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.