Unfolded Protein Response and A Possible Treatment for CFS

mariovitali

mariovitali

Senior Member
Messages
1,214
@op2pig

Welcome to the forum!

What you describe is in tandem with the theory that Chronic Fatigue, Post-Finasteride Syndrome and Accutane Permanent Side Effects may possibly have the same basis.

The proposed steps :

1) Have DNA test. This will help you understand what actions you need to take (as you correctly mention)
2) Visit promethease.org and upload your data there. Then download the HTML Files necessary for running Promethease to your computer
3) I will prepare a new list of specific SNPs that you should look. These involve Methylation, Choline Absorption, Redox cofactors (credit to @ppodhajski), ER Stress handling. There are no additional requests to 23andme after you get your results.

Hang in there. There are many people that will start following the new regimen (which includes Redox homeostasis) and post their results.

All i can say is that i got my life back from many-many years of Frustration and numerous repeated failures to feel better.


Good Luck! :)
 
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jump44

Senior Member
Messages
122
@mariovitali

just thought id update after having my appt with my cfs doctor. I found out that my Natural killer cells and their function are abysmally low, so ive been prescribed LDN plus some other supplement recommendations like vit c, d, and ubiquinol which I already take. I asked about Tudca but they werent aware of it but said my liver is definitely struggling. I am gonna get the 23 and me done, as well as more viral and hormone tests. Im still taking fmn at half a tab/day and its still helping. I started Ldn the other night as well. I will order the Tudca today..

I also am taking resveratrol. Do you think the Tudca is a key supp for us with liver issues?I always feel better when I drink a red bull and just realized it has taurine in it. hmm. anyways just thought id throw the natural killer cell thing into it, I wonder if that might be another item to add to your search inputs. thanks!
 
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skwag

Senior Member
Messages
226
op2pig said:
@mariovitali

I've been reading and re-reading this post from head-to-toe and I'm very exited to see how this proposed treatment develops. I took accutane in 2002 and have had chronic fatigue and sexual side effects since. I'm interested in attempting this protocol later this fall/winter and reporting back its impact from the accutane side of the chronic-illness-world. Am I correct in understanding that a DNA testing and review of SNPs is a necessary first step before proceeding with this treatment? Can I simply order the testing kit, 23andme and post the SNP results here for analysis or are there additional steps, or requests specific to 23andme that I need to make?
Cheers!
Click to expand...

I just wanted to throw my two cents in here on DNA testing. I've done it and I think it's interesting, but not terribly useful at this point, at least for me. I do recommend that people should get it done. You might just find something important. And the more people that have it done, the more likely we will be to identify patterns that might help us all.

But I would not recommend basing treatment decisions too heavily on current unproven theories based on common snps. I think it is more important to simply observe how you feel using different treatments, and base your decisions on that. And I certainly would not wait on DNA testing before trying something that I think might be helpful.
 
O

op2pig

op2ig
Messages
17
@skwag

Thanks for your two cents, its helpful to know that the 23andMe DNA data is more auxiliary. Here is my approach: in addition to being diagnosed with low 5ar-THF last week, I was also diagnosed with low levels of DHEA. My plan is to treat the DHEA levels first then begin the MarioVitali-PpodHajski2015Protocol. (MVPH15P?) :DCheers!

P.S. Other forum posters on an accutane forum I frequent have shared this thread and some are trying the protocol as well.
 
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skwag

Senior Member
Messages
226
op2pig said:
P.S. Other forum posters on an accutane forum I frequent have shared this thread and some are trying the protocol as well.
Click to expand...

Excellent. Can you share which accutane forum? I'm interested in checking out their results with the protocol.
We still don't have much anecdotal evidence at this point.
 
mariovitali

mariovitali

Senior Member
Messages
1,214
@op2pig

MVPH15P? LOL

Yes, i would be very interested to know too. I already posted about this regimen to "All things male" is this the forum you are referring to?

@skwag
I have SNPs at :

-Choline absorption and Inositol - several heterozygous mutations
-BH4 Production
-Biotin Absorption
-FAD Production (FMN supplementation fixes this) - several heterozygous mutations
-MTHFR Gene (homozygous)
-several homozygous mutations at NOS1 (neuronal NOS). NOS2 and NOS3 look better. FYI NOS1 has as cofactors Tetrahydrobiopterin, FAD, FMN and Iron. Many of my problems originated from these homozygous mutations i believe.



I am trying to supplement according to my SNPs and so far i do not regret it.


My current regimen is as follows :


08:00 Metafolin 2000 mcg, Iron, FMN, Dibencozide, Biotin
10:00 Choline/Alpha GPC 350 mg, Inositol 1 gram
12:00 TUDCA 250 mg, P5P 50 mg, Selenium (100 mcg)
16:00 Vitamin C 500 mg
20:00 Choline/Alpha GPC 350 mg, Inositol 1 gram, Selenium 100 mcg
23:00 TUDCA 250 mg

I also eat Navy beans daily for Molybdenum until a supplement arrives.

I am in the process of stopping TUDCA. I tried stopping Choline/Inositol and something wasn't right...so now i re-introduced Choline and Inositol and i am trying slowly to stop TUDCA by going from 500 mg to 250 mg daily for a week. After a week i will completely stop TUDCA and report back.
 
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mariovitali

mariovitali

Senior Member
Messages
1,214
ahmo said:
@mariovitali Why are you quitting TUDCA? Do you believe it's only a short-term need?
Click to expand...

Because i want to get to the bottom of this condition : Is it ER Stress, Redox dysregulation or both?

Also i feel much better knowing that i am taking the absolutely necessary supplements.

As already discussed i dropped Choline and Inositol for a week and i felt that i began having some minor problems..so i re-introduced them. Now it's time to evaluate TUDCA's necessity to my regimen.
 
S

skwag

Senior Member
Messages
226
mariovitali said:
I am trying to supplement according to my SNPs and so far i do not regret it.
Click to expand...
That's good. I didn't mean to suggest you shouldn't. I think it is definitely worthwhile to try to understand these things. I'm just saying we shouldn't rely too heavily on our snps. Our knowledge is limited and in many cases may turn out to be wrong. Treatment outcomes carry much more weight with me.

As an example, I can imagine that someone might not have any of the relevant snps related to choline and conclude that he doesn't need to supplement it, when in fact he would benefit from the supplementation. The only way to know for sure is to trial it.

mariovitali said:
I am in the process of stopping TUDCA. I tried stopping Choline/Inositol and something wasn't right..
Click to expand...

In reading about Alpha GPC, I came across a few reports of problems developing after stopping. Check out the fifth post of this thread from longecity.

I don't know what to make of it myself, but you could test whether this is some sort of Alpha GPC withdrawal effect by switching to another choline source.
 
mariovitali

mariovitali

Senior Member
Messages
1,214
@skwag

Actually i did this because i ran out of Alpha GPC (which i cannot get hold of in my country) and switched to Choline without problems. The problems showed up when i stopped Choline supplementation.

So the timeline looks like this :

1. Supplementing with Alpha GPC
2. Stopped Alpha-GPC because i ran out of the supplement and started with Choline bitartate (no problems from the switch)
3. Continued Choline bitartate for 20 days
4. Stopped Choline Bitartate/ Inositol to see if i will have Symptoms
5. Problems begin to show up (minor OI, minor nerve pains barely noticeable)
6. Re-started Choline Bitartate and Inositol
7. Problems stopped

Alpha-GPC has just arrived, i haven't decided whether i will re-switch to it and ditch Choline bitartate.
 
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skwag

Senior Member
Messages
226
mariovitali said:
@skwag

Actually i did this because i ran out of Alpha GPC (which i cannot get hold of in my country) and switched to Choline without problems. The problems showed up when i stopped Choline supplementation.

So the timeline looks like this :

1. Supplementing with Alpha GPC
2. Stopped Alpha-GPC because i ran out of the supplement and started with Choline bitartate (no problems from the switch)
3. Continued Choline bitartate for 20 days
4. Stopped Choline Bitartate to see if i will have Symptoms
5. Problems begin to show up (minor OI, minor nerve pains barely noticeable)
6. Re-started Choline Bitartate
7. Problems stopped

Alpha-GPC has just arrived, i haven't decided whether i will re-switch to it and ditch Choline bitartate.
Click to expand...

I'll report more later, but I'm really getting a boost from using citicoline. Anyway, glad to hear there is no problem with Alpha GPC. I've got a bottle but still haven't opened it.

What kind of OI did you have? And where was your nerve pain?
 
mariovitali

mariovitali

Senior Member
Messages
1,214
@skwag

That's interesting i've never used Citicoline so please keep us posted.

As already discussed, if this Theory proves itself then i will say about several Patterns that i found from analyzing data being recorded on a daily basis. One of them has to do with OI and since you asked specifically for it, it goes like this (speaking to what i experienced of course..i am not suggesting this holds for everyone)

-First you have a stressor. The stressor may be a negative thought (yes, that too) or Wind picking up considerably or abrupt Temperature drop or Working out.

-Then i would feel a pain located on the base of my head and a bit to the right (always the same spot).

-Then i would get OI.

In other words i know that if i experience pain in that area for any reason then OI will kick in. I would feel full-headedness instead of light-headedness when i would stand up.
 
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Naibaf

Messages
7
Awesome work until now @mariovitali and co

Since its my first post here let me introduce myself in a short manner:

Im a 28 year old electrical engineer / data scientist. Im ill since 8 years now my main symptoms are:

Depression / severve anxiety and inner tension
Deliberating fatigue
Tinnitus (its also an indicator for me since it changes over time and supps)
Massive brain fog
Histamine problems
IBS
Gluten and casein sensitivity
Early morning insomnia
Insomnia in general
Kryptopyrolurie (KPU)
Mitochondria dysfunction
Impaired speech

I was 3 time in a psychatric clinic, had 19 ECT right unilateral, have tried dozens of antidepressant and supplements.
Im typing from my smarthphone right now, will give an in depth post the next days.

Most helpful are 30mg methylphenidat a day Its a life saver!
And a really small amount of duloxetin.
50mg Pregabalin before bed: wow fatiguethe next day is much better.
Phosphatidylserine -> helped with inner tension but subtile the longrun

Some interesting stuff:
If I take protein powder, brain fog is extensive.
Sauna -> tinnitus is getting much louder

a few years ago i tried 50mg p5p -> Took it a month, it made me much more anxious and raised my inner tension.

500mg choline bitarate -> massive brain fog, stopped it after one time use.

Mario, which tools do you use, would you provide the source code? Could you take a analysis on phosphatidylserine?

Keep up the good work!!!!!

I will give more interesting experiences the next days.Ahhh you are using Weka? I have experience with weka, can I help? Would give me some hope to do such stuff
:):oops:
 
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L

Lou

Senior Member
Messages
582
Location
southeast US
mariovitali said:
@op2pig

MVPH15P? LOL

Yes, i would be very interested to know too. I already posted about this regimen to "All things male" is this the forum you are referring to?

@skwag
I have SNPs at :

-Choline absorption and Inositol - several heterozygous mutations
-BH4 Production
-Biotin Absorption
-FAD Production (FMN supplementation fixes this) - several heterozygous mutations
-MTHFR Gene (homozygous)
-several homozygous mutations at NOS1 (neuronal NOS). NOS2 and NOS3 look better. FYI NOS1 has as cofactors Tetrahydrobiopterin, FAD, FMN and Iron. Many of my problems originated from these homozygous mutations i believe.



I am trying to supplement according to my SNPs and so far i do not regret it.


My current regimen is as follows :


08:00 Metafolin 2000 mcg, Iron, FMN, Dibencozide, Biotin
10:00 Choline/Alpha GPC 350 mg, Inositol 1 gram
12:00 TUDCA 250 mg, P5P 50 mg, Selenium (100 mcg)
16:00 Vitamin C 500 mg
20:00 Choline/Alpha GPC 350 mg, Inositol 1 gram, Selenium 100 mcg
23:00 TUDCA 250 mg

I also eat Navy beans daily for Molybdenum until a supplement arrives.

I am in the process of stopping TUDCA. I tried stopping Choline/Inositol and something wasn't right...so now i re-introduced Choline and Inositol and i am trying slowly to stop TUDCA by going from 500 mg to 250 mg daily for a week. After a week i will completely stop TUDCA and report back.
Click to expand...



@mariovitali How do you address biotin absorption problem? Thanks.
 
mariovitali

mariovitali

Senior Member
Messages
1,214
Naibaf said:
Awesome work until now @mariovitali and co

Since its my first post here let me introduce myself in a short manner:

Im a 28 year old electrical engineer / data scientist. Im ill since 8 years now my main symptoms are:

Depression / severve anxiety and inner tension
Deliberating fatigue
Tinnitus (its also an indicator for me since it changes over time and supps)
Massive brain fog
Histamine problems
IBS
Gluten and casein sensitivity
Early morning insomnia
Insomnia in general
Kryptopyrolurie (KPU)
Mitochondria dysfunction
Impaired speech

I was 3 time in a psychatric clinic, had 19 ECT right unilateral, have tried dozens of antidepressant and supplements.
Im typing from my smarthphone right now, will give an in depth post the next days.

Most helpful are 30mg methylphenidat a day Its a life saver!
And a really small amount of duloxetin.
50mg Pregabalin before bed: wow fatiguethe next day is much better.
Phosphatidylserine -> helped with inner tension but subtile the longrun

Some interesting stuff:
If I take protein powder, brain fog is extensive.
Sauna -> tinnitus is getting much louder

a few years ago i tried 50mg p5p -> Took it a month, it made me much more anxious and raised my inner tension.

500mg choline bitarate -> massive brain fog, stopped it after one time use.

Mario, which tools do you use, would you provide the source code? Could you take a analysis on phosphatidylserine?

Keep up the good work!!!!!

I will give more interesting experiences the next days.Ahhh you are using Weka? I have experience with weka, can I help? Would give me some hope to do such stuff
:):oops:
Click to expand...


@Naibaf

First of all : I believe that you must take the DNA Test. IMHO This is the only way to understand what is going on and what actions you should take.

Regarding the software : I use KNIME, Python but i also use GATE for analyzing PubMed entries. I havev't decided whether i will share the code at this point to be honest. The Weka output is from KNIME which incorporates WEKA Nodes. It's great that we have a second Data Scientist around so i'll think something!

I will add Phosphatidylserine and post the results.




Thank you and Good Luck :)
 
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A

aquariusgirl

Senior Member
Messages
1,734
Have you considered copper deficiency?

I read that copper deficiency could be a factor in misfolding proteins. (sorry no source!) I have made big improvements by supplementing proper copper, or mitosynergy's products. Acumen tests showed deficiencies with zinc/copper related SODASe years ago.
 
S

swan

Messages
10
Location
Canada
@mariovitali It seems you are going to have an influx of new comers, I will be +1:thumbsup:

Been following your thread with great interest for awhile. Feel compelled to share my thoughts and interact now that I have a grasp on the subject.

I am not on the protocol yet because my symptoms are mild comparatively to the people commenting, and I do not have a sense of urgency because I can live daily life with a few annoyances. Put me in the Accutane boat, but also pre existing symptoms before that.

No posting links yet, but it is my belief that TUDCA is the foundation of the protocol if ER stress is the main culprit in all this. Maybe you will be able to drop it because your body has cleaned up the mess so to speak, or maybe you will always need it because it allows your bucket to not get over filled.

But to anyone curious about the protocol, and wanting to know if TUDCA is necessary, if the culprit is ER stress then absolutely yes:cool: Its ability as a chemical chaperone to deal with misfolded proteins and prevent their aggregation makes it seem like a rockstar. That and sodium phenylbutyrate (4-pba), which is a prescription.
 
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