Unfolded Protein Response and A Possible Treatment for CFS

[wastwater]

Proteopathies https://en.wikipedia.org/wiki/Proteopathy some interesting ones in there, I was looking at serpinopathies and noticed something about microtubules(Tauopathies),heard that mentioned before as well.

 

[Sam7777]

Another mechanism to explore for what its worth...

Mold

I am playing around with the idea that I might have an issue with mold in my house currently...which will be a surprise if I am right because there aren't any signs of mold.

Again, it's not that unreasonable for me to see a connection in how heavy toxic compounds like Cipro, Mercury, Lead, and Mold affect certain liver metabolism issues. Mold does upregulate bile salt production and lead to bile salt metabolism disturbances as the body attempts to expel the mycotoxin.

I keep leaving this house and coming back and getting slammed with an uptick of all liver and bile and histamine symptoms. It's clockwork. It's not good, and definitely not coincidental.

 

[Sam7777]

And to add even worse to the mix...

Skip to 1:15 to 1: 20 (hour fifteen mark to hour twenty) to hear the gestalt. As USUAL America is UNDERregulated in this area compared to Europe. Death by tobacco science.

Persistent environmental agitations seem to always be involved with CFS like conditions. I still believe that this thread stumbled upon an important cellular mechanism for explaining how the body reacts, i.e., you get protein uncoupling response. It's an elucidation of stress responses and immune mechanics.

I've experimented with getting out of heavy duty EMF zones like DECT phones to see if that relieved my severe liver pains and gallbladder issues and hyper sensitive histamine reactions.......and so far it has. I think it was the DECT phone for the most part...

A useful site.
http://hbelc.org/

 

[ahmo]

@Sam7777 Congrats on your success related to DECT phones. Dietrich Klinghardt referes to a simple experiment in which 2 petri dishes of mold were put into a closed office, w/ typical equipment. One was enclosed in Farraday cage, the other not. The caged dish showed no change a week later; the uncaged dish had a hughe increase in growth. Take-away: electronic interference stirs up all sorts of things we might not understand.

 

[nicola]

I am trying Tudca and choline to calm down what appears to be a very angry gallbladder following a spell on antihistamines (anticholergenics) which added further insult to an already under-methylated gallbladder. I have been taking 2 x 250mg Tudca and choline a day for about a week. Today I have spikey pains in my gallbladder area and backache. Wondering whether this could be things moving along, or getting worse. Anyone got any experience? thanks.

 

[whodathunkit]

@nicola, I've been having "gall bladder issues" ever since I dropped a bunch of weight last year. But it seems like there's also an element of irritable bowel and partial gastroparesis in there when I have an "attack". I take Bile Acid Factors by Jarrow and Zypan by Standard Process before every meal, although if there's no fat in the meal I'll just do a Zypan. I seem to have made some progress lately by putting taurine and glycine together to help produce bile...this seems to have allowed me to eat more liberally without precipitating any symptoms. Biggest tip-off for me that an attack is imminent is that after eating I feel like I have to belch but can't. Can't even force it out...hence the element of gastroparesis. But at the same time, it seemed like maybe I was having hypermobility or spasming in the common bile duct. Now, though, belches are not only "fully formed" and more satisfying, but also seem to be decreasing in frequency. I'm taking this as a good sign since excessive belching is supposed to be a sign of gall bladder issues and was not an issue for me before I lost the weight and developed these gall bladder symptoms. Everything seems to be moving more in synch.

Other things I believe have helped are tweaking my acetylcholine (ACh) levels with ALCAR plus some phospholipids and an acetylcholinesterase inhibitor. It's a delicate balance to strike because I also sometimes experience some symtpoms of too much ACh, which is not good, either. But I am sure I was deficient because doing these things really helped me. Not only with digestion but some with mood and motivation. Just gotta find the balance.

I've also been working on cleaning out my liver...eating a very low fat diet/high carb diet (which I've come to see as an effective episodic intervention but not necessarily a 24/7/365 lifestyle), milk thistle, and I just added d-limonene for kicks.

Adding glycine to the taurine is what really seemed to calm digestion and gall bladder down. But I've only been doing it for a couple of weeks and the benefits just kicked in last week, so only time will tell if the benefits hold.

 

[ahmo]

@nicola I"ve found herb Chanca Piedra to be excellent for gall bladder, liver, kidney issues.

 

[Deltrus]

@mariovitali Amazing thread. Read through every page. I was lost but now I have a new avenue of attack for CFS. I've had a few complete remittances through supplementation and a few other variables, but I have extreme difficulty replicating these remittances. This thread may help me with that.

I have a question though. What role does the liver have in all this?

From what I gather: ER stress and viruses cause poor liver functioning -> this induces Cholestasis, in which bile harms the liver -> liver function stays bad -> toxic chemicals are increased, causing more ER stress.

TUDCA is used to prevent cholestasis which, along with supplements, allows the liver to function well. TUDCA, although not normally used all over the body, very effectively prevents ER stress from cholestasis, and so supplemental TUDCA can actually help cells all over the body because it is so effective at preventing ER stress.

Do I understand that right?

Have people here tried using sauna to increase HSP? Why do I only see like two mentions? Have you tried it?

 

[mariovitali]

@Deltrus

I have intentionally stayed away from posting until i have more coherent results. There are specific SNPs that are of particular interest which i cannot disclose at this point.

Regarding TUDCA : There are people that either have good results with TUDCA or with Conjugated Bile acids. I don't know why this is so.

Again, i wish i could disclose more regarding the theory but i can't at this point. If it's not a problem for you, it would be great if you can send me your DNA data along with your symptoms.

Please msg me.



Thanks,

Mario

 

[skwag]

There are specific SNPs that are of particular interest which i cannot disclose at this point.

Again, i wish i could disclose more regarding the theory but i can't at this point.

State Secrets Act? Family members being held hostage? C'mon Mario, what gives? Why mention it at all then?

 

[whodathunkit]

I have intentionally stayed away from posting until i have more coherent results. There are specific SNPs that are of particular interest which i cannot disclose at this point.

Can't wait for you to start posting again, mario!

State Secrets Act? Family members being held hostage? C'mon Mario, what gives? Why mention it at all then?

Ummm...because he doesn't want to get everyone chattering about ideas that he hasn't fully fleshed out yet? Things get "run away with" on a discussion board and thereby become incoherent. He mentioned snps as a possible answer to Deltrus' questions, but doesn't want to say more until he understands more about what he's thinking. I fully understand why he doesn't want to say anything. Drive-by comments like this in response to what he does post may be another reason why.

 

[Deltrus]

I also don't like posting theories anymore until I can 100% confirm them. A confirmed theory is worth 10,000 times that of an unconfirmed theory. Also I tend to get manic when I make theories which makes me run wild, so waiting a few months before posting is quite good.

The fact that a lot of people get good responses from TUDCA is good enough for me I guess.

I'l pm my symptoms and DNA if they are of use to you.

Interesting thing with aspirin and heat shock proteins:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC312987/

Comparison ofhsp70 expression in the treatment groups revealed that in all tissues examined, aspirin-plus-heat treatment resulted in 3–4 fold higher levels of hsp70 mRNA relative to those seen with heat treatment alone. Little or no hsp70 mRNA expression was detected in the unheated groups, regardless of aspirin treatment. In keeping with the mRNA expression, Hsp70 protein levels were also elevated in aspirin-plus-heat treated animals. Aspirin treatment did not alter hsp70protein expression in the absence of heat.

 

[mariovitali]

@skwag

I do understand what you are saying but this is not up to me only, there are other people involved in this too.


I will post more info very very soon

 

[Hip]

@mariovitali, you may be interested in this post, in which I speculate that coffee enemas, which increase bile secretion from the liver, may also reduce endoplasmic reticulum stress, as cholic acid, one of the primary bile acids secreted by the human liver, reduces ER stress.

It's also interesting that @douglasmich, who suffers from post-finasteride syndrome, is benefiting from coffee enemas.

 

[mariovitali]

@Hip

Thank you, i've heard some people talking about Coffee enemas and how they feel better.


Many things have progressed in my regimen. At the moment of writing it looks like this :

-Low dose zinc (50% RDA - daily)
-Bile Acid Factors from Jarrows (one capsule at lunch, one at dinner)

Selenium : One tablet (100 mcg) every other day

FMN, Dibencozide, Metafolin, P5P : once a week (...!)

As soon as i stop Bile Acids, the symptoms gradually come back.

This is what keeps me symptom-free. As discussed, i am waiting for complete remissions from several people (not just simply "feeling better") until i post more.

 

[Hip]

Bile Acid Factors from Jarrows (one capsule at lunch, one at dinner)

Looks like the Jarrow Bile Acid Factors supplement contains a range of bile acids, including cholic acid.

Do you feel you are getting better results with this Jarrow supplement, in comparison to the tauroursodeoxycholic acid (TUDCA) bile acid supplement that you originally used?

 

[mariovitali]

@Hip

I tried the following :

-TUDCA
-UDCA
-Conjugated Bile Acids

Unfortunately, it seems that long term TUDCA/UDCA Administration has changed my Appetite patterns (my appetite was reduced significantly)

For this reason i switched to Bile Acid Factors from Jarrows and now my appetite is back to normal. Results are the same as with TUDCA/UDCA (=no symptoms)

There is yet one more person who is in complete remission as long as he takes Bile acids. I expect him to post here soon.

He has been on the regimen for almost a year, just like myself.

 

[Hip]

Looking at the label, the Jarrow Bile Acid Factors supplement seems to contain both conjugated and unonjugated bile acids.


Recently I have been looking at ER stress from the point of view of its central role in the development of leptin resistance. Leptin resistance is where leptin receptors become more insensitive to this hormone, so that as a consequence, leptin levels in the body rise to try to compensate.

Leptin is of major significance to ME/CFS, since fatigue levels in ME/CFS correlate to leptin levels (see here). As leptin levels go up, this increases fatigue in ME/CFS. So any leptin resistance would presumably lead to increased fatigue in ME/CFS.

Now it seems that ER stress induces leptin resistance. Refs: 1 2

However, TUDCA is a leptin sensitizer, that can help combat leptin resistance (and thereby lower leptin) by reducing ER stress. Ref: 1 So by this mechanism, TUDCA may be helpful for ME/CFS.

 

[Deltrus]

I thought this was interesting.


STUDY: Functional role of TRP channels in modulating ER stress and Autophagy

Thread on TRP channels in CFS: http://forums.phoenixrising.me/index.php?threads/ion-channel-snp-paper.37386/

http://forums.phoenixrising.me/inde...or-potential-melastatin-3-ion-channels.44932/

http://www.la-press.com/examination...rphisms-snps-in-transient-recep-article-a4824

Phenibut 100% cures me for a few days before tolerance kicks in, and that drug has heavy interactions with calcium, so I always want to link calcium to other ideas. Perhaps the main interaction between phenibut and my fatigue is through calcium induced ER stress.

At the same time it may mean optimizing other pathways of ER stress may help me quite a bit.

 

[dannybex]

I tried the following :

-TUDCA
-UDCA
-Conjugated Bile Acids

Unfortunately, it seems that long term TUDCA/UDCA Administration has changed my Appetite patterns (my appetite was reduced significantly)

For this reason i switched to Bile Acid Factors from Jarrows and now my appetite is back to normal. Results are the same as with TUDCA/UDCA (=no symptoms)

There is yet one more person who is in complete remission as long as he takes Bile acids. I expect him to post here soon.

He has been on the regimen for almost a year, just like myself.

Very interesting @mariovitali. I've been following the thread off and on for months and just yesterday was wondering why ox bile wouldn't work as well as the pricier TUDCA. But at the same time, I've seen reports like this one of people who have found that TUDCA restored their appetite...

A couple quick questions if you don't mind:

Prior to UDCA/TUDCA, would you consider your appetite 'normal' or 'strong' (strong hunger pangs, stomach "growling" before meals)? (I'm assuming you don't take any betaine HCL.)

The reason I ask is that I've read that bile is alkaline, or akalinizing, so I would think they would interfere with gastric acid production.

Which leads me to question #2: Do you take the Bile Acid Factors before, during or after your meals?

Thanks.