Unfolded Protein Response and A Possible Treatment for CFS

[Valentijn]

@Valentijn
Could you comment in the following paper?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468676/

I think the involvement of heat shock proteins is an intelligent and interesting theory. Though with so many intelligent and interesting theories floating around, I have trouble getting too excited about any one of them

Regarding the paper itself, it seems like a good review of the relevant literature. Though I'd have to read all of the sources to see how accurate and reliable it all is, and I simply don't have the time or energy currently.

But it certainly is plausible that an abnormal HSP reaction to illness allows ME to result from a variety of infectious triggers. The only major weakness with that theory is that it sounds like there has only been one small study directly looking at HSP levels in ME patients. But that study (Jammes 2009) did use a good version of Fukuda with required PEM, and looks pretty sound. The other studies are merely supportive/non-contradictory of the possibility of the involvement of HSPs, but could support other theories as well.

I also don't see any real speculation in that paper about what causes the abnormal HSP reaction in some people but not others. Presumably genetics could be one factor, and could be pretty easily explored. Others, such as environmental factors or additional infections would be trickier. And there needs to be an explanation for why an infection suddenly triggers disease in someone who has recovered normally from similar (and even known ME-triggering) infections in the past.

So I think it's an area which has a lot of potential, but it needs a fair bit of work as well. The results from the Jammes paper badly need replicating in a bigger group - it's been 5 years now, so where are they with that? Are Jammes et al or Hooper et al looking into any factors which could cause the underlying abnormal HSP response? Genetic aspects are getting pretty cheap and easy to explore.

Also could you give us your comments/corrections on this Thread and what do you think for the theory that Protein Misfolding is a key aspect -so i am not suggesting that it is the cause- of CFS?

I'll take a look in a bit, and respond to that separately. I'm presuming (hoping!) everything relevant is in the first post of this thread.

Would you be willing to give to the regimen a try at some point?

I don't know enough about it at this point. I tend to dig into things pretty rigorously before trying anything, plus I'm a bit busy with several antibiotics currently.

 

[Violeta]

@Violeta

It is from the same paper. The paper is here : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468676/

Look at the red paragraph here :




So maybe the reason for not having symptoms while being sick, is the fact that HSPs are elevated. I must admit that i do not know the mechanics of how HSPs and ER Stress works so i wish there could someone here with a better understanding.

Let me repeat that i believe that the regimen proposed here could have a protective role for diseases such as Diabetes, Alzheimer's and even aging. I will post references for this.

I am also still trying to explain why my hearing frequency response range has improved after being at the regimen.

Yes, I saw that paragraph in the original, and that's why I said that one needs to be sure if they have a virus, and which virus it is, when trying to manipulate hsp.

The rest of your protocol, the part that doesn't affect hsp but relieves ER stress in other ways, I do agree is good for a variety of things including Alzheimer's, diabetes, Parkinson's, and ME/CFS.

But when it comes to any other "disease", it would be good to find out what virus is involved, because if it's any of the diseases that involve viruses that use hsp in their replication process, you need to find a workaround. There are, I believe, other ways to work around the issue. For example, avoiding heat stress!

 

[Valentijn]

Also could you give us your comments/corrections on this Thread and what do you think for the theory that Protein Misfolding is a key aspect -so i am not suggesting that it is the cause- of CFS?

I've read the first few pages pretty closely now, and I'm running into a bit of a problem.

You're sort of working backwards from your symptoms/treatments, toward science explaining those, and back towards more general ME/CFS and other issues, and as a result the presentation of information is too muddled.

What I'd like to see is a clear presentation starting with the research making the direct connection between ME/CFS and HSPs, and including a good explanation of exactly what HSPs are, what they do, and a brief list of other diseases they are pretty conclusively known to play an important role in. The two CFS HPS studies I've seen are the Hooper & Jammes papers, but perhaps there are others as well.

Clearly distinct from that (and each other), I'd like to see the more peripheral evidence of the hypothesis, speculation regarding the hypothesis (cause, detailed mechanisms, etc), and then maybe how you perceive that it has tied in with your symptoms and person experience. Currently it's all a bit backwards, and that makes it difficult to get from Point A to Point Z.

Your symptoms and experiences are the temporal beginning for you, but they are not a good logical beginning for outsiders, when it comes to understanding the whole picture of the hypothesis which is being proposed.

Regarding genes, there are probably a lot more of them involved in HSP pathways than are listed in the first post. I would expect dozens, which can be pretty overwhelming to look into, especially when each gene itself typically has dozens of SNPs on it tested by 23andMe. Is there a longer list of genes and/or SNPs in this thread, or is that something I could potentially help with a bit?

 

[ppodhajski]

I am also still trying to explain why my hearing frequency response range has improved after being at the regimen.

This! Wow! The SAME thing happened to me! I always used to need my television volume up at 14 but suddenly after starting B2 and B6 I could hear it fine down at 5.

Wondering if you also had/have tinnitus?

After searching for why this might have changed I found this
http://american-hearing.org/disorders/autoimmune-inner-ear-disease-aied/

The left ear was worse but so is the whole left side of my body. I had nerve weakness on my left leg as well bad enough for them to think I might have MS. Wondering if you noticed if things are worse on one side of your body.

 

[Violeta]

Yes, I saw that paragraph in the original, and that's why I said that one needs to be sure if they have a virus, and which virus it is, when trying to manipulate hsp.

The rest of your protocol, the part that doesn't affect hsp but relieves ER stress in other ways, I do agree is good for a variety of things including Alzheimer's, diabetes, Parkinson's, and ME/CFS.

But when it comes to any other "disease", it would be good to find out what virus is involved, because if it's any of the diseases that involve viruses that use hsp in their replication process, you need to find a workaround. There are, I believe, other ways to work around the issue. For example, avoiding heat stress!

And the diseases involved in autoimmunity would benefit greatly from a protocol that relieves or reverses endoplasmic reticulum stress.

So I am actually saying that if anyone doesn't find your information helpful, they are unfortunate, because I do believe it is not only helpful, but necessary.

The only thing that I know of that would need to be changed for a protocol for diseases involving viruses is that instead of avoiding hsp inhibitors, use them wisely. And find out what is causing heat shock (cellular heat, metals, even viruses cause heat shock) and deal with them.

 

[Violeta]

Look at the picture of the EBV and the proteins found in it at this link. I don't know how to copy and paste just the picture. See the hsp inside the virus. They found amounts of hsp inside ebv. I am wondering if that's where the hsp 70 is in people with chronic fatigue.

http://www.pnas.org/content/101/46/16286.full

 

[mariovitali]

@Valentijn

Yes, you are right.


The truth is that i do not have the knowledge and skills for collecting the relevant information and presenting it in a concisely formulated Research Hypothesis. I was hoping that this post may create an interest for skilled individuals (like yourself) to look into this hypothesis.

In other words the post was not made with the possibility that could be used from Researchers as a hypothesis. What i am trying to do (which admittedly has a lot more work to be done) is to come up wtih a post that formulates a Basic Hypothesis about a -possible- key aspect of CFS, namely ER Stress and the UPR. So the post discusses about NAFLD, Choline deficiencies, BH4, Methylation and agents that either enhance Quality control or prevent Protein Misfolding.

@Violeta is saying that induction of HSPs could be helping other types of viruses to replicate which is true. But again, i am just trying to draw attention for more skilled people to say "let's look at this more closely".

I am sure that there are mistakes -and many of them- in the posts i wrote. This reminds me of an incident that happened 2 weeks ago. I was sitting with 2 biologists on the same table so of course i took the opportunity and talked to them about CFS and my story.

So i started talking about my Theory on Protein Misfolding, ER Stress and how after years of Symptoms and Thousands of $$$ spent in Supplements, Doctors etc i became symptom-free. One of them said that

"You made one mistake already : Proteins do not enter the ER. They are created in the ER" with a bit of smile on his face

A comment which i felt was great because i learned something important. However making a mistake -even such a big one- is irrelevant as to whether my theory is wrong OR right.

Then i continued telling him things HE didn't know - with a bit of smile on MY face this time.

Does this fact made my Hypothesis more plausible? Absolutely not!


@Violeta I am trying to look at the connection of EBV virus and HSPs however i feel that this information is much more that i can handle given the fact that i have no relevant knowledge


@ppodhajski

Yes Tinnitus was there, mostly unilateral (left ear) i also had incidences of SSHL which were pretty scary. Tinnitus (2-3 seconds) would signal beginning of my problems (OI, Impotence, Bad Mood, Insomnia, Constipation etc,etc)

This is how i found what was going on. Every day -450 of them- i kept a log of what i was feeling and then asking from a Machine Learning algorithm to tell me what where the common features of good vs bad days. This technology will be used in the near future in wearable devices and the subsequent analysis of data that these devices will be generating.

 

[Violeta]

"You made one mistake already : Proteins do not enter the ER. They are created in the ER" with a bit of smile on his face

A comment which i felt was great because i learned something important. However making a mistake -even such a big one- is irrelevant as to whether my theory is wrong OR right.

Then i continued telling him things HE didn't know - with a bit of smile on MY face this time.

Does this fact made my Hypothesis more plausible? Absolutely not!

Good piece of information. No, it doesn't make your hypothesis less plausible or less relevant, it just helps to refine it.

Such as, it might not be necessary to avoid protein found in foods or specific amino acids that you have already found helpful, such as taurine, and such as I have found helpful, beta alanine.

The avoidance of red meat found in information about Parkinson's disease can be more related to the avoidance of excess iron instead of excess protein.

Or, the avoidance of excess protein might merely be needed in cases of protein containing purines, because uric acid does cause endoplasmic reticulum stress.

And I need to find out if viruses, being proteins, "enter" the endoplasmic reticulum, or simply utilize the hsp being recruited to the ER for replication. They for sure are inside the cells, but are the inside the endoplasmic reticulum.

 

[Violeta]

Good piece of information. No, it doesn't make your hypothesis less plausible or less relevant, it just helps to refine it.

Such as, it might not be necessary to avoid protein found in foods or specific amino acids that you have already found helpful, such as taurine, and such as I have found helpful, beta alanine.

The avoidance of red meat found in information about Parkinson's disease can be more related to the avoidance of excess iron instead of excess protein.

Or, the avoidance of excess protein might merely be needed in cases of protein containing purines, because uric acid does cause endoplasmic reticulum stress.

And I need to find out if viruses, being proteins, "enter" the endoplasmic reticulum, or simply utilize the hsp being recruited to the ER for replication. They for sure are inside the cells, but are the inside the endoplasmic reticulum.

Oh, well, here you go! I think you were right. Or maybe we are both right??? Look at this:
http://www.ncbi.nlm.nih.gov/pubmed/21849482

So far, to me this means that dealing with endoplasmic reticulum stress should inhibit EBV replication.

Endoplasmic reticulum stress causes EBV lytic replication.
Taylor GM1, Raghuwanshi SK, Rowe DT, Wadowsky RM, Rosendorff A.
Author information

Abstract
Endoplasmic reticulum (ER) stress triggers a homeostatic cellular response in mammalian cells to ensure efficient folding, sorting, and processing of client proteins. In lytic-permissive lymphoblastoid cell lines (LCLs), pulse exposure to the chemical ER-stress inducer thapsigargin (TG) followed by recovery resulted in the activation of the EBV immediate-early (BRLF1, BZLF1), early (BMRF1), and late (gp350) genes, gp350 surface expression, and virus release.

 

[mariovitali]

@ppodhajski

I just ran FMN through my PubMed topics. Look at this :

*********Topic : flavin mononucleotide ***************
riboflavin.csv : 2.67 %
p5p.csv : 0.58 %
gtp_cyclohydrolase.csv : 0.49 %
tetrahydrobiopterin.csv : 0.40 %
nadh_human.csv : 0.18 %
nadph_human.csv : 0.16 %
vitamin_b6.csv : 0.15 %
p450oxidoreductase.csv : 0.14 %
neuronal_nos.csv : 0.13 %
pqq.csv : 0.13 %
tmao.csv : 0.10 %
thioredoxin_reductase.csv : 0.08 %
steroidogenesis_human.csv : 0.07 %
inducible_nos.csv : 0.06 %
l-arginine.csv : 0.05 %
oxidative_stress_protection.csv : 0.05 %
vitamin_k2.csv : 0.05 %
asymmetric_dimethylarginine.csv : 0.04 %
ros.csv : 0.04 %
mthfr.csv : 0.04 %
5-htp.csv : 0.04 %
coenzymeq10.csv : 0.04 %
endothelial_nos.csv : 0.03 %
l_tyrosine.csv : 0.03 %
adrenal_hyperplasia.csv : 0.03 %
peroxynitrite.csv : 0.03 %
resveratrol.csv : 0.03 %
oxalates.csv : 0.03 %
lipoic_acid.csv : 0.02 %
5alphareductase.csv : 0.02 %
acetyl-coa.csv : 0.02 %
l_tryptophan.csv : 0.02 %
cyp2e1.csv : 0.02 %
cyp1a2.csv : 0.02 %
upr.csv : 0.02 %
glutamate.csv : 0.02 %
urea_cycle.csv : 0.02 %
tau.csv : 0.02 %
probiotics.csv : 0.02 %
hydroxysteroid_dehydrogenase.csv : 0.02 %
freet3.csv : 0.02 %
cyp3a4.csv : 0.02 %
l_carnitine.csv : 0.02 %
taurine.csv : 0.01 %
iron_deficiency.csv : 0.01 %
heat_shock_protein.csv : 0.01 %
tinnitus.csv : 0.01 %
er_stress.csv : 0.01 %
hepatotoxicity.csv : 0.01 %
microglia.csv : 0.00 %
chaperones.csv : 0.00 %
calcium_homeostasis.csv : 0.00 %
phospholipid_human.csv : 0.00 %
mitochondrial_dysfunction.csv : 0.00 %
hepatocytes.csv : 0.00 %
phosphatidylcholine.csv : 0.00 %
selenium.csv : 0.00 %
steatohepatitis.csv : 0.00 %
uric_acid.csv : 0.00 %
angiotensin_human.csv : 0.00 %
glycosylation.csv : 0.00 %
inflammatory_response.csv : 0.00 %
p53.csv : 0.00 %
cholestasis.csv : 0.00 %
tudca.csv : 0.00 %
choline_deficiency.csv : 0.00 %
dolichol.csv : 0.00 %
insomnia.csv : 0.00 %
norepinephrine.csv : 0.00 %
insulin_resistance.csv : 0.00 %
omega3.csv : 0.00 %
vitamin_d3.csv : 0.00 %
immune_response.csv : 0.00 %
mastocytosis.csv : 0.00 %
scfa.csv : 0.00 %
isotretinoin.csv : 0.00 %
reduced_glutathione.csv : 0.00 %
p450scc.csv : 0.00 %
nmda.csv : 0.00 %
limbic_system.csv : 0.00 %
dopamine.csv : 0.00 %
il_10.csv : 0.00 %
sirt1.csv : 0.00 %
5mthf.csv : 0.00 %
panic_disorder.csv : 0.00 %
ampa.csv : 0.00 %
protease_inhibitor.csv : 0.00 %
adhd.csv : 0.00 %
dpagt1.csv : 0.00 %
udpgluc.csv : 0.00 %
stat1.csv : 0.00 %
pgc1.csv : 0.00 %
dht.csv : 0.00 %
advanced_glycation_end.csv : 0.00 %
hmgb1.csv : 0.00 %
n-acetylglucosamine.csv : 0.00 %
histone_deacetylase.csv : 0.00 %
phenylketonuria.csv : 0.00 %
irritable_bowel.csv : 0.00 %
sshl.csv : 0.00 %
rxr.csv : 0.00 %
ire1.csv : 0.00 %
nafld.csv : 0.00 %
ebv.csv : 0.00 %
misfolded_proteins.csv : 0.00 %
3betahsd.csv : 0.00 %
nlinkedglycosylation.csv : 0.00 %
mast_cell_activation.csv : 0.00 %
hmgcoa.csv : 0.00 %
insp3.csv : 0.00 %
kainate.csv : 0.00 %
gaba_human.csv : 0.00 %
gpr78.csv : 0.00 %
xbp1.csv : 0.00 %
autism.csv : 0.00 %
orthostatic_intolerance.csv : 0.00 %
cerebrovascular_amyloidosis.csv : 0.00 %
butyrate.csv : 0.00 %
social_anxiety.csv : 0.00 %
systemic_amyloidosis.csv : 0.00 %
microbiome_humans.csv : 0.00 %
caspase_human.csv : 0.00 %
udpglcnac.csv : 0.00 %
ngf.csv : 0.00 %
adrenal_insufficiency.csv : 0.00 %
mcp-1.csv : 0.00 %
perk.csv : 0.00 %
crohns_disease.csv : 0.00 %
finasteride.csv : 0.00 %
cfs.csv : 0.00 %
hexosamine.csv : 0.00 %
adrenergic_receptor.csv : 0.00 %
atf6.csv : 0.00 %
selenium_deficiency.csv : 0.00 %
glycerylphosphorylcholine.csv : 0.00 %
gluten.csv : 0.00 %
benfotiamine.csv : 0.00 %
vcam-1.csv : 0.00 %
cimetidine.csv : 0.00 %
anhedonia.csv : 0.00 %
tocotrienol.csv : 0.00 %
human_proteinuria.csv : 0.00 %
cyp2d6.csv : 0.00 %
fmo3.csv : 0.00 %
baroreceptor.csv : 0.00 %
rar.csv : 0.00 %
o-glcnacylation.csv : 0.00 %
fads2.csv : 0.00 %
neurite_outgrowth.csv : 0.00 %
sinusitis.csv : 0.00 %
beta-alanine.csv : 0.00 %
testosterone_production.csv : 0.00 %
car.csv : 0.00 %
mucuna.csv : 0.00 %
inositol.csv : 0.00 %
dysautonomia.csv : 0.00 %
ckd.csv : 0.00 %
cox-2.csv : 0.00 %
amyloid.csv : 0.00 %
fads1.csv : 0.00 %
ginkgo.csv : 0.00 %
caloric_restriction.csv : 0.00 %
allopregnanolone.csv : 0.00 %
monosodium_glutamate.csv : 0.00 %
amyloidosis.csv : 0.00 %
human_semen.csv : 0.00 %
erad.csv : 0.00 %
curcumin.csv : 0.00 %
creatine_supplementation.csv : 0.00 %
cyp1b1.csv : 0.00 %
serotonin_levels.csv : 0.00 %
glycoproteins.csv : 0.00 %
oxidative_stress_markers.csv : 0.00 %
dihydroprogesterone.csv : 0.00 %
cyp1a1.csv : 0.00 %
hsc.csv : 0.00 %
osmolytes.csv : 0.00 %
floaters.csv : 0.00 %
pregnenolone.csv : 0.00 %
pbmc.csv : 0.00 %
acetylcholine.csv : 0.00 %
triiodothyronine_levels.csv : 0.00 %
cortisol_levels.csv : 0.00 %
rituximab.csv : 0.00 %
d-limonene.csv : 0.00 %
resistant_starch.csv : 0.00 %
trpv.csv : 0.00 %
l-dopa.csv : 0.00 %
zinc_supplementation.csv : 0.00 %
excitotoxicity.csv : 0.00 %
hpa_axis.csv : 0.00 %
hgh.csv : 0.00 %
atrial_fibrillation.csv : 0.00 %
magnesium_deficiency.csv : 0.00 %
subclinicalhypo.csv : 0.00 %
hsp70.csv : 0.00 %
o-glcnac.csv : 0.00 %
star.csv : 0.00 %
srd5a3.csv : 0.00 %
pxr.csv : 0.00 %

Seeing anything interesting? what is interesting to me is that there appears to be a connection between FMN and TMAO (which aids in Proper Protein Folding)

Well i guess its time to re-run with FMN added as a proper Topic. 7 more hours of fun haha

 

[Gondwanaland]

I see tinnitus mentioned here by @mariovitali and @ppodhajski
Things that trigger my tinnitus:

• resveratrol
• malic acid
• anything citrate
• .....

Then back in May I fook Boswellia serrate for a few days which left me with permanent tinnitus. I am looking for suggestions about what to try. I think it has something to do with oxalate displacement.

I just ran FMN through my PubMed topics.

It was about time I read somewhere that choline supplementation increases the need for B2.

 

[Violeta]

I see tinnitus mentioned here by @mariovitali and @ppodhajski
Things that trigger my tinnitus:

• resveratrol
• malic acid
• anything citrate
• .....

Then back in May I fook Boswellia serrate for a few days which left me with permanent tinnitus. I am looking for suggestions about what to try. I think it has something to do with oxalate displacement.


It was about time I read somewhere that choline supplementation increases the need for B2.

I truly don't know if this applies for sure, but you might find it interesting or you might know someone else who knows more about human chemistry who could tell you if it does. This is from the wikipedia page about FAD, the other redox cofactor of B2.

One well-known reaction is part of the citric acid cycle (also known as the TCA or Kreb's cycle); succinate dehydrogenase (complex II in the electron transport chain) requires covalently bound FAD to catalyze the oxidation of succinate to fumarate by coupling it with the reduction of ubiquinone toubiquinol.[7]

 

[Gondwanaland]

I just ran FMN through my PubMed topics.

BTW there are A LOT of topics very relevant to me personally in that list

 

[mariovitali]

Dear Dream Team ;-)

Look how nicely Thioredoxin reductase is associated with :

@ppodhajski any comments?

 

[mariovitali]

This maybe?

Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress


The endoplasmic reticulum (ER) is responsible for protein folding, modification, and trafficking. Accumulation of unfolded or misfolded proteins represents the condition of ER stress and triggers the unfolded protein response (UPR), a key mechanism linking supply of excess nutrients to insulin resistance and type 2 diabetes in obesity. The ER harbors proteins that participate in protein folding including protein disulfide isomerases (PDIs). Changes in PDI activity are associated with protein misfolding and ER stress. Here, we show that thioredoxin-interacting protein (Txnip), a member of the arrestin protein superfamily and one of the most strongly induced proteins in diabetic patients, regulates PDI activity and UPR signaling. We found that Txnip binds to PDIs and increases their enzymatic activity. Genetic deletion of Txnip in cells and mice led to increased protein ubiquitination and splicing of the UPR regulated transcription factor X-box-binding protein 1 (Xbp1s) at baseline as well as under ER stress. Our results reveal Txnip as a novel direct regulator of PDI activity and a feedback mechanism of UPR signaling to decrease ER stress.

<SNIP>

Thioredoxin-interacting protein (Txnip) is one of the most dramatically upregulated genes in response to glucose, suggesting a prominent role of Txnip in either adaptive or maladaptive changes in metabolism in response to glucose. We identified a protein-protein interaction of Txnip with protein disulfide isomerases (PDIs), which are chaperones essential for protein folding in the endoplasmic reticulum. We found that Txnip increases PDI activity suggesting a regulatory role for protein folding. We hypothesized that deletion of Txnip would lead to decreased PDI activity and an increased amount of misfolded proteins. We found that deletion of Txnip leads to increased levels of ubiquitinated proteins that are targeted for degradation and to increased levels of ER stress signaling in vitro and in vivo.

 

[Violeta]

It's actually interesting how many of the markers in that list relative to FMN are 0.00%! But actually not much study has been put into B2.

And here's a study that expands on the topic of hsp and Alzheimer's and Parkinson's.

http://www.hindawi.com/journals/omcl/2015/645157/

 

[ppodhajski]

DISCLAIMER: EVERYTHING I SAY IS JUST MY THEORY.

@ppodhajski

I just ran FMN through my PubMed topics. Look at this :

Seeing anything interesting? what is interesting to me is that there appears to be a connection between FMN and TMAO (which aids in Proper Protein Folding)

Well i guess its time to re-run with FMN added as a proper Topic. 7 more hours of fun haha

FAD and FMN are coenzymes that we make from riboflavin using the RFK enzyme. NAD is another coenzyme made from Niacin. I see imbalances in these coenzymes leading to different large subgrouping of symtoms.

More:
http://www.fastbleep.com/biology-notes/40/116/1183

The reason why TMAO pops up because FAD is a coenzyme for all the amine oxidases.

NO uses FAD and FMN as well.

I think that focusing on all the things that cause ER stress is missing the one common factor; all of these things also create oxidative stress. If we see in out genetics where our weaknesses are in either creating too much ROS or not getting rid of them quickly enough we can supplement accordingly. For me, it is my GPX4, TRXDN, MAOA and MAOB genes.

 

[ppodhajski]

It's actually interesting how many of the markers in that list relative to FMN are 0.00%! But actually not much study has been put into B2.

And here's a study that expands on the topic of hsp and Alzheimer's and Parkinson's.

http://www.hindawi.com/journals/omcl/2015/645157/

I think FMN and FAD deficiencies are rampant. The greatest source of riboflavin is liver and organ meats and most people do not go near it. They have done some good studies with migranes and riboflavin and on oxidative stress:
http://www.ncbi.nlm.nih.gov/pubmed/24650639
http://www.neurology.org/content/50/2/466.short

But we will usually not see much of this since B2 is not patentable. $$$$$

 

[mariovitali]

@ppodhajski

Yes i see your point with ER Stress, totally agree


OK let's look at FAD then :

*********Topic : flavin adenine dinucleotide ***************
fad.csv : 32.92 %
fmn.csv : 10.30 %
riboflavin.csv : 2.80 %
fmo3.csv : 1.61 %
pqq.csv : 1.13 %
thioredoxin_reductase.csv : 0.69 %
tetrahydrobiopterin.csv : 0.43 %
gtp_cyclohydrolase.csv : 0.41 %
tmao.csv : 0.39 %
nadh_human.csv : 0.31 %
nadph_human.csv : 0.27 %
p5p.csv : 0.26 %
3betahsd.csv : 0.19 %
neuronal_nos.csv : 0.15 %
mthfr.csv : 0.15 %
p450oxidoreductase.csv : 0.11 %
reduced_glutathione.csv : 0.11 %
coenzymeq10.csv : 0.11 %
vitamin_b6.csv : 0.10 %
vitamin_k2.csv : 0.09 %
hexosamine.csv : 0.09 %
cyp2e1.csv : 0.09 %
acetyl-coa.csv : 0.09 %
hydroxysteroid_dehydrogenase.csv : 0.07 %
lipoic_acid.csv : 0.07 %
steroidogenesis_human.csv : 0.07 %
5alphareductase.csv : 0.07 %
l-arginine.csv : 0.07 %
osmolytes.csv : 0.06 %
mitochondrial_dysfunction.csv : 0.05 %
l_carnitine.csv : 0.05 %
l_tryptophan.csv : 0.05 %
ros.csv : 0.05 %
oxidative_stress_protection.csv : 0.04 %
choline_deficiency.csv : 0.04 %
perk.csv : 0.03 %
oxalates.csv : 0.03 %
urea_cycle.csv : 0.03 %
selenium.csv : 0.03 %
l_tyrosine.csv : 0.03 %
uric_acid.csv : 0.03 %
rxr.csv : 0.03 %
adrenal_hyperplasia.csv : 0.03 %
chaperones.csv : 0.03 %
ginkgo.csv : 0.03 %
glutamate.csv : 0.03 %
resveratrol.csv : 0.03 %
glycosylation.csv : 0.02 %
endothelial_nos.csv : 0.02 %
cyp1a2.csv : 0.02 %
inducible_nos.csv : 0.02 %
upr.csv : 0.02 %
misfolded_proteins.csv : 0.02 %
5-htp.csv : 0.02 %
er_stress.csv : 0.02 %
steatohepatitis.csv : 0.02 %
caloric_restriction.csv : 0.02 %
probiotics.csv : 0.02 %
freet3.csv : 0.02 %
advanced_glycation_end.csv : 0.02 %
udpgluc.csv : 0.02 %
serotonin_levels.csv : 0.02 %
pregnenolone.csv : 0.01 %
peroxynitrite.csv : 0.01 %
monosodium_glutamate.csv : 0.01 %
oxidative_stress_markers.csv : 0.01 %
kainate.csv : 0.01 %
inositol.csv : 0.01 %
tau.csv : 0.01 %
butyrate.csv : 0.01 %
calcium_homeostasis.csv : 0.01 %
p53.csv : 0.01 %
caspase_human.csv : 0.01 %
n-acetylglucosamine.csv : 0.01 %
cimetidine.csv : 0.01 %
hepatotoxicity.csv : 0.01 %
adrenal_insufficiency.csv : 0.01 %
pbmc.csv : 0.01 %
inflammatory_response.csv : 0.01 %
iron_deficiency.csv : 0.01 %
heat_shock_protein.csv : 0.01 %
microglia.csv : 0.00 %
ckd.csv : 0.00 %
phosphatidylcholine.csv : 0.00 %
dopamine.csv : 0.00 %
amyloid.csv : 0.00 %
phospholipid_human.csv : 0.00 %
insulin_resistance.csv : 0.00 %
angiotensin_human.csv : 0.00 %
norepinephrine.csv : 0.00 %
atrial_fibrillation.csv : 0.00 %
hepatocytes.csv : 0.00 %
cholestasis.csv : 0.00 %
tudca.csv : 0.00 %
dolichol.csv : 0.00 %
insomnia.csv : 0.00 %
omega3.csv : 0.00 %
vitamin_d3.csv : 0.00 %
immune_response.csv : 0.00 %
mastocytosis.csv : 0.00 %
scfa.csv : 0.00 %
isotretinoin.csv : 0.00 %
p450scc.csv : 0.00 %
nmda.csv : 0.00 %
limbic_system.csv : 0.00 %
il_10.csv : 0.00 %
5mthf.csv : 0.00 %
panic_disorder.csv : 0.00 %
ampa.csv : 0.00 %
protease_inhibitor.csv : 0.00 %
adhd.csv : 0.00 %
dpagt1.csv : 0.00 %
stat1.csv : 0.00 %
pgc1.csv : 0.00 %
dht.csv : 0.00 %
hmgb1.csv : 0.00 %
histone_deacetylase.csv : 0.00 %
phenylketonuria.csv : 0.00 %
irritable_bowel.csv : 0.00 %
sshl.csv : 0.00 %
ire1.csv : 0.00 %
nafld.csv : 0.00 %
ebv.csv : 0.00 %
nlinkedglycosylation.csv : 0.00 %
mast_cell_activation.csv : 0.00 %
hmgcoa.csv : 0.00 %
insp3.csv : 0.00 %
gaba_human.csv : 0.00 %
gpr78.csv : 0.00 %
xbp1.csv : 0.00 %
autism.csv : 0.00 %
orthostatic_intolerance.csv : 0.00 %
cerebrovascular_amyloidosis.csv : 0.00 %
social_anxiety.csv : 0.00 %
systemic_amyloidosis.csv : 0.00 %
microbiome_humans.csv : 0.00 %
udpglcnac.csv : 0.00 %
ngf.csv : 0.00 %
mcp-1.csv : 0.00 %
crohns_disease.csv : 0.00 %
finasteride.csv : 0.00 %
cfs.csv : 0.00 %
adrenergic_receptor.csv : 0.00 %
atf6.csv : 0.00 %
selenium_deficiency.csv : 0.00 %
glycerylphosphorylcholine.csv : 0.00 %
gluten.csv : 0.00 %
benfotiamine.csv : 0.00 %
vcam-1.csv : 0.00 %
anhedonia.csv : 0.00 %
tocotrienol.csv : 0.00 %
cyp3a4.csv : 0.00 %
human_proteinuria.csv : 0.00 %
cyp2d6.csv : 0.00 %
baroreceptor.csv : 0.00 %
rar.csv : 0.00 %
o-glcnacylation.csv : 0.00 %
fads2.csv : 0.00 %
neurite_outgrowth.csv : 0.00 %
sinusitis.csv : 0.00 %
sirt1.csv : 0.00 %
beta-alanine.csv : 0.00 %
testosterone_production.csv : 0.00 %
car.csv : 0.00 %
mucuna.csv : 0.00 %
dysautonomia.csv : 0.00 %
cox-2.csv : 0.00 %
fads1.csv : 0.00 %
allopregnanolone.csv : 0.00 %
taurine.csv : 0.00 %
amyloidosis.csv : 0.00 %
human_semen.csv : 0.00 %
erad.csv : 0.00 %
curcumin.csv : 0.00 %
creatine_supplementation.csv : 0.00 %
cyp1b1.csv : 0.00 %
glycoproteins.csv : 0.00 %
dihydroprogesterone.csv : 0.00 %
cyp1a1.csv : 0.00 %
hsc.csv : 0.00 %
floaters.csv : 0.00 %
acetylcholine.csv : 0.00 %
asymmetric_dimethylarginine.csv : 0.00 %
triiodothyronine_levels.csv : 0.00 %
cortisol_levels.csv : 0.00 %
rituximab.csv : 0.00 %
d-limonene.csv : 0.00 %
resistant_starch.csv : 0.00 %
trpv.csv : 0.00 %
l-dopa.csv : 0.00 %
tinnitus.csv : 0.00 %
zinc_supplementation.csv : 0.00 %
excitotoxicity.csv : 0.00 %
hpa_axis.csv : 0.00 %
hgh.csv : 0.00 %
magnesium_deficiency.csv : 0.00 %
subclinicalhypo.csv : 0.00 %
hsp70.csv : 0.00 %
o-glcnac.csv : 0.00 %
star.csv : 0.00 %
srd5a3.csv : 0.00 %
pxr.csv : 0.00 %

FAD matches even with a very small percentage to many Topics. Very interesting...

 

[Gondwanaland]

Dear Dream Team ;-)

Indeed I am loving to read the interaction of great minds here
Now off to find out what Thioredoxin reductase does