Unfolded Protein Response and A Possible Treatment for CFS

[dannybex]

Leptin is of major significance to ME/CFS, since fatigue levels in ME/CFS correlate to leptin levels (see here). As leptin levels go up, this increases fatigue in ME/CFS. So any leptin resistance would presumably lead to increased fatigue in ME/CFS.

Now it seems that ER stress induces leptin resistance. Refs: 1 2

However, TUDCA is a leptin sensitizer, that can help combat leptin resistance (and thereby lower leptin) by reducing ER stress. Ref: 1 So by this mechanism, TUDCA may be helpful for ME/CFS.

@Hip, would leptin resistance then equate with poor appetite and/or possibly even gastroparesis?

Re bile acids: Also worth noting is that bile helps reduce inflammation by inhibiting gut permeability. They also 'cleanse' endotoxins directly, again, reducing inflammation, in this study w/psoriasis patients.

 

[mariovitali]

@dannybex

Prior to TUDCA/UDCA my appetite was normal. I take Bile Acid Factors after a meal. I also had an incident of gastroparesis (i think). The meal just wouldn't go away...i am saying "i think" because a special test is needed to confirm gastroparesis...but the feeling was that the food just couldn't be digested.

I am also looking at other causes of my appetite problems, it may be Selenium supplementation but i am not sure yet.

In any case i will update as soon as i have a definitive cause.

 

[Hip]

@Hip, would leptin resistance then equate with poor appetite and/or possibly even gastroparesis?

I don't really know.

 

[Sidereal]

@Hip, would leptin resistance then equate with poor appetite and/or possibly even gastroparesis?.

Leptin is a satiety hormone. When the hypothalamus becomes leptin resistant, it can't read leptin signals properly, leading to increased appetite & weight gain. Obesity tends to be associated with faster gastric emptying which is the opposite of gastroparesis.

 

[brenda]

Leptin is a satiety hormone. When the hypothalamus becomes leptin resistant, it can't read leptin signals properly, leading to increased appetite & weight gain. Obesity tends to be associated with faster gastric emptying which is the opposite of gastroparesis.

Yes this is what drjackkruse.com says, apart from faster gastric emptying, who is a neurosurgeon and has biohacked his own problems with obesity and I'll health. I am following his advice about resetting leptin resistance through a type of paleo diet ( stricter than his because of metabolic syndrome and autoimmunity) l don't have severe weight problems but need to get a few stones off though it is going slowly. . He advises lifestyle changes which include timing of meals, breakfast being high protein at 50 grams within half an hour of waking. I am on day three with that and it seems to be helping.

Leptin resistance causes slower metabolism. He claims it is about prehybernation mode.

He is into the longevity side of things but says that CFS will improve with his advice. My energy levels are hugely improved since cutting out grains and wish l had done it years ago. Might give TUDCA a go.

 

[brenda]

I have gall stones, due l think to eating a high carb low fat diet for years. Once l started hflc the gall stones started to be expelled ,*ouch*.

I handle the pain with heat and magnesium malate but would love to have the guts to do a flush. They say that you do not develop gall stones on a paleo diet.

 

[Gondwanaland]

They say that you do not develop gall stones on a paleo diet.

I have read plenty of reports from people following a paleo diet for like 2 years and then develop gall stones. I think people aren't getting enough glycine from a skewed customized version of the diet.

 

[brenda]

I have read plenty of reports from people following a paleo diet for like 2 years and then develop gall stones. I think people aren't getting enough glycine from a skewed customized version of the diet.

Thanks interesting. I am eating loads of green leafies bone broth and chicken skin so hope am oky. Must buy liver must buy liver....

 

[dannybex]

Leptin is a satiety hormone. When the hypothalamus becomes leptin resistant, it can't read leptin signals properly, leading to increased appetite & weight gain. Obesity tends to be associated with faster gastric emptying which is the opposite of gastroparesis.

Thanks @Sidereal. I'm either definitely not leptin resistant, and/or I have low levels to begin with. Or perhaps some other reason (chronic infections, insulin resistance, etc.?)...

 

[Sidereal]

Thanks @Sidereal. I'm either definitely not leptin resistant, and/or I have low levels to begin with. Or perhaps some other reason (chronic infections, insulin resistance, etc.?)...

If you're very skinny/underweight, you probably have low leptin levels because leptin is a hormone secreted by fat tissue and the more fat tissue you have, the more leptin you have. (The exception to this is formerly obese people who diet down to a lower weight. In those individuals, even if they're still overweight, leptin levels tend to be abnormally low compared to healthy BMI-matched un-dieted controls. This metabolic problem contributes to the almost universal weight regain experienced by dieters.)

 

[Hip]

Leptin is a satiety hormone. When the hypothalamus becomes leptin resistant, it can't read leptin signals properly, leading to increased appetite & weight gain.

That makes sense, although in leptin resistance, you also get increased levels of the leptin hormone, presumably to try to make up for the way the hypothalamus has become desensitized to leptin. So possibly that brings you back to square one (you have less leptin less sensitivity, but more leptin in the blood to make up for it).

But I don't really know. I do know that the suspected coxsackievirus B virus that appeared to trigger my ME/CFS also caused me (as well as others who contracted the same virus) to put on a lot of belly fat (abdominal obesity). I still have an athletic physique, but now with this large add-on stomach budge of fat, that if I were female would make me look pregnant.

I read that two causes of abdominal obesity are leptin resistance, and also low growth hormone levels. I suspect leptin resistance may be behind my abdominal obesity. I don't have a great appetite though.


As well as ER stress, elevated SOCS-3 may also be responsible for leptin resistance, and thus in turn responsible for abdominal obesity. Ref: 1

A main function of SOCS3 (suppressor of cytokine signaling) is to put the brakes on the immune system. Coxsackievirus and other viruses induce both SOCS1 and SOCS3 to evade the immune response. Ref: 1 So perhaps this is how my coxsackievirus B infection triggered my abdominal obesity.

The drug pioglitazone (Actos) suppresses SOCS3. Ref: 1

SelfHacked has a page on SOCS3: SOCS3: The Root Cause of Leptin Resistance - Selfhacked

 

[Avengers26]

@Hip @mariovitali Where do you buy TUDCA? It might be worth a try if I can find it a reasonable price.

 

[Hip]

I bought Brawn Nutrition TUDCA 250 mg x 60 capsules for £30 on the UK eBay.

 

[mariovitali]

@Avengers26

TUDCA : I bought mine from nutriverse.com, the brand is from Olympus Labs.
UDCA : I can find it with out prescription on my local Pharmacy store.

 

[jengonwin]

I have read that if tudca is taken before or during alcohol it may cause damage.

Can it be taken whilst on antibiotics? Or should it be taken after.

Mario have you investigated mercury toxicity? Mercury has disastrous effects on the liver and also methylation. Sadly its no so easy to detect when your exposure was a long time ago.

Andrew Hall Cutler PhD is the world expert on mercury toxicity and chelation. Maybe have a read?

Common exposures:
-CFL Bulbs
-Dental Amalgms
-Vaccines
-Certain seafood

 

[dannybex]

FYI: an interesting review on the many different types of animal bile (over 44!) used in TCM:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123376/

 

[whodathunkit]

I finally bit the bullet and decided to give TUDCA the old college try. Dragged out my old bottles that have been sitting around for a year. I've been on it now for about a week.

@mariovitali , in any of your readings about TUDCA did you come across anything that seemed to contraindicate taking iron at the same time? As you may or may not remember I'm anemic, and I started to take some iron right before I started TUDCA. For the first time ever, after fixing up my liver a bit with very low fat diet and some B2, it seemed like iron might actually have started to help me. I think I could feel it. But I stopped the iron when I started TUDCA because after some consideration I decided the potential boost in liver function from TUDCA was at this point more crucial than iron supplementation, iron supp. probably being a moot point until I get monthly blood loss down to a normal amount, anyway. I've been jacking around with the anemia for years because of that.

Anyway, if iron supplementation isn't clearly contraindicated while on TUDCA I'd like to start it up again. Anything you know or can remember would be appreciated.

 

[Gondwanaland]

Thanks interesting. I am eating loads of green leafies bone broth and chicken skin so hope am oky. Must buy liver must buy liver....

I don't eat liver very often because it can trigger gout for me - I do eat a little bit of liver pate (1/2 Tbsp) for a few days in a month or every couple of months.

I have read a report of someone who was eating liver 3x weekly plus a lot of betacarotenes from vegetables and leafy greens. His liver stopped to convert betacarotenes into vitamin A and he got orange hand palms and feet soles - his thyroid probably got overstimulated from too much vit A and then he ended up hypothyroid and hypoglycemic.

 

[mariovitali]

@jengonwin I haven't looked at Mercury toxicity so far.

@whodathunkit To the best of my knowledge there is no such problem but i do agree with your way of thinking : Fix your Liver first. This will also fix -hopefully- all major detoxification pathways.

 

[mariovitali]

I just wanted to inform all of you of the work that has been taking place.

So far, 37 individuals have sent over their raw DNA Data. This enables us to analyze these Raw files and extract potentially useful insights.

For example, the following screenshot shows a list of Genes that were found to have a large proportion of Variant Alleles.

Note that the list of Genes has been blurred on purpose. For various reasons, i cannot disclose which genes are listed at the moment.

Take for example the first row : Among the 37 individuals, for the particular Gene :

34.21% have Homozygous mutation
55.26% have Heterozygous mutation
10.53% do not have any mutation.

The column name not_in_chip is used to select Genes that exist on all analyzed Raw files (therefore the percentage of missing Genes is 0%, meaning we do not want to take into account any Genes that are not being analyzed by 23andme ).

Unfortunately there are other Genes (such as SUOX) that are not being analyzed by 23andme at all, hence the percentage of missing is 100%. Other potentially interesting Genes have a much less missing percentage (around 30-20%) but in this case -especially- more Raw Data are needed.


If you wish to support this Research (by sending me your raw data) , please contact me