Background: There is an increasing interest in diet as a modifying factor in multiple sclerosis (MS), and gluten has been suggested to affect MS.

Objective: The aim of this systematic review is to qualitatively evaluate the evidence on the role of gluten in MS.

Methods: A review protocol was submitted to PROSPERO. A systematic literature search was conducted in PubMed, Web of Science, Scopus, Embase, Cab Abstracts, and Google Scholar. Studies on patients with MS, clinically isolated syndrome, or celiac disease presenting with MS-related markers were included, if they investigated effects of diets containing specified amounts of gluten or associations between gluten sensitivities and MS.

Results: Forty-nine publications presenting 50 studies/cases met the inclusion criteria. Study designs, methods, and outcomes varied broadly across studies. Two intervention studies found a positive effect of a gluten-free diet on disease-related markers in patients with MS. One prospective cohort study also found a positive effect of a gluten-free diet, while a survey found intake of cereal/bread to be protective against MS. Four observational studies did not find increased comorbidity of MS and celiac disease. Seventeen studies investigated the level of different gluten-sensitivity markers in patients with MS with inconsistent results. Finally, 12 cases and 13 posters/abstracts/master's theses contributed to shed light on the topic.

Conclusions: There is still not sufficient evidence to state whether gluten plays a role in MS, but limitations of current evidence have been identified and directions of future research have been suggested.