Alcohol Intolerance poll. Please do the poll even if your answer is no.

[Jonathan Edwards]

Is there any way to take this hypothesis forward?

Quite possibly. Once we have thought of all the reasons it might be wrong and not found too many!

 

[forestglip]

We now have over 100 votes so I shall welcome discussion of interpretation.

What do you think of liver-related, as mariovitali was saying:

I believe this thread and poll is very important and seeing that some members have mentioned the liver, I would like to give my two cents :

-Alcohol is a toxin. The liver is the organ responsible for most of detoxification that is taking place in the human body.

-Regarding detoxification , from Jackson Labs Dr Shuzhao identified increased levels of xenobiotics in ME/CFS patients : https://twitter.com/user/status/1816144339195641960
. Apart from Dr Shuzhao , 2 other studies have found elevated Butyrylcholinesterase in LC and ME/CFS patients. Assay of BCHE can be used for (surprise,surprise) assay of Liver function test

https://twitter.com/user/status/1782060521283301515




-Medications are being metabolised by the liver. Impaired liver function raises the risk of adverse events.

-In 2018, -I believe that @Jonathan Edwards was also there during my presentation- at the London School of Hygiene and Tropical Medicine I presented my work where using several analytical methods I generated a hypothesis that a liver injury is responsible for the initiation of ME/CFS and similar syndromes such as GWI.

-In the following slide #56 from this presentation ,I hypothesised that patients with ME/CFS have less than optimal liver function. This is why many patients when asked, say that they couldn't tolerate alcohol even before ME or that they "simply do not like drinking". Note in the slide also the mention on UPR (Unfolded Protein Response) that @Murph mentioned in this thread and ER Stress (Endoplasmic reticulum stress) that Dr Hwang has found with protein WASF3. Again, this was in 2018.

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-There were also slides that showed snapshots of patients discussing liver function. For those who have Liver function tests (LFTs) normal, unfortunately normal LFTs DO NOT rule out liver disease.

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-Finally, fast forward in 2024, we have @Chris Ponting study which has identified liver issues.

-A question that I have for those who mention that they feel better with alcohol, does this include cases where they had too much or this positive effect is achieved only with a tiny dose?

Please forgive me for coming up as a bit edgy but for so many years (since 2017) I am asking again and again for researchers to look more closely at the liver of ME/CFS patients.

 

[Jonathan Edwards]

What do you think of liver-related

I would be led more in that direction if the problem was chiefly an increased hangover. Failure to metabolise alcohol might aggravate things but I don't see it being the primary cause of the unpleasant reaction.

 

[NelliePledge]

Had one glass of fizz 1/2 glass white wine yesterday plus sugary pudding. I was tipsy after 1/2 glass of fizz hence the subsequent glass. Obviously I was sitting at restaurant table for 3 hours as well, but then I’m always sitting up when drink anything so the alcohol is only ever going to be one element of the overall “stress” of socialising.
Main symptom that’s worse today is body aching ramped up brain is slower than normal. I was a bit dehydrated yesterday evening but not feeling hangoverish today. I think the last time I had any alcohol was early August.

 

[MrMagoo]

I’m willing to attempt graded alcohol therapy. For science. I’d see if I could manage a glass of something.

 

[Kitty]

Failure to metabolise alcohol might aggravate things but I don't see it being the primary cause of the unpleasant reaction.

it doesn't sound as if that would start in as little as 20 minutes?

 

[EndME]

DecodeME had a question on how well alcohol is tolerated. Did anybody have a look at what the results were and whether there was a difference in the ratio according to sex or whether there were any interesting relationships relating to alcohol tolerance?

 

[hotblack]

I like this idea of a “hypothalamus mediated 'negative' signal” and “that human beings normally have two opposing hypothalamic responses to alcohol”. Partially because so much in our bodies seems to be a constantly changing precariously managed balance between different, often opposing factors. But also because it sits well with my comment about my experience being “perhaps like all the bad bits of drinking without any of the good bits?”

If there was something like this I do wonder how it would (1) be able to be studied and measured and (2) sit with all the theories we’ve had in the past over motivational factors and effort preference?

 

[Jonathan Edwards]

If there was something like this I do wonder how it would (1) be able to be studied and measured and (2) sit with all the theories we’ve had in the past over motivational factors and effort preference?

Maybe we just have to find a pharmacological agent that blocks the negative signal specifically and show that it makes people suddenly feel fine, like the dopamine analogs do for Parkinson's or pyridostigmine for myasthenia. I doubt it would be that easy but even if there was a clear effect with something it might be possible to pin down a pathway.

I think this may be an oversimplified model but sometimes things are simpler than you think.

 

[obeat]

(Fezolinetant) is a hormone-free medication

It's a neurokinin 3 (NK3) receptor antagonist and
doesn't contain estrogen."

Just posting this because hot flushes originate in the hyposalamus and the chemicals involveda are known.

I always felt poisoned with hot flushes.

 

[AliceLily]

(Fezolinetant) is a hormone-free medication

It's a neurokinin 3 (NK3) receptor antagonist and
doesn't contain estrogen."

Just posting this because hot flushes originate in the hyposalamus and the chemicals involveda are known.

I always felt poisoned with hot flushes.

@obeat The hot flushes I experienced at menopause were really severe, it was more a sudden burn up. It got quite scary for me for a time. It was different though from the ME poisoned feeling.

It sounds like the poisoned feeling could be due to a neuro-toxin though?

Aside from that I remember one particular day in my very severe years where I questioned whether I had MS because the feeling of weakness that I had in my legs did not feel like weakness in the muscle but strange nerve weakness or some kind of nerve input.

 

[TigerLilea]

Regarding fatty liver, I have come across various references over the years to people with ME being thought to have fatty liver. I wonder if anyone else here remembers this? The one specific mention I do remember was in the case of Sophia Mirza: http://www.investinme.org/article-050 sophia wilson 01-rip.htm : "Sophia had a high BMI when she died and a “fatty” liver."

If Sophia had a high BMI then it's not surprising that she had a fatty liver as being overweight is apparently an almost given that you will have a fatty liver as fat stores in the liver first and then elsewhere in the body.

 

[TigerLilea]

Maybe we need a survey on heat intolerance next...

I didn't have heat intolerance until menopause. Now it is my unwanted friend who won't go away.

 

[TigerLilea]

All my Asian friends get that 'flush' from alcohol intolerance.

Ever since menopause I get the facial flushing and that is from just one drink.

 

[Haveyoutriedyoga]

I would be led more in that direction if the problem was chiefly an increased hangover. Failure to metabolise alcohol might aggravate things but I don't see it being the primary cause of the unpleasant reaction.

Many of us appear to be affected differently by medications, needing lower doses, slower titration, and experiencing different side effects. How could that inform or be interpreted by your theory?

 

[EzzieD]

If Sophia had a high BMI then it's not surprising that she had a fatty liver as being overweight is apparently an almost given that you will have a fatty liver as fat stores in the liver first and then elsewhere in the body.

It may have been the case for Sophia, but the idea of people with ME having a fatty liver is something I remember coming across for multiple patients and it was not stated that they were overweight. I myself am very slim, so if my weird liver problems are due to having a fatty one, it won't be because of being overweight. So I wonder what else might be going on in there...

 

[Jonathan Edwards]

Many of us appear to be affected differently by medications, needing lower doses, slower titration, and experiencing different side effects.

My guess would be that the side effects are part of a general environmental intolerance problem that could be mediated by the hypothalamus (the most likely place to mediate it). I am not sure about evidence for needing lower doses or slower titration. That is a popular idea amongst private 'ME' specialists but I have not seen any scientific data on it.

 

[hotblack]

One example that I found interesting was zopiclone. Used it occasionally years ago and found it worked well. Then had no need for many years. Since ME tried it again and had all sorts of problems, notably a significant rebound effect.
Given how it works I have often wondered how this fits in with odd things happening with neurotransmitters.

I wonder if there are just certain medications which interact with things mediated by the hypothalamus which are particularly problematic for people?

 

[Haveyoutriedyoga]

Not sure what my question is here, but it’s interesting that we may possibly have a sort of opposite effect to alcohol and many patients report feeling good on low dose naltrexone (although many dont), which supposedly acts in a sort of opposite way to full dose naltrexone, which is used for alcoholism.

 

[Hutan]

I wouldn't be surprised if there was an effect on vasodilation, compounding the effects of sitting upright for the length of time it takes to drink and socialise. So, blood goes to the feet, not the brain. And that can make us feel a bit ill, quite rapidly, as well as perhaps triggering PEM.

Effect of Ethanol on Micro-Vessels Diameter and Prevention of Thrombosis

In the present study, vessel diameter in both arteries and veins were larger in ethanol group when compared to the control group [in rabbits]. Surprisingly, this effect and enlargement in vessel diameter was more significant in venous group than arterial group.

Ethanol has various effects on different body systems. Alteration in peripheral blood flow including increased blood flow to face, skin and extremities occurs as vasodilation in periphery and is common after ethanol use.13 In animal models, ethanol causes relaxation of smooth muscles in vessels wall by activation and induction of NO and prostaglandins.14In several in vivo and in vitro studies, it was shown that ethanol lowered vascular tone and vessels spasm.15 Ethanol also prevents thrombosis by inhibition of platelet aggregation and increasing the levels of plasminogen activators.16 Ethanol also induces its vasodilation effect by increasing bioavailability of nitric oxide (NO) and decreasing endothelin-1 synthesis.17,18

(Ignore the 'thrombosis' bit, ironically the authors were suggesting the use of alcohol to reduce thrombosis risk after surgery. Also, the write-up is poor in that report, may be an English language issue. I expect there are better references to find.)

They found substantial differences in peripheral blood vessel diameter 7 days after injection with alcohol as opposed to saline. I find that a bit hard to believe, and I'm not sure what concentration they used. But still. They also mention botulinum toxin as achieving the same effect - stopping vascular nerve function results in vasodilation and a lack of ability to constrict when faced with a challenge.

Exercise probably does something similar - peripheral vasodilation.

I also see there that alcohol is reported to increase prostaglandins in muscle - and I think it's possible that localised prostaglandins are part of the problem in ME/CFS, maybe contributing to pain and lack of muscle control.