Unfolded Protein Response and A Possible Treatment for CFS

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jump44

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@mariovitali

Could you perhaps expand upon what the importance of manganese could be in this whole thing? I had an old bottle of it lying around and took about 4mg yesterday and woke up much earlier today than I normally do feeling somewhat more refreshed- felt almost like a dopamine boost if that makes sense.. Also had a ghost of a libido, something I havent really experienced for 3 years.I have seen it mentioned in connection w CFS in certain places on and off but it appears as if no one really has a grasp on what it does or why it might be important. Also a lot of warnings about toxicity etc.. I had seen you mention it a few times in this thread but Im not quite gathering why exactly its important. Thanks

edit sorry I realize youre getting a lot of questions. Again I want to thank you for putting these ideas forth I know for me incorporating some of your ideas has led to a slow but steady improvement in my condition..
 
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J

jump44

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mariovitali said:
@jump44 Regarding manganese you should thank @aquariusgirl

Please read the following paper and count how many times Bile Acids (and the disruption of their homeostasis due to Glyphosate) are found.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392553/

Manganese is needed for MnSOD (SOD2) but i would suggest that you test for the levels you have before supplementing with it

I am really glad you are feeling better.
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Thanks man.. I am still having ups and downs but overall I am better off than I was a few months ago. wow that paper is very in depth, the part about bilirubin etc are very relevant to me I think as Ive stated before I always have very high bilirubin.. I wonder if there is a connection with porphyria, as I also have high porphyrins as well.the For anyone that might know, would it be harmful to take a small dose of manganese a few times a week or even every day until Im able to get my levels checked? Ive had so many tests done Its absurd and Im a little low on funds at the moment. At this point if I find something that helps I like to keep it in my regimine, its just hard w something like Mn because theres a tone of conflicting info out there, but it looks like it could be necessary at least to some extent. All I know is I had a very powerful reaction to it.
 
mariovitali

mariovitali

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@jump44 Too much manganese can be toxic, so please make sure that you do not supplement with it too much.

The association of Porphyria and (possible) Liver disease has been previously discussed here.
 
J

jump44

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@Violeta thanks I believe I took spirulina a long time ago but I cant remember how I did with it.. I think Ill just stick with a very low dose(I have 8mg tablets) Ill break them into pieces and just take it a few times a week and see how I get on. Just intuition is telling me it might be something I really need, of course I know testing is the smartest way to go but
 
Violeta

Violeta

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mariovitali said:
@jump44 Too much manganese can be toxic, so please make sure that you do not supplement with it too much.

The association of Porphyria and (possible) Liver disease has been previously discussed here.
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@mariovitali , are you saying too much manganese is correlated to porphyria? But if so, small amounts are good? Because I know that people with porphyria do really well with spirulina. It's one of the few things they do well with.
Spirulina and activated charcoal are both good for porphyria.
 
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Bdeep86

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278
jump44 said:
Thanks man.. I am still having ups and downs but overall I am better off than I was a few months ago. wow that paper is very in depth, the part about bilirubin etc are very relevant to me I think as Ive stated before I always have very high bilirubin.. I wonder if there is a connection with porphyria, as I also have high porphyrins as well.the For anyone that might know, would it be harmful to take a small dose of manganese a few times a week or even every day until Im able to get my levels checked? Ive had so many tests done Its absurd and Im a little low on funds at the moment. At this point if I find something that helps I like to keep it in my regimine, its just hard w something like Mn because theres a tone of conflicting info out there, but it looks like it could be necessary at least to some extent. All I know is I had a very powerful reaction to it.
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Porphyrins and heme synthesis is a big part of this. It seems that this system is downstream of the bile synthesis.
 
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jump44

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Bdeep86 said:
Porphyrins and heme synthesis is a big part of this. It seems that this system is downstream of the bile synthesis.
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Yeah Ive begun to gather this.. Ive had 4 or 5 porhyria tests done including urine/stool tests which revealed consistently elevated levels(I think I had 3 of the 9 porphyrins elevated in each test)..Of course the "specialist" I went to claimed that it "could" be pointing to a problem but she had no clue what it could be. All I know is from everything I read porphyrins are certainly not something you want elevated in your body to any extent.
 
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aquariusgirl

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jump44 said:
Ive had 4 or 5 porhyria tests done including urine/stool tests which revealed consistently elevated levels(I think I had 3 of the 9 porphyrins elevated in each test)... All I know is from everything I read porphyrins are certainly not something you want elevated in your body to any extent.
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What test is this? Tnx
 
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jump44

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aquariusgirl said:
What test is this? Tnx
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I had two blood tests done after a routine one by my endo showed elevated corporphyrins(sp?)..then I went to a cancer specialist( endo said he dealt with porphyria) who ordered 24 hour urine tests of the 9 porphyrins..which revealed 3 elevated porphyrins. Then he had me do the stool sample which once again showed 3 out of range porhpyrins... heres a page which describes the 24 hour urine and stool tests, also you can find info on the 9 different porphyrins if youre interested.

http://www.porphyriafoundation.com/testing-for-porphyria

THeres a lot they still dont know about porphyria, and Ive found that there indeed are chronic versions of the disease although the current medical stance is that it is strictly an acute disease. I wouldnt be shocked if a lot of people with cfs had issues with this, and its fascinating how it could be interrelated with the bile acids and unfolded protein response.
 
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jump44

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Violeta said:
See how there are several places along the chain where the process can be stifled by a missing enzyme.

http://www.porphyriafoundation.com/...ing-for-porphyria/sensitivity-and-specificity
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Thats really interesting, I hadnt seen that chart before. The porphyria thing has constantly been in the back of my mind ever since I had those tests done. Besides reactivated Epstein barr virus, low nk cell function and elevated bilirubin, this has been the most "out of whack" lab result Ive had during this whole thing. I wonder if it could be the root cause.
 
Violeta

Violeta

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Bdeep86 said:
@mariovitali what do you feel is going on with the FXR receptor? Do you feel its being over activated?
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In porphyria caused by incomplete production of heme, too much δ-aminolevulinate synthase, (the rate limiting enzyme of porphyrin-heme synthesis) will be produced because the negative feedback chain which says, hey, we have enough heme, you can stop with production, never happens because the process is never completed. It's never completed because the chain is broken by lack of an enzyme or blockage along the way).

I didn't realize until today though that one can have high porphyrins due to breakdown of heme. I guess that is where the bile acids come into play, they facilitate removal of porphyrins.
 
Violeta

Violeta

Senior Member
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3,191
jump44 said:
Thats really interesting, I hadnt seen that chart before. The porphyria thing has constantly been in the back of my mind ever since I had those tests done. Besides reactivated Epstein barr virus, low nk cell function and elevated bilirubin, this has been the most "out of whack" lab result Ive had during this whole thing. I wonder if it could be the root cause.
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Yes, I think it is near to the root of the cause. I have EBV too, and a few other viruses. The iron build up, though, might have a deeper root, the EBV takes advantage of the iron. I don't know the bottom line, yet, though.

Either way, taking B2 and quitting red meat is helpful.
 
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jump44

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http://www.ncbi.nlm.nih.gov/pubmed/15439371

This talks about the benefits of Riboflavin in treatment of porhpyria.. unfortunately I cant access the article but at least its out there. Theres also another article on there that talks about innefectiveness of B2 but along with ACTH... would be cool to be able to read these. I notice a rather strong effect mostly good from FMN.
 
J

jump44

Senior Member
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122
Violeta said:
Yes, I think it is near to the root of the cause. I have EBV too, and a few other viruses. The iron build up, though, might have a deeper root, the EBV takes advantage of the iron. I don't know the bottom line, yet, though.

Either way, taking B2 and quitting red meat is helpful.
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Im curious have you ever found relief from phlebotomies? I actually had them prescribed to me for awhile and I would notice when I got them done I would feel lighter and much more clear headed, as if it was removing something toxic from my system.. of course this is what people with hemochromatosis do to get rid of iron. I stopped doing them at the request of my cfs doc who said they would ultimately be detrimental( I was feeling sort of run down eventually after getting them too often) but I always found it interesting I could get almost immediate relief from a lot of my symptoms from getting blood taken out.
 
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Bdeep86

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278
jump44 said:
Im curious have you ever found relief from phlebotomies? I actually had them prescribed to me for awhile and I would notice when I got them done I would feel lighter and much more clear headed, as if it was removing something toxic from my system.. of course this is what people with hemochromatosis do to get rid of iron. I stopped doing them at the request of my cfs doc who said they would ultimately be detrimental( I was feeling sort of run down eventually after getting them too often) but I always found it interesting I could get almost immediate relief from a lot of my symptoms from getting blood taken out.
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I think copper and iron dysregulation play a huge role in this, and that high levels of stored and unbound iron drive a lot of symptoms.
 
Violeta

Violeta

Senior Member
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3,191
jump44 said:
Im curious have you ever found relief from phlebotomies? I actually had them prescribed to me for awhile and I would notice when I got them done I would feel lighter and much more clear headed, as if it was removing something toxic from my system.. of course this is what people with hemochromatosis do to get rid of iron. I stopped doing them at the request of my cfs doc who said they would ultimately be detrimental( I was feeling sort of run down eventually after getting them too often) but I always found it interesting I could get almost immediate relief from a lot of my symptoms from getting blood taken out.
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I never actually had that done. I have been under normal weight and haven't even been able to donate blood. Also, I think I tend toward low blood volume. But yes, phlebotomy would clear out excess iron.

Have you ever had elevated liver enzymes, such as ALT or AST? I haven't had very many blood tests done over the years, but whenever I have, my AST has been high.
Bdeep86 said:
I think copper and iron dysregulation play a huge role in this, and that high levels of stored and unbound iron drive a lot of symptoms.
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Oh yes, I believe that, too. And that might explain why stress can bring on an acute attack. There is something about cortisol that raises free copper (and thus I suppose reduced copper where it is needed). And copper and iron can build up in the liver. That's why that's important that bile flow be improved, to keep the copper, iron, and porphyrins moving out of the system.
 
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