The Effects of Melatonin Supplementation on Cognitive Outcomes in Multiple Sclerosis: A Systematic Review

Melatonin is a neurohormone secreted predominantly by the pineal gland that is found to be associated with improving cognitive outcomes in Alzheimer's Diseases. This study was executed following the PRISMA 2020 statement. Ovid, PubMed, Scopus, Embase, and Web of Science databases were searched for a comprehensive coverage of the published studies on this topic and there was no time and study design restriction. Out of 1304 results of database searches, 3 randomized clinical trials (RCTs), were included. The RCT of Jalluoli and colleagues studied the cognitive effects of nocturnal ingestion of 6 mg melatonin for 6 months in 14 relapsing-remitting MS (RRMS) patients, based on Montreal cognitive assessment (MoCA) and simple Reaction time (SRT). The results showed that melatonin could safely improve cognitive function in MS patients. Roostaei and colleagues established an RCT to observe the effects of 3mg melatonin for 12 months on motor, cognitive, and neuroimaging indices in 25 RRMS patients. Findings showed beneficial cognitive outcomes through the Modified Fatigue Impact Scale (MFIS). Finally, the RCT of Drake et al. assessed the self-reported cognitive function, in 31 patients with various MS subtypes (RRMS, secondary progressive MS, and primary progressive MS). Cognitive function did not differ significantly between melatonin and placebo groups. This study found scattered, inconsistent and limited evidence regarding the cognitive efficacy of melatonin supplementation in MS, which suggested the need foe future well-designed clinical studies on this topic.