Title: Effects of a Low-FODMAP Diet on Patients with Endometriosis, a Prospective Cohort
Study
Version: 4 Date: 17 Feb 2025
Reviewer:  Rachel Reid-McCann
Reviewer's report:
Thank you for your time and effort in undertaking this important work. I think there is a little
work to be done to bring this to a publishable standard. I have some comments and suggestions:
Line 37 - methods section, should this contain some info on statistical methods, i.e. differences
in pre- and post-intervention scores (and at which time points) were assessed using X test. It's
also unclear whether the results presented below relate to baseline and 4 weeks or baseline and
10 weeks
Line 39 "after these periods" is vague to me, could you be more specific if word count permits?
I.e. "at baseline,  ~4 weeks and ~10 weeks? Many people will skim the abstract only so it would
be useful to include the detail here
Line 40, if you have space consider adding the score limits for the primary outcome, as it
is unclear whether the decrease by 2 points is considered to be small or large without this
information presented beforehand and again many will just skim the abstract
Line 47, again "various reasons" is vague. Could you add N=x for reason a, N=x for reason b...etc
Line 47 "completed the diet"—what was considered completion? Maybe add in methods of
abstract that completion was considered as x% adherence, assessed by x method
Lines 51-55, I think it would be easier to read with the statistics after each outcome as it's a
relatively sizeable list and at present readers have to count the positions to figure out
which stat corresponds to which outcome
Lines 61-62, I think the last sentence could be more meaningful if you explain why this would
be necessary considering you found significant results anyway, i.e. it should be validated in
more diverse populations? in different disease phenotypes? maybe a note on exploring barriers
to non adherence?
Line 98, there is no citation provided for this statistic
Line 102 '30%', for consistency?
Line 111 "The diet eliminates", I would say 'the diet involves elimination of' as it is the person
rather than the diet that is acting
Line 115 - I would reword this as it suggests that there are no best practice guidelines for
treatment, perhaps that there are limited treatment options that are effective long term therefore
many patients opt for lifestyle modifications
Lines 116-118, they chose a dietary strategy as their no1 management strategy over medical
approaches? Or alongside other approaches? Maybe reword 'chose a dietary intervention' to
'reported dietary changes/modifications' to remove the suggestion that they opted for diet over
other treatments and that the intervention was provided to them when presumably they are
talking about making their own dietary changes
Line 122 "retrospective study of prospective collected data", should this just say "a study
using prospectively collected data", as a retrospective study suggests that data were collected
retrospectively
Line 124 it is not clear to me what the (>50%)  is referring to
Line 125-again, if the previous study used prospectively collected data then there are two
prospective studies to me?
Line 126 what is 'endometriosis diet'? Could you explain briefly in brackets afterwards perhaps
i.e. is it an anti inflammatory diet
Line 132 has never been studied before - to the authors knowledge
Line 143 - a feasibility study usually focuses on update/adherence/completion as the primary
outcomes of interest and is more concerned with the acceptability of the intervention rather than
the efficacy, I don't think this study is a feasibility study?
Line 174 - I think process should say progress?
Line 176 - the reintroduction period, did this mean immediately they could eat all FODMAPs
again? How was the 'time required' determined? Maybe also add in a sentence  to justify why
it’s ok for participants to have outcomes assessed at variable timepoints, i.e. why can they have
different lengths of reintroduction period
Lines 183, 187 - should ‘after the diet’/‘post diet’ say ‘at 4 weeks’? Is this when the primary
outcome was assessed? I think this needs to be clearer
Lines 196, 197 - when referring to the EHP-30, eg the pain domain, could you be more specific
so readers don’t have to go and find the EHP and read themselves, i.e. you could say X number
of questions which enquire about endometriosis-associated pain on activities of daily living e.g.
sleeping, eating … on a Likert scale, (never; rarely…etc)
Line 197 - again, 'after the diet' - at 4 weeks?
Line 202 - were any participants excluded from analysis if their adherence dropped below a
certain %?
Lines 212-214 - I think the reasons for drop out should be in the results section rather than in
methods
Line 234 - ‘completed the diet’ - does this mean 100% adherence? This is not likely
Line 251 - there is an extra word here (up)
For the 10 non-completers, do you have data for how long they maintained the diet? Did most
of them stop after only a few weeks for example
Line 253 talks about mean difference, but the test statistic produced by Wilcoxon signed rank
tests is not the mean difference
Line 262 - ‘after the study’ what does this mean? At x weeks?
Line 311 - citation for this previous publication?
I think you also need to explicitly mention in this statistical
analysis section how to deal with missing data (eg baseline carried
fwd method - https://pmc.ncbi.nlm.nih.gov/articles/PMC2819899/#:~:text=The%20baseline
%2Dobservation%2Dcarried%2Dforward%20(BOCF)%20approach,nontreatment%2Drelated
%20reasons%20for%20discontinuation.) and non-adherence (what was classified as adherence)
I think it's important to remember that the pain domain in EHP-30 is asking about pain
interference rather than pain levels, and that there may be differences between completers and
non completers for pain interference while their pain ratings may be similar (i.e. more 'stoic'
individuals may experience less interference and may also be more likely to complete the diet,
this could bias results
In limitations I think you need to mention the risk of maturation effects (natural changes that
occur over time regardless of the intervention) and the lack of confounder adjustment. I also
think in limitations you should acknowledge
Figure 1
- No symptoms, pregnancy - why were they “included into the study” pregnancy was an
exclusion criterion and debilitating symptoms was an inclusion criterion?
- Why are there n=5 participants with data at baseline and 4 weeks who are not included in
analysis, but also n=2 participants with baseline and 4wk data who are included in analysis?
- Add footnote for any abbreviations in the figure i.e. FU follow-up, or just write follow up as
it will fit in the box
Table 1
- Some of the % in brackets don’t add up to 100, if there are others who should be in a ‘none’
category for example, then that should be added
- There is no information in the methods for how covariates were measured or defined. For
example smoking - ever vs never? Current vs previous/never? Is alcohol intake defined using a
cut off point? were medical/health data self reported or taken from clinical records?
Figure 2
- I recommend reformatting this in a way that it’s clear that the top row is the sum of the numbers
below, its a bit confusing right now
- Add “N(%)” in the first column where relevant
- What does reaction to FODMAP mean? They reported an adverse reaction to this specific
FODMAP? How would they know if they excluded all at same time? More detail is needed in
the methods for how outcomes were assessed
Table 2
- This isn’t referenced anywhere in the text
- “Mean difference” column should just be called P-value and should include P for the non
parametric, parametric and chi-2 tests. Mean difference is the subtraction difference of means
which isn’t a hypothesis test
- If you’re interested in isolating the effect of the low-FODMAP diet then surely the pre-post
comparisons should be between baseline and 4 weeks? I suggest you provide P values for this
elimination phase and another column of P values for baseline to end of reintroduction.
- Also these comparisons are with N=24 at baseline and N=21 after reintroduction, this
introduces bias as there may be important differences between the N=3 missing and the
remaining group. Best practice would be to carry their baseline data forward and use this at the
second timepoint - you need to explain in methods how you plan to deal with missing data in
these cases. They would need to be imputed or the participants excluded