@mariovitali -- yes, definitely had very pale stools for years. I'm pretty sure I have cholestasis issues, but haven't had a total bile acids test or a fibroscan. I'll google those for more info, thanks.
Unfolded Protein Response and A Possible Treatment for CFS
- Thread starter mariovitali
- Start date
Wayne
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Hey @dannybex, in the past year I've gotten into eating raw egg yolks, and discarding most of the whites. I like putting a couple of egg yolks in a large cup of bone broth, and find it to be one of my favorite "comfort" foods, as it has quite a calming effect on my entire system. I probably have this every other day or so. -- All the Best!
And more details on the benefits of olive oil in particular for the liver:
Liver Protective Effects of Extra Virgin Olive Oil: Interaction between Its Chemical Composition and the Cell-signaling Pathways Involved in Protection.
Olive leaf extract in high doses, though, has been found to induce undesirable changes in rodents.
High doses of olive leaf extract induce liver changes in mice
Toxicity of Olive Leaves (Olea europaea L.) In Wistar Albino Rats
thanks--yea I love olive oil and vinegar on my salads
olive leaf extract on the other hand always felt like cr*p after trying that stuff in years past, decided a big NoPe on that one
Liver Protective Effects of Extra Virgin Olive Oil: Interaction between Its Chemical Composition and the Cell-signaling Pathways Involved in Protection.
Olive leaf extract in high doses, though, has been found to induce undesirable changes in rodents.
High doses of olive leaf extract induce liver changes in mice
Toxicity of Olive Leaves (Olea europaea L.) In Wistar Albino Rats[/QUOTE]
olive leaf extract on the other hand always felt like cr*p after trying that stuff in years past, decided a big NoPe on that one
Liver Protective Effects of Extra Virgin Olive Oil: Interaction between Its Chemical Composition and the Cell-signaling Pathways Involved in Protection.
Olive leaf extract in high doses, though, has been found to induce undesirable changes in rodents.
High doses of olive leaf extract induce liver changes in mice
Toxicity of Olive Leaves (Olea europaea L.) In Wistar Albino Rats[/QUOTE]
frozenborderline
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Where did you hear the bolded?? it would be quite surprising to me if that was true!
Gondwanaland
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frozenborderline
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haha wayne this is such a ray peat thing to do. But yeah I've been very, very ill recently and the thing I tolerate the best is eggs with potatoes, but especially the yolks, which are easier to digest. it's high quality protein and vitamins and very digestible
Wayne
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Not quite sure who Ray Peat is, but if he's doing the same thing, he must have gotten the idea from me!
Violeta
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I used to read at one of the Ray Peat forums. I had been reading Peat's papers forever and noticed a huge difference in the type of writing in the newer articles and brought up the subject. Someone there confirmed they were being written by someone else and that the site had been sold.
Malea
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I‘ve got a question: If I remember it right I read somewhere in this thread that in @mariovitali ‘s theory taking p450-inhibitors would be not good.
Now I was wondering if medications that are metabolised through the p450-cytochromes are automatically inhibitors? (For example the betablocker propranolol or many antibiotics)
Now I was wondering if medications that are metabolised through the p450-cytochromes are automatically inhibitors? (For example the betablocker propranolol or many antibiotics)
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I would still like to try UDCA/TUDCA but my doctor will never prescribe it as he easily dismissed my pale stools as "absolutely normal" phenomenon. Does anyone know where can I buy a good UDCA without prescription?
I would like to start with UDCA rather TUDCA as taking taurine alone not only doesn't help but makes some symptoms worse(including the pale stools and varicose veins).
I would like to start with UDCA rather TUDCA as taking taurine alone not only doesn't help but makes some symptoms worse(including the pale stools and varicose veins).
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Has anyone seen this? @mariovitali
"Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor"
https://www.ncbi.nlm.nih.gov/m/pubmed/23004356/
"Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor"
https://www.ncbi.nlm.nih.gov/m/pubmed/23004356/
Wayne
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- Ashland, Oregon
From THIS ARTICLE -- "Lithium increases Heat Shock Proteins (HSPs), which promote folding of proteins, refolding of misfolded proteins, and disposal of abnormal proteins" [R].
Below is an article by a woman who goes into detail on how she believes lithium orotate helped her recover from CFS.
RECOVERING WITH LITHIUM OROTATE
Below is an article by a woman who goes into detail on how she believes lithium orotate helped her recover from CFS.
RECOVERING WITH LITHIUM OROTATE
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invisiblejungle
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I found several sources for UDCA:
https://www.mimaki-family-japan.com/item/list?keyword_pc=Ursodeoxycholic+acid&x=0&y=0
http://www.buypharma1.com/Products/search/?keyword=Ursodeoxycholic+acid
brandmedicines.com
goldpharma.cn
I've ordered from all of these pharmacies before and can vouch for them.
frozenborderline
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Is UDCA preferred over tudca
invisiblejungle
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I don't know. The poster was asking specifically for UDCA rather than TUDCA, which is available as a supplement.
Interesting thing about TUDCA. It's found naturally in large amounts in bear bile, and Asian bears have a lot more than American bears. Bear gallbladders have been used in traditional oriental medicine for millennia. I'm Korean, and my parents said that when they were growing up in Korea, bear gallbladder was known as a panacea and was one of the most expensive medicines.
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Although Ive seen positive effects in my gut irritation and some kind of anxiety lowering effect from UDCA, I´ve noticed it has increased some nasty overgrowths. This hypothesis made sense after readig this :
"UDCA increased mortality of mice following Escherichia coli infection due to the worsening of infection". Seems it lowers lymphocites so those of us with poor inmune funcion should be careful with it.
I´ve also noticed increased fatigue while on it. Has anybody experienced something similar?
Glucocorticoid receptor-dependent immunomodulatory effect of ursodeoxycholic acid on liver lymphocytes in micehttps://www.physiology.org/doi/full/10.1152/ajpgi.00205.2012
"UDCA increased mortality of mice following Escherichia coli infection due to the worsening of infection". Seems it lowers lymphocites so those of us with poor inmune funcion should be careful with it.
I´ve also noticed increased fatigue while on it. Has anybody experienced something similar?
Glucocorticoid receptor-dependent immunomodulatory effect of ursodeoxycholic acid on liver lymphocytes in micehttps://www.physiology.org/doi/full/10.1152/ajpgi.00205.2012
OK, so I got here while searching for keywords "choline PEM". This thread drew my attention so I decided to read it in whole but I immediately found that the thread and the theory have issues, multiple issues.
In case you are wondering if you should read this thread (and devote your mental resources to it for a few days experiencing different "mental PEM states" in the meantime) I am trying to provide a critical review - after reading it. It may also be easier for you to understand what is going on in this thread.
Introductory remarks:
How long did it take to read? 20 days. On and off. Maybe 10 days of pure reading, maybe less.
Was it worth reading? Not exactly. The first post summarizes the protocol and the theory pretty well, I'd only add rhodiola rosea to the protocol (or to the list of things that you should try if you prefer it this way) as it is mentioned within the thread in one of the posts but it is not mentioned in the first post (I think).
However, there is a lot of articles mentioned along the way, at least two of which I found very interesting. So, if one is willing to learn something new, there is something to be learned here but beware: the path is treacherous and you have to be very careful.
Background/experience: 20 years of CFS, whole genome sequenced 2 times (research facility + commercial) + 23 and me, worked on my own genetic data for 6 months after receiving the research genome sequence as those were the times when no commercial sequencing was available (and I was actually a subject #1 in the research facility), worked with the professor, queried the databases, etc.
***
Good things about this thread and theory:
- it introduces TUDCA and shows that it is used to battle Parkinson's disease so it IS actually working on a cellular level. I'd never find out about TUDCA if it wasn't for this thread. However, even though I planned I am not using it currently because something else worked for me very well in the meantime. Yes, it's a very strange coincidence indeed but it is what it is.
- it shows how important choline and taurine is - not only for the muscle and nerve cells but also for the liver. This is probably why high dose lecithin worked for my gut issues and consequently other things. This high dose lecithin - started two weeks ago.
- it shows how to look for research papers in a more ordered fashion ie. using data mining. However, this approach will lead to problems when incorrectly used with SNPs, see below.
- provides you with many articles, many stories, a few starting points for other protocols
Bad things about this thread and theory:
- the data mining approach to SNPs (ie. assigning scores to all possible SNPs within a gene, summing the scores up and assuming that the higher the sum the worse your condition potentially is) is completely incorrect - as described by Valentijn in post number 1365: https://forums.phoenixrising.me/thr...-possible-treatment-for-cfs.37244/post-690695
... among other posts.
The readers (if you decide to read it) should be aware of that from the beginning as this approach is presented much much earlier within the thread. Why was this model of data mining constructed this way (I'm trying to understand mariovitali here)?
In data mining it is common to construct a model like this, find correlations, refine the model (or change it completely) based on these correlations, etc.
Given a lot of data and many iterations we will arrive at a correct answer (in theory). However SNPs and gene interaction will not fit to any simple model like this. Besides: why start with such a simple model when it is already well known how to approach this problem?
But it gets even worse. You simply can't do such an analysis with 23 and me data. There are too many errors. Many years ago I compared my data from research quality genome sequencing (= very high quality, many passes, error ratio less than one in a thousand) to 23 and me data. Looks like the error rate is about 4%. With such an error rate there is almost no way any analysis can give correct results. And the professor that I worked with, when we found a suspicious SNP, he ordered a sequencing procedure of that gene called Sanger sequencing - that's how certain you need to be when it comes to looking for very rare (disease-causing) SNPs. Basically the error rate has to be lower than that of the frequency of that SNP otherwise it's turning to a guessing game. With Sanger sequencing, the error rate is lower than 1 in 1000.
So... with 23 and me you'd need to look for SNPs with a frequency higher than around 4% but then SNPs with such a frequency will most often not cause any disease at all. These are simply too frequent and had it been a disease-causing SNP there would have been too many patients and somebody would have identified this SNP as a disease-causing and this disease a long time ago.
For comparison: incidentally 4% ie. 1 in 25 people carry a mutation for cystic fibrosis which is the most frequent genetic disease.
But it gets even worse: with whole-genome sequencing you will receive data about all possible SNPs within your genes and with 23 and me data... you'll only receive data on the SNPs handpicked based on many different criteria (a very very pitiful subset of what you get with WGS actually) - most of the time these will not be the less frequent SNPs - so, again, it's pointless to even start the analysis. The data is skewed.
Of course, even though this way of explaining the genetic origin of CFS is incorrect, the theory about unfolded protein response in CFS looks quite solid.
- it's not all about genes. A simple dietary deficiency of choline or taurine or mechanical obstruction of gallbladder may cause you similar symptoms as if you had a genetic condition. When people report different symptoms mariovitali is always somehow able to connect them to a liver dysfunction via genes. That's pretty amazing but that would be too easy... there are dietary, mechanical, bacterial and god knows what other factors involved...
****
OK, now I have a few remarks.
But from a broader perspective - if it helps like 20% (maybe more, who knows but I personally doubt it) of the people who follow her advice - it is still worth it for the people to try it, right? You have to try something or die trying, right? Like you just can't be sick and stay in bed for the rest of your life...
From an even broader perspective - that 80% of the people who pay her and it doesn't work for them still pay her so for her it actually works 100% of the time. This quick business calculation shows that this venture will be/is profitable...
In case you are wondering if you should read this thread (and devote your mental resources to it for a few days experiencing different "mental PEM states" in the meantime) I am trying to provide a critical review - after reading it. It may also be easier for you to understand what is going on in this thread.
Introductory remarks:
How long did it take to read? 20 days. On and off. Maybe 10 days of pure reading, maybe less.
Was it worth reading? Not exactly. The first post summarizes the protocol and the theory pretty well, I'd only add rhodiola rosea to the protocol (or to the list of things that you should try if you prefer it this way) as it is mentioned within the thread in one of the posts but it is not mentioned in the first post (I think).
However, there is a lot of articles mentioned along the way, at least two of which I found very interesting. So, if one is willing to learn something new, there is something to be learned here but beware: the path is treacherous and you have to be very careful.
Background/experience: 20 years of CFS, whole genome sequenced 2 times (research facility + commercial) + 23 and me, worked on my own genetic data for 6 months after receiving the research genome sequence as those were the times when no commercial sequencing was available (and I was actually a subject #1 in the research facility), worked with the professor, queried the databases, etc.
***
Good things about this thread and theory:
- it introduces TUDCA and shows that it is used to battle Parkinson's disease so it IS actually working on a cellular level. I'd never find out about TUDCA if it wasn't for this thread. However, even though I planned I am not using it currently because something else worked for me very well in the meantime. Yes, it's a very strange coincidence indeed but it is what it is.
- it shows how important choline and taurine is - not only for the muscle and nerve cells but also for the liver. This is probably why high dose lecithin worked for my gut issues and consequently other things. This high dose lecithin - started two weeks ago.
- it shows how to look for research papers in a more ordered fashion ie. using data mining. However, this approach will lead to problems when incorrectly used with SNPs, see below.
- provides you with many articles, many stories, a few starting points for other protocols
Bad things about this thread and theory:
- the data mining approach to SNPs (ie. assigning scores to all possible SNPs within a gene, summing the scores up and assuming that the higher the sum the worse your condition potentially is) is completely incorrect - as described by Valentijn in post number 1365: https://forums.phoenixrising.me/thr...-possible-treatment-for-cfs.37244/post-690695
... among other posts.
The readers (if you decide to read it) should be aware of that from the beginning as this approach is presented much much earlier within the thread. Why was this model of data mining constructed this way (I'm trying to understand mariovitali here)?
In data mining it is common to construct a model like this, find correlations, refine the model (or change it completely) based on these correlations, etc.
Given a lot of data and many iterations we will arrive at a correct answer (in theory). However SNPs and gene interaction will not fit to any simple model like this. Besides: why start with such a simple model when it is already well known how to approach this problem?
But it gets even worse. You simply can't do such an analysis with 23 and me data. There are too many errors. Many years ago I compared my data from research quality genome sequencing (= very high quality, many passes, error ratio less than one in a thousand) to 23 and me data. Looks like the error rate is about 4%. With such an error rate there is almost no way any analysis can give correct results. And the professor that I worked with, when we found a suspicious SNP, he ordered a sequencing procedure of that gene called Sanger sequencing - that's how certain you need to be when it comes to looking for very rare (disease-causing) SNPs. Basically the error rate has to be lower than that of the frequency of that SNP otherwise it's turning to a guessing game. With Sanger sequencing, the error rate is lower than 1 in 1000.
So... with 23 and me you'd need to look for SNPs with a frequency higher than around 4% but then SNPs with such a frequency will most often not cause any disease at all. These are simply too frequent and had it been a disease-causing SNP there would have been too many patients and somebody would have identified this SNP as a disease-causing and this disease a long time ago.
For comparison: incidentally 4% ie. 1 in 25 people carry a mutation for cystic fibrosis which is the most frequent genetic disease.
But it gets even worse: with whole-genome sequencing you will receive data about all possible SNPs within your genes and with 23 and me data... you'll only receive data on the SNPs handpicked based on many different criteria (a very very pitiful subset of what you get with WGS actually) - most of the time these will not be the less frequent SNPs - so, again, it's pointless to even start the analysis. The data is skewed.
Of course, even though this way of explaining the genetic origin of CFS is incorrect, the theory about unfolded protein response in CFS looks quite solid.
- it's not all about genes. A simple dietary deficiency of choline or taurine or mechanical obstruction of gallbladder may cause you similar symptoms as if you had a genetic condition. When people report different symptoms mariovitali is always somehow able to connect them to a liver dysfunction via genes. That's pretty amazing but that would be too easy... there are dietary, mechanical, bacterial and god knows what other factors involved...
****
OK, now I have a few remarks.
I'd say - try whatever you can as fast as you can (ie. without hesitation if money permits) because you can never know what will work for you. You may try both of these approaches but try them anyway.
No, don't try to reduce the number of supplements solely for the purpose of reducing it. It will end up badly.
When I reached that post... I knew it. I know from experience. It's not worth it.Just wanted to let you know that i just crashed really badly. ATM I have SEVERE brainfog, OI, irregular heartbeat. I am a mess actually
I stupidly decided to stop TUDCA *and* Choline...i feel so bad now because i realize how fine i felt and my condition reminds me of the s**t i've been through having this for so long
Yup, looks like a marketing ploy. Just trying to sell ordinary vitamins (or whatever she sells? books, appointments?) as a part of an elaborate protocol. And statistically, this protocol will work for a fraction of people implementing it - after all it's the vitamins that we're talking about so they have to work for some people. Then she can claim that it's all because of her discovery of methylation problems...
But from a broader perspective - if it helps like 20% (maybe more, who knows but I personally doubt it) of the people who follow her advice - it is still worth it for the people to try it, right? You have to try something or die trying, right? Like you just can't be sick and stay in bed for the rest of your life...
From an even broader perspective - that 80% of the people who pay her and it doesn't work for them still pay her so for her it actually works 100% of the time. This quick business calculation shows that this venture will be/is profitable...
- Messages
- 22
@Mick - please share, what worked for you?
That will be the most unhelpful answer ever. But... everything. I literally take every supplement there is. Every vitamin, every mineral, every body-building compound. I invented my own "Theory of everything" (the pun is intended - for those who like physics and understand what I'm talking about).
But it's been only day 5 (?) of the improvement so I'd rather not to be so joyful about it yet. But it's promising - some aspects are better than ever before, even when I was supposedly healthy (ie. before the onset of the CFS but actually I had CFS for my whole life). Right now I'm at a capacity of 50% of a normal man. Today I was lifting 60-pound boxes for 5 hours... Completely unreal. But I said to myself: if this improvement is to wear off at least these boxes will be moved... so long overdue... And all of this time I was between 1 and 5% depending on the day. Anyways... there are many aspects to it and like 20 years of research. And I'd rather not hijack this thread... but...
I started with this particular approach 12 months ago. And slowly increased the number of supplements. But I knew that there would be problems along the way because I tried many of these supplements some time ago and knew that they will cause side effects, sometimes severe. I was basically oversensitive to 50% of them (and it's not about allergy, it's about stupid interactions). So the first attempt was to try it again - if it worked then it's OK and I'd continue to take it. If it didn't work I'd try to work around it. If I failed - the supplement had to be interrupted. But that was most unfortunate because what if it was the right supplement in the first place? I have come across this situation multiple times.
One such example, the worst one: I was never able to take niacin. It made me so terribly drowsy (it works just like GABA neurotransmitter). Even very small doses (like in the RDA range). But it gets worse. Niacin causes flushing (causes production of PG2 prostaglandin) and I got this flushing when taking even normal RDA doses but after a few days in a row. So when I took it 3 times in a row - I got this flushing and I got drowsy (once it made me sleeping 20 hours a day so I had to stop it and that was it).
And it gets worse. Niacin is recommended when you get overmethylated and inflamed after taking methyl-folate. So there was no way to do this. Bummer.
I tried many many times to find a way to reduce that stupid drowsiness after taking niacin.
But when you take everything you may finally come across something that works. And something worked, namely L-aspartic acid and tyrosine. Though it's kind of hard to identify what worked and what didn't.
What else interesting is there... polyphenols... they reduce my joint inflammation... you might wanna ask what works best? What is that I'm taking... almost everything: quercetin, green tea, green coffee (ie. chlorogenic acid as a supplement, I hate brewed coffee), fisetin, chamomile tea, and resveratrol. I also tried to take luteolin which might be even better in quenching the inflammation but there is no place to buy it easily. Of course, there is artichoke extract (contains luteolin) but I am allergic to it (this time it's a real allergy to it or to a tablet component, I think). I'm mentioning resveratrol here because it tipped the balance. But... 5 days ago only 1 capsule was more than sufficient (made me terribly hot) and today 2 are not working as good.
No need to say that I tried this resveratrol 5 years ago and it didn't do anything for me, just the opposite. So this one is actually the one that was left on the bottom shelf for 5 years... and I'm wondering if there may be something that happened to it during such a long storage... some kind of breakdown...
It is still possible that I will get back to old miserable me.
Nevertheless, during these last 5 days I proved that it is possible for me to get better. Up until now I was kind of convinced that there is no simple way to make me better (haha, this is not a simple way neither, I have to take so many capsules and tablets but first I need to purchase them at an affordable price so it's a logistical nightmare but it's still simpler than getting involved with doctors and the healthcare system, begone!).
Obviously, prescription drugs, injections and gene therapy are beyond our capabilities even though I'd try any of them, one by one, doesn't matter if there was a good reason to do it or not. I simply didn't care.
So when I'm thinking that I might actually do something in and with my life - that doesn't mean anything to me yet. I'm in the 5-th stage after a loss: acceptance. So I've accepted that I mean nothing and I have to struggle to survive.
I guess it would be best to first figure out exactly what helped me and share that information with those in need... but I have no idea how to do it, how detailed the information should be, etc.
PS. Along the way there were also some other things that helped me. Many of them, like MCT oil and BCAA (I'd say every other supplement that I took helped me but some of them more than others). But I guess there is no point in listing them all - these will be different for everybody. There was a slow improvement, a build-up over time and then bam, resveratrol, and everything clicked into place.
On the other hand, there were supplements that made me feel terrible: arginine, folate, niacin... and yeah... even MCT oil made feel sick for a long long time but then when other supplements kicked in I only experienced benefits and no side effects.
PS2. My condition is actually strange because for example tendons kill me (inflammation), I can barely move in the morning but then I can walk it off and it gets better...
PS3. Yesterday I also moved heavy boxes for 5 hours. I guess I have a lot of boxes to move
EDIT: PS4. Mick, after all these years you get a break, and all you can do is move boxes? Come on, you've got to be kidding me...
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