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Background  Multiple sclerosis (MS) is an inflammatory disease, which has a wide range of effects on patients. There are controversies regarding the role of vitamin D in clinical and laboratory improvements in MS patients.    Objective  The aim of this systematic review protocol is to evaluate the efficacy of vitamin D supplements on relapse rate, gadolinium-enhancing lesions of magnetic resonance imaging (MRI), and cytokine profiles.    Methods  We will search PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, ProQuest, American College of Physicians Journal Club database, Health Technology Assessment Database (The Cochrane Collaboration), and National Health System Economic Evaluation Database (The Cochrane Collaboration) and gray literature including reference of included studies and conference abstracts. Clinical trials reporting the effect of any doses of vitamin D on relapse rate, gadolinium-enhancing lesions of MRI, and cytokine profiles will be included. In total, 2 independent researchers will independently assess the studies, extract data, and evaluate the quality of primary studies.    Results  This systematic review was started in September 2017 and the process is continuing. The included articles are evaluated and researchers are going to extract the data.    Conclusions  To our knowledge, this will be the first comprehensive systematic review aiming to assess the effect of vitamin D supplements on clinical and para-clinical outcomes in patients with multiple sclerosis.    International Registered Report Identifier (IRRID)  DERR1-10.2196/12045

The Effect of Vitamin D Supplements on Clinical and Para-Clinical Outcomes in Patients With Multiple Sclerosis: Protocol for a Systematic Review