Unfolded Protein Response and A Possible Treatment for CFS

[mariovitali]

@Violeta

Patients with chronic liver disease have a tendency to accumulate an excessive amount of iron in their liver parenchyma. Those with alcoholic liver disease, nonalcoholic steatohepatitis or hepatitis C virus infection have a particular tendency toward secondary hemosiderosis.

Patients who have secondary iron overload must be distinguished from those with hered- itary hemochromatosis, in which a primary genetic defect leads to an excessive hepatic and total-body iron load. The level of iron loading is much greater in patients with pri- mary hemochromatosis than in those with secondary hemosiderosis.

As many as 30 percent of patients with liver disease have high serum iron levels, and 10 percent have excessive amounts of iron in their liver tissue.30,31 The reason for the iron excess is not known, but postulated mechanisms include the release of iron from injured hepatocytes and their uptake by Kupffer cells, acute-phase reactions associated with chronic inflammatory states, increased uptake of iron through the gastrointestinal tract, and ineffec
tive erythropoiesis with redistribution of iron from sites of utilization to sites of storage. The most likely mechanisms of liver injury from excess iron are increased generation of free radicals and increased peroxidation of lipids, which, in turn, lead to mitochondrial dysfunction, lysosomal fragility and cell death.

Iron has recently been shown to influence the natural history of hepatitis C virus infec- tion and the response of chronic hepatitis C to treatment. Several studies32,33 in patients with chronic hepatitis C virus infection have found a high iron concentration in the liver to be predictive of failure to respond to inter- feron therapy. Some evidence indicates that phlebotomy improves liver function tests in patients with chronic hepatitis C virus infection.34 Recent studies have also shown an increased response of the hepatitis C virus to interferon combined with phlebotomy, although not all studies are in agreement

 

[Violeta]

@mariovitali ,

It wouldn't put this in quotes: but yes, that is what I wanted to hear. Thank you.
"The most likely mechanisms of liver injury from excess iron are increased generation of free radicals and increased peroxidation of lipids, which, in turn, lead to mitochondrial dysfunction, lysosomal fragility and cell death."

 

[jump44]

I am underweight as well @Violeta. I used to weigh 170 lbs now Im about 155 and cant seem to put that weight back on, no matter what I do. I also find things like natto and pycnogenol, serrapeptase to help me. I know that excess iron and ebv or any virus can cause thick blood and these supplements help with this.

 

[Violeta]

I am underweight as well @Violeta. I used to weigh 170 lbs now Im about 155 and cant seem to put that weight back on, no matter what I do. I also find things like natto and pycnogenol, serrapeptase to help me. I know that excess iron and ebv or any virus can cause thick blood and these supplements help with this.

Yes, I took a very good enzyme supplement and it helped so much. Vitalzym. I stopped because it was expensive. After I finished it I realized that I should have been taking K2 along with it because it breaks up fibrin, and there can be calcium in the fibrin. I figured that out afterwards because a friend with Hashimoto's was taking it too. Her goiter got smaller but the nodules (calcification) enlarged.

Nattikinase is from natto. Natto consists of nattokinase AND K2! Too bad it tastes so awful!

I should really bite the bullet and buy more vitalzym. I have a Dr.'s Best type, I'll start taking that again.

 

[jump44]

Yes, I took a very good enzyme supplement and it helped so much. Vitalzym. I stopped because it was expensive. After I finished it I realized that I should have been taking K2 along with it because it breaks up fibrin, and there can be calcium in the fibrin. I figured that out afterwards because a friend with Hashimoto's was taking it too. Her goiter got smaller but the nodules (calcification) enlarged.

Nattikinase is from natto. Natto consists of nattokinase AND K2! Too bad it tastes so awful!

I should really bite the bullet and buy more vitalzym. I have a Dr.'s Best type, I'll start taking that again.

Yeah I just use the natto in supplement form, right now I just have pycnogenol I just ran out of serrapeptase. DIgestive enzymes are useful for me as well.. do you take anything for your EBV? Im on imunovir and ldn as well. Im on week 12 of the imunovir and it seems that a lot of the supplements we discuss in this thread really started working better for me when I got on the imunovir. Its been a bit of a bumpy ride but overall I believe its been a good addition as well for me.

 

[Violeta]

A friend and I have noticed that when the iron is coming out we get signs of viral infection and then we take apolactoferrin.

 

[Flo]

Now *there's* a statement. IMO anyone who makes statements like that should be ignored completely. Except I'm not dumb enough to ignore anyone completely just because they say one or two things I don't agree with. Would that everyone felt the same way.

http://www.theguardian.com/lifeandstyle/2014/dec/05/detox-myth-health-diet-science-ignorance

 

[Violeta]

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.

@jump44 Did your doctor say anything about secondary porphyria? It's different from the other type where the heme production cycle is never completed.

Secondary porphyrinuria
Several diseases unrelated to porphyrias may involve increased urinary excretion of porphyrins; this phenomenon is described as secondary porphyrinuria.

Hematologic disorders, hepatobiliary diseases, and toxins (eg, alcohol, benzene, lead) can cause elevated urinary coproporphyrin excretion. Elevated coproporphyrin excretion in the urine can occur in any hepatobiliary disorder because bile is one the routes of porphyrin excretion. Uroporphyrin may also be elevated in patients with hepatobiliary disorders. Protoporphyrin is not excreted in urine because it is water insoluble.

Some patients present with abdominal pain and neurologic symptoms mimicking acute porphyrias. Urinary ALA and PBG are typically not elevated in these diseases, and normal levels help distinguish secondary porphyrinuria from acute porphyrias. However, some patients with lead poisoning can have elevated urinary ALA levels. Blood lead levels should be measured in such patients. If urinary ALA and PBG are normal or only slightly increased, measurement of urinary total porphyrins and high-performance liquid chromatography profiles of these porphyrins are helpful for differential diagnosis of acute porphyric syndromes.

From here:
http://www.merckmanuals.com/profess...c-disorders/porphyrias/overview-of-porphyrias

 

[Flo]

@jump44 Did your doctor say anything about secondary porphyria? It's different from the other type where the heme production cycle is never completed.

Secondary porphyrinuria
Several diseases unrelated to porphyrias may involve increased urinary excretion of porphyrins; this phenomenon is described as secondary porphyrinuria.

Hematologic disorders, hepatobiliary diseases, and toxins (eg, alcohol, benzene, lead) can cause elevated urinary coproporphyrin excretion. Elevated coproporphyrin excretion in the urine can occur in any hepatobiliary disorder because bile is one the routes of porphyrin excretion. Uroporphyrin may also be elevated in patients with hepatobiliary disorders. Protoporphyrin is not excreted in urine because it is water insoluble.

Some patients present with abdominal pain and neurologic symptoms mimicking acute porphyrias. Urinary ALA and PBG are typically not elevated in these diseases, and normal levels help distinguish secondary porphyrinuria from acute porphyrias. However, some patients with lead poisoning can have elevated urinary ALA levels. Blood lead levels should be measured in such patients. If urinary ALA and PBG are normal or only slightly increased, measurement of urinary total porphyrins and high-performance liquid chromatography profiles of these porphyrins are helpful for differential diagnosis of acute porphyric syndromes.

From here:
http://www.merckmanuals.com/profess...c-disorders/porphyrias/overview-of-porphyrias

All this talk about Porphyria is off point IMO. You can talk about it and test it all day, but if you are not looking for the source of oxidative stress you will not get better.

http://www.ncbi.nlm.nih.gov/pubmed/8274157
http://www.ncbi.nlm.nih.gov/pubmed/18567368

It is just another in a long line of "auto-immune" diseases.

Which brings me to the point of this whole thread. It is much too complicated, the cause, the treatment.

 

[Violeta]

@Flo, I agree, that's what I meant when I said this:

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.

The secondary porphyria thing is a sort of clue, I would think. Is there anything in there that helps to know what type of problem one is dealing with or what to do about it when someone is deep in the pit?

 

[mariovitali]

@Flo

Why don't you start your own Thread with your version of the Theory on what is happening? If there is anything i can do to help let me know.

 

[mariovitali]

I am posting the latest Associations Analysis between matchings of the Topics i collected so far :

Topics that are seen towards the top positions may be of special interest. Note Oxidative Phosphorylation, Flavoproteins, Liver Disease, FXR, Bile Acids, AMPA Receptor (among others)

 

[Bdeep86]

A friend and I have noticed that when the iron is coming out we get signs of viral infection and then we take apolactoferrin.

How do you feel on the apolactoferrin? Do you have iron overload?

 

[Violeta]

How do you feel on the apolactoferrin? Do you have iron overload?

I don't take it all the time. I took it when I had a bad lung infection until it cleared up and whenever something like that returns. It helps. I think I did have iron in my tissue and when I started to take B2 it started to come out.

 

[mariovitali]

Yet one person with High Total Bile Acids : Main symptoms : Myasthenia, Chronic Fatigue, Brain Fog, Constipation :

So far 3 out of 5 with increased TBAs. Note also that there may be intermittent Cholestasis happening (so problem may not be showing in every test).

Here is the snapshot of his tests (Total Bile Acids in Red rectangle) :

 

[Violeta]

Maybe he's not clearing the bile acids out of his blood. Is that Greek?

Poor Phase II processing.

Maybe glucuronidation?

I see Mn is in high range, Mn is related to myasthenia gravis, but I don't know blood levels, I thought it was low levels. High is more polymyositis, a myopathy, I guess you could say a mitochondrial disease. Oh wait, myasthenia might be low levels of Mn in the cell, which would leave high levels of it in the blood. (???)

Interesting picture, even though there are some things that aren't translated to ingles.

 

[Bdeep86]

So you are expecting to see elevated BA metabolites?

 

[mariovitali]

@Violeta Yes they are Greek, let me know what you need and i will translate.


@Bdeep86 i do not know which Bile Acids (there are primary and secondary) this test looked at. However these values confirm Cholestasis.

 

[GreatGig]

Thanks for all your contributions so far @mariovitali. I had a strange reaction to some of your supps I would like your opinion on. So I already had methylation supplements in place. As soon as I added TUDCA, ALPHA-GPC, and selenium around a week ago, I am experiencing increased fatigue, reduced appetite, nausea, darker urine and stools alternating between pale and yellow greasy looking. What do you think is the issue?

I also have genetic data through 23andme I could provide you if you want, but you'd have to tell me how to get it into a form that is useful to you. I only know how to get the raw data.

 

[skwag]

Thanks for all your contributions so far @mariovitali. I had a strange reaction to some of your supps I would like your opinion on. So I already had methylation supplements in place. As soon as I added TUDCA, ALPHA-GPC, and selenium the other day, I am experiencing increased fatigue, reduced appetite, nausea, darker urine and stools alternating between pale and yellow greasy looking. What do you think is the issue?

Fatigue and nausea are common symptoms of too much acetylcholine. I would try dropping the Alpha-GPC and see how it goes.