What research do you want to see? (study ideas)

I would like to see more research on alcohol-induced symptoms & intolerance, both mechanistic and epidemiological; the latter to determine how common it is in well-characterised ME/CFS cohorts, the precise nature of the symptoms experienced and their time-course, and to determine whether those who report it also report intolerance to other medications that act on the central nervous system in differing ways.

Bansal (BMC Family Practice (2016) 17:81) suggested that this was an unusual symptom that "may be used to confirm the diagnosis", stating that from his clinical experience "nearly all patients. . . have reduced their intake of alcohol and I have not seen a single patient who had increased his/her alcohol intake".

There are very few conditions that result in unusual alcohol-induced symptoms or significant alcohol intolerance. There are many reports of alcohol-associated pain in Hodgkin's disease which seems to have been first described in 1950 (Amer J Roentgenol 64:613) followed by a number of case reports in the 1950s and 1960s; the first systematic investigation of it seems to have been in 1960 (Quart Journ Med XXIX:113). There was a suggestion in a letter to the Lancet in the 1970s that alcohol intolerance in Hodgkin's was not as commonly found as implied by the initial reports. Nonetheless, case reports of the same phenomenon continue; there was one in 2019 (BMJ Case Rep 2019;12:e228440) in which it was a presenting symptom.

Alcohol intolerance also occurs in the hypereosinophilic syndrome: in 1988 two cases where alcohol intolerance was a presenting feature were reported (Alcohol Clin Exp Res 12(1):147-8). There is also the well-known "alcohol flush" syndrome reported to result from a variant in ALDH2 causing deficiency of aldehyde dehydrogenase II. Alcohol intolerance can also be deliberately induced by medication as treatment for alcoholism: disulfiram (Antabuse) acts by inhibiting aldehyde dehydrogenase resulting in the accumulation of acetaldehyde from which a number of unpleasant symptoms flow. There was a broader discussion of alcohol intolerance syndromes in "Alcohol: intolerance syndromes, urticarial and anaphylactoid reactions" (Clin Dermatol 17(4):417-422). Flushing associated with alcohol has also been reported in carcinoid syndrome.

Alcohol intolerance in ME/CFS has only very rarely been studied. One of the few publications of significance is "Alcohol use in chronic fatigue syndrome" (J Psychosom Res 56(2004):203-206) where it was reported that in a study of 114 CFS patients 2/3rds self-reported a reduction in alcohol use and the most common reasons for this were exacerbations of physical symptoms.

In "Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome" (Front Paediatr 7:2019) there is a small table showing the prevalence of alcohol intolerance in ME/CFS in various studies.

Interestingly there are also occasional references to it in the historical neurasthenia literature, some of which may have been cases of ME/CFS.

 

Another one:

There was a single paper in Frontiers in 2019 that reported downregulation of a single proprotein convertase in postural tachycardia syndrome (Front Neurosci 13:301). I'd like to see a replication attempt and also to see if there is evidence of it in a well-characterised ME/CFS cohort.

 

I've seen a few people with ME/CFS on PhoenixRising and Reddit order online WGS tests. I wonder if it might be good to do a cheaper preliminary study where researchers put out a call for people who already have their results to send them in.

 

Many moons ago, long before this forum, there was discussion somewhere about the use of nicotinamide as a painkiller in ME/CFS.

I can't remember much detail, except that among those who tried it there was a clear dividing line: it either worked well or had no effect. I was so sceptical I nearly didn't do it, but then was taken aback by the effect—for the 'ME/CFS burn' it worked as well as the weak opioids I was prescribed.

I keep wondering now if that very unscientific but interesting experiment could have told us something about subgroups.

If @Caroline Struthers eventually manages to set up a multi-arm trial testing possible disease-modifying drugs, maybe it could be discussed a candidate—not as a treatment for ME/CFS, but as a potential symptom reliever. If it's shown in a real trial that it works for some and not others, it might even offer a clue about what might be going on with our muscles.

 

It's especially interesting as alcohol consumption is generally associated with mental illness, depression and distress. Whether it's accurate or not is hard to tell, and I frankly wouldn't put much trust in the health care industry's ability to research this competently, which is really a missed opportunity.

So much has been made about the social measures during pandemic restrictions and it has been attributed mostly to that, to the hardship of being isolated and having disrupted routines. All signs of mental illness and distress, according to the experts on mental health. Most of which would agree this is basically what we have. But then they don't care that we instead barely drink any. The perks of falling at the 'interface' of medicine and medicine (i.e. psychiatry, which despite odd classifications is definitely a medical thing).

One of those "in a just world" thing. With a competent profession handling mental health care scientifically, this could be a useful lead worth researching. But instead I would assume that even with dozens of studies they'd just never even get around to doing it right, can't even figure out which questions to ask.

 

I would like to see someone with access to NHS referral data (presumably at a Trust-wide level although perhaps it is available at a national level as well?) determine whether there are any seasonal (or other timing or event-driven) patterns in the referrals to NHS ME/CFS clinics.

Basis for this suggestion: in November 2024 there was a piece of typically dreadful psychosomatic research that nonetheless included an interesting statement suggesting such seasonality:

However, this was to a paediatric clinic and so referral patterns may be influenced by school holidays and so forth; the obvious next step would be to check whether the same pattern holds across adult clinics.

If there are such patterns, I'd like to see further research to determine whether they relate to ME/CFS onset. I'd also like to see whether it is possible to correlate referral patterns to other events - e.g. is there often a surge of referrals a few months after a particularly severe winter flu season?

 

NHS England month-by-month data for July 2021 to Feb 24 is here. https://www.england.nhs.uk/statistics/statistical-work-areas/covid-19-post-covid-assessment-service/

 

The data there is for the post-COVID clinics. Looking at pre-COVID-19 referral patterns would be best; a global pandemic is something of a confounder.

 

Sorry - had a brainfade there.

 

Apologies if this was raised already. I would like to see research into the metabolism. Areas as liver, stomach, gallbladder.

Especially since the most severe seem to have a malfunctioning stomach. How is this in the less severe and moderate?