Impact of Restrictive Diets on Inflammation and Quality of Life in Autoimmune Thyroiditis (TAILOR)

Background:

Previous studies have investigated the effects of gluten-free diets, casein-free diets, or the restriction of high-glycemic-index carbohydrates separately in individuals with autoimmune thyroid disease (AITD), yielding heterogeneous and inconclusive findings. The present study aims to evaluate the combined effect of simultaneously excluding these dietary components on immunological, clinical, and patient-reported outcomes in women with AITD. The dietary intervention is intended as a nutritional strategy under investigation and is not designed to replace standard medical treatment or routine clinical care.

Dietary Intervention:

Participants assigned to the intervention group will simultaneously eliminate gluten-containing cereals (wheat, barley, and rye), dairy-derived casein, and high-glycemic-index carbohydrates from the start of the study. No sequential elimination or reintroduction phases are planned. The study periods (months 0-4, 4-8, and 8-12) correspond exclusively to predefined assessment intervals. Apart from the dietary exclusions under investigation, participants will be advised to maintain a stable dietary pattern with comparable energy intake and macronutrient distribution throughout the study.

Group Allocation:

This is a prospective, non-randomized study. Group assignment will be determined at baseline, prior to initiation of the intervention, according to each participant's willingness and ability to follow the dietary protocol. To minimize potential selection bias associated with the absence of randomization, propensity score methods based on baseline characteristics, including age, body mass index (BMI), baseline anti-thyroid peroxidase antibody (anti-TPO) levels, thyroid-related treatment, and relevant lifestyle factors, will be incorporated into the statistical analysis through adjustment, stratification, or inverse probability of treatment weighting, as appropriate.

Adherence Assessment:

Adherence to the dietary protocol will be evaluated using a Nutritional Adherence Index calculated as: Adherence (%) = (days with complete compliance / total days evaluated) x 100. In the intervention group, satisfactory adherence will be defined as a compliance rate of at least 90%.

Sample Size Calculation:

The sample size is based on the primary outcome (change in anti-TPO antibody concentrations from baseline to month 12). In a comparable non-randomised trial of a gluten-free diet in women with Hashimoto's thyroiditis (Krysiak R, Szkróbka W, Okopień B. Exp Clin Endocrinol Diabetes. 2019;127(7):417-422. doi: 10.1055/a-0653-7108), the standard deviations of the 6-month change in anti-TPO were 105 and 25 U/mL (pooled SD approximately 74 U/mL), with a between-group difference of 229 U/mL. Assuming a pooled SD of 74 IU/mL, a two-sided alpha of 0.05 and 80% power, 24 evaluable participants per group allow detection of a between-group difference of about 60 IU/mL, approximately one quarter of the effect previously reported. Allowing for approximately 20% attrition, 30 participants per group will be recruited (total N = 60).

Statistical Analysis:

The primary analysis will evaluate changes in anti-TPO antibody concentrations between groups using multivariable regression models adjusted for potential confounding factors. Longitudinal changes across follow-up visits will be assessed using repeated-measures analysis of variance (ANOVA) or linear mixed-effects models, as appropriate. Both intention-to-treat and per-protocol analyses will be performed. Missing data will be addressed using multiple imputation methods.

Safety Monitoring:

Participants will be monitored throughout the study for potential adverse effects related to the dietary intervention. Predefined safety criteria include unintentional weight loss exceeding 5% of body weight within one month, clinically significant thyroid dysfunction requiring treatment adjustment, persistent gastrointestinal symptoms, evidence of nutritional deficiency, and significant psychological distress. Adverse events will be evaluated within 48 hours of notification, and serious adverse events will be reported to the relevant Ethics Committee within 7 calendar days, in accordance with applicable regulations.