Unfolded Protein Response and A Possible Treatment for CFS

[CCC]

@sflorence

I will be making a new Thread as soon as i have info/evidence of complete recoveries. In a nutshell :

TUDCA/UDCA/Bile Acids from jarrows appear to be working almost equally well. I would say that the order of effectiveness appears to be the following :

1. TUDCA
2. UDCA
3. Bile Acids from Jarrows

The protocol uses :

1) UDCA or TUDCA or Bile Acids from Jarrows
2) Methylation support (especially Metafolin and P5P)
3) Molybdenum and/or Zinc and/or Manganese for Copper Level control if it is found to be high
4) Selenium


Note : It appears that this regimen requires many Months to show its effects.

I have been watching this thread with interest. Can't wait for the next instalment.

 

[mariovitali]

More interesting things coming up.


The gene of interest is called HSD11B1 (see http://www.ncbi.nlm.nih.gov/gene/3290)


For all women reading this, have you ever took Anti-androgens to control severe Acne? Did/Do you have Acne problems?


Here is how it looks for me :

Not good at all as it seems. Let's see what HSD11B1 is involved in:

11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) plays a key role in glucocorticoid receptor (GR) activation. Besides, it metabolizes some oxysterols and bile acids (BAs). The GR regulates BA homeostasis; however, the impact of impaired 11β-HSD1 activity remained unknown. We profiled plasma and liver BAs in liver-specific and global 11β-HSD1-deficient mice. 11β-HSD1-deficiency resulted in elevated circulating unconjugated BAs, an effect more pronounced in global than liver-specific knockout mice.

and

Cortisone reductase deficiency is caused by dysregulation of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), otherwise known as cortisone reductase, a bi-directional enzyme, which catalyzes the interconversion of cortisone to cortisol in the presence of NADH as a co-factor. If levels of NADH are low, the enzyme catalyses the reverse reaction, from cortisol to cortisone, using NAD+ as a co-factor.

Interestingly HSD11B1 is also involved in PCOS ang Hyperandrogenism

Investigators searching for PCOS genes have also looked to cortisone reductase deficiency (CRD), a condition that is partly attributed to a decrease in 11β hydroxysteroid dehydrogenase (11β-HSD1) activity. HSD11B1 is a keto reductase, whose function is to reduce cortisone to cortisol in the liver; a decrease in its activity leads to adrenal hyperandrogenism via the compensatory elevation of adrenocorticotropic hormone (Draper et al., 2003). The phenotype of CRD is in some ways similar to that of PCOS and includes traits such as hirsutism, oligo-amenorrhea and infertility in women, raising interest in the possible involvement of HSD11B1 in PCOS.

 

[Gondwanaland]

I don't know if this study has already been brought to attention
The chemical chaperones tauroursodeoxycholic and 4-phenylbutyric acid accelerate thyroid hormone activation and energy expenditure

 

[Violeta]

Someone in a group that I read has been losing her hair, along with other issues, since taking accutane in 2006. She recently found out through her doctor that she is low in esterified carnitine. While looking into it I found this study.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575043/


Cholestatic Jaundice Associated with Carnitine Palmitoyltransferase IA Deficiency

 

[jengonwin]

I started taking 1000mg TUDCA (250mg 4x day) and my urine has taken on a green tinge and it smells weird . Has anyone experienced this? It literally started the day i hopped on TUDCA.

Thanks

 

[mariovitali]

@jengonwin This is too much of a dose. Is there a reason you chose to take this much?

I started taking 250 mg and upped the dose up to 500 mg, not more

 

[jump44]

jarrow bile acids was a rough supplement for me. I got on fine w TUDCA for a while but last tim I ran out I decided to go to health store and pick these up instead of waiting for a shipment of TUDCA. anyways ive taken it about 7-8 times the first couple times it went ok, but then I started getting extreme nausea after each dose and even vomited once after taking it. also there was intense burning in my upper abdomen and throat.

anyways ill be going back to TUDCA when I get the money, just an FYI. maybe I got a bad batch as Ive not seen anyone else mention these effects. and I always took them after a meal and never on an empty stomach. worst supp Ive ever taken to be honest.

 

[Sam7777]

this monster thread still going?

update for me: Found out I have environmental/chemical sensitivity ...to the entire air ventilation system in the house I was staying in, continuing to react to cig smoke, exhaust...The cause was likely the indoor garage full of petrol chemicals and paints and fertilizers/pesticides......

Also possibly dealing with mold in the other house, could have been in the other as well.

So.......some of my main symptoms being extreme liver spasm/bile issues, chronic fatigue, and histamine sensitivity....that subsided by like 90% upon leaving that house/blocking indoor air ventilation.

It does seem that all this thread and these issues I had revolve around bile metabolism.

But it'd take a separate thread to talk about avoiding the causes of it.

I guess that adds some perspective to the matter. It seems to me that environmental triggers and epigenetic changes must be really predominant here. I have basically four cases of outright pollution or drug damage or environmental illness. So I would caution leaning on hereditary genetic models too greatly.

1. Cipro/Finastid/Acne med/other antibiotic damage
2. toxic black mold.
3. heavy metals
4. VOC air contamination

I haven't had a chance to read much on here lately. But a while ago I learned about a concept called 'heteroplasmy'. This seems to be related to gene behavior caused by pollution (or 'environmental stress').

A good question would be Can TUDCA affect heteroplasmy in mitochondria? Can other supplements improve heteroplasmy levels in mitochondria while supporting the effects of TUDCA?

When are people going to take TUDCA and R lipoic together? What about milk thistle?

 

[mariovitali]

Regarding Bile acids : They can have nausea as a side effect.

I have seen this happening when one is taking many capsules per day.

 

[ahmo]

I looked into getting UDCA, but found it was as horribly expensive as TUDCA, so I haven't gone that route. But I have added ox bile back into my diet. I'd been taking this for a couple years on GAPS diet, then quit when it no longer seemed necessary. (leaving an unopened bottle in my stash.)

Thanks to the suggestion here, I resumed ox bile a few weeks ago. About a week ago I increased to 2 w/ my 2 meals. My energy at present seems pretty good. I'd say excellent, but that does not translate into the ability to Do, ie activity. However, I can report that at last my poops have been daily and perfect consistency, unlike typical for a long time. I'd say my liver is functioning better.

I've also added pomegranate, as dried juice powder, to support mitochondria. And it's a few weeks since I completed Candida protocol. So it's hard to attribute my current well-being just to ox bile, but I believe it's played a significant role.

I can't get my screenshot of HSD11B1 to upload....

s1000283(C;C)
60.4% Frequency

rs11119328(C;C)
69.9% Frequency

rs11807619(G;G)
71.2% Frequency

rs3753519(G;G)
80.5% Frequency

rs4844880(T;T)
69.6% Frequency

 

[mariovitali]

@ahmo

Really glad you are feeling better, let us know if this continues!


HSD11B1 seems ok so is your CYP7A1. However there are some issues in :

-CYP8B1
-NR1H4
-AKR1C4
-GPBAR1
-AKR1D1
-SRD5A2 (5 and all heterozygous)
-HSD3B7

All of these have to do with Bile acid metabolism.

Unfortunately we do not have information about your CDO1 in your chip but i also believe that you would benefit from low dose molybdenum and FMN (both for boosting your Cysteine Dioxygenase and thus breaking down of L-Cysteine)

Also we do not know if the problem lies in not enough Bile acids or having Bile acids which are not metabolised in Conjugated Bile acids. Primary Bile acids are toxic to Intestines, the Liver and the Pancreas (credit to Bob M for this).

@all

As discussed, we are very close in having two cases with complete remission of symptoms of Fibromyalgia/CFS, both of them having problems for almost 20 years. Both of them have steady (and slow...)improvement in Symptoms of Low Energy and Pain. They are very early on to the regimen but especially one of them is very close in becoming symptom-free.

I tried so many times in stopping this one capsule of Bile acids i am taking at Lunch time and symptoms started appearing. So let me be clear : we are not talking about recovery, just complete lack of Symptoms.

My regimen is P5P, Metafolin, Molybdenum (around 70% RDA) and one capsule of Jarrows Bile acids at Lunch.

 

[adreno]

Is there a difference between Jarrow BAF and regular ox bile? Jarrows is conjugated? Regular ox bile gives me stomach pain.

 

[mariovitali]

Is there a difference between Jarrow BAF and regular ox bile? Jarrows is conjugated? Regular ox bile gives me stomach pain.

Jarrow BAF has 95% Conjugated BAs.

One thing i didn't mention is that i take the capsule in the middle of my Lunch, not before or after. Perhaps you could try Jarrow BAF , just one capsule at Lunch and see how you feel.

 

[mariovitali]

And here is a snapshot from the tool that i am using for my research that summarises Genes along with their Variant alleles as these are found to the DNA samples i have :

Notice MYO9B, NDUFS7 but also -and this is where it gets interesting- NR1H4.

NR1H4 is the Farnesoid X Receptor.

http://www.malacards.org/search/results/NR1H4

Of interest is also ATP7B which has to do with Copper transportation from the Liver to other parts of the body.

Again, the combination of Genes and their mutations is important...NOT the individual Genes/mutations!!!

 

[adreno]

@mariovitali did you see the metabolomics study by Naviaux?

 

[mariovitali]

@adreno

Just had a quick look, Thanks for pointing this out.

NDUFS7 is related to mitochondria. XBP1 to Endoplasmic Reticulum and the Unfolded Protein response regulation.

 

[Violeta]

@mariovitali , if bile acids helps so much, then you most likely can return to good health by cleaning up liver and gallbladder congestion so that your body makes it's own bile the bile is able to flow.

And on another note, do you have any information about DCYTB, a cupric reductase?
This enzyme also works in the duodenum, and if things are messed up there, copper might not be reduced, leading to copper being absorbed in it's biounavailable form, which actually causes copper deficiency. This can then lead to iron deficiency, but that's for later.

 

[Valentijn]

However there are some issues in :
-CYP8B1
-NR1H4
-AKR1C4
-GPBAR1
-AKR1D1
-SRD5A2 (5 and all heterozygous)
-HSD3B7

Is there an actual reason (published research) to think that these genes are having problems, or are you making assumptions based on the presence of a few SNPs which are somewhat rare?

 

[Violeta]

@mariovitali , if bile acids helps so much, then you most likely can return to good health by cleaning up liver and gallbladder congestion so that your body makes it's own bile the bile is able to flow.

And on another note, do you have any information about DCYTB, a cupric reductase?

I started to find some answers to my chronic fatigue/fibromyalgia when I was looking at downstream results of bariatric surgery. I found that it had something to do with cholecystokinin.

https://en.wikipedia.org/wiki/Cholecystokinin

The area of the small intestines is greatly affected after bariatric surgery, and very shortly afterwards patients usually have copper deficiency and hyperoxaluria.

"CCK also causes the increased production of hepatic bile, and stimulates the contraction of the gall bladder and the relaxation of theSphincter of Oddi (Glisson's sphincter), resulting in the delivery of bile into the duodenal part of the small intestine. Bile salts formamphipathiclipids, micelles that emulsify fats, aiding in their digestion and absorption."

 

[Violeta]

Good for the liver, phosphorus.

https://www.naturalhealthcarestore.com/superphos.htm