Unfolded Protein Response and A Possible Treatment for CFS

[Violeta]

@Violeta

I am looking for Associations between all CFS symptoms and Topics in Pubmed.

Yes i do take FMN, half a tablet.

Regarding Hydrogen, i will have to read more

Oh, yes, better to go by symptoms. What did you use for asking for association in that last run?

 

[mariovitali]

@Violeta

It is called Association Rule Learning


https://en.wikipedia.org/wiki/Association_rule_learning

 

[ahmo]

I hoped that by the time I got back to this thread someone would have stated or asked: WTF does all this mean,@mariovitali ? do you know?? does anyone else? Is there something practical I can take away from this? thx.

 

[mariovitali]

@ahmo

You are absolutely right.

The unfortunate thing about forums is the fact that knowledge gets dispersed inside the posts.

Let me try giving you a summary :

This Thread was about Endoplasmic Reticulum stress and the fact that is an important part and possibly the solution to CFS : If you can control ER Stress then you may become symptom-free as i have.

It now appears that one other aspect could be equally important : namely ROS homeostasis and Redox Regulation.


So apart from the things discussed here there are also other cofactors that can be used to have a better Redox homeostasis (apart from controlling ER Stress) :

1) FMN (= coenzymated Vit. B2)
2) Selenium, about 200 mcg per day (boosts Thioredoxin production)
3) Vitamin C
4) Molybdenum

Note that if youa re following this regimen, it already has Selenium and Vitamin C (although they were used for another reason).

So now i am trying to see if ER Stress + Redox have to be looked at OR just Redox Regulation/Homeostasis (with the 4 supplements i discussed above)

-have you tried the original regimen discussed here? Did you check the genes discussed on the first post?

 

[Gondwanaland]

@Violeta

It is called Association Rule Learning


https://en.wikipedia.org/wiki/Association_rule_learning

I think she meant what symptoms you typed into the search

@ahmo

You are absolutely right.

The unfortunate thing about forums is the fact that knowledge gets dispersed inside the posts.

I think she meant what this latest search brings in terms of new supplements to take

 

[ahmo]

@mariovitali Yes, I'm taking FMN and selenium, molybd, no longer taking additional C. Thanks.

 

[skwag]

Trial Update Day 30

I'm currently taking,

3x250 mg TUDCA
3x1400 mg NAG
3x10 mg R5P
100 mcg selenium
235 mg choline
750 mg inositol

along with methylation supplements. I have also been on the autoimmune paleo diet for two weeks.

We have had some significant improvements:

1) lightening of sun damge/ liver spots on forearm ( onset one year ago )
2) decreased urinary frequency. Now I go every 2-3 hours vs every hour
3) lighter urine color
4) better urinary flow ( probably due to less prostate inflammation )
5) 33% improvement in folloculitis on arms and legs ( onset one year ago )
6) 70% improvement in noise intolerance/ headaches.
7) 95% improvement in lower back pain ( onset one year ago )
8) 33% improvement in energy levels
9) 50% improvement in groin pull injury ( onset 5 months ago, little improvement over previous 4 months )

Things that I can't for sure say have improved, but I suspect are a little better.

1) eye floaters ( onset one year ago )
2) nasal congestion

Things which have not improved.

1) POTS - my heart rate still consistently increases 35-40 bpm upon standing, but interestingly what I thought
were POTS symptoms ( headache, irritablitity and trouble thinking on my feet ) have decreased.
2) skin texture/ wrinkling ( onset one year ago )

Things seem to be heading in a good direction, but the going is slow. I had a much stronger and faster reaction when I first started Freddd's protocol.

Over the last ten days, I have felt good for the most part, except for two days where I experienced a little mini crash. Interestingly, the onset of the crash was about 12 hours before a brief period of rain and cooler temperatures.

 

[wastwater]

What is a protein kinase inhibitor and would it be helpful In ME. Protein kinase C is of interest to me not sure what it is or does though

 

[mariovitali]

@skwag

OK Great! Thank you for the update -as always- and you are mentioning some important things :

1) Urine Color : That is an interesting one. Urine color can be affected by the amount of water we drink, some supplements (e.g B Complex, Magnesium)..BUT i have also found that i had Darker Urine Color when i was crashing. So Urine Color is a good way to monitor your progress. It seems that ER and/or Oxidative stress affects Kidney Function and as a result you get darker Urine color (?)

2) The weather pattern : Recall how i discussed over and over again that weather affects us in a negative way. Keep looking for this pattern and please do let us know what you think. As time passes by your crashes will have lower severity (= they will affect you less) and less frequency.

I would advise you to raise Selenium to 200 mcg per day and Choline to 700 mg per day -try it for 10 days- and see how you feel. Hang in there, this will take time! I have the FOXO3 variant which is associated with longevity, therefore maybe i saw improvements much faster (since this variant aids in better oxidative stress handling).



@wastwater

I do not know what would happen. I saw that PKIs have a lot of side effects.


@ahmo @Gondwanaland

How are you doing with the regimen?



@all

I realized that the Photophobia i had for years is gone! I do not have the urge to wear sunglasses as i used to (even with a cloudy weather)

 

[ahmo]

How are you doing with the regimen?

What exactly? selenium? or rather, se, mbd, z, FMN...? I'm doing great. For me, great means that since my interventions of this year, I am essentially symptom-free. That is, My cognitive and physical energy remains extremely limited, but I'm not crashing. And I'm not itching, generally not irritable, agitated. I've had to recently aknowledge that I've got brain fog big time, am able to accomplish so little at my computer. but no headaches, vastly improved sensitivities to noise and light, no neurological symptoms, insomnia. These last things were resolved w/ B12/folate.

 

[mariovitali]

@ahmo

OK let's break down the regimens proposed here:

ER Stress supplements : Selenium, Vitamin C, TUDCA, Choline, Inositol, Dibencozide+P5P+Metafolin, Resveratrol, Curcumin, NAG(?), Taurine


Redox/Oxidative stress supplements/cofactors : Selenium, Magnesium(?), Molybdenum, FMN, Vitamin C (and others that i do not currently know)


(?) implies that i am not sure if the specific supplement indeed works/is applicable.


Could you tell us more about your interventions?

 

[ahmo]

R Stress supplements : Selenium, Vitamin C, TUDCA, Choline, Inositol, Dibencozide+P5P+Metafolin, Resveratrol, Curcumin, NAG(?), Taurine

I've not tried TUDCA. As I recall, it's N/A through iherb, so I didn't go further.

I'm getting 12.5mg inositol from my B Complex. Either this year or sometime last year, I no longer self-tested + for the additional inositol caps I used to take.

I'm taking choline, twice daily;

p5p 25mg from the B comp: I'd been taking extra p5p until beginning of this year, when it became clear tyhat it was adding to my ammonia/peroxynitrite burden (I stopped trying to differentiate these, tho here, it's probably ammonia)

Dibencizide: 40mg, once/week

Metafolin: 1mg AM/PM

Resveratrol: no longer testing + for it since starting FMN

I don't use taurine, NAG, curcumin due to sulfur issues. A couple weeks ago I pushed my molybdenum up again, to see how I went w/ sulfur. I ate an egg, then a week later, another. I no longer tested + for choline or lecithin for almost a week after this single egg. But this did not seem to be worth taking such high doses of molybdenum, so I'm back to 450mcg AM/PM.

 

[mariovitali]

@ahmo OK Great

FYI : Vitamin C is an important redox regulator. You could take 500 mg if you don't want to take a gram. Regarding choline how many mgs are you taking per day? Too bad you cannot have TUDCA but i do understand that it may not be available in 'Down Under'

 

[ahmo]

I think I'm taking about 250mg choline 2x/day, ie 500mg. I have some C ascorbate, I'll give it a try. Thx.

Ah, I see TUDCA is for liver. I use chanca piedra when liver is stressed, and coffee enemas, and feel my liver's in pretty good condition. Unless you're suggesting it for other reasons, which I'd have to review the thread to recall. I found some online in Aus, but it's expensive. I'd want to expect some big bang for my bucks.

 

[mariovitali]

I think I'm taking about 250mg choline 2x/day, ie 500mg. I have some C ascorbate, I'll give it a try. Thx.

Ah, I see TUDCA is for liver. I use chanca piedra when liver is stressed, and coffee enemas, and feel my liver's in pretty good condition. Unless you're suggesting it for other reasons, which I'd have to review the thread to recall. I found some online in Aus, but it's expensive. I'd want to expect some big bang for my bucks.

Ah yes, i see. OK then in this case i suggest that you stop drinking alcohol completely. Hopefully Choline will fix things. Did you have tests for Liver Function and/or an U/S (Ultrasound) of your Liver?

TUDCA ameliorates ER Stress which -in the theory of this thread- is an important factor of what is going on with us .

 

[Ema]

I'm wondering if you could take taurine and UDCA together for the same effect as TUDCA. UDCA is a old cheap rx drug that an open minded physician might be willing to prescribe.

 

[skwag]

I'm wondering if you could take taurine and UDCA together for the same effect as TUDCA. UDCA is a old cheap rx drug that an open minded physician might be willing to prescribe.

I think you are correct. This paper suggests the effects of UDCA and TUDCA are similar:

The Unexpected Uses of Urso- and Tauroursodeoxycholic Acid in the Treatment of Non-liver Diseases

From the conclusion section:

With the exception of greater solubility, and somewhat different pharmacokinetics, TUDCA and UDCA, are essentially identical molecules that both have the unique ability to increase cell survival and inhibit programmed cell death, or apoptosis. The protective mechanisms of T/UDCA have been studied in a wide range of cell types and animal models of human disease. T/ UDCA is a strong inhibitor of apoptosis by interfering early on with the mitochondrial pathway of cell death and associated processes such as ROS and reducing endoplasmic reticulum stress. T/UDCA serves as a neuroprotectant against acute injuries such as stroke, as well as chronic neurodegenerative diseases including AD, PD, and HD. It protects against cell death in transgenic mouse models of retinitis pigmentosa, ameliorates the insulin resistance associated with obesity, inhibits ER stress associated with type II diabetes, and is approved in South Korea for the treatment of patients with amyotrophic lateral sclerosis.82 It has been reported to be effective in a phase II clinical study for the treatment of transthyretin amyloidosis in combination with doxycycline.83 T/UDCA has been shown to be effective in animal models of spinal cord injury,84 head trauma, glaucoma, acute renal failure, pancreatitis, metabolic syndrome, psoriasis,85,86 myocardial infarction, neuropathic pain,87 ischemia reperfusion syndromes, GI disorders, and diabetic retinopathy in addition to the obvious liver-related disorders. Obese patients seem to benefit from T/UDCA via the inhibition of ER stress and UPR dysfunction. Patients with macular degeneration, hair loss and early onset of aging may benefit from the remarkable properties of T/UDCA.

You may not even need the taurine.

 

[Gondwanaland]

@ahmo @Gondwanaland
How are you doing with the regimen?

Hi Mario, my TUDCA bottle is still unopened. I am really afraid of trying things that promotes liver detox since I am terribly intolerent to tiny doses of

• inositol
• taurine
• malic acid
• vitamin C
• can't take methylation supps b/c I do not tolerate potassium (stomach ulcer+adrenals)
• resistant starch
• oats
• Clostrydium butyricum
• resveratrol
• NAG
• curcuma (don't have access to curcumin locally)

My husband responded wonderfully to the addition of 2 eggs to his dinner (no more lower back stiffness - until I gave him 1 Tbsp of oat porridge 2x )

@all

I realized that the Photophobia i had for years is gone! I do not have the urge to wear sunglasses as i used to (even with a cloudy weather)

I am interested in that! Plus I need help with my tinnitus

It started in May when I took Boswellia for joint pain and didn't stop anymore Boswellia slows down liver phase I - it took me several weeks to tolerate the city smog again All the supps above worsen my tinnitus

@all
Dizziness and POTS may respond to Choline

 

[ahmo]

i suggest that you stop drinking alcohol completely. Hopefully Choline will fix things. Did you have tests for Liver Function and/or an U/S (Ultrasound) of your Liver?

I haven't drunk for nearly 4 years; no ultrasound; my liver function tests, if any, would be some years old. Even pre-ME, my acupuncturist cautioned me that liver was my weakness, always treated spleen, instead of liver directly. I attribute coffee enemas for my reasonable liver health.

BTW, I recalled that I'd quit inositol a year ago, after major detox event. It's biotin that I eliminated this year, after fungal/bacterial purge, 3-day water fast, FMN.

@Ema Excellent. This is on our pharmaceutical benefits scheme, so will cost me $7/rx. ...or maybe not, maybe $37, which is still cheaper than TUDCA.

Now I'll have to review this thread to really get a handle on this stuff.

@Gondwanaland wow, oats are so powerful!

 

[mariovitali]

Hi Mario, my TUDCA bottle is still unopened. I am really afraid of trying things that promotes liver detox since I am terribly intolerent to tiny doses of

• inositol
• taurine
• malic acid
• vitamin C
• can't take methylation supps b/c I do not tolerate potassium (stomach ulcer+adrenals)
• resistant starch
• oats
• Clostrydium butyricum
• resveratrol
• NAG
• curcuma (don't have access to curcumin locally)

My husband responded wonderfully to the addition of 2 eggs to his dinner (no more lower back stiffness - until I gave him 1 Tbsp of oat porridge 2x )

I am interested in that! Plus I need help with my tinnitus

It started in May when I took Boswellia for joint pain and didn't stop anymore Boswellia slows down liver phase I - it took me several weeks to tolerate the city smog again All the supps above worsen my tinnitus

@all
Dizziness and POTS may respond to Choline

Can you explain a bit more what "intolerant' means? What symptoms do you have?


-Have you tried Methylation supplements B12+P5P+Metafolin ?
-How about Choline? Can you tolerate it?
-Have you tried Taurine at all?