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

BACKGROUND: Concurrent aerobic-resistance training has been reported to be beneficial for oxidative stress, inflammation, hyperlipidemia, and body composition in patients living with multiple sclerosis (PwMS). Exogenous melatonin also showed its anti-oxidant and anti-inflammatory effects in this population. However, no previous study has associated training with melatonin in PwMS despite their endogenous melatonin deficiency. To enhance the training's benefits, we aimed to investigate the impact of 12-week self-paced training combined with melatonin supplementation on biological adaptations and body composition in PwMS. METHODS: Forty-nine PwMS participated in this parallel and randomized controlled study. Participants were randomly assigned to four groups: training + melatonin (TMG, n = 11), training + placebo (TPG, n = 11), melatonin (MG, n = 15), or placebo (PG, n = 12). All groups ingested either melatonin or placebo (3 mg/night), while only the TMG and TPG additionally performed a concurrent training based on two aerobic high-intensity interval exercises and four resistance exercises (3 times/week, in the afternoon). Selected biochemical and hematological parameters as well as body composition were assessed pre- and post-intervention. RESULTS: Levels of reduced glutathione, total bilirubin, and uric acid increased in TMG comparatively with TPG (all: p < 0.001) and MG (p = 0.002; p = 0.0002; p < 0.001, respectively). The TMG showed a decrease in malondialdehyde, advanced oxidation protein products, and low-density lipoprotein cholesterol levels compared with TPG (p < 0.001; p = 0.038; p = 0.0003, respectively) and MG (p = 0.0034; p = 0.004; p < 0.001, respectively). There was a decrease in white blood cell, neutrophil, and lymphocyte counts in TMG comparatively with TPG (p = 0.0005; p = 0.0001; p = 0.014, respectively) and MG (p = 0.023; p = 0.007; p = 0.026, respectively). Lean mass increased (p = 0.025) while fat mass (p = 0.0013) and body mass index (p = 0.034) decreased in TMG compared with TPG. CONCLUSION: Concurrent training combined with melatonin supplementation showed greater anti-inflammatory, antioxidant and hypolipidemic effects than each intervention alone, and was more beneficial than training alone for body composition in PwMS.