Study demonstrates the effects of melatonin & exercise in MS

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation, oxidative stress, demyelination, and progressive neurological dysfunction. In addition to neurological symptoms, individuals with MS commonly experience increased oxidative stress, immune dysregulation, and alterations in body composition.

Exercise has long been recognized as an important non-pharmacological intervention for individuals with MS. Aerobic and resistance training has been shown to improve physical function, fatigue, and quality of life. In addition, melatonin has gained interest due to its potent antioxidant and anti-inflammatory properties and because individuals with MS often demonstrate lower melatonin levels.

A recently published randomized controlled trial in Brain Research Bulletin investigated whether combining exercise training with melatonin supplementation could provide greater benefits than either intervention alone.

The study enrolled 49 individuals with relapsing-remitting multiple sclerosis who were randomized into one of four groups: training plus melatonin, training plus placebo, melatonin alone, or placebo. Participants in the melatonin groups received 3 mg of melatonin nightly for 12 weeks. The training groups completed a supervised self-paced concurrent exercise program consisting of high-intensity interval aerobic exercise and resistance training three times per week.

After 12 weeks, the combination of training and melatonin produced the most significant improvements in biomarkers of oxidative stress, inflammation, lipid metabolism, and body composition. Compared with exercise alone or melatonin alone, the combined intervention significantly increased antioxidant defenses, including glutathione, uric acid, and bilirubin levels, while reducing markers of oxidative damage such as malondialdehyde and advanced oxidation protein products.

The training plus melatonin group also demonstrated significant reductions in LDL cholesterol and decreases in inflammatory immune cell populations, including white blood cells, neutrophils, and lymphocytes. Improvements in body composition were observed as well, with reductions in body mass index and fat mass accompanied by increases in lean body mass.

Researchers further observed a strong relationship between improvements in oxidative stress markers and reductions in inflammatory immune activity, suggesting that attenuation of oxidative stress may be an important mechanism underlying the anti-inflammatory benefits of the intervention.

Overall, the findings suggest that combining melatonin supplementation with aerobic and resistance exercise may provide a synergistic approach for improving oxidative stress, immune function, lipid metabolism, and body composition in individuals with MS.

Given melatonin’s favorable safety profile and the established benefits of exercise, healthcare practitioners should consider this combined strategy as part of a comprehensive lifestyle-based approach for supporting patients with multiple sclerosis. Additional research is warranted to determine whether these benefits extend to broader MS populations and whether long-term improvements can be maintained.

By Michael Jurgelewicz, DC, MSCR, CNS, LDN

Source: Jallouli S, Jallouli D, Kallel C, et al. (2026). Benefits of 12-week self-paced training combined with melatonin supplementation on oxidative stress, inflammation, hyperlipidemia, and body composition in multiple sclerosis patients: a randomized controlled trial. Brain Research Bulletin. doi:10.1016/j.brainresbull.2026.111968.