Investigating reduced tolerance to alcohol in ME?

[cassava7]

One question that has been bugging my mind is whether studying the lowered tolerance to alcohol that is commonly reported in ME would yield insights into the pathophysiology of the disease.

In the few studies that asked ME patients about their tolerance to alcohol, 60% to 2/3 of them report that it was reduced compared to when they had been healthy. But to my knowledge, no study has looked at the biological effects of alcohol in ME.

Alcohol can either cause PEM or increased symptoms, including, for some, a feeling of poisoning that can be present in their usual experience of PEM. So does the toxic nature of alcohol exacerbate whatever pathological processes that are going on in ME, maybe neurological ones or those related to energy production, and what biological markers would be worth looking into? Liver function, cerebral blood flow?

In my mind, the design of a controlled study of alcohol tolerance in ME could resemble this: participants fast for 12h+, then they are given the same dose of alcohol orally -- a glass of wine or a shot of liquor's worth? -- and report their symptoms for the next 48-72h. (Ideally the study would allow for a placebo group.)

Biological measures should be taken at multiple time points: before ingestion, shortly after (20-30 mins?) then every hour or few hours afterwards. Possibly, or maybe importantly, they would need to be taken on the next day, since healthy controls would be expected to have recovered fine by then from this small dose of alcohol while ME patients are likely to experience increased symptoms or PEM.

The main difficulties would be:

- obtaining ethical approval for such a study

- asking ME patients to travel, especially the day after consuming alcohol, is hardly feasible. Either nurses would have to travel to their homes or they would have to be admitted to a hospital.

- adequate controlling:

1) matching age, sex and weight is a minimum requirement, very likely ME severity too, and possibly activity levels (i.e. sedentary controls)

2) because ME patients rarely drink alcohol, controls would need to have a flush-out period of at least 2-3 weeks prior to participating during which they stop consuming alcohol

3) depending on the measured biological markers and when they are measured, controls could need to have a non-physically and non-mentally exerting day after consuming alcohol.

 

[Mij]

I don't have any issues drinking a couple of glasses of red wine on occasion.

 

[Peter T]

Normally studies looking at intolerances, assuming what we are seeing in ME in relation to alcohol is an intolerance, is to withdraw the foodstuff/drink from the diet completely for a number of weeks or even months before reintroducing it.

One of the problems with examining the effects of alcohol is that it comes in lots of different forms. I am not certain whether I am intolerant to alcohol or not because my response is very variable, both in relation to different drinks (eg beer, wine, spirits) and to the same drink at different times. I have found it easiest to cut out alcohol completely from my diet, but I don’t actually know if it is alcohol itself or different components in different drinks that are the problem.

 

[Colin]

A much lowered tolerance is something that I can report certainly was my experience. And while I've been aware that it is a known thing, one aspect of my experience of it I've never seen reported. When I did still drink, socially only, when I was younger, it was the one thing that would make me wake early the next day, rather than have to struggle out of a deep torpor around noon. I'd occasionally use that if I really had to get up early; but it was rarely worth it, because the hangovers were bad. And I haven't had more than the odd glass of wine for years so I can't really say if it still works.

I'd like to see such a study and would be happy to volunteer.

 

[MeSci]

I would be interested in such a study, but wonder whether alcohol is just one of many food and drink (and smell, sound, etc.) intolerances that develops during ME. It's one that didn't develop for about 21 years for myself. Smell intolerance developed much earlier - near the beginning.

 

[Mij]

Is it the alcohol or is it the elements of allergens (traces of yeast antigens) that some are reacting to? One would have to try various forms of alcoholic drinks to know for certain.

 

[cassava7]

I don't have any issues drinking a couple of glasses of red wine on occasion.

The dose is important, yes. My impression is that even moderate people can tolerate a glass of wine if not a little more, so a higher dose of alcohol would be required. The equivalent of a strong liquor, possibly.

Is it the alcohol or is it the elements of allergens (traces of yeast antigens) that some are reacting to? One would have to try various forms of alcoholic drinks to know for certain.

I think that, as confounding factors, other components in alcoholic beverages can be ruled out by simply taking ethanol in water as the source of alcohol. I admit it would taste awful but it works!

 

[Mij]

Alcohol is made by the fermentation of substrate. Spirits would be better tolerated than the wines and beers because the alcohol has been distilled off, removing most of the antigen.

 

[Colin]

Alcohol is made by the fermentation of substrate. Spirits would be better tolerated than the wines and beers because the alcohol has been distilled off, removing most of the antigen.

I could eat yeast by the glassful, with milk, and did for awhile as one of many health experiments, and I never had any sort of allergic reaction to it or to anything else that one might find in the various sorts of flavoured ethanol that are made. But straight vodka could, and did, have the usual effect on me. I am quite convinced that it was the ethanol that was the active ingredient. But, of course, that would have to be tested.

 

[leokitten]

The other thing is this phenomenon can change over time, so that’s important to take that into account during study. But I agree it’s a super interesting thing to study because the symptom appears suddenly and is very pronounced.

During the first 6 months of ME, after the triggering viral infection, if I even had one swig from a glass of wine my body would immediately go into a state of terrible hangover and nausea like I’d drank bottles of vodka. Before the triggering viral infection I had no problem drinking alcohol.

Very slowly after that stage the symptom started reducing in severity. It coincided with other symptoms during the early stages that slowly reduced or went away over the first couple years even though my ME severity has gotten worse over time. Now I can drink a few glasses of wine with little issue, though not as freely as pre-ME, but the symptom from the early stages doesn’t appear to be there anymore.

 

[Guido den Broeder]

It's not an allergy. ME often comes with hypoglycemia, hence the intolerance. The insulin response in ME is off as well, starting late and stopping late. Therefore ME patients should avoid sugar, too.

In time, both intolerances may be somewhat reduced as your sugar level in the fasting state goes up with age while the insulin response to sugar intake weakens.

 

[Kitty]

I've had the intolerance throughout, and the type of alcohol doesn't make any difference. I basically stopped drinking before I was legally old enough to start! The awful nausea and hangover would start within 20 to 30 minutes, and just isn't worth it.

I also have what is probably a histamine reaction, which – due to my Dad's tendency to treat childhood tummy aches with a teaspoon of brandy in a warm drink – I know dates back at least to the age of four. I get a deep scarlet flush covering all the skin from my chest upwards, I often feel itchy, and I occasionally get dermatographia as well. (The reaction isn't connected to the 'Asian flush' phenomenon, as I have no east Asian ancestry.)

 

[Trish]

It's not an allergy. ME often comes with hypoglycemia, hence the intolerance. The insulin response in ME is off as well, starting late and stopping late. Therefore ME patients should avoid sugar, too.

In time, both intolerances may be somewhat reduced as your sugar level in the fasting state goes up with age while the insulin response to sugar intake weakens.

Can you provide a link to some research evidence to support your statements about a link between ME and hypoglycemia, and about the effects of ageing on insulin and sugar?

 

[Guido den Broeder]

Most ME research is not online. Hypoglycemia is mentioned by Ramsay. From my own studies, some 15% of ME patients actually get diagnosed with it, which is a lot since it will typically only get checked if you ask for it and even then not always. You can google for the effects of ageing.

 

[TigerLilea]

I don't have any issues drinking a couple of glasses of red wine on occasion.

I don't either.

 

[Colin]

It's not an allergy. ME often comes with hypoglycemia, hence the intolerance. The insulin response in ME is off as well, starting late and stopping late. Therefore ME patients should avoid sugar, too.

In time, both intolerances may be somewhat reduced as your sugar level in the fasting state goes up with age while the insulin response to sugar intake weakens.

When the GI diet came in, in the late 1990s, I reduced my sugar intake greatly and it was one of the few things that have made a difference; albeit not a great one. So while I find that connection quite plausible, I'd like to see more evidence for it, too. Obviously, many people have sugar-metabolism problems but don't have ME/CFS. So that woud be another good reason for an ethanol study; which, one would hope, would be published.

 

[arewenearlythereyet]

From my experience our perception of the impact of what we eat or drink is subject to an enormous amount of bias.

On a daily basis retailers and manufacturers of food and drink have to deal with this. Over 90% of complaints received about food poisoning are attributed incorrectly ...mainly because most people believe that the last thing they ate caused it (if it was actually food poisoning which many cases aren’t). Most cases of genuine food poisoning are due to something eaten at least 24 hrs ago (and a lot of common food poisoning mo’s are greater than 48 hr incubation time).

it’s a similar thing for allergens, foreign bodies etc etc. Normally there are plenty of objective measures to get to the truth (chemical and micro testing, type of glass or metal found, type of hair found etc.).

I believe that one of the reasons that this bias is so high is that our brain is hard wired to process sensory input around “toxins” to learn to avoid certain foods. This is one of the many biases to overcome in experimental design.

This means that any subjective questionnaire on symptoms associated with alcohol is more that likely to end up with a similar level of misinterpretation/incorrect attribution (i.e garbage results). It also doesn’t help that even small amounts of alcohol can alter our perceptions so you already have a problem with variance in your test group vs. the control.

ideally there should be objective measures to run alongside the subjective ones (probably quite a few depending upon how many symptoms you want to measure)... perhaps something around metabolites from samples taken? I think this would be a challenge though.

It would also be good to start with a sound foundation for the premise. A reasonably large scale study that shows a statistical analysis of perceived alcohol intolerance prevalence vs age matched control groups. The results of this could then determine the size and spec of your test group/s.

It’s highly possible that perceived alcohol intolerance is unrelated to ethanol consumption so diluted pure ethanol is probably better than wine or commercially available spirit. I suspect this is a non starter due to the challenges mentioned though.

 

[Colin]

From my experience our perception of the impact of what we eat or drink is subject to an enormous amount of bias.

Of course there is bias but if there is any bias regarding drinking beer, here, it's way in favour of it, still, despite the known toxic effects. And you would be hard-pressed to convince me that the three days that I spent in bed after the last time I attempted to be normally social by drinking beer at a party was the result of some sort of perceptual difficulty.

I believe that one of the reasons that this bias is so high is that our brain is hard wired to process sensory input around “toxins” to learn to avoid certain foods. This is one of the many biases to overcome in experimental design.

I had the impression that what was being proposed was a proper biochemical study, not just a questionaire. Though the subjects would have to be selected on the basis of self-reporting, I suppose, are there really so many people with so much time on their hands as to make something like that up in order to bias such a study?

It’s highly possible that perceived alcohol intolerance is unrelated to ethanol consumption so diluted pure ethanol is probably better than wine or commercially available spirit. I suspect this is a non starter due to the challenges mentioned though.

Ignoring the attempt to smuggle in a bit of bias of your own with that "highly" possible, I don't see the difficulty. Apart from obtaining ethical approval, and finding willing participants, what's the problem? Apart from knowing what to look for and all the technical considerations, which I am not qualified to opine upon.

 

[Shinygleamy]

I always believed it was due to a sluggish liver, struggling to clear the alcohol from your bloodstream, the same goes for drugs.

 

[Guido den Broeder]

When the GI diet came in, in the late 1990s, I reduced my sugar intake greatly and it was one of the few things that have made a difference; albeit not a great one. So while I find that connection quite plausible, I'd like to see more evidence for it, too. Obviously, many people have sugar-metabolism problems but don't have ME/CFS. So that woud be another good reason for an ethanol study; which, one would hope, would be published.

A third of the patients we've questioned developed alcohol intolerance when they hadn't this problem before, and another 30% who already had this issue saw it increase in severity. Alcohol was the most significant of all the intolerances on our list, followed by tobacco.

Link: http://www.mevereniging.nl/volop-voedselintoleranties-bij-me/