30 adults (average age of 53; 23 women, 7 men) diagnosed with relapsing-remitting MS in the United States.

All of the participants were receiving stable doses of oral disease-modifying therapies.

During this 12-month randomized controlled trial, the participants took 3 mg or 5 mg of melatonin every night between 7 p.m. and 9 p.m.

Assessments were conducted at baseline, 3 months, 6 months, and 12 months.

The median serum melatonin concentrations were 5 pg/mL at baseline, and the median 24-hour urine excretions were 19–22 ng.

Serum and urine melatonin concentrations increased in both groups over 12 months, with higher average concentrations observed in the participants who received 5 mg compared to 3 mg.

When comparing concentrations at specific time points, serum concentrations were higher in the 5-mg group at 3 months but did not differ significantly between the groups at 6 or 12 months. Urine concentrations differed only at 12 months, with higher concentrations in the 5-mg group.

MS symptom severity, fatigue, and sleep quality scores remained similar to baseline in both groups.

All of the participants reported experiencing adverse events during the study period. The prevalence of moderate or severe adverse events was similar between the groups.

These findings should be considered exploratory, as this was a pilot trial with a small sample size and no placebo control.

The baseline urine concentrations in this cohort appear to be relatively low in comparison with other cohorts without MS.^[1] Reduced melatonin production has been noted in some individuals with MS, which may be attributable to impaired pineal gland function.^[2][3]