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Unfolded Protein Response and A Possible Treatment for CFS

skwag

Senior Member
Messages
222
Other forum posters on an accutane forum I frequent have shared this thread and some are trying the protocol as well.

Because, as a new member, op2pig was unable to post links, he kindly sent me this link to post from acne.org where at least one other person is trialing the ER stress protocol.
 
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Messages
10
Location
Canada
WRT accutane and er stress, it is important to note the altered folate and methionine metabolism coupled with the up regulation of gnmt.

These are possibly things aggravating the ER and leading to the upr in accutane users. @name pointed this out previously and lead me on quite the investigation

This protocol will help handle the upr but I am curious in incorporating other supplements to attenuate ER stress, which are specific to tane users but should also benefit anyone.

Glycine is a 'supplement' I would like to incorporate more of and I would say the majority of people do not get enough of. Especially true in an upregulated gnmt state.

Glycine is considered an osmolyte, indirectly assisting in the folding of proteins. It seems 8g is a good daily goal.

And no I am not the guy promoting glycine on the acne site, I'm actually not a user.
 
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Ema

Senior Member
Messages
4,729
Location
Midwest USA
Glycine is a 'supplement' I would like to incorporate more of and I would say the majority of people do not get enough of. Especially true in an upregulated gnmt state.
I may be an anomaly but on neurotransmitter testing, which admittedly has its own set of issues, I've always come out high in GABA and glycine.

Taking any of these in supplement form has always worked out very poorly for me. I think it is because of the dysregulated glutamate system common in MECFS. If glutamate is abnormally high, it makes sense that GABA and glycine would also be high trying to mitigate some of that excitotoxicity.
 
Messages
10
Location
Canada
I may be an anomaly but on neurotransmitter testing, which admittedly has its own set of issues, I've always come out high in GABA and glycine.

Taking any of these in supplement form has always worked out very poorly for me. I think it is because of the dysregulated glutamate system common in MECFS. If glutamate is abnormally high, it makes sense that GABA and glycine would also be high trying to mitigate some of that excitotoxicity.

Browsing this forum has definitely showed me what works for one person definitely does not work for another. I put supplement in quotations cause I am trying to incorporate more glycine through food choices opposed to an individual amino acid powder, but will be ordering some powder to add to whey to alter the amino profile.
Do you do better with glycine rich whole foods?
 

DeGenesis

Senior Member
Messages
172
The worst reaction I've ever had to a supplement was to glycine. I can't explain it, and because of chronic eyestrain I have little ability to research why. I don't mean to derail this thread.
 
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Violeta

Senior Member
Messages
2,949
@mariovitali, I've seen NAFLD show up on quite a few of your runs. And choline and TUDCA are supps specifically for fatty liver. Have you ever done a run specifically on NAFLD? Doesn't that seem strange that fatty liver would have an effect on ER's all over the body? I wonder how that works?

And for those of us with autoimmune or virus involvement, I found this with respect to fatty liver.

" Blood tests (serology) are usually used to rule out viral hepatitis (hepatitis A, B, C and herpesviruses like EBV or CMV), rubella, and autoimmune related diseases."
 

mariovitali

Senior Member
Messages
1,214
@Violeta


Screen Shot 2015-10-03 at 14.31.33.png
 

mariovitali

Senior Member
Messages
1,214
@Naibaf

Here are the results from matching "Phosphatidylserine" to PubMed Concepts :

*********Topic : phosphatidylserine ***************
phosphatidylserine.csv : 73.28 %
phosphatidylcholine.csv : 5.02 %
phospholipid_human.csv : 4.22 %
caspase_human.csv : 2.00 %
glycerylphosphorylcholine.csv : 1.17 %
choline_deficiency.csv : 0.70 %
omega3.csv : 0.67 %
pdi.csv : 0.58 %
ros.csv : 0.51 %
inositol.csv : 0.47 %
cofactor.csv : 0.45 %
mitochondrial_dysfunction.csv : 0.42 %
nac.csv : 0.40 %
dolichol.csv : 0.39 %
oxidative_stress_protection.csv : 0.37 %
reduced_glutathione.csv : 0.30 %
hmgb1.csv : 0.28 %
resveratrol.csv : 0.28 %
microglia.csv : 0.28 %
human_semen.csv : 0.27 %
curcumin.csv : 0.27 %
oxidative_stress_markers.csv : 0.25 %
gpr78.csv : 0.24 %
peroxynitrite.csv : 0.23 %
redox_homeostasis.csv : 0.22 %
mast_cell_activation.csv : 0.21 %
er_stress.csv : 0.21 %
tocotrienol.csv : 0.20 %
udpglcnac.csv : 0.19 %
peroxiredoxin.csv : 0.19 %
excitotoxicity.csv : 0.19 %
hsc.csv : 0.16 %
sirt1.csv : 0.16 %
calcium_homeostasis.csv : 0.16 %
h2o2.csv : 0.15 %
l_carnitine.csv : 0.15 %
nadph.csv : 0.15 %
ptp1b.csv : 0.15 %
pbmc.csv : 0.15 %
p53.csv : 0.14 %
advanced_glycation_end.csv : 0.14 %
5alphareductase.csv : 0.14 %
nrf2.csv : 0.14 %
taurine.csv : 0.14 %
protease_inhibitor.csv : 0.14 %
n-acetylglucosamine.csv : 0.13 %
creatine_supplementation.csv : 0.12 %
hepatocytes.csv : 0.12 %
oxalates.csv : 0.11 %
ire1.csv : 0.11 %
coenzymeq10.csv : 0.11 %
histone_deacetylase.csv : 0.10 %
nad.csv : 0.10 %
nadh_dehydrogenase.csv : 0.10 %
rar.csv : 0.10 %
vcam-1.csv : 0.10 %
inflammatory_response.csv : 0.10 %
butyrate.csv : 0.10 %
il_10.csv : 0.10 %
hsp70.csv : 0.10 %
redox_potential.csv : 0.09 %
3betahsd.csv : 0.09 %
vitamin_k2.csv : 0.09 %
nlinkedglycosylation.csv : 0.09 %
iron_deficiency.csv : 0.09 %
catalase.csv : 0.09 %
beta-alanine.csv : 0.09 %
udpgluc.csv : 0.09 %
amyloid.csv : 0.09 %
hexosamine.csv : 0.09 %
chaperones.csv : 0.09 %
redox_regulation.csv : 0.09 %
p450scc.csv : 0.09 %
ppp.csv : 0.09 %
biotin.csv : 0.09 %
atf4.csv : 0.08 %
p5p.csv : 0.08 %
hmgcoa.csv : 0.08 %
cyp3a4.csv : 0.08 %
inducible_nos.csv : 0.08 %
glycosylation.csv : 0.07 %
glycoproteins.csv : 0.07 %
heat_shock_protein.csv : 0.07 %
lipoic_acid.csv : 0.07 %
scfa.csv : 0.07 %
glutamate.csv : 0.07 %
xanthine_oxidase.csv : 0.07 %
disulfide_bonds.csv : 0.07 %
xbp1.csv : 0.07 %
l_tryptophan.csv : 0.07 %
urea_cycle.csv : 0.07 %
ngf.csv : 0.07 %
immune_response.csv : 0.06 %
hepatotoxicity.csv : 0.06 %
star.csv : 0.06 %
insp3.csv : 0.06 %
sod2.csv : 0.06 %
steatohepatitis.csv : 0.06 %
pregnenolone.csv : 0.06 %
upr.csv : 0.06 %
p450oxidoreductase.csv : 0.06 %
redox_cofactor.csv : 0.06 %
ginkgo.csv : 0.06 %
ampa.csv : 0.06 %
chop.csv : 0.06 %
cyp1b1.csv : 0.05 %
thioredoxin.csv : 0.05 %
cox-2.csv : 0.05 %
neuronal_nos.csv : 0.05 %
hydroxysteroid_dehydrogenase.csv : 0.05 %
mastocytosis.csv : 0.05 %
cholestasis.csv : 0.05 %
magnesium_deficiency.csv : 0.05 %
adrenergic_receptor.csv : 0.05 %
l-arginine.csv : 0.05 %
hydrogen_sulfide.csv : 0.05 %
neurite_outgrowth.csv : 0.05 %
endothelial_nos.csv : 0.04 %
tau.csv : 0.04 %
molybdenum.csv : 0.04 %
rituximab.csv : 0.04 %
mcp-1.csv : 0.04 %
misfolded_proteins.csv : 0.04 %
intestinal_motility.csv : 0.04 %
selenium.csv : 0.04 %
nmda.csv : 0.04 %
l-dopa.csv : 0.04 %
serotonin_levels.csv : 0.04 %
vitamin_d3.csv : 0.03 %
perk.csv : 0.03 %
acetylcholine.csv : 0.03 %
monoamine_oxidase.csv : 0.03 %
ckd.csv : 0.03 %
stat1.csv : 0.03 %
acetyl-coa.csv : 0.03 %
fmn.csv : 0.03 %
rxr.csv : 0.03 %
monosodium_glutamate.csv : 0.03 %
isotretinoin.csv : 0.03 %
kainate.csv : 0.03 %
selenium_deficiency.csv : 0.03 %
cyp1a1.csv : 0.03 %
acetyl_coa_carboxylase.csv : 0.03 %
ebv.csv : 0.02 %
steroidogenesis_human.csv : 0.02 %
dopamine.csv : 0.02 %
trpv.csv : 0.02 %
sod1.csv : 0.02 %
cyp2e1.csv : 0.02 %
zinc_supplementation.csv : 0.02 %
cyp1a2.csv : 0.02 %
gaba_human.csv : 0.02 %
riboflavin.csv : 0.02 %
adhd.csv : 0.02 %
cortisol.csv : 0.02 %
cyp2d6.csv : 0.02 %
autism.csv : 0.02 %
angiotensin_human.csv : 0.02 %
peristalsis.csv : 0.02 %
probiotics.csv : 0.02 %
freet3.csv : 0.02 %
insulin_resistance.csv : 0.01 %
norepinephrine.csv : 0.01 %
nafld.csv : 0.01 %
testosterone_production.csv : 0.01 %
amyloidosis.csv : 0.01 %
sshl.csv : 0.01 %
cortisol_levels.csv : 0.01 %
triiodothyronine_levels.csv : 0.01 %
human_proteinuria.csv : 0.01 %
dysautonomia.csv : 0.01 %
cimetidine.csv : 0.01 %
crohns_disease.csv : 0.01 %
sinusitis.csv : 0.00 %
atrial_fibrillation.csv : 0.00 %
social_anxiety.csv : 0.00 %
tudca.csv : 0.00 %
insomnia.csv : 0.00 %
5-htp.csv : 0.00 %
adrenal_hyperplasia.csv : 0.00 %
limbic_system.csv : 0.00 %
fad.csv : 0.00 %
5mthf.csv : 0.00 %
panic_disorder.csv : 0.00 %
dpagt1.csv : 0.00 %
pgc1.csv : 0.00 %
dht.csv : 0.00 %
phenylketonuria.csv : 0.00 %
irritable_bowel.csv : 0.00 %
l_tyrosine.csv : 0.00 %
gtp_cyclohydrolase.csv : 0.00 %
propionyl_coa_carboxylase.csv : 0.00 %
orthostatic_intolerance.csv : 0.00 %
constipation.csv : 0.00 %
cerebrovascular_amyloidosis.csv : 0.00 %
ero1.csv : 0.00 %
systemic_amyloidosis.csv : 0.00 %
microbiome_humans.csv : 0.00 %
adrenal_insufficiency.csv : 0.00 %
finasteride.csv : 0.00 %
glutaredoxin.csv : 0.00 %
cfs.csv : 0.00 %
atf6.csv : 0.00 %
gluten.csv : 0.00 %
benfotiamine.csv : 0.00 %
anhedonia.csv : 0.00 %
fmo3.csv : 0.00 %
sulfite_oxidase.csv : 0.00 %
sod3.csv : 0.00 %
baroreceptor.csv : 0.00 %
o-glcnacylation.csv : 0.00 %
fads2.csv : 0.00 %
pqq.csv : 0.00 %
car.csv : 0.00 %
uric_acid.csv : 0.00 %
mucuna.csv : 0.00 %
vitamin_b6.csv : 0.00 %
fads1.csv : 0.00 %
caloric_restriction.csv : 0.00 %
allopregnanolone.csv : 0.00 %
tetrahydrobiopterin.csv : 0.00 %
mthfr.csv : 0.00 %
pyruvate_carboxylase.csv : 0.00 %
erad.csv : 0.00 %
bradycardia.csv : 0.00 %
3methylcrotonyl_coa_carboxylase.csv : 0.00 %
dihydroprogesterone.csv : 0.00 %
osmolytes.csv : 0.00 %
floaters.csv : 0.00 %
asymmetric_dimethylarginine.csv : 0.00 %
d-limonene.csv : 0.00 %
resistant_starch.csv : 0.00 %
tinnitus.csv : 0.00 %
sirt2.csv : 0.00 %
hpa_axis.csv : 0.00 %
hgh.csv : 0.00 %
tmao.csv : 0.00 %
subclinicalhypo.csv : 0.00 %
o-glcnac.csv : 0.00 %
sirt3.csv : 0.00 %
hypobaric_hypoxia.csv : 0.00 %
srd5a3.csv : 0.00 %
pxr.csv : 0.00 %

FYI : pdi=protein disulfide isomerase


For the rest, it takes 7 hours to run so i can add the results for performing association analysis, so stay tuned ;-)
 

Violeta

Senior Member
Messages
2,949
I was going to go straight to the ROS in the above list, but instead went to mitochondrial malfunction because I had no idea what the connection of phosphatidylserine to mitochondrial function might be. Lots of articles, but this one is very good.

Making heads or tails of phospholipids in mitochondria

http://jcb.rupress.org/content/192/1/7.full

A clip from the article:

The biosynthesis of PE and CL occurs, at least in part, within mitochondria and relies on an intricate exchange of precursor forms between the membrane of the ER and the mitochondrial outer membrane at distinct contact sites, whose structural basis we are just beginning to understand. We will highlight recent advances and unresolved questions regarding this interorganellar communication and the intramitochondrial trafficking of phospholipids.




 

ScottTriGuy

Stop the harm. Start the research and treatment.
Messages
1,402
Location
Toronto, Canada
I guess the last line is most pertinent in terms of treatment....

"this study indicates that antioxidants might be effective for inhibiting N-nitroso compound-induced EBV reactivation and therefore could be promising preventive and therapeutic agents for EBV reactivation-associated malignancies"
 

skwag

Senior Member
Messages
222
Trial Update Day 40

In the following, changes from my last update will be in bold.

I'm currently taking,

2x250 mg TUDCA : cut down from 3x250 mg
3x1400 mg NAG
3x10 mg R5P
100 mcg selenium
2x250 mg citicoline
750 mg inositol

along with methylation supplements. I have also been on the autoimmune paleo diet for 24 days.

Improvements:

1) 50% 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) 50% improvement in folloculitis on arms and legs ( onset one year ago ) : up from 33%
6) 80% improvement in noise intolerance/ headaches. up from 70%
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 )
10) 33% improvement in nasal congestion : up from no improvement

No change:

1) eye floaters ( onset one year ago )
2) skin texture/ wrinkling ( onset one year ago )

Things which are worse:

1) POTS: Poor man's tilt table test results: 40-50 bpm :This is up from the 35-40 bpm average that I posted last time.

The worsening of the POTS result is strange, because I actually feel better. Although my heart is racing, I don't necessarily feel it, and I'm not getting the headache symptoms I had associated wth lack of blood to the brain. Well, at least for short periods of time on my feet. Say 15 min or so. Longer periods are still problematic.

I've also started trialing citicoline, which replaced choline bitartrate. I didn't notice much the first couple days, but starting on day 4 I started feeling a slight sense of euphoria. It has now been 7 days, and I still feel it. It reminds me of the feeling I had when I first started methylfolate years ago. Choline and folate metabolism are clearly interrelated, so I've been wondering if this slight euphoric feeling can be pinned down to a particular process or pathway.

I still feel short on energy, but I am much more comfortable. It's nice to shed some of the nagging pains and tension.
 
Messages
7
@mariovitali
Do you know when your depression vanished? Happened that with only a few supps?

Thanks a lot for for Phosphatidylserine - I think it is related to choline.
Im living in Germany, but will check the 23andme DNA test.
 

mariovitali

Senior Member
Messages
1,214
@skwag

Thanks as always for the update. POTS may be due to adrenergic receptor (so Citicoline should deal with that) and/or impaired NOS (?)

Anyway, i strongly believe that you should try taking FMN and see how you feel. Again, without DNA data this is just guesswork but FMN and FAD is a key cofactor for many things including proper NOS function... Taurine might also help you even more but may upregulate GABA (which could be a good thing or may lead to anhedonia). If we knew your SNPs then we could be more specific on what is needed what not and what shouldn't been done.

Hopefully you will see as time passes by that Symptoms become less and less evident...it *will* take time but this is the road to recovery :)


@Naibaf

Depression vanished when i stopped "crashing" (=experiencing tinnitus). For the symptoms that you listed i would stay away from MSG sources and also would try FMN. But -you guessed it right- 23andme data give us a much better picture of what is going on and what should be used.
 

brenda

Senior Member
Messages
2,270
Location
UK
I am getting on well with inositol and am up to 100 mg along with 200 selenium and FMN very small amount and will have my citicoline in a few days.

So far l am having better urine flow and some of the puffiness on my knuckles has decreased. However my thyroid feels more swollen but l don't know the cause yet.
 

skwag

Senior Member
Messages
222
Thanks as always for the update. POTS may be due to adrenergic receptor (so Citicoline should deal with that) and/or impaired NOS (?)

That was my thinking too. It may be an increase in aceytcholine that has made it worse, or maybe it's just a random fluctuation.

Anyway, i strongly believe that you should try taking FMN and see how you feel. Again, without DNA data this is just guesswork but FMN and FAD is a key cofactor for many things including proper NOS function.

I know there is some confusion around, but I believe there is no difference between R5P ( riboflavin 5-phosphate ) and FMN. I've been taking 30 mg R5P ( Douglas brand ) daily. I am awaiting an order of the Source Naturals Coenzymated B2, which I believe is the recommended brand.

If we knew your SNPs then we could be more specific on what is needed what not and what shouldn't been done.
I have had 23andme testing done. If you direct me to the latest list of relevant snps, I'll post my results.

Cheers
 
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