Efthymios’s AI aided protocol

[lyran]

I didn't saw a separate discussion about this topic yet so I made one because I think he is into something. There have been other discussions where some of his supplements were mentioned and discussed and @mariovitali has talked about some of these several years ago but this subject deserves it's own thread.

I'm not going into his background and story. You can read them from here:
https://www.healthrising.org/blog/2...telligence-chronic-fatigue-syndrome-recovery/
https://www.healthrising.org/blog/2023/10/21/ai-driven-chronic-fatigue-syndrome-clues/

The protocol is made for him but there are many things that pwME may have in common. Basically the protocol consists of the following supplements (copied from healthrising):

• TUDCA – I started with 250 mg and gradually upped the dose to 750 mg, providing 250 mg every 8 hours in order to ameliorate endoplasmic reticulum stress (and subsequent unfolded protein response events) and also support liver function. TUDCA, a supplement and bile acid derivative, is another “version” of a medication called Ursodeoxycholic acid aka ursodiol: the liver produces bile acids which are metabolized in the intestines into TUDCA. These bile acids digest fat-soluble vitamins, break down food and cholesterol, help fight off pathogens, and regulate our metabolism. In an energy-intensive process, most of the bile in our body ends up getting reused. (More on bile acids and the liver in the next blog on Efthymios’s work on artificial intelligence and ME/CFS.)
• Methylcobalamin (B-12) (1000 mcg) – to support methylation)
• Methylfolate (200 mcg) – to support methylation)
• Taurine (500 mg) – to help in conjugation of bile acids via CYP7A1, regulate NMDA / glutamate excitotoxicity, and also upregulate PGC1-α (for mitochondrial biogenesis)
• Vitamin C (250 mg) and N-acetyl cysteine (100 mg – I couldn’t tolerate more) – antioxidants to minimize oxidative stress
• Ubiquinol (100 mg) – provides intermediate metabolites for energy production
• Zinc (25mg) – which has been low whenever I tested it
• Selenium (50 mcg) – (combat oxidative stress)
• Vitamin K2 (As MenaQ -100 mcg) – (combat oxidative stress)
• Choline (500 mg) and important cofactors such as FMN (Flavin Mononucleotide) (10 mg) (combat oxidative stress)
• D-Limonene (250 mg) twice a week to induce P450 (liver support and detox) (Caution: this may affect drug metabolism)

I have tried many of these supplements in the past with no avail but TUDCA was something new to me. I have been using it now for 2 weeks and it does clear my head slightly and also helps with constipation issues. I'm using a supplement that has 600mg of TUDCA in 1 capsule and I have been taking it once a day in the morning. It may need to be taken 2-3 times a day. I may also add Taurine to see if it helps in conjunction with TUDCA.

I would like to hear your experiences. I'm most interested in liver function and ER stress, not that much of methylation or mitochondria boosting as these have been discussed many times in many threads already.

 

[Violeta]

@mariovitali names a new supplement, ellagic acid, that some algorithms have ranked even higher than TUDCA.


https://x.com/lifeanalytics/status/1716711437530226902?s=20

 

[lyran]

@mariovitali names a new supplement, ellagic acid, that some algorithms have ranked even higher than TUDCA.


https://x.com/lifeanalytics/status/1716711437530226902?s=20

I have to check this out. I tried taking pomegranate extract which is a source of ellagic acid a while back but it caused me insomnia even when taking it in the morning.

 

[mariovitali]

@lyran Thank you for the mention at the work I have been doing. @Violeta I am always Thankful to you as well !

I will have to stress out that most likely a personalized approach is required. We are in the process of identifying the key biological entities of these syndromes and we are getting closer I think. There is a possibilty that a specific ordering of interventions could also be required.

The massive analysis of patient medical histories will be key I think along with better understanding why certain interventions are extremely beneficial for some individuals while for others the complete opposite happens.

 

[lyran]

@lyran Thank you for the mention at the work I have been doing. @Violeta I am always Thankful to you as well !

I will have to stress out that most likely a personalized approach is required. We are in the process of identifying the key biological entities of these syndromes and we are getting closer I think. There is a possibilty that a specific ordering of interventions could also be required.

You're welcome and your work definitely needs appreciation.

Yeah I'm sure of the need of personalized approach. For example I don't tolerate sulfur containing supplements but active B2 (Flavin Mononucleotide) does help with that, molybdenum for some reason does not. I also don't tolerate methylfolate or folinic acid even in tiny doses. Choline does seem to make me worse.

 

[hapl808]

I will have to stress out that most likely a personalized approach is required. We are in the process of identifying the key biological entities of these syndromes and we are getting closer I think. There is a possibilty that a specific ordering of interventions could also be required.

One problem I have is that I think the personalized approach itself…will have to be personalized. I've never noticed any obvious connections with how I feel based on what I take, but there are some more tenuous connections. For instance, if I take very high doses of Buhner herbs, I tend to feel worse while taking them. However, when I stop I 'think' I feel better than before I started - but it doesn't last. Then other things complicate issues - working on the computer or talking on the phone crashes me. I started tracking phone calls, but computer is tough to turn into data because watching a Youtube or posting on a forum doesn't usually crash me, but working on something more challenging will do so - but I don't always know what that'll be.

So for me, the algorithm would likely have to not only look at immediate effects, but some kind of broader architecture (LSTM?) that could notice events days or weeks after, etc. Another difficulty for me is Garmin doesn't really show my overall health, just day to day. I feel crappy every day (haven't had a 'good' day since 2017), so it's very hard to judge. My improvements tend to be qualitative like, "I talked on the phone in the evening last night, and I only had two days of mild reflux afterward." Not sure how you would encode that.

 

[Violeta]

@mariovitali's blogspot

http://algogenomics.blogspot.com/2017/10/latest-network-analysis-results.html

 

[mariovitali]

@hapl808 I was lucky because the variations of my symptoms were very noticeable. It goes without saying that severely ill patients will most likely -and that is very unfortunate- not have such variations . And this will make identification of patterns from AI algorithms impossible.

 

[hapl808]

@hapl808 I was lucky because the variations of my symptoms were very noticeable. It goes without saying that severely ill patients will most likely -and that is very unfortunate- not have such variations . And this will make identification of patterns from AI algorithms impossible.

That's kind of my impression. It's a shame because I was sick from 1997 to 2017 with relatively moderate symptoms - meaning I crashed constantly, but some things helped me (TCM, abx, etc) and some made me worse (long days of work, travel, etc). I think there were relatively easy patterns that may not have been immediate, but a 3-4 day window would've warned me (assuming I even thought to track things like work, phone calls, etc).

Now that I'm more severe, my variations are quite minor. This makes it more of a challenge, since my improvements might be 1%-5% at best, and I've been unable to maintain them (ie. improving over a longer period with small interventions).

Hoping more advanced algorithms will help more people.

 

[Mary]

@lyran - I take all those supplements except for TUDCA and d-limonene. My liver and gallbladder are in good shape, though years ago they weren't, liver was overloaded with toxins and for years I had trouble with detoxing. A combination of a liver detox (which took a month), and then taking betaine HCL with pepsin, and finally a course of glycine seemed to get my liver detox pathways working properly. Anyways, my digestion is quite good now. And nothing touches my crashing, except for BCAAs which reduced my PEM recovery time, but have not solved the basic problem of ME/CFS. I also have been taking a pomegranate supplement for several months which at one time seemed to expand my energy envelope, only now it's stopped doing that.

I also take a bunch of other stuff.

 

[lyran]

@lyran - I take all those supplements except for TUDCA and d-limonene. My liver and gallbladder are in good shape, though years ago they weren't, liver was overloaded with toxins and for years I had trouble with detoxing. A combination of a liver detox (which took a month), and then taking betaine HCL with pepsin, and finally a course of glycine seemed to get my liver detox pathways working properly. Anyways, my digestion is quite good now. And nothing touches my crashing, except for BCAAs which reduced my PEM recovery time, but have not solved the basic problem of ME/CFS. I also have been taking a pomegranate supplement for several months which at one time seemed to expand my energy envelope, only now it's stopped doing that.

I also take a bunch of other stuff.

Good to know as I have issues getting detox pathways working properly. I have also tried taking betaine HCL but could only tolerate small doses or I got diarrhea. I probably don't need it as my stomach acid levels seem to be ok. Glycine has stimulating effect on me and that's why I can't take magnesium glycinate before bed. BCAAs make me tired for some reason. We are all so different but with the same diagnosis.

TUDCA has many other effects beyond liver health but it may also lost its effects after taking it for a while like everything else (fingers crossed it does not).

 

[mariovitali]

Please note the other things I mentioned in my regimen, I believe they are equally important :

1) No to : sugar, glutamate, fructose, soy, foods with HFCS, Palm Oil, any foods spiking significantly insulin
2)No simple carbohydrates (Pasta,Rice, Potatoes etc)
3) No too much protein or whey protein
4) Yes to : Legumes, Olive Oil, Fiber-rich foods
5) Intermittent fasting (which I do) is also beneficial I believe

Putting the above together, we end up with a number of interventions that most of them improve mitochondrial function.

 

[linusbert]

looks like a sound protocoll!
maybe add carnitine?

TUDCA i also tried, not sure if it did anything for me, but i didnt crash from it at least.
also there seams to be only one real TUDCA suppplement out there, all others dont have TUDCA or in low dose or mainly other things. which ones are you using?

what i noticed, after i took TUDCA for a few weeks, my bloodwork of HDL and LDL came back with HDL lowered a lot and LDL raised. i usually had a good ratio. i dont know yet if it was for sure the TUDCA or some other thing. i draw blood next week, i didnt use the TUDCA for months, lets see if it improved.

what i believe could be the problem with TUDCA:
it thins the bile acids which for one improves flow and congestion if any, but also causing a deficit in bile. the liver needs to make more. therefore the liver needs to use cholesterol and following is my theory now; it mainly uses the good HDL for this. which could explain my shift in HDL/LDL ratio.
if this is indeed the case, eating more egg yolks could help with this / which i didnt do at that time. (i checked both theories with chatgpt... it supports the theory, but faulty answers in AI are not reliable for proofing anything)
also as expected the liver enzymes went down with TUDCA.

Yeah I'm sure of the need of personalized approach. For example I don't tolerate sulfur containing supplements but active B2 (Flavin Mononucleotide) does help with that, molybdenum for some reason does not. I also don't tolerate methylfolate or folinic acid even in tiny doses. Choline does seem to make me worse.

thats interesting, i might try the B2 out.
methylfolate and choline are heavy methylators. probably overmethylation? can you fix this with non methylated vitamins or even niacin?

Taurine (500 mg) – to help in conjugation of bile acids via CYP7A1, regulate NMDA / glutamate excitotoxicity, and also upregulate PGC1-α (for mitochondrial biogenesis)

this is also very interesting, i noticed after use of whey protein that i get somewhat tingly legs. i was suspecting that glutamic acid from the whey is due to some fault in metabolism converted too much into glutamate causing this problem. if i understand this correct, Taurine might help here. will try this as well.
though it somewhat calmed down, maybe the body adapted. but i am only using at max 5g a day. i take like 1-2g when i eat my bread to bring blood sugar down a bit.


EDIT: i have been reading the Efthymios story, and i really liked it because i am also IT guy and thats my kinda approach to things. (https://www.healthrising.org/blog/2...telligence-chronic-fatigue-syndrome-recovery/)

But when he was talking about his alkohol abuse, somehow his whole story collapsed in plausability to me, because i am now suspecting that his alcohol abuse could have induced/aggravated a beriberi (b1 deficiency + later other deficiencies on top)... and he actually successfully treated beri beri + refeeding and not cfs.

Incorporating these changes of DOs and DON’Ts, and limiting significantly my alcohol intake, resulted in putting a stop to my continued worsening of symptoms and set the basis for my improvement.

not sure what to think about this now.
i am still thinking this approach is a good one, and it might have solved his problem but the problem he was thinking to solve probably wasnt cfs but some other deficiencies.


though what i have been seeing in his protocol in comparison to my deficiencies... its somewhat similiar and logical.
my first bloodwork after first crash was a massive vitamin C and folate deficiency, also low b12 levels (thou no megaloplastic anaemia) and low D and low but not deficient magnesium levels, high normal calcium, BUT a clear deficient phosphorus.
thats a clear indication that methylation is broken. but somehow i am not able to fix it.
i am also now in a much better state then i was a year ago after basically only supplementing high dose vitamin D. especially my diabetes improved like crazy. i am now almost off the insulin and stil A1C in the 6'ish area. also my body recovers much better and crashes much less.. i have the feeling things which took me down for days are now fixed in 12-24 hours. though despite better recoverability, i do not get a massive remission. i still need to find the switch to start massive remission, if this does exist.

 

[mariovitali]

But when he was talking about his alkohol abuse

I just wanted to make clear : I never implied I was abusing alcohol intake in any way.

 

[lyran]

also there seams to be only one real TUDCA suppplement out there, all others dont have TUDCA or in low dose or mainly other things. which ones are you using?

thats interesting, i might try the B2 out.
methylfolate and choline are heavy methylators. probably overmethylation? can you fix this with non methylated vitamins or even niacin?

though what i have been seeing in his protocol in comparison to my deficiencies... its somewhat similiar and logical.
my first bloodwork after first crash was a massive vitamin C and folate deficiency, also low b12 levels (thou no megaloplastic anaemia) and low D and low but not deficient magnesium levels, high normal calcium, BUT a clear deficient phosphorus.
thats a clear indication that methylation is broken. but somehow i am not able to fix it.

Is that so? what TUDCA supplement were you using? I'm just using a "cheaper" one from Amazon which is produced in UK.

I'm not sure about methylation. I don't notice anything from non methylated vitamins but I don't tolerate methylfolate. I can still use methylcobalamin without issues. My bloodwork showed that my B12 and folate levels are just fine, just like every other vitamin level I have tested. I probably get enough folate from my diet as I didn't use any folate supplement for a year before getting tested. But I think B12 and folate lab levels are quite useless to show if you have methylation issues or not.

 

[linusbert]

just wanted to make clear : I never implied I was abusing alcohol intake in any way.

just my interpretation because this sounded rather like a lot and it seamed important enough to add it to the list

and limiting significantly my alcohol intake

. in my head its like how would you significantly lower alcohol if you didnt significantly drink it. but glad you clarified.

Is that so? what TUDCA supplement were you using? I'm just using a "cheaper" one from Amazon which is produced in UK.

this is weird , i was just checking amazon.de again, and there are now a lot more than half a year ago when i tried it - also my expensive brand was shortly later sold out. though i am always looking for pure supplements, meaning its the only ingredient in the list.
maybe the supplier got a restock and now other brands sell again now as well. cant speak for US or uk markets, but in germany there seamed to be a shortage of many supplements i used to take for a while.

 

[lyran]

I don't notice anything anymore from taking TUDCA. It is very common that something helps at first but then loses its benefits when taken for a while. I'm still going to finish the bottle to see if it takes some time to do its job.

 

[mariovitali]

I don't notice anything anymore from taking TUDCA. It is very common that something helps at first but then loses its benefits when taken for a while. I'm still going to finish the bottle to see if it takes some time to do its job.

My understanding is that this is a typical effect when the interventions being taken do not fully apply to what is needed to be done. I like to give the example of a bucket full of water which has a number of holes in it. We need to block every hole , otherwise water is going to be lost eventually.

It is interesting to note that for a number of patients , there is an improvement which lasts (I am not talking about this regimen only).

There was a person who got well by taking plasmalogens. I think this may be a very important case study.

 

[godlovesatrier]

Just started TUDCA thismorning. Took 250mg with NAC 300mb in isolation. Noticed a big improvement in lowered fatigue scores (my fatigues suddenly got bad recently probably due to stress to be honest).

https://www.nature.com/articles/s41598-018-21621-5
"Anti-inflammatory effect of Tauroursodeoxycholic acid in RAW 264.7 macrophages, Bone marrow-derived macrophages, BV2 microglial cells, and spinal cord injury"

So I will see how I progress, normally things give me terrible side effects but I am not noticing that with tudca which is a relief! But I'll see how the next few days ago, will prob check 250mg is ok before I start increasing it. Was a bit worried about starting at that dosage but I think it's prob worthit.

 

[godlovesatrier]

Hi guys. Definite improvements in cognitive acuity (clarity) with TUDCA (only taking 250mg at the moment) and improvements in fatigue for sure. I am guessing it's an anti microbial and antiviral effect (it does do both). Side effects right now are feeling giddy/happy, mild brainfog (hoping this will go with time), dry mouth (again hoping that's just temporary - I have had both chronic and temp dry mouth before).

"Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases"
https://pubmed.ncbi.nlm.nih.gov/35659112/

"Tauroursodeoxycholic Acid Inhibits Clostridioides difficile Toxin-Induced Apoptosis"
https://pubmed.ncbi.nlm.nih.gov/35862710/

"Tauroursodeoxycholic acid (TUDCA) inhibits influenza A viral infection by disrupting viral proton channel M2"​

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104969/

And something about entereoviral interaction here:
"Involvement of Endoplasmic Reticulum Stress Mediated C/EBP Homologous Protein Activation in Coxsackievirus B3-Induced Acute Viral Myocarditis"
https://www.researchgate.net/public...ackievirus_B3-Induced_Acute_Viral_Myocarditis

https://www.researchgate.net/figure...evirus-B3-CVB3-induced-cardiac_fig3_277083643
"Tauroursodeoxycholic acid (TUDCA) pre- vents coxsackievirus B3 (CVB3)–induced cardiac C/EBP homologous protein (CHOP) activation and cardiomyocytes apoptosis in vivo."

I'd just like to say my crashes and my PEM are a lot better since my anti inflammatory scores improved from my 16s results however I haven't got my results for October yet and I have been struggling with fatigue and lethargy due to stress for about 3-4 months now that got a lot worse last week. So TUDCA may not crash me as much as it would have before, but we will see.

I'll try and do another update in a week.