Unfolded Protein Response and A Possible Treatment for CFS

[Violeta]

@Violeta,

Thanks for the links, from what i've read there exist both Endogenous and Exogenous ROS. So Cadmium and pollutants are just one part of the story

Do you know the other part of the story?

 

[Violeta]

@Violeta,

Thanks for the links, from what i've read there exist both Endogenous and Exogenous ROS. So Cadmium and pollutants are just one part of the story

What do you consider cadmium to cause, endogenous or exogenous?

Something that is alive has to be producing the ROS, so I looked up a common pathogens and found a lot of hits to Lyme with respect to ROS.


I don't know the whole chain of events, but I have seen that Lyme caused induced NOS.

Thank you, that explains a LOT!!!

Here's one.
http://www.sciencedirect.com/science/article/pii/S2213231715000282

 

[Violeta]

I don't know where this is leading, but this is with respect to RNA viruses and ROS.

http://www.hindawi.com/journals/ijcb/2014/467452/

It's leading to this:

Reactive oxygen species (ROS) are well known for being both beneficial and deleterious.

And this:

Peterhan and his coworkers were the first to demonstrate that a virus could generate ROS from phagocytes

 

[Violeta]

My brain is all over the place, what do we do to deal with ROS? This is a biggie, what if all the pain that people with Lyme, viruses, etc, is simply being caused by the ROS. Well, I guess you still have to deal with the cause, but maybe this will help a few of my friends.

 

[skwag]

: my intention is to give at the regimen suggested by ppodhajski a try. To do this i will have to wait until the supplements arrive (20 days) but i will let you know as soon as i start. FYI i already started taking Biotin (which is part of ppodhajski's suggestions)

Which supplements will you be adding?

 

[mariovitali]

Which supplements will you be adding?

Coenzymated B2 (aka FMN) and Biotin which i already started. Possibly also Magnesium and Zinc.

I believe that i will know if this regimen works very soon. I can immediately recognize the first warning signs / symptoms (e.g Irregular Heartbeat, Tinnitus, OI).


@Violeta,


Yes we need some help with this. I wish i was a Biochemist...

 

[Violeta]

Coenzymated B2 (aka FMN) and Biotin which i already started. Possibly also Magnesium and Zinc.

I believe that i will know if this regimen works very soon. I can immediately recognize the first warning signs / symptoms (e.g Irregular Heartbeat, Tinnitus, OI).


@Violeta,


Yes we need some help with this. I wish i was a Biochemist...

You probably already know this, but your body can only use a small amount of B2 at a time and the rest is excreted, so it's best to take small doses throughout the day. (as per the B2 I Love You thread)

 

[skwag]

You probably already know this, but your body can only use a small amount of B2 at a time and the rest is excreted, so it's best to take small doses throughout the day. (as per the B2 I Love You thread)

That's a real bear of a thread!

What size dose is recommended? How much total for the day?

Thanks

 

[Dreambirdie]

: my intention is to give at the regimen suggested by ppodhajski a try. To do this i will have to wait until the supplements arrive (20 days) but i will let you know as soon as i start. FYI i already started taking Biotin (which is part of ppodhajski's suggestions)

Coenzymated B2 (aka FMN) and Biotin which i already started. Possibly also Magnesium and Zinc.

I believe that i will know if this regimen works very soon. I can immediately recognize the first warning signs / symptoms (e.g Irregular Heartbeat, Tinnitus, OI).

Not wanting to read all 37 pages of this thread... . I'm just wondering if you could summarize why Biotin, B2, magnesium and zinc are the chosen supplements in this regimen...? and are these 4 supps the ONLY ones on the to-do list?

Thanks in advance for your response.

 

[Dreambirdie]

That's a real bear of a thread!

What size dose is recommended? How much total for the day?

Thanks

I know that Source Naturals makes a coenzymated B2 that is sublingual 25 mg.

 

[brenda]

I have just read through the B2 l love you thread because l have started to take coenzymated riboflavin again. Christine claimed that it would release iron into the bloodstream, and l had to stop it eventually when she said to take only manganese which l stopped after developing problems.

So this time l am keeping the dose low - 2 mg x 4 . l have already experienced the positive effects l had before, like improved sleep and feeling more oxygenated. I think it is best to stay low on it.

 

[Violeta]

That's a real bear of a thread!

What size dose is recommended? How much total for the day?

Thanks

It was recommended to start with 12.5 mg doses, but I don't know how many times a day...at least 4 times a day, though. I use NOW B2 which comes in 100mg capsules, and I can't stand the taste, so I have to break it down into other capsules. I break it down into 4 or 5 capsules, and on a good day I take 3. It does waste some, but that's the best I can do for now.

There is a possibility of your body not being able to keep up with the detoxification that the B2 causes and you might experience various symptoms, and if you think that might be happening just cut back. It can cause the release of stuff and if the stuff doesn't make it out of your body due to inefficient bile flow, the stuff recirculates. I think that's why a lot of people on the thread and the other thread about B2 had problems. They didn't realize what was going on or how to deal with it.

I'll just add this, but don't want to scare anyone off. Several months after I started taking it I had a very bad lung infection. I had had recurring lung issues for years and years along with a chronic cough, after you get over one, the metal that the pathogens grow on just gets redeposited and then the pathogen revives. I wasn't ready for it but I had to work my way through it. I found apolactoferrin helped enormously, because it helps to deal with iron. I can't take meds, so I had to do it naturally. Since then I haven't had any lung infections.

 

[mariovitali]

@Dreambirdie

Haha yes you are right regarding the size of the Thread. I wish i could compress it somehow

Ok so here goes :

1) I think that CFS, Post-Finasteride Syndrome and people with permanent side effects from Accutane have the same basis : Uncontrolled ER Stress / Oxidative Stress (?) / Unfolded Protein Response. This generates a multitude of problems

2) I used agents like TUDCA, Selenium, Taurine, Resveratrol to prevent excessive protein misfolding which leads to Unfolded Protein response and ER Stress (and as a consequence our several symptoms which point to a multi-systemic disease). This -along with Methylation- has helped me to become Symptom-free. It took 2 months to achieve this.

3) A user called ppohadjski said that these agents (Taurine, TUDCA, etc) should not be used but instead we should use Biotin and FMN which are key cofactors for regulating redox functions.

4) I believe that (3) may be correct and may be i was wrong in believing that ER Stress is the key issue. ER Stress AND Oxidative Stress are interrelated which means that Oxidative Stress has to be taken into account also.

Therefore i will try to see if Methylation Regimen+FMN+Biotin could work for me. If not we may need the full stack (which means handling ER + Oxidative stress)

I know it sounds very complicated. Hopefully we will find out more soon

 

[A.B.]

@mariovitali I thought you might find this interesting (if you don't already know)

I recently read a paper where prion proteins were described as having cytoprotective functions, in particular against oxidative stress and stressors that can induce apoptosis in cells.

Prion proteins could also be interacting with heat shock protein and chaperones.

http://www.sciencedirect.com/science/article/pii/S0925443907000609

Background: I wast tested for prion protein function and it came back very low. I haven't been able to figure out what this means concretely.

 

[Violeta]

I supposed ROS has been implicated in PEM, but just thought I would mention it here.

http://www.ncbi.nlm.nih.gov/pubmed/11708399

Studies during the past 2 decades suggest that during strenuous exercise, generation of reactive oxygen species (ROS) is elevated to a level that overwhelms tissue antioxidant defense systems.

 

[Dreambirdie]

@mariovitali Thanks for your response. Here are a few questions related to the below.

What does ER stand for in this context? What does TUDCA stand for? And are there specific SNPs that are indicated for these issues?

@Dreambirdie

1) I think that CFS, Post-Finasteride Syndrome and people with permanent side effects from Accutane have the same basis : Uncontrolled ER Stress / Oxidative Stress (?) / Unfolded Protein Response. This generates a multitude of problems

2) I used agents like TUDCA, Selenium, Taurine, Resveratrol to prevent excessive protein misfolding which leads to Unfolded Protein response and ER Stress (and as a consequence our several symptoms which point to a multi-systemic disease). This -along with Methylation- has helped me to become Symptom-free. It took 2 months to achieve this.

3) A user called ppohadjski said that these agents (Taurine, TUDCA, etc) should not be used but instead we should use Biotin and FMN which are key cofactors for regulating redox functions.

4) I believe that (3) may be correct and may be i was wrong in believing that ER Stress is the key issue. ER Stress AND Oxidative Stress are interrelated which means that Oxidative Stress has to be taken into account also.

 

[mariovitali]

@Dreambirdie

ER = Endoplasmic Reticulum
TUDCA= Tauroursodeoxycholic acid (Ameliorates ER Stress and Protein Misfolding)

Regarding SNPs : It is not my area, i have listed some SNPs that should be looked at. They are for :

-Choline Metabolism
-BH4 Production
-Response to ER Stress
-NAFLD (Non-alcoholic Fatty Liver Disease)

FYI @Valentijn points out that many of the SNPs listed are actually non-pathogenic.

@A.B. I did not know what prion proteins are. I matched them on the topics from PubMed and the matchings are as follows. Notice how many topics that are discussed here are matched towards the top of the list :

*********Topic : cellular prion protein ***************
misfolded_proteins.csv : 2.53 %
amyloid.csv : 0.33 %
nlinkedglycosylation.csv : 0.25 %
tudca.csv : 0.19 %
upr.csv : 0.17 %
glycosylation.csv : 0.17 %
xbp1.csv : 0.14 %
oxidative_stress_protection.csv : 0.14 %
sod2.csv : 0.12 %
excitotoxicity.csv : 0.12 %
er_stress.csv : 0.12 %
insomnia.csv : 0.12 %
microglia.csv : 0.11 %
chaperones.csv : 0.11 %
tmao.csv : 0.10 %
neurite_outgrowth.csv : 0.09 %
nmda.csv : 0.08 %
perk.csv : 0.07 %
kainate.csv : 0.07 %
ampa.csv : 0.06 %
osmolytes.csv : 0.06 %
nadph_oxidase.csv : 0.06 %
heat_shock_protein.csv : 0.06 %
tau.csv : 0.05 %
calcium_homeostasis.csv : 0.05 %
hsp70.csv : 0.05 %
sod1.csv : 0.05 %
caspase_human.csv : 0.04 %
glycoproteins.csv : 0.04 %
ros.csv : 0.04 %
amyloidosis.csv : 0.04 %
disulfide_bonds.csv : 0.03 %
mitochondrial_dysfunction.csv : 0.03 %
inositol.csv : 0.03 %
phospholipid_human.csv : 0.03 %
sirt1.csv : 0.03 %
gpr78.csv : 0.03 %
resveratrol.csv : 0.03 %
neuronal_nos.csv : 0.03 %
systemic_amyloidosis.csv : 0.02 %
n-acetylglucosamine.csv : 0.02 %
p53.csv : 0.02 %
hmgcoa.csv : 0.02 %
glutamate.csv : 0.02 %
ngf.csv : 0.02 %
pbmc.csv : 0.02 %
vcam-1.csv : 0.01 %
peroxynitrite.csv : 0.01 %
curcumin.csv : 0.01 %
hpa_axis.csv : 0.01 %
histone_deacetylase.csv : 0.01 %
acetylcholine.csv : 0.01 %
dysautonomia.csv : 0.01 %
serotonin_levels.csv : 0.01 %
immune_response.csv : 0.01 %
chop.csv : 0.01 %
gaba_human.csv : 0.01 %
biotin.csv : 0.01 %
reduced_glutathione.csv : 0.01 %
inducible_nos.csv : 0.01 %
oxidative_stress_markers.csv : 0.01 %
social_anxiety.csv : 0.01 %
protease_inhibitor.csv : 0.01 %





and now matching "prion disease"



*********Topic : prion disease ***************
misfolded_proteins.csv : 7.35 %
insomnia.csv : 1.42 %
amyloid.csv : 1.25 %
microglia.csv : 0.77 %
systemic_amyloidosis.csv : 0.62 %
amyloidosis.csv : 0.44 %
tudca.csv : 0.38 %
upr.csv : 0.37 %
cerebrovascular_amyloidosis.csv : 0.37 %
sod1.csv : 0.32 %
er_stress.csv : 0.32 %
tau.csv : 0.31 %
chaperones.csv : 0.28 %
nlinkedglycosylation.csv : 0.25 %
glycosylation.csv : 0.24 %
atf6.csv : 0.23 %
pgc1.csv : 0.21 %
erad.csv : 0.20 %
sod2.csv : 0.18 %
perk.csv : 0.17 %
atf4.csv : 0.16 %
gpr78.csv : 0.16 %
dysautonomia.csv : 0.14 %
sirt1.csv : 0.14 %
pqq.csv : 0.13 %
glycoproteins.csv : 0.12 %
osmolytes.csv : 0.11 %
ire1.csv : 0.11 %
excitotoxicity.csv : 0.10 %
mitochondrial_dysfunction.csv : 0.10 %
hsp70.csv : 0.10 %
tmao.csv : 0.10 %
pdi.csv : 0.10 %
calcium_homeostasis.csv : 0.09 %
oxidative_stress_protection.csv : 0.09 %
caspase_human.csv : 0.09 %
heat_shock_protein.csv : 0.09 %
ginkgo.csv : 0.09 %
inflammatory_response.csv : 0.08 %
resveratrol.csv : 0.08 %
lipoic_acid.csv : 0.07 %
xbp1.csv : 0.07 %
hgh.csv : 0.07 %
oxidative_stress_markers.csv : 0.07 %
limbic_system.csv : 0.06 %
ros.csv : 0.06 %
advanced_glycation_end.csv : 0.06 %
inositol.csv : 0.06 %
ngf.csv : 0.06 %
neurite_outgrowth.csv : 0.06 %
inducible_nos.csv : 0.06 %
nmda.csv : 0.06 %
phospholipid_human.csv : 0.05 %
disulfide_bonds.csv : 0.05 %
curcumin.csv : 0.04 %
nadph_oxidase.csv : 0.04 %
anhedonia.csv : 0.04 %
immune_response.csv : 0.04 %
glutamate.csv : 0.04 %
coenzymeq10.csv : 0.04 %
cox-2.csv : 0.03 %
caloric_restriction.csv : 0.03 %
chop.csv : 0.03 %
mcp-1.csv : 0.03 %
peroxynitrite.csv : 0.03 %
ampa.csv : 0.03 %
histone_deacetylase.csv : 0.03 %
kainate.csv : 0.03 %
neuronal_nos.csv : 0.03 %
n-acetylglucosamine.csv : 0.02 %
il_10.csv : 0.02 %
gaba_human.csv : 0.02 %
monoamine_oxidase.csv : 0.02 %
omega3.csv : 0.02 %
p53.csv : 0.02 %
biotin.csv : 0.02 %
autism.csv : 0.02 %
iron_deficiency.csv : 0.02 %
cyp3a4.csv : 0.02 %
udpgluc.csv : 0.02 %
cfs.csv : 0.02 %
cortisol_levels.csv : 0.01 %
nad.csv : 0.01 %
endothelial_nos.csv : 0.01 %
triiodothyronine_levels.csv : 0.01 %
human_semen.csv : 0.01 %
tinnitus.csv : 0.01 %
irritable_bowel.csv : 0.01 %
gluten.csv : 0.01 %
riboflavin.csv : 0.01 %
xanthine_oxidase.csv : 0.01 %
norepinephrine.csv : 0.01 %
cimetidine.csv : 0.01 %
probiotics.csv : 0.01 %
phosphatidylcholine.csv : 0.01 %
p450oxidoreductase.csv : 0.01 %
cortisol.csv : 0.01 %
dopamine.csv : 0.01 %
protease_inhibitor.csv : 0.01 %
pbmc.csv : 0.01 %
adrenergic_receptor.csv : 0.01 %
hepatocytes.csv : 0.01 %
serotonin_levels.csv : 0.01 %

 

[mariovitali]

@A.B. @Valentijn @adreno

I decided to look more closely at the "redox" Topic. So i queried different redox topics across the topics of interest of CFS that i have on my disk (downloaded from PubMed). Have a look :

"Redox potential" and "Redox homeostasis" have the most matchings across all CFS Topics of interest. So i decided to add them to my software for subsequent analysis. I also added NAC (which i should have added long time ago) and more symptoms which have been left out (e.g constipation).

Of interest is the fact that Thioredoxin reductase is matched across redox queries (and therefore appears at the top of positions)

My intention is to then group all CFS symptoms to one field and then run an analysis to find common features (i.e Topics of Interest) that appear to be associated with Symptoms. For example we may find that a common Topics that co-occur with any Symptom are Peroxynitrite and Excitotoxicity.

 

[aquariusgirl]

just a random thought.... biotin and FMN ... seem to be important for detoxing oxolates....Oxolates = oxidative stress and apparently cause cells to hold on to metals... So I'm wondering if there is an oxolate problem.

 

[mariovitali]

just a random thought.... biotin and FMN ... seem to be important for detoxing oxolates....Oxolates = oxidative stress and apparently cause cells to hold on to metals... So I'm wondering if there is an oxolate problem.

My feeling is that oxalates are just another addition to burden our bodies with ROS but i do not think that CFS is due to oxalate issues.

I am sure there are many people in PR that follow a low oxalate diet and they feel better possibly because of lowering their ROS burden.