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.
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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...
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OK, now I have a few remarks.
3) A user called ppohadjski said that these agents (Taurine, TUDCA, etc) should not be used but instead we should use Biotin and FMN which are key cofactors for regulating redox functions.
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.
I will continue working to reach the absolute basics. I started FMN, Biotin, Molybdenum per @ppodahjski suggestions.
If this all is just a matter of providing cofactors then why not, i will follow it.
No, don't try to reduce the number of supplements solely for the purpose of reducing it. It will end up badly.
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
When I reached that post... I knew it. I know from experience. It's not worth it.
What we've seen from Yasko is a lot of strict SNP claims which turned out to be obvious BS. Some people then moved to assuming that there must be some mechanism involving genetic expression which causes these irrelevant SNPs to suddenly become relevant.
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...