Unfolded Protein Response and A Possible Treatment for CFS

[Carribeanboy]

Hello Everyone,

I came across this tread (I read the entire tread in 4 days)while doing intensive research on tudca.Im a 29 years old man living in the french carribean.Long story cut short, I became sick 7 years ago after drinking every 2 hours a shake made of canola oil,honey,olive oil,peanut butter,protein powders.I stayed 4 months on this diet and started to develop strange symptoms 2 months after starting the drink.

My sex drive and motivation vanished, I felt different and more fatigued.8 months later I lost 20 pounds in 2 weeks and my stools became pale.During the last few years blood test shown extremely low cholesterol levels,high prolactin,high reverse t3,low phosphatidyl serine,low testosterone,high estrogen,low alkaline phosphatase,low phosphorous,parasites.

I became a pubmed geek and became researching on my own on orhomolecular medicine.It took me years to finally discover I destroyed my liver and poisoned myself with methyl mercury.

I stayed away from natural health and research for two years for spiritual reason, and attended university in order to become a data scientist.I transcended my disease spiritually and this year I felt strong enough to go back to research in order to heal myself with serenity.Unfortunately I got an testicles infection which I wasn't able to cure with my herbs.I had to take doxycycline (I hate drugs) which left me with a disease called increased intracranial hypertension.I developed extreme head pressure,photophobia,dry eyes,dark circles under eyes,kidney pain.After 4 months of endless torture I got a bit better and decided to fight back.

Here are my areas of research:

Tetracycine induced B12 deficiency leading to increased intracranial hypertension

cholestasis induced hypothyroidism/high cortisol/adrenal fatigue

I have gained some knowledge during the years on alternative treatment and I hope we can help each other.

Some of you may know the power of bile acids especially the mighty tauroursodeoxycholic acid (tudca) but there is a new kid on the block.I dont know how tudca act on the gallbladder but the key to gallbladder health is regular bile dumping.No liver flushes,milk thistle,even coffee enema will do the trick.

It appears that Cholic and chenodeoxycholic acids are the emperors when it comes to bile dumping.
ALLOCHOL ( not alcohol) manifactured in the belarus republic is natural supplement containing dried bile packed with these two acids.A very knowledgeable bodybuilder cured his gallbladder problems using alcohol and tudca.He claimed he puked like crazy and expelled green bile trough feces while on it.

I havent started serious research on it yet but I ordered mine from eBay.Beware of the website homeapteka its a scam.

I plan to try it along with the protocol designed by @mariovitali.When I have more infos and datas I will let you know.Also I recommend people on the protocol to use real selenomethionine not the synthetic form.Its is yeast based.Only 3 laboratories in the world provide yeast based selenomethionine.I can provide data later since I dont want to go in all directions.

warm regards

Kevin

 

[Eastman]

It appears that Choline has helped many people i talk to (including my self)...

I wouldn't be surprised. I'm just concerned about the effect on appetite.

Fast forward, I am under the suspicion that complete recovery may be taking place, meaning no need of taking Bile Acids, TUDCA/UDCA or anything similar. I will report back.

Look forward to your report then.

 

[mariovitali]

@Eastman

So far i am the only one who had that problem. Looking back i do recall that i had a sense of fullness very early but it wasn't that much of a deal. As time passed by (2-3 months) i could feel the difference greatly.

I do not think that one could run into these problems overnight but then again we cannot really know how everyone will react.

Combining TUDCA and Choline was too much for me i guess.

 

[whodathunkit]

So far i am the only one who had that problem. Looking back i do recall that i had a sense of fullness very early but it wasn't that much of a deal. As time passed by (2-3 months) i could feel the difference greatly.

If we're talking about changes in appetite due to choline supplementation, then I experienced it, too. I had a pretty intense experience with choline supplementation (with added acetylcholine boosters and some acetylcholinesterase inhibitors) at the end of 2014 that changed my appetite for the better. I had a problem with overeating for years before that, though.

I don't necessarily think the appetite suppression with choline is a long term thing, and suspect it probably has to do with liver function and detoxification processes (toxin mobilization). I can't necessarily prove that, but I base that opinion on my experience. I ended my choline supplementation when I crashed with a "choline flu" in December 2014. I'd been going pretty heavy with choline (1000mg - 2000mg/day) and the other supps for a month or at most two. When the flu/crash started I was nauseous/vomiting and had watery, green diarrhea. After a day the vomiting subsided but the nausea and green water poo remained for another week. Felt like I was "cleaning out". After that my appetite never returned to what it had been prior, and I lost a bunch of weight in 2015, which I've kept off to this day. However, my appetite has recovered to a more normal level compared to how depressed it was after the choline flu.

Incidentally, that choline flu was my last crash. I haven't crashed since, and my energy levels keep slowly increasing towards normalcy. Knock wood.

 

[mariovitali]

@Carribeanboy

Welcome to the Thread! Nice to have a second Data Scientist around ;-)


Many of the things you discuss make sense to me. I never heard of ALLOCHOL but seems very interesting. A person who is completely recovered from Post-Finasteride Syndrome told me very recently that he is taking something called Noni which also aids in stimulating Bile acid production. This keeps him symptom-free so we have yet one more agent that is a cholagogue that appears to be beneficial for some cases.

If you read this Thread thoroughly (i know it's a pain to do this) you must have seen some questions i have which ideally should be answered by an expert in Bile acid homeostasis. In other words :

a) You might have cholestasis
b) You might have Bile acids that are not been converted to their Conjugated form.

If your situation is (b), stimulating Bile would not be a good idea Perhaps for (a) too. So i think that caution is required.

However there is no doubt that what you provided is a very interesting piece of Information.

BTW, If you have your DNA Data available please let me know.

Thanks and Good Luck!

 

[aquariusgirl]

How do you figure out if I am in the (a)group or (b) group?

 

[Carribeanboy]

@mariovitali

Unfortunately I am not a data scientist.I wasn't accepted at school because I was 28.French's educational system is by far the stupidest on earth not to mention the medical system.For exemple 23andme tests are forbidden in France.I can send the kits in Belgium though.

I do not have dna data yet.Just my intuition.

I may be in both situations concerning my gallbladder.What I know for sure is I need to get my bile to dump.ALLOCHOL will do it I guess.

here are some interesting data on bile acids and gallbladder.I think you could find something interresting on this blog.

http://gallbladderetc.blogspot.com/2015/04/allochol-ingredients-activated-charcoal.html

Here is the video from the bodybuilder

Kevin

 

[ahmo]

@whodathunkit Congrats on your successful detox.

I've been using GPC + citicoline + sunflower lecithin for about a year. My body used to want more when stressed, but no longer asks for more than my baseline amount.

 

[dannybex]

If we're talking about changes in appetite due to choline supplementation, then I experienced it, too. I had a pretty intense experience with choline supplementation (with added acetylcholine boosters and some acetylcholinesterase inhibitors) at the end of 2014 that changed my appetite for the better. I had a problem with overeating for years before that, though.

I don't necessarily think the appetite suppression with choline is a long term thing, and suspect it probably has to do with liver function and detoxification processes (toxin mobilization). I can't necessarily prove that, but I base that opinion on my experience. I ended my choline supplementation when I crashed with a "choline flu" in December 2014. I'd been going pretty heavy with choline (1000mg - 2000mg/day) and the other supps for a month or at most two. When the flu/crash started I was nauseous/vomiting and had watery, green diarrhea. After a day the vomiting subsided but the nausea and green water poo remained for another week. Felt like I was "cleaning out". After that my appetite never returned to what it had been prior, and I lost a bunch of weight in 2015, which I've kept off to this day. However, my appetite has recovered to a more normal level compared to how depressed it was after the choline flu.

Incidentally, that choline flu was my last crash. I haven't crashed since, and my energy levels keep slowly increasing towards normalcy. Knock wood.

I've had terrible reactions to choline supplementation every single time. Which is frustrating because it is important for liver and gallbladder health. But I would get symptoms of excess acetylcholine -- worsening anxiety, irritability, muscle twitching, cramping, etc., so in my case it may have something to do with insufficient acetylcholinesterase levels (the enzyme that breaks down acetylcholine).

There are studies that suggest B12, carnitine and melatonin deficiencies are associated w/lower levels of acetylcholinesterase.

Also, not sure if this has been posted, but cholinergic function is messed up in ME/CFS and Gulf War patients:

http://www.clinsci.org/content/106/2/183

"The response to acetylcholine was significantly higher in patients with CFS than in controls (P=0.029, repeated-measures ANOVA), but was normal in those with GWS and those exposed to organophosphates. The methacholine response was higher than the acetylcholine response in all patient groups except for those with CFS, where there was no difference between the responses. Although there are many clinical similarities between these three illnesses, our results indicate peripheral cholinergic abnormalities in the vascular endothelium of only patients with CFS, suggesting that this syndrome has a different aetiology, which might involve inhibition of vascular cholinesterase."

 

[Violeta]

@mariovitali , I've been wondering if in trying to reverse your symptoms caused by finasteride you have slowed down your hair loss?

 

[mariovitali]

@mariovitali , I've been wondering if in trying to reverse your symptoms caused by finasteride you have slowed down your hair loss?

Actually it was the other way around. As soon as Post-Finasteride kicked in my hair loss stopped. I hypothesize that this happened because Hormones were not being metabolized properly.

I could clearly see that my hairline started receding very rapidly 6 months ago so i started derma-rolling. Hopefully it will work...

 

[Gondwanaland]

I want to throw in some info for consideration here (actually I need help to break it down).

The late Rich van K gave some input on Accutane (I took it for 3 months in 2010):

Hi, Gestalt and the group.

With regard to Accutane, here's something else to consider: Accutane has been found to raise the gene expression of the enzyme glycine N-methyl transferase. The effect of this is to lower the ratio of SAMe to SAH, and that lowers the methylation rates of the methyltransferase reactions, including the ones that methylate DNA and thus silence gene expression.

I have encountered several people who became chronically ill after Accutane (or Roaccutane in Australia) treatment. I think that what might have happened is that the gene expression for glycine N-methyltransferase got "stuck" high because of a positive feedback mechanism. Since methylfolate downregulates glycine N-methyltransferase at the biochemical level, taking a fairly high dosage of it may break this vicious circle.

Best regards,

Rich

Another piece of the puzzle:

1991 Gout and Vitamin A Intoxication: Is There a Connection? (enclosed file)

A number of cases of increased uric acid levels have been reported following the use of isotretinoin (Accutane, Hoffman LaRoche, Nutley, NJ, 13-cis-retinoic acid), a synthetic derivative of vitamin A, for severe acne.“’ Hyperuricemia was detected after 16 to 109 days of treatment with 40 to 80 mg of isotretinoin daily.

Looking at this chart we can imagine a complementary route gearing right there in the middle coming towards our noses made by B2 and iodine, which in its turn is fed by methyl donors like choline, supplemental melatonin etc.

I am under the impression that the dietary B2 or B2 supplemented in non-coenzymated form is funneled by this route when there is abundance of dietary molybdenum and vit A (not carotenoids). To divert B2 from this route, I think B5 and manganese (and perhaps copper, both Mn and Cu to improve the estrogen route and thus balance T4 production). Sulfur is needed to divert Molybdenum to the transsulfuration route (to process sulfites).

So far I have no experience with supplemental FMN or R5P, and am not sure if it wouldn't be funneled to the uric acid pathway at some point.

I think SNPs aren't important here, because I might have a slow estrogen breakdown by the liver, but being grain free since 2013 simply shot down my estrogen production (lacking dietary Mn and PABA). Also I found in the enclosed paper a good explanation to the side effects I have from eating eggs (e.g. hair loss) due to the high content of vit A in the yolks.

So, the solution I see is taking PABA (to slow estrogen breakdown) and K2-MK4 for its role in modulation of sex hormones. Unfortunately I can't handle the side effects I get from MK4, and am yet to find out how the PABA acts in my body. B5 is an important piece as well for steroid synthesis. I still need to put together further citations.

I have taken small amount of manganese in the past, but it won't work (and can even be harmful) without the proper co-factors. I look up foods rich in Mn and make my choices. I had a pleasant experience with chickpeas which cleared much of my sulfite problems (high Mn and high Mo). Small amounts of 70 - 85 % cocoa chocolate have been helpful (Mn + Cu + Mg).

 

[Violeta]

Protein folding and Parkinson's and Alzheimer's.

http://msutoday.msu.edu/news/2014/m...-parkinsons-treatment-toward-clinical-trials/

Research at Michigan State University, published in the Journal of Biological Chemistry, shows that a small “molecular tweezer” keeps proteins from clumping, or aggregating, the first step of neurological disorders such as Parkinson’s disease, Alzheimer’s disease and Huntington’s disease.

 

[mariovitali]

@Gondwanaland

Have your CFS problems started AFTER taking Accutane?


I think the solution may be elsewhere (just a hypothesis of course) but cannot really say anything until i see your DNA Data.

 

[Gondwanaland]

Have your CFS problems started AFTER taking Accutane?

I would say that my health went downhill one year later when I had endothelium injury followed by a reactive thrombosis. What caused the endothelium disfunction? Could it be due to high uric acid? (I wasn't taking blood tests back then)

 

[Eastman]

Protein folding and Parkinson's and Alzheimer's.

http://msutoday.msu.edu/news/2014/m...-parkinsons-treatment-toward-clinical-trials/

Research at Michigan State University, published in the Journal of Biological Chemistry, shows that a small “molecular tweezer” keeps proteins from clumping, or aggregating, the first step of neurological disorders such as Parkinson’s disease, Alzheimer’s disease and Huntington’s disease.

The advantage of the molecule, CLR01, which is patented, is that it can cross the blood-brain barrier. No doubt, it will eventually become a drug if trials prove successful.

For Alzheimer's, we already have Ashwagandha, or Withania somnifera, which doesn't seem to need to cross the BBB to clear β-amyloid peptides.

Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver

 

[Eastman]

@Gondwanaland, have you seen these?

The Independent Association of Serum Retinol and β-Carotene Levels with Hyperuricemia – A National Population Study

Associations between concentrations of uric acid with concentrations of vitamin A and beta-carotene among adults in the United States.

A composition for lowering a blood uric acid level is characterized by comprising taurine as an active ingredient.

 

[Gondwanaland]

@mariovitali and everyone else, taking B6/P5P has a sinilar effect to finasteride on 5 alpha reductase enzyme.

https://en.wikipedia.org/wiki/5α-Reductase
5α-reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in 3 metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism.

http://meridianvalleylab.com/clinical-significance-of-5a-reductase
5-α Reductase Inhibitors

Some inhibition of 5AR may be desirable when 5AR activity is seen to be quite elevated. Natural 5AR inhibitors can provide effective moderate inhibition without shutting down 5AR altogether, which is seen with 5AR inhibiting drugs. Natural 5AR inhibitors include:

• Gamma-linolenic (GLA) , docosahexaenoic acid (DHA), and other fatty acids.5,6
• Serenoa repens (Saw palmetto)7,8,9,10
• Zinc 11,12

Research on the effects of zinc on 5AR has shown that its inhibitory effects can be potentiated by vitamin B6. Supplements containing highly concentrated Saw Palmetto extracts may result in over-inhibition of 5AR. 5AR activity can be monitored in a 24-hour urine hormone profile.

Over-inhibition of 5AR decreases the production of dihydrotestosterone (DHT) resulting in increased levels of testosterone. The consequent aromatization of testosterone à estradiol may cause gynecomastia, a known side effect of 5AR inhibitor drugs.

Finasteride® and Dutasteride®

Patent medicines that inhibit 5AR are used to treat benign prostatic hyperplasia, prostate cancer, and baldness (androgenic alopecia).

So taking B6/P5P will increase the need for bile acids, TUDCA, UDCA, Taurine, Choline...

 

[Gondwanaland]

OTOH, taking methyl donors like bile acids and bile acid precursors might indeed raise the need for B6/P5P to balance uric acid formation.

 

[mariovitali]

@Gondwanaland

Hmm....Thanks for that, will look it up although i no longer take B6/P5P.