Gluten-Free Diet for Hashimoto’s Thyroiditis: Systematic 

Effects of Gluten-Free Diet Intervention in the Treatment of Hashimoto’s Thyroiditis in Non-Celiac Disease

Systematic Review Protocol | Published in Endocrine Regulations, 2025

• Hashimoto's Thyroiditis (HT): Autoimmune condition where immune system attacks the thyroid.
• Characterized by lymphocytic infiltration, thyroid dysfunction, and elevated autoantibodies.
• Leading cause of hypothyroidism worldwide.
• Significant health impact: fatigue, metabolic changes, long-term medication requirement.

Current Limitations Standard care focuses primarily on synthetic hormone replacement (levothyroxine). It manages hormone levels but often fails to address the underlying autoimmune etiology or persistent symptoms.

Dietary Interest Increased patient and clinical interest in lifestyle and dietary interventions, specifically the role of inflammation-modulating diets in managing autoimmunity.

• What is Gluten: Protein complex in wheat, rye, and barley.
• Mechanism: Potentially increases intestinal permeability ('leaky gut').
• HT Correlation: Increased immune activity might worsen thyroid autoimmunity in sensitized individuals.
• Proposed Benefit: Reduction of systemic inflammation through strict GFD.

• Evidence is currently fragmented and often relies on observational or uncontrolled studies.
• Lack of standardized, high-quality RCTs evaluating GFD for HT in the absence of celiac disease.
• Systematic review is required to synthesize available data and inform clinical decision-making.

• Aim: To evaluate the efficacy of GFD intervention for Hashimoto's Thyroiditis in patients without celiac disease.
• Primary Objective: Determine effects on thyroid function tests (T3, T4, TSH) and anti-thyroid antibodies (TPOAb, TgAb).
• Secondary Objective: Assess impacts on markers of systemic inflammation (CRP), vitamin D levels, BMI, and quality of life (QoL).

• Thyroid Hormone Profile (T3, T4, TSH)
• Antibody Titers (TPOAb, TgAb)
• Systemic Inflammation (C-reactive protein)
• Nutritional Status (Vitamin D levels)
• Metabolic Indicators (BMI)
• Patient-Reported Quality of Life (QoL) outcomes

Risk of Bias Assessment Utilizing the Cochrane Risk of Bias 2 (RoB2) tool to rigorously evaluate the methodological quality of included studies.

Evidence Strength Applying the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to determine the certainty of evidence.

• Clinical Relevance: Provide evidence-based recommendations for the use of GFD in HT.
• Impact on Patient Care: Guide physicians on whether to recommend GFD as an adjunct therapy for autoimmune thyroiditis.
• Informing Future Research: Identify knowledge gaps for future intervention trials.

• Adherence Challenges: High difficulty in maintaining strict long-term adherence to GFD.
• Study Heterogeneity: Expected differences in study design, duration of intervention, and populations.
• Assessment of Inadvertent Intake: Potential for confounding factors in patient-reported dietary compliance.

• Gluten's Potential Pro-inflammatory Effect: Modulation of gut-thyroid axis.
• Impact on Thyroid Function: Does removing gluten normalize TSH/T4 or reduce autoantibody levels?
• Nutritional Optimization: Role of diet-induced nutrient changes (e.g., selenium, iron) in autoimmune stabilization.

Conclusion: Ensuring Evidence-Based Dietary Guidelines for Hashimoto's Thyroiditis

Systematic review will clarify the role of dietary interventions in autoimmune thyroid care.

• 1. Hashimoto's Thyroiditis (HT) pathophysiology and autoimmune mechanisms.
• 2. Gluten-related disorders and the gluten-free diet (GFD) definition.
• 3. PRISMA guidelines for systematic reviews and meta-analyses.
• 4. Cochrane RoB2 for risk of bias assessment.
• 5. GRADE handbook for assessing the certainty of evidence.
• 6. Recent studies on diet-induced anti-thyroid antibody reduction.