Unfolded Protein Response and A Possible Treatment for CFS

[mariovitali]

@ppodhajski

I added new Topics and re-executed the Topic totals. The new topics added where (with csv extension) :

-rw-r--r-- 1 staff 15023340 Aug 31 19:26 biotin.csv
-rw-r--r-- 1 staff 34218951 Aug 31 19:25 pubdata.txt
-rw-r--r-- 1 staff 3158765 Aug 31 19:13 pdi.csv
-rw-r--r-- 1 staff 246534 Aug 31 19:11 ero1.csv
-rw-r--r-- 1 staff 17251563 Aug 31 19:10 chop.csv
-rw-r--r-- 1 staff 5100162 Aug 30 17:19 ppp.csv
-rw-r--r-- 1 staff 67843199 Aug 30 09:49 cortisol.csv
-rw-r--r-- 1 staff 640964 Aug 30 09:41 sod3.csv
-rw-r--r-- 1 staff 2807437 Aug 30 09:40 sod2.csv
-rw-r--r-- 1 staff 6754865 Aug 30 09:39 sod1.csv
-rw-r--r-- 1 staff 5722865 Aug 29 18:14 fad.csv
-rw-r--r-- 1 staff 3505082 Aug 29 16:51 fmn.csv

ppp = Pentose Phosphate Pathway


Topic totals are as follows :

>0

>0.1

Notice how SOD2 gets into the picture. Reduced GSH also


finally >1

So what is SOD2 used for ?

SOD2 is one of the major antioxidant enzymes and constitutes the first- line of defense against ROS in mitochondria. Therefore, it is conceivable that structural and functional polymorphisms of SOD2 gene are important in the maintenance of ROS levels in the cell. Low expression of SOD2 has often been accounted for different types of cancer formation, whereas over expression has been linked with inhibition of cancerous growth in humans, implicating it as a tumor suppressor (Tamini et al. 2004). Sutton et al. (2003) studied the most common polymorphism of SOD2, a SNP in codon 16 of mitochondrial target sequence which consists in substitution from Valine (Val) (GTT) to Alanine (Ala) (GCT), called SOD2 Val16Ala.

Reference : Role of Oxidative Stress in Chronic Disease by Dichi et al.

 

[Violeta]

This paper has some information related to oxalate poisoning from oxaliplatin, a cancer drug. The interesting thing is that the neuropathy caused by the drug is caused by the release of oxalates, oxalates chelating calcium.

It talks about a remedy, which contains manganese and B6. The remedy actually works through it's effect on ROS

http://www.jci.org/articles/view/68730

I would only use spirulina for manganese.
http://www.naturalnews.com/034194_spirulina_superfood.html

And the complete package would be B2 for it's FMN, B6, and spirulina.

 

[JaimeS]

Whoa, did the conversation ever move on without me!

Okay, first of all, I tried Rhodiola at a micro-dose. Initial reaction is as per usual - that is, good. I'll report back in a couple of days.

The reason I'm trying this out is that I tried Rhodiola before I really understood PWME's reactions to sub-clinical dosages. I divided my Rhodiola pills 8x and thought that was enough. As discussed elsewhere and exhaustively, maybe not.

I look a leap of faith and went instinctively to a tincture I used to take, sometimes. It contains, from greatest to least:

• Eleutherococcus sp. (Siberian ginseng)
  
• Dioscorea sp. (Wild Yam)
  
• Glycerrhiza sp. (Licorice)
  
• Centella asiatica (Gotu kola)
  
• Withania somnifera (Ashwagandha)
  
• Rhodiola rosea (Rhodiola / Redroot)
  
• Serenoa repens (Saw palmetto)
  
• Zingiber sp. (Ginger)
  
• Stevia

This means it contains corticoids, serotinergic substances, estrogenic substances, etc. etc, but maybe at a low enough dose that it won't crash me. I'm only taking a few drops twice a day.

And, as stated re: the Rhodiola, the dosage did not appear to matter.

I guess we'll see.

I've always had good luck with licorice especially.

Ema, without starting the cortisol debate again (please!) your good response to licorice is probably connected to your good response to cortisol-enhancers, since licorice contains a decent amount of glucocorticoids. I noted that in the discussion of GCs, no one mentioned that they occur naturally.

Something I have noticed on the boards that can occasionally lead to contention is when we begin to presume that what is true of us must be true of others. We are a very heterogeneous patient group. I've noticed patterns, for sure - like, the same bloodwork is 'off' - but not always in the same direction. Again, as discussed in depth before, there seems to be an excitatory and a suppressive phase of ME, and if the slide is slow from one side to the other, then there's probably also a brief phase of some bloodwork being more-or-less normal. That being the case, what works for one person or is true of one person may not be true of every person with ME; and what works for someone at one point may not be useful for them later.

Hence my experimentation; I'll report back.



-J

 

[JaimeS]

Wow Nature 2015 open access

Wow indeed, Gondwanaland! That's certainly an intriguing hypothesis.

My reading list... is... so.... loooong.

-J

 

[ppodhajski]

@ppodhajski

I added new Topics and re-executed the Topic totals. The new topics added where (with csv extension) :

-rw-r--r-- 1 staff 15023340 Aug 31 19:26 biotin.csv
-rw-r--r-- 1 staff 34218951 Aug 31 19:25 pubdata.txt
-rw-r--r-- 1 staff 3158765 Aug 31 19:13 pdi.csv
-rw-r--r-- 1 staff 246534 Aug 31 19:11 ero1.csv
-rw-r--r-- 1 staff 17251563 Aug 31 19:10 chop.csv
-rw-r--r-- 1 staff 5100162 Aug 30 17:19 ppp.csv
-rw-r--r-- 1 staff 67843199 Aug 30 09:49 cortisol.csv
-rw-r--r-- 1 staff 640964 Aug 30 09:41 sod3.csv
-rw-r--r-- 1 staff 2807437 Aug 30 09:40 sod2.csv
-rw-r--r-- 1 staff 6754865 Aug 30 09:39 sod1.csv
-rw-r--r-- 1 staff 5722865 Aug 29 18:14 fad.csv
-rw-r--r-- 1 staff 3505082 Aug 29 16:51 fmn.csv

ppp = Pentose Phosphate Pathwa


Notice how SOD2 gets into the picture. Reduced GSH also

So what is SOD2 used for ?

Reference : Role of Oxidative Stress in Chronic Disease by Dichi et al.

SOD turns superoxides into Hydrogen Peroxide (H2O2). Too much superoxides you get cancer, too much H2O2 and you get Neuro Degenerative diseases.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078500/

(Tinnitis pops in my head here)

We need to make sure we do not have too much of either.

I am trying to get a friend with neuro issues to stop excersizing because it increases H2O2 so was looking for things to show him.

And look what popped up... HSP!

http://www.ncbi.nlm.nih.gov/pubmed/12826253
Effect of voluntary exercise on H2O2 release by subsarcolemmal and intermyofibrillar mitochondria
Mitochondrial H(2)O(2) release per unit of O(2) consumed was 2-fold higher
Furthermore, chronic exercise enhanced heat shock protein 72 accumulation within skeletal muscle. It is concluded that the antioxidant status of muscle can be significantly improved by prolonged wheel exercise without necessitating an increase in mitochondrial oxidative capacities.

So, my idea is that there can either be too many superoxides AND too much hydrogen peroxide produced which leads to pressure on SOD and/or GPX, which depletes manganese, copper, zinc, selenium and B2, which eventually shuts down SOD and/or GPX. If we do not replenish the cofactors we end up with cancer (if SOD is slow) or neuro degenerative diseases is SOD is fast and GPX is slow. For those of us with GPX and SOD genes that are slower, we deplete these nutrients faster and get sicker faster.

 

[Ema]

since licorice contains a decent amount of glucocorticoids. I noted that in the discussion of GCs, no one mentioned that they occur naturally.

Actually, licorice inhibits 11b-HSD1 which prolongs the life of one's own cortisol.

It doesn't actually contain any steroid.

It also stimulates interferon gamma which makes it a pretty nice little herbal antiviral.

I've never said that what works for me must work for everyone. All I said was that cortisol is better seen as an immunomodulatory agent than strictly an immunosuppressant because the effects seem to be dose dependent.

 

[JaimeS]

Actually, licorice inhibits 11b-HSD1 which prolongs the life of one's own cortisol.

It doesn't actually contain any steroid.

You're right, @Ema! It has glycerrizic acid (sp?) which has an inhibitory effect on 11-B-OH-steroid dehydrogenase as you say, preventing the breakdown of cortisol. This information is firmly stuck in my head, and I'm sure I was taught that this was the case; but I'm incorrect.

I've never said that what works for me must work for everyone.

I wasn't referring to you! Someone said, "so we should not try to lower our cortisol", which presumes that cortisol tends to be high in ME/CFS and people might think they ought to lower it, but that this was not wise. I know that you use cortisol because yours is low (which I hope is all right to mention, since you have said so in other locations on the board.) My cortisol is normal. Therefore, we cannot use information about our own lab values/bodies/experiences to directly relate to anyone else's. I didn't want to mention who had said the comment to which I referred, in case they got offended. But honestly I've noticed this often, and not necessarily in confrontational situations.

For example, my VEGF is extremely low, but when people hypothesize about the causes or contributors to ME/CFS I have heard people say things like, "that fits, since that would mean elevated VEGF" as though everyone's experience of the illness is similar enough to make that generalization. My experience is that this kind of assumption occasionally leads to conflict.

cortisol is better seen as an immunomodulatory agent than strictly an immunosuppressant because the effects seem to be dose dependent.

I agree to the plausibility here. My issue is that there appears to be no 'subclinical' dosage for me. FOR ME. JUST ME. EVERYONE ELSE IS WELCOME TO AS MUCH OF IT AS THEY WANT.

-J

 

[ppodhajski]

I agree to the plausibility here. My issue is that there appears to be no 'subclinical' dosage for me. FOR ME. JUST ME. EVERYONE ELSE IS WELCOME TO AS MUCH OF IT AS THEY WANT.
-J

There is no plausibility there. Licorice increases cortisol. If it makes someone feel better, it makes them feel better because they needed to cortisol to suppress the immune system. If it makes you feel worse it is a sign that you probably have enough cortisol at the time.

 

[Ema]

There is no plausibility there. Licorice increases cortisol. If it makes someone feel better, it makes them feel better because they needed to cortisol to suppress the immune system. If it makes you feel worse it is a sign that you probably have enough cortisol at the time.

Or maybe it increases estrogen...or interferon gamma. Or maybe something else. The body is not as black and white as that.

There's no evidence that licorice gives everyone who feels better high cortisol. If it simply raised low cortisol to normal levels, that would not be suppressive to the immune system.

 

[Sushi]

There is no plausibility there. Licorice increases cortisol. If it makes someone feel better, it makes them feel better because they needed to cortisol to suppress the immune system.

It could also be raising BP that is too low.

 

[ppodhajski]

Or maybe it increases estrogen...or interferon gamma. Or maybe something else. The body is not as black and white as that.

There's no evidence that licorice gives everyone who feels better high cortisol. If it simply raised low cortisol to normal levels, that would not be suppressive to the immune system.

? You brought up the cortisol licorice connection....nevermind.

 

[ahmo]

thanks @mariovitali I don't understand what it is you're doing, but I'm fascinated.

Here's what Promethease has to say about my first SOD2, CC:

The (C) allele gives rise to an alanine at this position is it also known as Val16Ala manganese superoxide dismutase, or A16V. There appears to be some conflict in the literature over the effect of this SNP. Having a valine at codon 16 is said to reduce enzyme activity , and thus lead to increased oxidative stress, yet in at least one study of the actual enzyme levels measured in people, SOD2 activity was 33% higher in (C;T) or (T;T) individuals compared to (C;C) individuals . Regardless of how this resolves, several phenotypic associations have been reported for this SNP, includi...

Searching for causes of oxidative stress, and loading on the antioxidants, has been what my focus has been this year. You show me that some of it is foundational, that I can manage it, but something here is probably not going away.

 

[ppodhajski]

thanks @mariovitali I don't understand what it is you're doing, but I'm fascinated.

Here's what Promethease has to say about my first SOD2, CC:

Searching for causes of oxidative stress, and loading on the antioxidants, has been what my focus has been this year. You show me that some of it is foundational, that I can manage it, but something here is probably not going away.

What do you mean by " but something here is probably not going away."?

Also, we really do not want to load on the antioxidants, oxidation has some uses in the body. Getting rid of it will cause other issues, like cancer.

 

[ahmo]

What do you mean by " but something here is probably not going away."?

I've been trying to find causes for feeling under high oxidative stress. And I see here that there doesn't have to be any external reason, ie environmental, dietary, exercise. There's an inherent tendency that I have to manage.

Also, we really do not want to load on the antioxidants, oxidation has some uses in the body. Getting rid of it will cause other issues, like cancer.

Great, how does one find the balance in antioxidants?

 

[mariovitali]

thanks @mariovitali I don't understand what it is you're doing, but I'm fascinated.

Haha i know @ahmo i feel like a mad scientist sometimes!

In a nutshell this Thread discusses the fact that i became symptom-free by treating Methylation issues while ALSO making sure that ER Stress and the Unfolded Protein Response does not take place. To become symptom-free took a couple of months.

To achieve the second goal you can use agents such as TUDCA, Taurine, Resveratrol, Selenium, and avoiding things that cause ER Stress (such as Choline Deficiency, being overweight etc).

@ppodhajski came up with the idea that you shouldn't use agents but cofactors. If this sort of regimen (using just cofactors) keeps me symptom-free then obviously it will be preferred. Perhaps though we have to use agents to stop the vicious cycle :

Oxidative/ER stress - > Mitochondrial Dysfunctioning -> more Oxidative/ER Stress -> more Mitochondrial Dysfunctioning

I can definitely say (based on my observations on how i feel) that TUDCA, Taurine, Selenium, Choline+Inositol and Resveratrol when used together work. I am not sure about NAG. It was also a very interesting "side-effect" of the regimen that i can hear much better than i used to (...!)

I will probably use these agents and cycle them for the rest of my life given their protective effects discussed in numerous studies. But I will definitely try seeing how I feel without them.


In asking how do you find the balance, i would say that you should listen to your body. If you feel well then the balance is right. Overly simplistic -i know- but i am not sure if there is any other way to find this oxidant/antioxidant balance.

 

[ahmo]

Haha i know @ahmo i feel like a mad scientist sometimes!

In a nutshell this Thread discusses the fact that i became symptom-free by treating Methylation issues while ALSO making sure that ER Stress and the Unfolded Protein Response does not take place. To become symptom-free took a couple of months.

n asking how do you find the balance, i would say that you should listen to your body. If you feel well then the balance is right

Here's a current experience for me. Maybe it makes sense to one of you, in this context. I've been on GAPS diet 3.5 years. At least a year ago my body wanted me to stop adding vinegar to my bone broth, which is done to help leach out the minerals. And to not continue using the bones until they were crumbling.

This past week I elicited a response that said to halve my broth intake, from about 2 cups twice a day to 1/2 that. This seemed to lessen my oxidative stress symptoms. Then when I asked more closely, body said to stop the broth altogether. Which I have. Today is my 3rd day broth-free. And I feel better than I can remember. Although I'd been focussing on antioxidants, following symptoms, I can't recall feeling so clear-headed, so without the need for extra carrots and the seed/nut spread my body had been asking for.

Do you know of a distinct role of calcium in all this? Has it been that I've been having to balance excess calcium by my antioxidant intake, as well as the high levels of other minerals in the seeds/nuts?

 

[mariovitali]

@ahmo

Do you know of a distinct role of calcium in all this? Has it been that I've been having to balance excess calcium by my antioxidant intake, as well as the high levels of other minerals in the seeds/nuts?

I don't have an answer to your question unfortunately. What i can tell you is that initially Calcium intake would signal problems for me. However now i can take Calcium with no problems.

I feel that Calcium intake is a good thing *after* you solve issues with Excitotoxicity/ER Stress

@all

I started following directions from @ppodhajski . I dropped NAG and started Biotin. Whatever i do is based on my SNPs so this doesn't mean that you should take Biotin as well. I am also expecting FMN but it will take 15-20 days for this supplement to arrive from USA (unfortunately).

My goal is to stop TUDCA, Resveratrol and Choline/Inositol as well. I will keep you updated.

Hopefully at the end of this we will have a clear Roadmap on which Genes & SNPs have to be looked at and the appropriate agents/cofactors that should be used in order to feel normal again.

 

[ahmo]

I feel that Calcium intake is a good thing *after* you solve issues with Excitotoxicity/ER Stress

Once I started FMN I no longer self-tested + for biotin. There's still some in my B Comp, 25 mcg, but I no longer am using additional. Stopped inositol after major detox last year. And it seemed as if as soon as I found alternatives, my body no longer wanted resveratrol.

Hopefully at the end of this we will have a clear Roadmap on which Genes & SNPs have to be looked at and the appropriate agents/cofactors that should be used in order to feel normal again.

 

[mariovitali]

FYI @ppodhajski

More goodies on Biotin :

Regulation of immunological and inflammatory functions by biotin.
Kuroishi T1,2.
Author information

Abstract
Biotin is a water-soluble B-complex vitamin and is well-known as a co-factor for 5 indispensable carboxylases. Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of carboxylases and other proteins, whereas biotinidase catalyzes the release of biotin from biotinylated peptides. Previous studies have reported that nutritional biotin deficiency and genetic defects in either HLCS or biotinidase induces cutaneous inflammation and immunological disorders. Since biotin-dependent carboxylases involve various cellular metabolic pathways including gluconeogenesis, fatty acid synthesis, and the metabolism of branched-chain amino acids and odd-chain fatty acids, metabolic abnormalities may play important roles in immunological and inflammatory disorders caused by biotin deficiency. Transcriptional factors, including NF-κB and Sp1/3, are also affected by the status of biotin, indicating that biotin regulates immunological and inflammatory functions independently of biotin-dependent carboxylases. An in-vivo analysis with a murine model revealed the therapeutic effects of biotin supplementation on metal allergies. The novel roles of biotinylated proteins and their related enzymes have recently been reported. Non-carboxylase biotinylated proteins induce chemokine production. HLCS is a nuclear proteininvolved in epigenetic and chromatin regulation. In this review, comprehensive knowledge on the regulation of immunological and inflammatory functions by biotin and its potential as a therapeutic agent is discussed.

I entered the following on my Topic-matching software

"pyruvate carboxylase","propionyl-coa carboxylase","acetyl-coa carboxylase","3-methylcrotonyl-coa carboxylase"

Here are the results (Notice how many topics are matched by Acetyl-coa carboxylase) :

*********Topic : pyruvate carboxylase ***************
acetyl-coa.csv : 2.91 %
ppp.csv : 1.77 %
biotin.csv : 1.71 %
oxalates.csv : 1.26 %
o-glcnacylation.csv : 0.37 %
l_carnitine.csv : 0.33 %
glutamate.csv : 0.29 %
osmolytes.csv : 0.23 %
urea_cycle.csv : 0.22 %
p5p.csv : 0.18 %
lipoic_acid.csv : 0.14 %
monosodium_glutamate.csv : 0.14 %
pqq.csv : 0.13 %
hepatocytes.csv : 0.10 %
o-glcnac.csv : 0.10 %
tmao.csv : 0.10 %
nadh_human.csv : 0.09 %
steatohepatitis.csv : 0.08 %
reduced_glutathione.csv : 0.07 %
iron_deficiency.csv : 0.07 %
caloric_restriction.csv : 0.07 %
taurine.csv : 0.06 %
mitochondrial_dysfunction.csv : 0.05 %
gaba_human.csv : 0.05 %
magnesium_deficiency.csv : 0.05 %
l_tryptophan.csv : 0.05 %
nadph_human.csv : 0.04 %
hexosamine.csv : 0.04 %
fad.csv : 0.04 %
excitotoxicity.csv : 0.03 %
inositol.csv : 0.03 %
rxr.csv : 0.03 %
peroxynitrite.csv : 0.03 %
riboflavin.csv : 0.03 %
sirt1.csv : 0.03 %
cortisol_levels.csv : 0.03 %
selenium_deficiency.csv : 0.03 %
neuronal_nos.csv : 0.03 %
n-acetylglucosamine.csv : 0.02 %
selenium.csv : 0.02 %
adrenergic_receptor.csv : 0.02 %
insulin_resistance.csv : 0.01 %
chaperones.csv : 0.01 %
phenylketonuria.csv : 0.01 %
heat_shock_protein.csv : 0.01 %
oxidative_stress_markers.csv : 0.01 %
protease_inhibitor.csv : 0.01 %
hmgcoa.csv : 0.01 %
hsp70.csv : 0.01 %
ros.csv : 0.01 %
butyrate.csv : 0.01 %
l-arginine.csv : 0.01 %
calcium_homeostasis.csv : 0.01 %
er_stress.csv : 0.01 %
mcp-1.csv : 0.01 %
hydroxysteroid_dehydrogenase.csv : 0.01 %
histone_deacetylase.csv : 0.01 %
uric_acid.csv : 0.01 %
norepinephrine.csv : 0.01 %
nmda.csv : 0.01 %
serotonin_levels.csv : 0.01 %

*********Topic : propionyl-coa carboxylase ***************
biotin.csv : 0.66 %
acetyl-coa.csv : 0.63 %
l_carnitine.csv : 0.14 %
lipoic_acid.csv : 0.12 %
urea_cycle.csv : 0.05 %
steatohepatitis.csv : 0.04 %
choline_deficiency.csv : 0.04 %
gpr78.csv : 0.03 %
mitochondrial_dysfunction.csv : 0.02 %
chaperones.csv : 0.02 %
nadh_human.csv : 0.02 %
resveratrol.csv : 0.01 %
pbmc.csv : 0.01 %
oxidative_stress_protection.csv : 0.01 %
butyrate.csv : 0.01 %
omega3.csv : 0.01 %
riboflavin.csv : 0.01 %
oxalates.csv : 0.01 %
glutamate.csv : 0.01 %
gaba_human.csv : 0.01 %
sshl.csv : 0.01 %
hepatocytes.csv : 0.01 %
heat_shock_protein.csv : 0.01 %
hsp70.csv : 0.01 %

*********Topic : acetyl-coa carboxylase ***************
acetyl-coa.csv : 19.67 %
l_carnitine.csv : 1.72 %
biotin.csv : 0.99 %
hmgcoa.csv : 0.69 %
sirt1.csv : 0.65 %
pgc1.csv : 0.63 %
nafld.csv : 0.59 %
steatohepatitis.csv : 0.57 %
sirt3.csv : 0.55 %
fads1.csv : 0.50 %
fads2.csv : 0.41 %
lipoic_acid.csv : 0.33 %
hepatocytes.csv : 0.32 %
resveratrol.csv : 0.31 %
ppp.csv : 0.29 %
xbp1.csv : 0.28 %
triiodothyronine_levels.csv : 0.19 %
tudca.csv : 0.19 %
caloric_restriction.csv : 0.18 %
hexosamine.csv : 0.18 %
gpr78.csv : 0.16 %
choline_deficiency.csv : 0.16 %
er_stress.csv : 0.15 %
perk.csv : 0.14 %
endothelial_nos.csv : 0.13 %
cyp2e1.csv : 0.13 %
curcumin.csv : 0.11 %
ire1.csv : 0.11 %
insulin_resistance.csv : 0.10 %
o-glcnac.csv : 0.10 %
udpglcnac.csv : 0.10 %
omega3.csv : 0.09 %
upr.csv : 0.08 %
pxr.csv : 0.08 %
peroxynitrite.csv : 0.07 %
freet3.csv : 0.06 %
creatine_supplementation.csv : 0.06 %
star.csv : 0.06 %
sod2.csv : 0.06 %
rxr.csv : 0.06 %
mcp-1.csv : 0.06 %
nadh_human.csv : 0.06 %
mitochondrial_dysfunction.csv : 0.05 %
ros.csv : 0.05 %
probiotics.csv : 0.05 %
phosphatidylcholine.csv : 0.04 %
monosodium_glutamate.csv : 0.04 %
thioredoxin_reductase.csv : 0.04 %
adrenergic_receptor.csv : 0.04 %
nadph_human.csv : 0.04 %
misfolded_proteins.csv : 0.04 %
hepatotoxicity.csv : 0.04 %
cox-2.csv : 0.03 %
stat1.csv : 0.03 %
heat_shock_protein.csv : 0.03 %
phospholipid_human.csv : 0.03 %
l_tyrosine.csv : 0.03 %
tetrahydrobiopterin.csv : 0.03 %
inositol.csv : 0.03 %
hmgb1.csv : 0.03 %
vcam-1.csv : 0.03 %
phenylketonuria.csv : 0.03 %
caspase_human.csv : 0.03 %
p53.csv : 0.03 %
oxidative_stress_markers.csv : 0.03 %
neuronal_nos.csv : 0.03 %
chop.csv : 0.02 %
glutamate.csv : 0.02 %
calcium_homeostasis.csv : 0.02 %
sod1.csv : 0.02 %
butyrate.csv : 0.02 %
l-arginine.csv : 0.02 %
cortisol_levels.csv : 0.02 %
urea_cycle.csv : 0.02 %
n-acetylglucosamine.csv : 0.02 %
hsp70.csv : 0.02 %
chaperones.csv : 0.01 %
hpa_axis.csv : 0.01 %
inducible_nos.csv : 0.01 %
histone_deacetylase.csv : 0.01 %
protease_inhibitor.csv : 0.01 %
testosterone_production.csv : 0.01 %
taurine.csv : 0.01 %
uric_acid.csv : 0.01 %
oxidative_stress_protection.csv : 0.01 %
riboflavin.csv : 0.01 %
hydroxysteroid_dehydrogenase.csv : 0.01 %
p450oxidoreductase.csv : 0.01 %
pbmc.csv : 0.01 %
ckd.csv : 0.01 %
inflammatory_response.csv : 0.01 %
iron_deficiency.csv : 0.01 %
tau.csv : 0.01 %

*********Topic : 3-methylcrotonyl-coa carboxylase ***************
biotin.csv : 0.26 %
l_carnitine.csv : 0.18 %
urea_cycle.csv : 0.15 %
acetyl-coa.csv : 0.12 %
phenylketonuria.csv : 0.06 %
mitochondrial_dysfunction.csv : 0.01 %
adrenal_hyperplasia.csv : 0.01 %
chop.csv : 0.01 %
reduced_glutathione.csv : 0.01 %
steatohepatitis.csv : 0.01 %
pbmc.csv : 0.01 %

 

[Gondwanaland]

Very interesting synchronicity. We are talking about biotin at the oxalate thread.

And I was about to ask about calcium's role with so much choline supplementation.

And I was thinking to start making bone broth as a way to have a glycine intake. Glycine as a supplement can get converted into oxalates, but I think I need to up my collagen synthesis.

I started following directions from @ppodhajski . I dropped NAG and started Biotin.

So now I am unsure to take NAG or not. @ppodhajski what were your criteria concerning it?