Brand from people i talked with except for TUDCA, it seems that "Premium Powders" is the best.

Resveratrol can help, especially if you are female. I am sorry but i am not aware of the different kinds available and the differences these may have.

 

[ahmo]

@mariovitali I take rather high doses of molybdenum 3x 150mcg AM/PM. And FMN made a huge difference in my histamine issues.

if bile acids helps so much, then you most likely can return to good health by cleaning up liver and gallbladder congestion so that your body makes it's own bile the bile is able to flow.

Coffee enemas have been a fantastic help for me. I'm no longer doing them more than about once a month. My liver and gb seem to be in good working order. And, the bile seems to have really added something extra.

 

[mariovitali]

@ahmo

I believe i read somewhere that high doses of Molybdenum for an extended amount of time is not a good idea. I think it affects sulfation but let me search about this.

 

[mariovitali]

Well, this is interesting :

@ahmo @adreno

Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q-TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS-induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury.

and

In the present work, increased levels of PC (L4-5, L7-8, L10, and L12), PE (L6, L9, L11, L14), and PA (L1), and reduced levels of glycerophospholipids derivatives [glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPEtn), L24 and L26] were detected in the liver tissue of CUMS-treated rats. The results indicated oxidative stress, inflammatory cell membrane damage, and even apoptosis in the liver during CUMS. Further, the disturbed phospholipid metabolism reduced the emulsification of bile acid, increased bile acids toxicity40and further promoted liver injury

TUDCA, Choline, Phospholipids are all there :



http://www.nature.com/articles/srep23441

 

[ahmo]

chronic unpredictive mild stress (CUMS) What's this? Is this what we have??

I'm ordering Jarrow Bile factors today.

 

[mariovitali]

@ahmo

Ah yes, i should have explained this.

I noticed that many people that i talked with having Fibromyalgia described to me that prior to getting it they had a rather prolonged stressful period followed by a virus infection . Then their symptoms have started.

It gets more interesting : In Greece we have a saying :

"Μου κόπηκε η χολή"

which literally means "My bile flow has stopped" an expression that we use when we say that we got very scared from something.....!

http://forum.wordreference.com/threads/%CE%BA%CF%8C%CF%80%CE%B7%CE%BA%CE%B5-%CE%B7-%CF%87%CE%BF%CE%BB%CE%AE-%CE%BC%CE%BF%CF%85.258471/

So maybe, for some people prolonged stress affects them in many more ways (= also affects the Liver and Bile too) than we may think.

 

[ahmo]

I noticed that many people that i talked with having Fibromyalgia described to me that prior to getting it they had a rather prolonged stressful period followed by a virus infection . Then their symptoms have started.

Yes, I had prolonged stress. And then there was a terrible illness. At the time, it was attributed to stressed liver (!), following 50th birthday celebrations w/ too much rich food and drink. Acupuncturist believed it was caused by taking herbals w/ oily supps at the same time. In any case, it was like an extreme flu. Following that, my energy never returned. I began researching CFS, eventually calling myself chronically fatigued. Four years later, more stress + heatstroke led to collapse, ME.

 

[Kathevans]

@mariovitali I take rather high doses of molybdenum 3x 150mcg AM/PM. And FMN made a huge difference in my histamine issues.

I'm wondering what your thinking is for taking so much molybdenum. After struggling with B2 and basic methylation protocols, it turned out I was fairly low in molybdenum. It took me two months to titrate up to 150mcg, but I still have tinnitus which Greg (famous of the B-12 Oils) says is a result of adrenaline and therefore perhaps not enough moly which he says processes it.

Just wondering. I have seen a 500mcg tablet by Seeking Health, but I don't know of anyone taking that much... Greg says that 150 ought to fill up the tanks, but of course, who knows!

 

[ahmo]

Hi @Kathevans I don't do my dosing by thinking. I proceed by self-testing. I tried significantly higher doses awhile back, following suggestions from aaron_c, in hopes of dealing better w/ sulfur. It didn't make a difference. I still avoid sulfur/high thiol foods, my body doesn't seem to like them. You've provoked me to try a smaller dose, and see how it goes. I've been using my current dose for somewhere between 1-2 years.

I don't know if molybd has a role in my tinnitus. Certainly adrenal health does. Now when I have a worsening of tinnitus, I use coffee enema to relieve adrenals. So, I'll be interested to see, in my lower dosage experiment, if tinnitus increases.cheers.

 

[Kathevans]

Thanks, @ahmo I have worked on the self-testing with a pendulum. I can't say I've perfected it, but I keep using it. I've wondered about my molybdenum levels. Just resting at 150mcg seemed a good idea, but your taking more has led me to think... Certainly my adrenal issues are coming to the fore. My right side has had uncomfortable twinges more on than off over the past month or so. I've got to pull myself together and post here, though I've been hoping that the issues would settle or come a bit clearer.

A little bit fuddled here.

Btw, apropos of this thread, according to Greg it is molybdenum that makes/or leads to FAD and without enough of it, B2 is converted to FMN, but not the FAD. So, of course it's important. Even though at the moment, I need to look up exactly what FAD does!

 

[ahmo]

@Kathevans I took 2 instead of 3 molybd last night w/ my meal, as usual. A couple hours later, when I asked body if it wanted more, I got a yes. I didn't experience any symptoms, but would rather trust my responses after all these years, than wait until I have symptoms.

 

[Kathevans]

@ahmo. I think I'll ask my body if it wants more moly! With the 150mcg tablets, I can divide it in four and that might be an evening dose to start with. The sleeplessness I'm experiencing Greg says an adrenaline issue, and more moly might well help...

 

[mariovitali]

Dear All,


As most of you following this Thread know, i have been using several cutting-edge methods including Machine Learning and Natural Language Processing (NLP) so that i may guide my Research towards the most promising areas.

Please see below how the algorithm(s) select Topics that are most likely to be associated with a possible solution for CFS/ME.

Notice how the following Topics can be found among the results :

-Acetylation
-Bile acids
-3β-HSD
-5α-Reductase
-Adrenal insufficiency
-Adrenal hyperplasia
-Leptin
-APOE
-Acetylcholine
-Mitochondria_human
-ABC transporters


Interestingly, many of the topics discussed in this Thread are also found in the Naviaux Study.

I copied/pasted the results for your reference in case you find anything interesting for your Research.

--------------------------------------------------
f1= 0.88
ADA-Boost Classifier
precision recall f1-score support

F 0.88 0.89 0.88 55
T 0.89 0.88 0.88 56

avg / total 0.88 0.88 0.88 111

['adrenal_hyperplasia' 'abc_transporter' 'acetyl_coa'
'asymmetric_dimethylarginine' 'avidin' 'betaine' 'ala_synthase'
'acetylation' 'adrenal_insufficiency' 'five_htp' 'acyl_coa'
'angiotensin_human' 'amyloid' 'beta_glucuronidase' 'artichoke'
'acetyl_coa_carboxylase' 'adrenergic_receptor' 'astrocytes'
'allopregnanolone' 'acetylcholine' 'acetylcholinesterase' 'bile_acid'
'baroreceptor' 'five_ala' 'ampa' 'beta_alanine' 'atf4' 'apoe' 'ae2'
'b_cell']
--------------------------------------------------
f1= 0.9
Decision Tree Classifier
precision recall f1-score support

F 0.93 0.89 0.91 62
T 0.87 0.92 0.89 49

avg / total 0.90 0.90 0.90 111

['leptin' 'metronidazole' 'mitochondria_human' 'norepinephrine'
'intestinal_motility' 'phospholamban' 'cystathionine_g_lyase' 'glycolysis'
'cimetidine' 'glutamate_dehydrogenase' 'amyloid' 'redox_regulation' 'mtor'
'ubiquitination' 'disulfide_bonds' 'iga' 'sulfation' 'porphyrins' 'ggt'
'chaperones' 'trpv' 'choline' 'nadh_dehydrogenase' 'three_betahsd'
'cyproterone' 'lcfa' 'dexamethasone' 'fas' 'oxytocin' 'ikk_beta']
--------------------------------------------------
f1= 0.9
ADA-Boost Classifier
precision recall f1-score support

F 0.86 0.96 0.91 57
T 0.96 0.83 0.89 54

avg / total 0.91 0.90 0.90 111

['three_betahsd' 'five_alphareductase' 'acetylcholine'
'acetylcholinesterase' 'angiotensin_human' 'apoe' 'astrocytes'
'acetylation' 'acetyl_coa' 'adrenal_insufficiency' 'abc_transporter'
'ala_synthase' 'acyl_coa' 'beta_alanine' 'bilirubin' 'bile_acid' 'atf4'
'acetyl_coa_carboxylase' 'beta_glucuronidase' 'five_ala'
'asymmetric_dimethylarginine' 'are' 'amyloid' 'b_cell' 'bdnf' 'betaine'
'ae2' 'five_ht2' 'atf6' 'allopregnanolone']
--------------------------------------------------

 

[ebethc]

Dear All,


As most of you following this Thread know, i have been using several cutting-edge methods including Machine Learning and Natural Language Processing (NLP) so that i may guide my Research towards the most promising areas.

Please see below how the algorithm(s) select Topics that are most likely to be associated with a possible solution for CFS/ME.

Notice how the following Topics can be found among the results :

-Acetylation
-Bile acids
-3β-HSD
-5α-Reductase
-Adrenal insufficiency
-Adrenal hyperplasia
-Leptin
-APOE
-Acetylcholine
-Mitochondria_human
-ABC transporters


Interestingly, many of the topics discussed in this Thread are also found in the Naviaux Study.

I copied/pasted the results for your reference in case you find anything interesting for your Research.

I didn't know that APOE and Bile Acids were related to CFS... Can you say more about these two?

thanks.

 

[mariovitali]

@ebethc

It seems that Bile Acids are important for a great deal of Body functions. It is really difficult for me to explain all of their functions. Regarding APOE i am working on it.

@all
Have you heard about the latest Project by Microsoft? (Note AI = Artificial Intelligence)

Google isn't the only tech giant hoping that artificial intelligence can aid the fight against cancer. Microsoft has unveiledProject Hanover, an effort to use AI for both understanding and treating cancers. To begin with, the company is developing a system that would automatically process legions of biomedical papers, creating "genome-scale" databases that could predict which drug cocktails would be the most effective against a given cancer type. An ideal treatment wouldn't go unnoticed by doctors already swamped with work.

https://www.engadget.com/2016/09/20/microsoft-ai-helps-find-cancer-treatments/

FWIW, This is what i did here. I used NLP, Machine Learning and AI Methods to guide my research.

I contacted the Biomedical research center in Athens University and talked with the Director. He listened very carefully and i explained to him very briefly what i did and how i guided my Research.

I will make a presentation to him and his Team of Researchers sometime after 4th of October. I will keep you all updated.

 

[dannybex]

Just wanted to let you know I'm finally getting some (almost) normal-colored stools (the kind I'd get with ox bile supplementation) and my constipation (that has lasted for 15 months) is gone, thanks to a different blend of digestive bitters (different from Swedish Bitters anyway), put out by a company called "Urban Moonshine".

Not sure if I'm getting any side effects -- feet have been a little colder -- but overall, I'm really pleased that this actually seems to be helping, digestion-wise.

 

[ebethc]

Just wanted to let you know I'm finally getting some (almost) normal-colored stools (the kind I'd get with ox bile supplementation) and my constipation (that has lasted for 15 months) is gone, thanks to a different blend of digestive bitters (different from Swedish Bitters anyway), put out by a company called "Urban Moonshine".

Not sure if I'm getting any side effects -- feet have been a little colder -- but overall, I'm really pleased that this actually seems to be helping, digestion-wise.

how is Urban Moonshine Bitters compared to Ox Bile? compared to Swedish Bitters?

Betaine/Pepsin does nothing for me... Swedish Bitters is sporadic, and I've been contemplating Ox Bile, but it seems gross..

 

[dannybex]

The bitters work to help your gallbladder/liver function better to release bile, while ox bile is just a temporary replacement.

It's my understanding that the 'moonshine' formula has more 'warming' bitter herbs (like fennel, gentian and orange peel) in it, compared to the more 'cooling' Swedish' bitters.