Letter on 'Clinical Trial: Effect of a 28-Day Low FODMAP Diet on Gastrointestinal Symptoms Associated With Endometriosis (EndoFOD)-A Randomised, Controlled Crossover Feeding Study'

Letter on ‘Clinical Trial: Effect of a 28-Day Low FODMAP Diet on Gastrointestinal Symptoms Associated With Endometriosis (EndoFOD)—A Randomised, Controlled Crossover Feeding Study’ Funding: The authors received no specific funding for this work. We read with great interest the randomised, controlled, crossover feeding trial by Varney et al. [1], which explored the effect of a low FODMAP diet in women with endometriosis and severe gastrointestinal symptoms. The authors have provided valuable preliminary evidence that a low FODMAP diet may alleviate gastrointestinal symptoms and improve quality of life. However, several methodological and interpretive issues merit further consideration. First, the small sample size (35 randomised; 25 completed) and a dropout rate of 28% limit statistical power and external validity. Since all participants resided in Melbourne due to logistical constraints related to food delivery, the study population lacks geographic and cultural diversity. This restriction reduces the feasibility of subgroup analyses such as stratification by disease stage or microbiome profile, and constrains the generalisability of findings to broader populations where dietary interventions may differ in accessibility and adherence. Recruitment via endometriosis advocacy websites and social media may have also introduced selection bias, favouring participants who were already motivated towards dietary management. In addition, approximately 71% of participants were using hormonal contraception; progesterone-based agents exacerbate gastrointestinal symptoms [2]. The exclusion of women with irregular menstrual cycles and those without English proficiency further narrows the study's applicability to the heterogeneous endometriosis population. Second, although the study was described as ‘single-blinded’, the adequacy of blinding is questionable. Given the characteristic gastrointestinal effects of a low FODMAP diet, such as reduced bloating and changes in stool form, participants may have inferred which diet they were receiving. The heavy reliance on subjective self-reported outcomes (VAS and PROMIS scales) increases the risk of expectancy bias. While full double-blinding is notoriously difficult in dietary trials, stronger blinding strategies could have enhanced internal validity. Third, the proposed mechanism that symptom improvement was driven by reduced luminal fermentation and osmotic load remains speculative, as no mechanistic biomarkers (e.g., hydrogen breath testing, microbiome profiling, or inflammatory markers) were included [3, 4]. Without such data, causal inference cannot be established. Future studies should incorporate objective physiological endpoints to validate these mechanisms and to determine whether low FODMAP interventions modify gut microbiota composition or intestinal permeability in women with endometriosis. Lastly, despite the ≥ 28-day washout period, the possibility of carryover effects inherent to crossover designs cannot be fully excluded, particularly given that gut microbial and metabolic adaptations may persist beyond one menstrual cycle. Although the authors reported no significant order effects, a parallel-group design may be more appropriate for dietary interventions with potentially lasting biological impacts. In conclusion, this trial represents an important step towards understanding non-pharmacological strategies for symptom management in endometriosis. However, before the low FODMAP diet can be recommended as a clinical intervention, future research should include larger and more diverse cohorts, integrate objective mechanistic measures, and conduct long-term follow-up to assess sustainability, nutritional adequacy, and disease-specific efficacy. Author Contributions Wancheng Zhao: writing – original draft. Lei Yu: conceptualization. Jiao Wang: writing – review and editing. Conflicts of Interest The authors declare no conflicts of interest. Linked Articles This article is linked to Varney et al. papers. To view these articles, visit https://onlinelibrary.wiley.com/doi/10.1111/apt.70161. Data Availability Statement Data sharing not applicable to this article as no datasets were generated or analysed during the current study.