Micronutrient Deficiencies Associated with a Gluten-Free Diet in Patients with Celiac Disease and Non-Celiac Gluten or Wheat Sensitivity: A Systematic Review and Meta-Analysis

Background: A gluten-free diet (GFD) has been shown to be nutritionally inadequate for those with wheat-related disorders. However, the differences in findings and the absence of quantitative analysis limits the interpretation of previous reviews. Objectives: We conducted a systematic review and meta-analysis to identify the risk of micronutrient deficiencies in patients with celiac disease (CeD) and non-celiac gluten or wheat sensitivity (NCWS). Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Science (Ovid) databases. The risk of bias was determined using the ROBINS-1, and the quality of evidence was assessed using the GRADE approach. Results We identified 7940 studies; 46 observational studies (11 cohort, 9 cross-sectional, and 26 case-control) were eligible for analysis. CeD patients had an increased risk of vitamin D and E deficiencies compared with the non-CeD controls. CeD on a GFD had a decreased risk of vitamin D, B12, E, calcium, and iron deficiencies compared with untreated CeD. NCWS had an increased risk of vitamin B12, folate, and iron deficiency compared to the controls. The overall quality of evidence was rated very low. Conclusions: The risk of various micronutrient deficiencies is increased in CeD but is decreased for some after a GFD. Adequately powered studies with a rigorous methodology are needed to inform the risk of nutrient deficiencies in patients with CeD and NCWS. Protocol registration: Prospero-CRD42022313508.