Could Phospholipid Dysregulation Contribute to ME/CFS?

[TamaraRC]

@TamaraRC may I ask how are you feeling now ? Do you experience PEM?

I don't experience PEM any more, I am mostly recovered now but I continue to take Bodybio PC, statins, Methylfolate, B12, Omega 3 and red ginseng. Also sometimes add creatine. I did have to take mast cell medications for a while but I stopped taking them over a year ago and mast cell issues haven't returned. A lingering symptom I have is that I sometimes get a mild hangover feeling in my head, but I noticed that taking the L. Reuteri yogurt (that Ron Davis has been researching for oxidative stress) quickly gets rid of the hangover feeling, so I think it's oxidative stress related. I think I have genes which predispose me to oxidative stress.

 

[mariovitali]

I don't experience PEM any more, I am mostly recovered now but I continue to take Bodybio PC, statins, Methylfolate, B12, Omega 3 and red ginseng. Also sometimes add creatine. I did have to take mast cell medications for a while but I stopped taking them over a year ago and mast cell issues haven't returned. A lingering symptom I have is that I sometimes get a mild hangover feeling in my head, but I noticed that taking the L. Reuteri yogurt (that Ron Davis has been researching for oxidative stress) quickly gets rid of the hangover feeling, so I think it's oxidative stress related. I think I have genes which predispose me to oxidative stress.

I am really happy to hear that. Currently looking at the mevalonate pathway and since you mentioned statins which are inhibiting HmG-CoA as a central mechanism, you may be affecting protein prenylation. I am not aware of any studies looking at isoprenoid intermediates.

The software I have been using has identified it as a potential metabolic bottleneck. Please investigate geranylgeraniol and see whether prenylation matches anything of interest to your research.

Again, very happy for you. Thank you for all of your work.

 

[DHagen]

I don't experience PEM any more, I am mostly recovered now but I continue to take Bodybio PC, statins, Methylfolate, B12, Omega 3 and red ginseng.

If you don't mind my asking, why the proprietary "Phospholipid Complex" in place of, say, Phosphatidylcholine alone (or at least a supplement where you know how much of an individual ingredient is included)?

 

[mariovitali]

@Hutan, being the expert would it be possible to comment regarding the methodology/design of the listed studies? There are many more obviously , I selected these as the most promising given their design.


1. Che et al. / Lipkin & Fiehn (2022)
"Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"
International Journal of Molecular Sciences 23(7):3842
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320121/

2. Hoel, Fluge, Mella, Tronstad et al. (2021)
"A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome"
JCI Insight 6(18):e149217
https://pmc.ncbi.nlm.nih.gov/articles/PMC8409979/

3. Nkiliza, Klimas, Abdullah et al. (2021)
"Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms"
Journal of Translational Medicine 19:370
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401202/

 

[Hutan]

@Hutan, being the expert

No more than many here, and certainly less on all sorts of aspects.

Picking one to start with. Other members might like to tackle the other papers.

3. Nkiliza, Klimas, Abdullah et al. (2021)
"Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms"
Journal of Translational Medicine 19:370
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401202/

Forum thread
I see that we didn't make any comments about the paper. It will be interesting to have a look at it. I'll post a comment on the paper's thread, but it might be tomorrow.

 

[leokitten]

Not sure why though?
Alcohol intolerance is not particularly a feature of insulin resistance and shifts in liver function do not stop people finding alcohol pleasurable by and large.

What causes sudden alcohol intolerance like what happens to so many of us after ME is triggered, when the week before getting ME we could drink alcohol no problem? In my case the intolerance manifested itself as even just a couple sips of any alcoholic beverage immediately gave me powerful symptoms as if I drank a gallon, I was so nauseated and sick, sudden major hangover, and dizzy and really drunk from almost nothing

 

[Jonathan Edwards]

What causes sudden alcohol intolerance like what happens to so many of us after ME is triggered, when the week before getting ME we could drink alcohol no problem?

Not that many things, apart from certain drugs like disulfiram.
It seems likely to reflect an impact on chemoreceptors. Maybe that is where OLFM4 fits in somwhere?

 

[mariovitali]

What causes sudden alcohol intolerance like what happens to so many of us after ME is triggered, when the week before getting ME we could drink alcohol no problem? In my case the intolerance manifested itself as even just a couple sips of any alcoholic beverage immediately gave me powerful symptoms as if I drank a gallon, I was so nauseated and sick, sudden major hangover, and dizzy and really drunk from almost nothing

Can you tell us what triggered your ME?

 

[leokitten]

Can you tell us what triggered your ME?

What felt like a massive viral infection and two week long flu. But the only circumstantial proof I have of that is when I finally went to the doctor two months later I had extremely high IgG antibodies to EBV and CMV that's it. They didn't measure EBV EA-D IgG at that time only many months later after I was already diagnosed, and that has been high multiple times throughout the years like EBV is reactivating all the time. Antivirals didn't work for me even Valcyte + Famvir together

 

[mariovitali]

What felt like a massive viral infection and two week long flu. But the only circumstantial proof I have of that is when I finally went to the doctor two months later I had extremely high IgG antibodies to EBV and CMV that's it. They didn't measure EBV EA-D IgG at that time only many months later after I was already diagnosed, and that has been high multiple times throughout the years like EBV is reactivating all the time. Antivirals didn't work for me even Valcyte + Famvir together

80 to 90% percent of people who get EBV have raised liver enzymes. Do all of them get ME/CFS ? Certainly not, but if you have a combination of specific metabolic defects then such an event could break a delicate compensatory state which you could be in before EBV hit you :









You also mentioned CMV :








But as it seems, even given the above and despite a large study by @Chris Ponting identifying liver dysfunction to patients with ME/CFS , scientists prefer to look elsewhere for answers. By the way the liver is responsible for metabolizing all medications and of course, alcohol.

 

[TamaraRC]

If you don't mind my asking, why the proprietary "Phospholipid Complex" in place of, say, Phosphatidylcholine alone (or at least a supplement where you know how much of an individual ingredient is included)?

I don't remember my thinking as I started taking it 18 months ago, I just noticed it helped a lot at the recommended dose so I kept taking it.

 

[leokitten]

What causes sudden alcohol intolerance like what happens to so many of us after ME is triggered, when the week before getting ME we could drink alcohol no problem? In my case the intolerance manifested itself as even just a couple sips of any alcoholic beverage immediately gave me powerful symptoms as if I drank a gallon, I was so nauseated and sick, sudden major hangover, and dizzy and really drunk from almost nothing

Just want to be more descriptive on the alcohol intolerance anecdote, that only lasted the first couple years or so of ME and slowly but eventually improved. But the ME didn't get better only got worse. Very very weird I don't know if other ppl had this happen the same way?

 

[Chandelier]

Just want to be more descriptive on the alcohol intolerance anecdote, that only lasted the first couple years or so of ME and slowly but eventually improved.

The psychobbabelist Raelan Agle tells a somewhat similar experience here:
First 1-2 years bedridden with ME/CFS, she couldn’t drink alcohol.
However, after those two years, alcohol became her "superpower".
Maybe harder hangover afterwards, but while drinking, she could party with friends as if she had recovered.

AI Subtitles:

[00:00] So when I was really sick, my first, I don't know, year or two years with this illness,
[00:05] when I could barely get out of bed, alcohol was out of the question.
[00:09] So I wasn't drinking at all.
[00:10] I don't think my body could have tolerated it, and I don't think I had much of a desire for it.
[00:15] But when I started to feel even a little bit better, maybe closer towards the end of that second year,
[00:21] I remember there was one occasion where I decided I was going to have some wine,
[00:25] and I had too much wine and I got a hangover from drinking that lasted almost two full weeks.
[00:34] So that really kept me from drinking for quite a while after that as well. So my hangovers were
[00:41] intense. But I did notice that while I was drinking, I was feeling much better. I had way
[00:47] more energy and I could do so many things that I couldn't normally do. It was like virtually all of
[00:53] symptoms disappeared. But that two week hangover left me scared. But eventually, as time went on,
[00:59] and my health continued to improve, and I started traveling, and I was hanging around with a lot of
[01:04] people where social drinking was very much the norm. And my not drinking was making me feel like
[01:13] I was outside of what was going on. So slowly, I started drinking more when I was out with other
[01:18] people and alcohol became like my superpower.
[01:22] It was crazy how good I felt once I was consuming alcohol.
[01:27] And now that I've started sharing my health journey publicly,
[01:30] because back then I actually didn't talk about it much.
[01:33] And most people in my life weren even aware that I had any kind of health issues And I think if any of them saw any of these videos now they think how were you sick Like I would sit out sometimes drinking with you until 3am How is that even possible It really was like my superpower And I still got
[01:51] hangovers. They didn't last two weeks. Thankfully, they were probably worse than
[01:56] a healthy person's hangover. But it kept me afloat. It allowed me to fit in and
[02:03] socialize and have friends and have energy to do things that I didn't normally do. But of course,
[02:09] alcohol consumption is very bad for chronic illness recovery. I think it's very bad for
[02:13] everybody. It's poison. So we're drinking poison, dumping it into a body that's already struggling.
[02:21] And then I've come to appreciate because I'm hypoglycemic. So I've read every single book,
[02:26] I think, on hypoglycemia that exists. And alcohol converts to glucose in our body faster than straight
[02:32] sugar even does. So it is really hard on our bodies in so many different ways. So I'm certainly
[02:40] not recommending that anyone who's struggling use alcohol as a way to feel normal. I'm just saying
[02:47] that that was my experience. So I just love to get the conversation going and I'd love to start
[02:52] getting some more information out there on this since there doesn't seem to be much. So please,
[02:57] if you have any experience with this or any thoughts or any insights, I'd love for you to
[03:01] share it in the comments so we can start to learn about this and understand this. Incidentally, when
[03:06] I finally did recover, I cut out alcohol almost completely. It was vital that I did. I was getting
[03:12] nowhere when I was consuming alcohol regularly. When I recovered, I'd cut it out often for months
[03:17] at a time. Now that I'm feeling strong and healthy and symptom-free, I do still consume alcohol on
[03:24] occasion.

Alternative interpretation. She’s trying to cover her back with a nice story for the scam she’s doing:

[01:33] And most people in my life weren even aware that I had any kind of health issues And I think if any of them saw any of these videos now they think how were you sick Like I would sit out sometimes drinking with you until 3am How is that even possible It really was like my superpower

 

[neophyte32]

Personal anecdote: alcohol masked my symptoms too... sometimes even the next day when I felt fine and pretty good. I hadn't had a drop for 16 months, since my severe illness and bed rest. But strangely, it acted like a benzodiazepine on my central nervous system. But sometimes I would also have panic attacks the next day, with my heart and nervous system in hypervigilance... I would stay in bed, terrified.

 

[V.R.T.]

strangely, it acted like a benzodiazepine on my central nervous system. But sometimes I would also have panic attacks the next day, with my heart and nervous system in hypervigilance... I would stay in bed, terrified.

This describes my experience with alcohol since prodromal onset. It was calming in the moment and moderate amounts allowed me to feel somewhat 'normal' in crowds or social situations. But the next day was hell.

Interestingly after definite onset I got more symptoms while drinking as opposed to next day. Partner got horrible alcohol intolerance from her ME onset, and she had never had more than a normal hangover before.

 

[neophyte32]

This describes my experience with alcohol since prodromal onset. It was calming in the moment and moderate amounts allowed me to feel somewhat 'normal' in crowds or social situations. But the next day was hell.

Interestingly after definite onset I got more symptoms while drinking as opposed to next day. Partner got horrible alcohol intolerance from her ME onset, and she had never had more than a normal hangover before.

I was still partying for two days with friends, and in September 2024, I could drink alcohol the next day and I was invincible... two days in a row, I was like normal, not even too drunk. However, the first night I got drunk very quickly, even though I've always had a high alcohol tolerance. But before the MECFS, I had a bad habit: alcohol, the next morning a run, the alcohol in the evening. My wife and friends are always impressed by my endurance and resilience in going for a run the next day with a hangover.
My weekends were like that for 15 years... I'm ashamed of it.

 

[V.R.T.]

I was still partying for two days with friends, and in September 2024, I could drink alcohol the next day and I was invincible... two days in a row, I was like normal, not even too drunk. However, the first night I got drunk very quickly, even though I've always had a high alcohol tolerance. But before the MECFS, I had a bad habit: alcohol, the next morning a run, the alcohol in the evening. My weekends were like that for 15 years... I'm ashamed of it.

My tolerance went down massively when I definitely got MECFS at 26 as well. Although i was also dieting and trying to cut down about then. sadly my urge to drink the pub dry didn't go down at the same time...

When I had my prodromal onset at 19, I went from being someone who cracked a can of coke and went into town the next morning with a bad hangover to someone who was feeling dreadful in bed when hungover, and missing out on stuff they really wanted to do.

But to be fair, I should have quit drinking then cos I was already an absolute mess!

 

[ChronicallyOverIt]

My tolerance went down massively when I definitely got MECFS at 26 as well. Although i was also dieting and trying to cut down about then. sadly my urge to drink the pub dry didn't go down at the same time...

When I had my prodromal onset at 19, I went from being someone who cracked a can of coke and went into town the next morning with a bad hangover to someone who was feeling dreadful in bed when hungover, and missing out on stuff they really wanted to do.

But to be fair, I should have quit drinking then cos I was already an absolute mess!

I too had I would say had disproportionate hangovers compared to my peers, sometimes the hangover lasting days when I was 20-25. Oddly my peers would only be hungover for a day. I would be stuck in bed for 2-3. I got sick sick at 25. I didn’t drink after that though cause it made me feel awful even during the drinking. Eye irritation and just feeling sick over all.

I too think I had a prodrome, I was legitimately dead exhausted after work days my peers handled fine. I’d have to nap after work everyday. I still during this time was able to work out in the evenings and have no ill effect.