Unfolded Protein Response and A Possible Treatment for CFS

[leela]

@leela

You said you have mild PKU, do you know which SNPs you have?

I am assuming that you are taking Methylation supplements (Metafolin, B12, P5P, etc) perhaps it would help you to start supplementing with TUDCA, not eating too much protein (which i believe you must be doing already)

You could also try supplementing with Choline, up to 700 mg per day to see how you feel but without taking any CB/Miyarisan to boost butyrate.

Thank you for all your suggestions. ME brain moment: I have KPU not PKU
I am actually not doing mehtylation treatment at all right now, but getting ready to.
Why can one not take choline and CB at the same time? My memory span is gnat-like at the moment, sorry.

 

[Gondwanaland]

IMHO you should try supplementing with Choline but without taking Clostridium Butyricum since it lowers TMAO.

If you are afraid for the consequences of TMAO (being atherogenic) you could try for a week taking 700 mg of Choline and seeing how you both feel.

I am confused about this TMAO info. I thought that lowering atherogenic risks were a good thing. my fibrinogen is very high at the moment.

 

[Ema]

OK, here are mine...what say you?

ER Stress response


rs13045 (EIF2AK3-PERK) : Risk C, CT
rs2239815(XBP1) : Risk C, TT
rs10918270(ATF6) : Risk A, AG
rs391957 (HSPA5 aka BIP aka GPR78) : Risk C, CC


GCH1, associated with lower levels of BH4 (low BH4 => ER Stress)

rs10483639 : ( Risk C), GG
rs3783641 : (Risk A), TT
rs8007267 : (Risk T), CC
rs12147422 : (Risk C), TT
rs3783637 : (Risk T), CC
rs3783641 : (Risk A), TT
rs41298442 : (Risk T), TT
rs4411417 : (Risk C), TT
rs752688 : (Risk T), CC
rs841 : (Risk A), GG
rs998259 : (Risk T), CC
rs7147286 : (Risk A), GG




Choline Metabolism (impaired Choline absorption => impaired TMAO => ER Stress+UPR)

rs3733890 (Risk A), GG
rs2461823 (Risk C) NAFLD Disease, CT
Rs7643645 Risk G NAFLD Disease, AA
rs7946 (Risk T) (PEMT), CT
rs4244593 (Risk G) (associated with PEMT), GT
rs2236225 (Risk A) (MTHFD1), GG
rs9001 (Risk G) (CHDH), TT

 

[mariovitali]

I am confused about this TMAO info. I thought that lowering atherogenic risks were a good thing. my fibrinogen is very high at the moment.

TMAO is a chaperone (along with TUDCA and 4-PBA) which aids in proper Protein Folding :

Reducing er stress in the treatment of obesity and diabetes

Endoplasmic reticulum stress has been found to be associated with obesity. Therefore, agents that reduce or prevent ER stress may be used to treat diseases associated with obesity including peripheral insulin resistance, hypergylcemia, and type 2 diabetes. Two compounds which have been shown to reduce ER stress and to reduce blood glucose levels include 4-phenyl butyric acid (PBA), tauroursodeoxycholic acid (TUDCA), and trimethylamine N-oxide (TMAO). Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide and glycerol. The present invention provides methods of treating a subject suffering from obesity, hyperglycemia, type 2 diabetes, or insulin resistance using ER stress reducers such as PBA, TUDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in ER stressed cells are also provided

and -unfortunately- it is also a proatherogenic. The thing is, that if you are deficient in Choline or your metabolism of Choline is impaired then most likely you are very low on TMAO. So raising TMAO towards normal levels shouldn't be a problem. OTOH if you don't have any problem with Choline metabolism and you supplement with Choline or Carnitine *and* you eat meat and eggs, well, that's an another story : Your TMAO levels will skyrocket..

 

[mariovitali]

OK, here are mine...what say you?

@Ema,

You have several SNPs in ER Stress handling and especially a homozygous SNP at GPR78 which is one of the major chaperones for ER Stress handling. You **definitely** need TUDCA and also you should avoid too much protein.

You also have -luckily- one SNP to GCH1 which means that a BH4 deficiency is probable but there are good chances that you don't have a problem.

Notice how many SNPs you have on Choline metabolism. I think you will definitely feel better if you supplement with Choline, 700 mg per day

@Ema please try the regimen, with TUDCA at 750 mg per day, Choline at 700 mg per day and any methylation supplements you are taking for MTHFR, CBS, etc.

You could also try cutting down on Animal Protein, say one medium portion every 7-8 days. If you are on CB i would advise you to stop taking it and to use N-Acetylglucosamine instead.

 

[Gondwanaland]

@mariovitali I must eat animal protein otherwise I get anemic pretty easily. What about eating meat and eggs and low dose supplementation like I am doing now? My intention is to raise supplementation slowly up to about 100mg? I do rounds of 2 eggs at breakfast for a week then back to only one. Trying to see what benefits me more.

 

[Ema]

@Ema please try the regimen, with TUDCA at 750 mg per day, Choline at 700 mg per day and any methylation supplements you are taking for MTHFR, CBS, etc.

I bought the TUDCA. I've not started it because I take cholestyramine for a mold issue and apparently they interact. Plus it seems to be a CYP 3A4 inducer and that scares the crap out of me due to adrenal insufficiency. I can't take antibiotics like Rifampin at all because of the speedy steroid metabolism. It's unclear to me exactly how much inducing the TUDCA does, but I'm worried enough to have delayed trying it for months. I wish there was another option that seemed a bit safer for me.

I used to take BodyBio PPC oil but they changed the formula and I hate the taste now. I wonder if the Citicoline I have would work as well instead?

You could also try cutting down on Animal Protein, say one medium portion every 7-8 days. If you are on CB i would advise you to stop taking it and to use N-Acetylglucosamine instead.

What is CB again? I will probably kick myself when you tell me...

 

[mariovitali]

FYI @Avengers26, @Violeta

I will try to explain what the software does. So on the one hand we have a total of 172 topics from PubMed abstracts on my disk. These topics are csv files on my disk with the following names :

er_stress
3betahsd
5-htp
5alphareductase
5mthf
accutane
acetyl-coa
acetylcholine
adhd
adrenal_hyperplasia
adrenal_insufficiency
advanced_glycation_end
allopregnanolone
amyloid
amyloidosis
anhedonia
asymmetric_dimethylarginine
atrial_fibrillation
autism
benfotiamine
beta-alanine
butyrate
calcium_homeostasis
car
caspase_human
cerebrovascular_amyloidosis
cfs
cholestasis
choline_deficiency
cimetidine
ckd
coenzymeq10
cortisol_levels
creatine_supplementation
curcumin
cyp1a1
cyp1a2
cyp1b1
cyp2d6
cyp2e1
cyp3a4
d-limonene
dht
dihydroprogesterone
dolichol
dopamine
dopamine_levels
dpagt1
dysautonomia
endothelial_nos
excitotoxicity
finasteride
floaters
fmo3
freet3
gaba_human
ginkgo
glutamate
gluten
glycerylphosphorylcholine
glycoproteins
glycosylation
grp78
gtp_cyclohydrolase
heat_shock_protein
hepatotoxicity
hexosamine
hgh
histone_deacetylase
hmgcoa
hpa_axis
hsp70
human_proteinuria
human_semen
hydroxysteroid_dehydrogenase
il_10
inducible_nos
inflammatory_response
insomnia
insulin_resistance
ire1
iron_deficiency
irritable_bowel
l_carnitine
l_tryptophan
l_tyrosine
l-arginine
l-dopa
limbic_system
lipoic_acid
magnesium_deficiency
mast_cell_activation
mastocytosis
mcp-1
microbiome_humans
misfolded_proteins
mitochondrial_dysfunction
monosodium_glutamate
mthfr
mucuna
n-acetylglucosamine
nadh_human
nadph_human
nafld
neurite_outgrowth
neuronal_nos
ngf
nlinkedglycosylation
o-glcnac
omega3
orthostatic_intolerance
osmolytes
oxalates
oxidative_stress_markers
oxidative_stress_protection
p450oxidoreductase
p450scc
p5p
panic_disorder
pbmc
perk
peroxynitrite
pgc1
phenylketonuria
phosphatidylcholine
phospholipid_human
pqq
pregnenolone
probiotics
protease_inhibitor
pxr
rar
resistant_starch
resveratrol
rituximab
ros
rxr
scfa
selenium
selenium_deficiency
serotonin_levels
sinusitis
sirt1
social_anxiety
srd5a3
sshl
star
steatohepatitis
steroidogenesis_human
subclinicalhypo
systemic_amyloidosis
tau
taurine
testosterone_production
tetrahydrobiopterin
tinnitus
tmao
tocotrienol
triiodothyronine_levels
trpv
tudca
udpglcnac
udpgluc
upr
urea_cycle
uric_acid
vcam-1
vitamin_b6
vitamin_d3
vitamin_k2
xbp1
zinc_supplementation

on the other hand i have several topics which each and every one of them are matched to each of the files above. These are :

research_subj=[" perk ","xbp1","ire1","il-10","protease inhibitor","interferon","mcp-1","vcam-1","cimetidine","cholestasis","anhedonia","interleukin","glycerylphosphorylcholine","selenocysteine"," l-arginine ","vitamin k2"," tyrosine kinase ","beta-alanine","trpv","histone deacetylase"," nitroglycerin ","limbic","insomnia","dysautonomia","dexamethasone","reactive oxygen species","rituximab"," tau ","udp-glcnac"," b6 "," dopamine "," gaba ","mucuna"," enos "," inos "," nnos ","fmo3","5-htp"," oxalate ","human growth hormone"," iron ","autism","adhd","osmolyte","manganese","calcium","magnesium","phosphatidylcholine","asymmetric dimethylarginine"," trimethylamine ","trimethylamine-n-oxide","phospholipid","mitochondrial dysfunction","visceral fat","nafld","acetyl-coa","choline acetyltransferase","acetylcholine","advanced glycation end","benfotiamine"," hpa axis ","glycoprotein","mpdu1","dpagt1","hyperlipidemia","o-glcnac","n-acetylglucosamine","hexosamine"," glucosamine ","srd5a3","selenoprotein","probiotic","finasteride","accutane"," bile ","cyp1b1","cyp2d6","floaters","social anxiety","d-limonene","cholecalciferol","pyrroloquinoline","mk-4","grapefruit","nigella","omega","curcumin","lipoic","alcar","carnitine","ashwagandha","resveratrol","omega","zinc","magnesium","manganese","butyric","butyrate","l-tyrosine","5-mthf","gpx1","gpx2","gpx3"," nos1 "," nos2 "," nos3 ","tyrosine hydroxylase","tinnitus","cardiovascular"," choline ","homocysteine","uric acid"," semen ","hypothyroid","mastocytosis","mast cell","mastocytosis","histamine","triiodothyronine","dopamine","nrf-2","serotonin","adrenaline","noradrenaline","epinephrine","monoamine oxidase","estrogen","nerve growth factor","cyp2d6","proteinuria"," ammonia " ,"nitric oxide","phenylalanine","sinusitis","nrf1","nrf2","arrhythmia","pgc-1"," creb ","modafinil","methylphenidate","piracetam"," tyrosine ","sirt3","melatonin"," tryptophan ","ritalin"," mtor ","chronic kidney","glutathione","cancer","nitric oxide","n-linked","acetylcholinesterase","piracetam","scfa","anxiety disorder","cortisol"," amyloid precursor protein ","gsk-3","beta-amyloid"," ttr ","neurodegenerati"," gut ","steatohepatitis","microbiome","acetylated histone","ischemic reperfusion","acetylated histone","mnsod","cuznsod","sod1","sod2","sod3","sod4","hypocortisolism","hypercortisolism"," mrna ","butyrate","calcitonin","tauopath","insulin resistance","sinusitis","personality","hydroxysteroid dehydrogenase","alzheimer","parkinson","hsf-1","cortisol","catecholamine","intestina","insulin","hypoxia","ankyrin","80-kda","ribonuclease","pbmc","37-kda","restless","ugt1a1","immune","caspase","dermatitis","gpr78","glutathione","glucose","apoptosis","diabetes","mitochondri","inflammat","gch1","hepatic","constipat","ca2","liver","lymph","cyp1","cyp2","cyp3","p450","dysautonomia","glutam","cd20","dolichol","interstitial","magnesium","lymph","irritable bowel","chaperone","orthostatic","hyperviscosity","neurologic","depression","autonomic","hsp90","er stress","calcium homeostasis","caspase","aplp1","gelsolin","amyloidosis","p53","retinoic","calcium","dihydroprogesterone","allopregnanolone","androstane","pregnane","dehydrotestosterone","gluten","celiac","neuphropathy","prostate","platelet aggregation","hmg-coa","vitamin d3","ascorbic acid","nitric oxide","cytochrome","oxidative stress","testosterone","mthfr","methylation","peroxynitrite","thyroid","misfolded proteins","unfolded protein response","endoplasmic reticulum","selenium","magnesium","taurine","tudca","resveratrol","hsp70","dht","glycosylation","tetrahydrobiopterin","pregnenolone","progesterone","steroidogenesis","phenylketonuria","estradiol","shbg","free testosterone","hypogonadism","adrenal insufficiency","adrenal hyperplasia","igf1","sirt1"]

So the program starts by taking the first research_subject (="perk") and searches this keyword to each of the files (csv) shown. As an example the first keyword PERK has the following results :

*********Topic : perk ***************
perk.csv : 45.20 %
ire1.csv : 18.09 %
upr.csv : 5.82 %
xbp1.csv : 5.73 %
er_stress.csv : 4.22 %
grp78.csv : 3.54 %
tudca.csv : 1.89 %
misfolded_proteins.csv : 1.12 %
dolichol.csv : 0.17 %
heat_shock_protein.csv : 0.16 %
caspase_human.csv : 0.15 %
star.csv : 0.12 %
nlinkedglycosylation.csv : 0.12 %
oxidative_stress_markers.csv : 0.11 %
neuronal_nos.csv : 0.10 %
o-glcnac.csv : 0.10 %
tocotrienol.csv : 0.10 %
trpv.csv : 0.09 %
p450scc.csv : 0.09 %
hsp70.csv : 0.08 %
ros.csv : 0.07 %
calcium_homeostasis.csv : 0.07 %
urea_cycle.csv : 0.07 %
nafld.csv : 0.05 %
oxidative_stress_protection.csv : 0.05 %
histone_deacetylase.csv : 0.05 %
steroidogenesis_human.csv : 0.05 %
asymmetric_dimethylarginine.csv : 0.04 %
curcumin.csv : 0.04 %
anhedonia.csv : 0.04 %
resveratrol.csv : 0.04 %
subclinicalhypo.csv : 0.04 %
choline_deficiency.csv : 0.04 %
mitochondrial_dysfunction.csv : 0.04 %
dopamine_levels.csv : 0.03 %
dht.csv : 0.03 %
neurite_outgrowth.csv : 0.03 %
advanced_glycation_end.csv : 0.03 %
tau.csv : 0.03 %
butyrate.csv : 0.03 %
ngf.csv : 0.03 %
vcam-1.csv : 0.03 %
glycosylation.csv : 0.03 %
sirt1.csv : 0.03 %
amyloid.csv : 0.03 %
protease_inhibitor.csv : 0.03 %
serotonin_levels.csv : 0.03 %
taurine.csv : 0.02 %
mcp-1.csv : 0.02 %
lipoic_acid.csv : 0.02 %
3betahsd.csv : 0.02 %
l-arginine.csv : 0.02 %
endothelial_nos.csv : 0.02 %
steatohepatitis.csv : 0.02 %
inducible_nos.csv : 0.02 %
inflammatory_response.csv : 0.02 %
excitotoxicity.csv : 0.02 %
limbic_system.csv : 0.02 %
glutamate.csv : 0.02 %
acetyl-coa.csv : 0.02 %
dopamine.csv : 0.02 %
hepatotoxicity.csv : 0.01 %
peroxynitrite.csv : 0.01 %
hpa_axis.csv : 0.01 %
monosodium_glutamate.csv : 0.01 %
pbmc.csv : 0.01 %
hmgcoa.csv : 0.01 %
ckd.csv : 0.01 %
l-dopa.csv : 0.01 %
n-acetylglucosamine.csv : 0.01 %
amyloidosis.csv : 0.01 %
hydroxysteroid_dehydrogenase.csv : 0.01 %
vitamin_d3.csv : 0.01 %
p450oxidoreductase.csv : 0.01 %
insulin_resistance.csv : 0.01 %
autism.csv : 0.01 %
insomnia.csv : 0.01 %
iron_deficiency.csv : 0.01 %
human_proteinuria.csv : 0.01 %
human_semen.csv : 0.01 %
nadph_human.csv : 0.00 %
omega3.csv : 0.00 %
glycoproteins.csv : 0.00 %
phospholipid_human.csv : 0.00 %
phosphatidylcholine.csv : 0.00 %
cortisol_levels.csv : 0.00 %
selenium.csv : 0.00 %
cholestasis.csv : 0.00 %
5-htp.csv : 0.00 %
adrenal_hyperplasia.csv : 0.00 %
mastocytosis.csv : 0.00 %
scfa.csv : 0.00 %
vitamin_k2.csv : 0.00 %
il_10.csv : 0.00 %
coenzymeq10.csv : 0.00 %
5mthf.csv : 0.00 %
panic_disorder.csv : 0.00 %
adhd.csv : 0.00 %
dpagt1.csv : 0.00 %
udpgluc.csv : 0.00 %
pgc1.csv : 0.00 %
phenylketonuria.csv : 0.00 %
irritable_bowel.csv : 0.00 %
sshl.csv : 0.00 %
rxr.csv : 0.00 %
l_tyrosine.csv : 0.00 %
gtp_cyclohydrolase.csv : 0.00 %
5alphareductase.csv : 0.00 %
mast_cell_activation.csv : 0.00 %
gaba_human.csv : 0.00 %
orthostatic_intolerance.csv : 0.00 %
probiotics.csv : 0.00 %
cerebrovascular_amyloidosis.csv : 0.00 %
social_anxiety.csv : 0.00 %
systemic_amyloidosis.csv : 0.00 %
oxalates.csv : 0.00 %
microbiome_humans.csv : 0.00 %
udpglcnac.csv : 0.00 %
adrenal_insufficiency.csv : 0.00 %
finasteride.csv : 0.00 %
cfs.csv : 0.00 %
hexosamine.csv : 0.00 %
selenium_deficiency.csv : 0.00 %
glycerylphosphorylcholine.csv : 0.00 %
gluten.csv : 0.00 %
benfotiamine.csv : 0.00 %
cimetidine.csv : 0.00 %
cyp3a4.csv : 0.00 %
cyp2d6.csv : 0.00 %
fmo3.csv : 0.00 %
rar.csv : 0.00 %
sinusitis.csv : 0.00 %
p5p.csv : 0.00 %
pqq.csv : 0.00 %
cyp1a2.csv : 0.00 %
beta-alanine.csv : 0.00 %
testosterone_production.csv : 0.00 %
freet3.csv : 0.00 %
car.csv : 0.00 %
uric_acid.csv : 0.00 %
mucuna.csv : 0.00 %
vitamin_b6.csv : 0.00 %
dysautonomia.csv : 0.00 %
nadh_human.csv : 0.00 %
ginkgo.csv : 0.00 %
allopregnanolone.csv : 0.00 %
tetrahydrobiopterin.csv : 0.00 %
mthfr.csv : 0.00 %
l_tryptophan.csv : 0.00 %
creatine_supplementation.csv : 0.00 %
cyp1b1.csv : 0.00 %
accutane.csv : 0.00 %
dihydroprogesterone.csv : 0.00 %
cyp2e1.csv : 0.00 %
cyp1a1.csv : 0.00 %
osmolytes.csv : 0.00 %
floaters.csv : 0.00 %
pregnenolone.csv : 0.00 %
acetylcholine.csv : 0.00 %
triiodothyronine_levels.csv : 0.00 %
rituximab.csv : 0.00 %
d-limonene.csv : 0.00 %
resistant_starch.csv : 0.00 %
tinnitus.csv : 0.00 %
zinc_supplementation.csv : 0.00 %
hgh.csv : 0.00 %
tmao.csv : 0.00 %
atrial_fibrillation.csv : 0.00 %
magnesium_deficiency.csv : 0.00 %
l_carnitine.csv : 0.00 %
srd5a3.csv : 0.00 %
pxr.csv : 0.00 %

So PERK was found more frequently in the file called perk.csv which contains all PubMed abstracts that mention PERK (and rightly so) but we see that there are mentions of PERK keyword in other PubMed entries such as

grp78.csv : 3.54 %
tudca.csv : 1.89 %
misfolded_proteins.csv : 1.12 %
dolichol.csv : 0.17 %.


So the same process continues so that all files and all research subjects are cross-checked. The run takes 3 hours to complete on my iMac.

So after this process finishes i can ask from the software to tell me how many hits each csv file had for percentages > 5%

In our PERK example we have :


perk.csv : 45.20 %
ire1.csv : 18.09 %
upr.csv : 5.82 %
xbp1.csv : 5.73 %
er_stress.csv : 4.22 %
grp78.csv : 3.54 %
tudca.csv : 1.89 %

so perk.csv, ire1.csv, upr.csv xbp1.csv will get one point whereas all the others no points (since they are all below 5%).

Here are the results for matching files with >=5%

er_stress.csv : 24
upr.csv : 23
tudca.csv : 22
xbp1.csv : 22
tetrahydrobiopterin.csv : 21
grp78.csv : 20
sirt1.csv : 20
gtp_cyclohydrolase.csv : 20
excitotoxicity.csv : 20
resveratrol.csv : 20
ire1.csv : 19
mitochondrial_dysfunction.csv : 19
oxidative_stress_markers.csv : 19
oxidative_stress_protection.csv : 19
ros.csv : 18
pgc1.csv : 18
perk.csv : 18
cyp2e1.csv : 18
o-glcnac.csv : 18
steroidogenesis_human.csv : 17
endothelial_nos.csv : 17
pxr.csv : 17
zinc_supplementation.csv : 17
srd5a3.csv : 17
p450scc.csv : 16
caspase_human.csv : 16
cyp3a4.csv : 16
star.csv : 16
5mthf.csv : 15
hydroxysteroid_dehydrogenase.csv : 15
cyp1a2.csv : 15
car.csv : 15
cortisol_levels.csv : 15
nadph_human.csv : 15
mcp-1.csv : 14
peroxynitrite.csv : 14
p450oxidoreductase.csv : 14
allopregnanolone.csv : 14
cyp1a1.csv : 14
asymmetric_dimethylarginine.csv : 14
inducible_nos.csv : 14
hsp70.csv : 14
pregnenolone.csv : 14
misfolded_proteins.csv : 13
3betahsd.csv : 13
l-arginine.csv : 13
fmo3.csv : 13
dopamine_levels.csv : 13
testosterone_production.csv : 13
scfa.csv : 13
curcumin.csv : 13
neuronal_nos.csv : 12
dpagt1.csv : 12
advanced_glycation_end.csv : 12
nafld.csv : 12
5alphareductase.csv : 12
glycosylation.csv : 12
heat_shock_protein.csv : 12
butyrate.csv : 12
histone_deacetylase.csv : 12
udpglcnac.csv : 12
hexosamine.csv : 12
selenium_deficiency.csv : 12
cyp2d6.csv : 12
il_10.csv : 12
cyp1b1.csv : 12
dihydroprogesterone.csv : 12
dopamine.csv : 11
udpgluc.csv : 11
mast_cell_activation.csv : 11
hpa_axis.csv : 11
benfotiamine.csv : 11
vcam-1.csv : 11
hepatotoxicity.csv : 11
lipoic_acid.csv : 11
steatohepatitis.csv : 11
pbmc.csv : 11
choline_deficiency.csv : 10
inflammatory_response.csv : 10
resistant_starch.csv : 10
magnesium_deficiency.csv : 10
nadh_human.csv : 10
serotonin_levels.csv : 10
acetylcholine.csv : 10
triiodothyronine_levels.csv : 10
n-acetylglucosamine.csv : 10
dht.csv : 10
dolichol.csv : 9
mastocytosis.csv : 9
calcium_homeostasis.csv : 9
nlinkedglycosylation.csv : 9
oxalates.csv : 9
gluten.csv : 9
freet3.csv : 9
uric_acid.csv : 9
ckd.csv : 9
taurine.csv : 9
acetyl-coa.csv : 9
tmao.csv : 9
rxr.csv : 9
5-htp.csv : 8
insulin_resistance.csv : 8
omega3.csv : 8
protease_inhibitor.csv : 8
vitamin_d3.csv : 8
coenzymeq10.csv : 8
irritable_bowel.csv : 8
l_tyrosine.csv : 8
urea_cycle.csv : 8
systemic_amyloidosis.csv : 8
microbiome_humans.csv : 8
tocotrienol.csv : 8
dysautonomia.csv : 8
monosodium_glutamate.csv : 8
human_proteinuria.csv : 8
trpv.csv : 8
hgh.csv : 8
vitamin_k2.csv : 7
adrenal_hyperplasia.csv : 7
phospholipid_human.csv : 7
hmgcoa.csv : 7
glutamate.csv : 7
cerebrovascular_amyloidosis.csv : 7
ngf.csv : 7
rar.csv : 7
amyloid.csv : 7
mthfr.csv : 7
glycoproteins.csv : 7
selenium.csv : 7
rituximab.csv : 7
l_carnitine.csv : 7
cholestasis.csv : 6
adhd.csv : 6
probiotics.csv : 6
finasteride.csv : 6
glycerylphosphorylcholine.csv : 6
anhedonia.csv : 6
vitamin_b6.csv : 6
beta-alanine.csv : 6
osmolytes.csv : 6
subclinicalhypo.csv : 6
l_tryptophan.csv : 5
social_anxiety.csv : 5
adrenal_insufficiency.csv : 5
mucuna.csv : 5
creatine_supplementation.csv : 5
d-limonene.csv : 5
limbic_system.csv : 4
panic_disorder.csv : 4
iron_deficiency.csv : 4
phosphatidylcholine.csv : 4
gaba_human.csv : 4
cimetidine.csv : 4
p5p.csv : 4
amyloidosis.csv : 4
accutane.csv : 4
floaters.csv : 4
l-dopa.csv : 4
insomnia.csv : 3
human_semen.csv : 3
phenylketonuria.csv : 3
sshl.csv : 3
orthostatic_intolerance.csv : 3
pqq.csv : 3
sinusitis.csv : 3
cfs.csv : 3
ginkgo.csv : 3
neurite_outgrowth.csv : 3
tau.csv : 3
atrial_fibrillation.csv : 3
tinnitus.csv : 1
autism.csv : 1

We can also ask from the software to tell us the number of times each csv file matched with a limit of 0.5% which means that we will have many more matches per file :

oxidative_stress_markers.csv : 85
choline_deficiency.csv : 83
oxidative_stress_protection.csv : 83
er_stress.csv : 82
benfotiamine.csv : 79
neuronal_nos.csv : 78
excitotoxicity.csv : 78
ros.csv : 77
resveratrol.csv : 77
dopamine_levels.csv : 77
nadph_human.csv : 77
endothelial_nos.csv : 76
serotonin_levels.csv : 76
nadh_human.csv : 76
mucuna.csv : 75
curcumin.csv : 75
tudca.csv : 74
xbp1.csv : 74
inducible_nos.csv : 74
hmgcoa.csv : 73
perk.csv : 73
peroxynitrite.csv : 73
taurine.csv : 73
ire1.csv : 72
upr.csv : 72
ginkgo.csv : 72
calcium_homeostasis.csv : 71
butyrate.csv : 71
l-arginine.csv : 71
mitochondrial_dysfunction.csv : 71
grp78.csv : 70
lipoic_acid.csv : 70
tetrahydrobiopterin.csv : 70
p450oxidoreductase.csv : 69
glutamate.csv : 68
testosterone_production.csv : 68
dopamine.csv : 67
rxr.csv : 66
sirt1.csv : 66
histone_deacetylase.csv : 66
creatine_supplementation.csv : 66
coenzymeq10.csv : 65
ngf.csv : 65
monosodium_glutamate.csv : 65
cyp1a1.csv : 65
gtp_cyclohydrolase.csv : 64
misfolded_proteins.csv : 64
caspase_human.csv : 64
amyloid.csv : 64
cyp2e1.csv : 64
cortisol_levels.csv : 64
o-glcnac.csv : 64
dht.csv : 64
omega3.csv : 63
p450scc.csv : 63
5mthf.csv : 63
hpa_axis.csv : 63
cyp1a2.csv : 63
pgc1.csv : 61
advanced_glycation_end.csv : 61
star.csv : 61
l_carnitine.csv : 61
mcp-1.csv : 60
cyp3a4.csv : 60
hepatotoxicity.csv : 60
nafld.csv : 59
acetylcholine.csv : 59
urea_cycle.csv : 59
tocotrienol.csv : 59
fmo3.csv : 59
asymmetric_dimethylarginine.csv : 59
steroidogenesis_human.csv : 58
l_tyrosine.csv : 58
pxr.csv : 58
cyp1b1.csv : 58
trpv.csv : 58
triiodothyronine_levels.csv : 58
l_tryptophan.csv : 57
inflammatory_response.csv : 57
selenium_deficiency.csv : 57
allopregnanolone.csv : 57
insulin_resistance.csv : 56
vcam-1.csv : 56
udpgluc.csv : 55
neurite_outgrowth.csv : 55
gaba_human.csv : 55
zinc_supplementation.csv : 55
tmao.csv : 55
hsp70.csv : 55
heat_shock_protein.csv : 54
car.csv : 54
vitamin_b6.csv : 54
steatohepatitis.csv : 54
osmolytes.csv : 54
dolichol.csv : 53
phospholipid_human.csv : 53
pqq.csv : 53
selenium.csv : 52
tau.csv : 52
protease_inhibitor.csv : 51
5-htp.csv : 51
3betahsd.csv : 51
glycosylation.csv : 51
hydroxysteroid_dehydrogenase.csv : 51
hexosamine.csv : 51
cimetidine.csv : 51
glycoproteins.csv : 51
acetyl-coa.csv : 51
pregnenolone.csv : 51
scfa.csv : 50
cfs.csv : 50
l-dopa.csv : 50
p5p.csv : 49
freet3.csv : 49
beta-alanine.csv : 48
rar.csv : 48
il_10.csv : 48
uric_acid.csv : 47
adrenal_hyperplasia.csv : 47
dihydroprogesterone.csv : 47
d-limonene.csv : 47
5alphareductase.csv : 46
mast_cell_activation.csv : 46
glycerylphosphorylcholine.csv : 46
finasteride.csv : 45
vitamin_d3.csv : 44
probiotics.csv : 44
udpglcnac.csv : 44
pbmc.csv : 43
hgh.csv : 43
nlinkedglycosylation.csv : 42
resistant_starch.csv : 42
magnesium_deficiency.csv : 42
adrenal_insufficiency.csv : 41
cyp2d6.csv : 40
ckd.csv : 40
limbic_system.csv : 39
cerebrovascular_amyloidosis.csv : 39
anhedonia.csv : 39
mthfr.csv : 39
iron_deficiency.csv : 38
cholestasis.csv : 37
vitamin_k2.csv : 37
phosphatidylcholine.csv : 37
irritable_bowel.csv : 37
oxalates.csv : 37
human_proteinuria.csv : 37
dysautonomia.csv : 37
n-acetylglucosamine.csv : 37
insomnia.csv : 36
amyloidosis.csv : 36
mastocytosis.csv : 35
microbiome_humans.csv : 35
subclinicalhypo.csv : 34
phenylketonuria.csv : 33
systemic_amyloidosis.csv : 32
human_semen.csv : 32
orthostatic_intolerance.csv : 31
gluten.csv : 31
panic_disorder.csv : 30
rituximab.csv : 30
autism.csv : 29
accutane.csv : 29
adhd.csv : 24
dpagt1.csv : 24
srd5a3.csv : 24
social_anxiety.csv : 23
sinusitis.csv : 19
floaters.csv : 19
sshl.csv : 18
tinnitus.csv : 18
atrial_fibrillation.csv : 18

So we see that ER Stress, Tetrahydrobiopterin and Choline deficiency are matched more frequently. That creates the hypothesis that these topics could be important elements of CFS.

 

[JPV]

@mariovitali...

ER Stress Response
rs13045 : --
rs2239815 : CT
rs10918270 : AG
rs391957 : --

GCH1
rs10483639 : CG
rs3783641 : AT
rs8007267 : CT
rs3783637 : CC
rs3783641 : AT
rs41298442 : TT
rs4411417 : CT
rs752688 : CT
rs841 : --
rs998259 : CC
rs7147286 : AG

Choline Metabolism
rs3733890 : AG
rs2461823 : CT
rs7643645 : AA
rs7946 : TT
rs4244593 : GT
rs2236225 : AG
rs9001 : TT

 

[mariovitali]

@Ema

CB=Clostridium Butyricum / Miyarisan (actually my mistake!)

OK i believe that you can try supplementing with Choline 700 mg per day and see how you feel. This will raise TMAO and as a result you will increase the folding capacity of ER. You could also supplement with Taurine 1 gram per day.

 

[mariovitali]

@JPV

Do you see the picture here? Several SNPs at Choline metabolism, ER Stress response and Tetrahydrobiopterin production.


You could be seriously deficient in Choline and as a consequence having NAFLD without even knowing it. That can have detrimental effects in ER Stress, Methylation and Liver function.

Humans eating low-choline diets develop fatty liver and liver damage. This dietary requirement for choline is modulated by estrogen and by single-nucleotide polymorphisms in specific genes of choline and folate metabolism. The spectrum of choline’s effects on liver range from steatosis to development of hepatocarcinomas, and several mechanisms for these effects have been identified. They include abnormal phospholipid synthesis, defects in lipoprotein secretion, oxidative damage caused by mitochondrial dysfunction, and endoplasmic reticulum stress. Furthermore, the hepatic steatosis phenotype can be characterized more fully via metabolomic signatures and is influenced by the gut microbiome. Importantly, the intricate connection between liver function, one-carbon metabolism, and energy metabolism is just beginning to be elucidated.

For all of you with Choline SNPs, Please make sure that you read the following thoroughly :


http://www.uncnri.org/index.php/cho...olic-fatty-liver-disease-and-its-progression/

 

[JPV]

@mariovitali...

CFS/ME as a Liver issue (Phoenix Rising)
H.pylori-Hypochlorhydria-Dysbiosis-Liver-CFS/ME Connection (Phoenix Rising)

 

[mariovitali]

@JPV

Forgot to mention that most likely you have BH4 deficiency so High-dose Metafolin, Vitamin C supplementation is needed, avoidance of too much protein, avoidance of Aspartame and Whey Protein drinks. See the list in foods with high Phenylalanine content and try to avoid them.

 

[Violeta]

Are we lost if we have viral infected ER?

http://www.ncbi.nlm.nih.gov/pubmed/15890928

 

[leela]

I can't tell the difference between choline bitartrate and CDP Choline. Any thoughts? Might it be good to take a little of each?

 

[leela]

Are we lost if we have viral infected ER?

http://www.ncbi.nlm.nih.gov/pubmed/15890928

We really have it coming at us from all directions, don't we? Sheesh.

 

[mariovitali]

@mariovitali I must eat animal protein otherwise I get anemic pretty easily. What about eating meat and eggs and low dose supplementation like I am doing now? My intention is to raise supplementation slowly up to about 100mg? I do rounds of 2 eggs at breakfast for a week then back to only one. Trying to see what benefits me more.

When you say "low dose supplementation", to which supplement are you referring exactly?


If you have to eat meat then please make sure that :

1) You don't eat other Phenylalanine sources (such as chewing gum with aspartame) or other aspartame sources, many egg whites
2) Supplement with Choline to raise TMAO (this will properly fold misfolded proteins). A good daily intake would be at least 550 mg per day
3) Supplement with TUDCA, up to 750 mg per day (which gives enhanced protection for misfolded proteins)

 

[mariovitali]

I can't tell the difference between choline bitartrate and CDP Choline. Any thoughts? Might it be good to take a little of each?

I would start with Choline Bitartate...actually this is what i take.

 

[mariovitali]

@Ema

I used to take BodyBio PPC oil but they changed the formula and I hate the taste now. I wonder if the Citicoline I have would work as well instead?

It should work but i am not sure. I am taking Choline Bitartate at the moment but i never tried CitiColine.

You can start with it but if you see no benefit then try switching to Choline Bitartate.

 

[mariovitali]

Thank you for all your suggestions. ME brain moment: I have KPU not PKU
I am actually not doing mehtylation treatment at all right now, but getting ready to.
Why can one not take choline and CB at the same time? My memory span is gnat-like at the moment, sorry.

The reason that you shouldn't take choline along with CB, is the fact that CB raises butyrate and butyrate lowers TMAO. TMAO being a chaperone, helps proper protein folding within the ER and as a consequence it helps with stress within the Endoplasmic Reticulum and avoidance of the Unfolded Protein Response.