The present study utilized a previously collected cross-sectional sample of adults with various chronic illnesses from a larger study[17]. Participant recruitment was conducted via email requests to national foundations as well as posts to social media outlets, research forums, and support group websites. Participants were directed to complete an online questionnaire after establishing informed consent. Approval was provided by the DePaul University Institutional Review Board for all study methods.

For the purposes of this investigation, participants were included if they reported a diagnosis of CFS, ME, or ME/CFS, and if they responded to the DePaul symptom questionnaire-2 (DSQ-2) questions used to classify alcohol intolerance (n = 304). Exclusion criteria consisted of a diagnosis of cancer, lupus, multiple sclerosis, post-polio syndrome, HIV/AIDS, or Gulf War syndrome.

Participants completed the DSQ-2[12], a self-report questionnaire that assesses ME/CFS symptomatology as well as social, occupational, and medical history, and demographic information. The DSQ-2 constitutes an addition of 34 items to the DePaul Symptom Questionnaire-1 (DSQ-1), which has previously shown favorable results for construct, convergent, and discriminant validity[18] and test-retest reliability[19]. The DSQ-2 is publicly available in the shared library of the Research Electronic Data Capture (REDCap)[20,21] and can be accessed at https://redcap.is.depaul.edu/surveys/?s=4NJ9CKW7JD.

Participants were asked to rate the frequency and severity of each symptom over the past 6 mo on 5-point Likert scales. For frequency, participants chose between the following options: 0 = none of the time; 1 = a little of the time; 2 = about half the time; 3 = most of the time; and 4 = all of the time. For severity, participants chose between the following options: 0 = symptom not present; 1 = mild; 2 = moderate; 3 = severe; and 4 = very severe. Composite scores were generated for each symptom by averaging respective scores for frequency and severity and multiplying by 25 for a 100-point scale. Higher scores indicate a higher burden of the designated symptom. Symptom domain scores were calculated by averaging the composite scores for each item within the following symptom domains, previously determined by exploratory factor analysis on DSQ-2 data, including post-exertional malaise, cognitive impairment, fever and flu, pain, sleep disruption, orthostatic intolerance, genitourinary, and temperature intolerance[12].

Table 1 lists the DSQ-2 questions used to classify alcohol intolerance. The DSQ-2 question relating to frequency of alcohol intolerance over the past 6 mo was omitted due to ambiguity as to whether responses reflected the frequency of drinking alcohol or the frequency of experiencing alcohol intolerance when drinking alcohol.

Participants were classified as alcohol intolerant if they met either condition: (1) Reported a severity of moderate or higher on alcohol intolerance within the past 6 mo (options 2-4 on question 1 in Table 1); or (2) Reported that they were avoiding alcohol (“Yes” on question 2), and their alcohol intolerance would be moderate or higher if they were to drink alcohol (options 2-4 on question 3 in Table 1).

Participants were classified as “not alcohol intolerant” if they met either condition: (1) Reported alcohol intolerance severity within the past 6 mo as “symptom not present” or “mild” (options 0-1 on question 1 in Table 1); or (2) Reported that they were avoiding alcohol (“Yes” or “No, I do not drink alcohol for other reasons” on question 2), and their alcohol intolerance would be mild or not present if they were to drink alcohol (options 0-1 on question 3).

For the linear regression, alcohol intolerance was coded as a linear variable based on the following conditions: (1) If the participant answered that they were avoiding alcohol (“Yes” on question 2), alcohol intolerance was coded as the score of how severe alcohol intolerance would be if they were to drink alcohol (question 3); and (2) If the participant was NOT avoiding alcohol, alcohol intolerance was coded as the score of alcohol intolerance severity in the past 6 mo (question 1).

In addition to the DSQ-2, participants were also asked to complete the MOS 36-item Short-Form Health Survey (SF-36)[22]. The SF-36 is a self-report measure that assesses health across eight general domains: Physical functioning; role limitations due to physical health problems (role physical); bodily pain; general health functioning; vitality; role limitations due to personal or emotional problems (role emotional); and mental health. Responses to each of the 36 items are recoded to a 100-point scale, and items are grouped together based on the eight domains. Subscale scores are then generated by averaging item scores within each domain, with higher scores indicating better functioning in the domain. Adequate psychometric properties have been demonstrated for SF-36 across diverse patient groups[23], and it has previously been shown to perform well in measuring fatigue-related functional impairment in ME/CFS[24].

Independent t-tests were performed using SPSS 26 for all DSQ-2 symptoms and SF-36 items. Participants were divided into a binary classification of “alcohol intolerant” or “not alcohol intolerant.” Due to the large number of items that were tested, we only considered findings significant if P ≤ 0.01, and we used two-tailed significance levels.

Multiple linear regression was conducted to determine if composite symptom scores in the eight DSQ-2 domains were predictors of alcohol intolerance severity scores. Age and sex (coded in the data set as: 1 = male; 2 = female; and 3 = other) were also evaluated in the regression model.

Table 2 describes the demographic characteristics of the sample separated by the binary alcohol intolerance classification. The alcohol intolerant group (n = 208) had a mean age of 45.48 (standard deviation = 16.49), and the not alcohol intolerant group (n = 96) had a mean age of 45.54 (standard deviation = 17.40). Both groups were predominantly female and Caucasian/White. The majority of the sample reported being on disability (50.0% for the alcohol intolerant group; 40.6% for the not alcohol intolerant group) and married/living with a partner (45.2% for the alcohol intolerant group; 55.2% for the not alcohol intolerant group).

t-tests were conducted on mean composite scores for 79 individual symptoms, mean composite scores for the 8 symptom domains (calculated by averaging composite scores for items within the symptom domain), and subscale scores for 8 SF-36 domains. Results of the independent t-tests for DSQ-2 symptoms are available in Table 3. Out of 79 individual symptoms, 33 (41%) were significantly different (P ≤ 0.01). For every statistically significant symptom, mean composite scores were higher for the alcohol intolerant group, indicating a higher symptom burden (in terms of frequency and severity of the symptom).

Of the eight symptom domains, five domain scores were significantly higher for the alcohol intolerant group, including post-exertional malaise, cognitive impairment, pain, orthostatic intolerance, and temperature intolerance. The fever and flu, sleep disruption, and genitourinary domains were not significantly different between the two groups.

Results of the t-tests for the SF-36 are presented in Table 4. The alcohol intolerant group scored significantly lower on physical functioning and bodily pain. Higher scores indicate better functioning on the SF-36, so lower scores for the alcohol intolerant group would indicate worse functioning.

Results of the multiple linear regression are available in Table 5. The overall multiple linear regression was statistically significant [R² = 0.14, F (10, 233) = 3.64, P ≤ 0.001]. Sex, age, and seven out of eight symptom domains did not significantly predict alcohol intolerance severity (P ≤ 0.05). Only the orthostatic intolerance domain significantly predicted alcohol intolerance severity (β = 0.21, P = 0.01). We did not use the SF-36 domains as predictors as our interest was in assessing which symptoms might be related to alcohol intolerance rather than physical or mental functioning.

There is a need to objectively measure alcohol intolerance among those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

There is a need to determine if those with ME/CFS with alcohol intolerance are more symptomatic than those without alcohol intolerance.

We aimed to carefully measure alcohol intolerance and determine its effects on those with ME/CFS.

We collected data from patients with ME/CFS using a validated symptom questionnaire.

We were able to determine that those with alcohol intolerance were more symptomatic than those without it among a sample of patients with ME/CFS.

It is important to measure alcohol intolerance carefully among patients who are not going to report using alcohol over the preceding months.

It is possible to reliably and validly measure alcohol intolerance among those with ME/CFS, and this should guide future research in this area.