12-week melatonin intake attenuates cardiac autonomic dysfunction and oxidative stress in multiple sclerosis patients: a randomized controlled trial

• Published in: Metabolic brain disease 2024-12, Vol.40 (1), p.52
• Main Authors: Jallouli, Sonda, Jallouli, Dana, Damak, Mariem, Sakka, Salma, Ghroubi, Sameh, Mhiri, Chokri, Driss, Tarak, de Marco, Giovanni, Ayadi, Fatma, Hammouda, Omar
• Format: Article
• Language: English
• Subjects: 25-Hydroxyvitamin D; Adult; Antioxidants - administration & dosage; Antioxidants - pharmacology; Antioxidants - therapeutic use; Autoimmune diseases; Autonomic Nervous System Diseases - drug therapy; Autonomic Nervous System Diseases - etiology; Biochemistry; Biological analysis; Biomarkers; Biomedical and Life Sciences; Biomedicine; C-reactive protein; Calciferol; Cholinesterase; Clinical trials; Dietary supplements; Double-Blind Method; Dysautonomia; Female; Glutathione; Heart diseases; Heart rate; Heart Rate - drug effects; Humans; Low frequencies; Male; Malondialdehyde; Melatonin; Melatonin - administration & dosage; Melatonin - pharmacology; Melatonin - therapeutic use; Metabolic Diseases; Middle Aged; Multiple sclerosis; Multiple Sclerosis - drug therapy; Neurology; Neurosciences; Night; Nighttime; Oncology; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Placebos; Proteins; Sleep; Sleep disorders; Variability; Vitamin D; Vitamin deficiency
• ISSN: 0885-7490; 1573-7365; 1573-7365
• DOI: 10.1007/s11011-024-01428-2

Multiple sclerosis (MS) can induce cardiac autonomic dysfunction identified by a decreased heart rate variability (HRV) which was linked to oxidative stress, vitamin D deficiency and sleep disturbance. Previous MS studies revealed the antioxidant and anti-inflammatory effects of exogenous melatonin, as well as its benefits on sleep and vitamin D. We aimed to investigate the change in HRV, oxidative stress, systemic inflammation and sleep following melatonin supplementation in MS patients. Participants were randomly allocated to either a melatonin group (MG, n  = 15) or a placebo group (PG, n  = 12) (3 mg/night during 12 weeks). Pre- and post-tests included HRV analysis (Kubios software), sleep dairy and biological analysis [oxidative stress biomarkers (malondialdehyde (MDA), advanced oxidation protein products (AOPP) and reduced glutathione (GSH)); 25-hydroxyvitamin D; C-reactive protein and cholinesterase Gen.2 (CHE2)]. Based on the pre-post supplementation change (Δ (T1₋T0) ), melatonin increased the root mean square of successive differences between normal heartbeats [Δ MG (14.17 ± 16.93) vs. Δ PG (₋8.61 ± 12.67), p  = 0.0007] and the HRV high-frequency band [Δ MG (6.86 ± 14.85) vs. Δ PG (₋12.58 ± 13.30), p  = 0.0016] comparatively with placebo. MG showed a decrease in the HRV low-frequency band [Δ MG (₋4.96 ± 10.08) vs. Δ PG (10.22 ± 13.54), p  = 0.003] as well as in the MDA [Δ MG (₋2.27 ± 1.92) vs. Δ PG (0.22 ± 2.30), p  = 0.005] and AOPP levels [Δ MG (₋113.97 ± 137.72) vs. Δ PG (156.46 ± 230.52), p  = 0.0008] compared with PG. Melatonin enhanced the GSH [Δ MG (10.51 ± 14.93) vs. Δ PG (₋5.05 ± 10.18), p  = 0.004] and CHE2 levels [Δ MG (407.07 ± 723.26) vs. Δ PG (₋22.92 ± 506.52), p  = 0.029] as well as sleep quality [scores: Δ MG (1.50 ± 1.28) vs. Δ PG (₋1.05 ± 2.05), p  = 0.0006] and quantity [weighted total sleep time: Δ MG (0.74 ± 1.14) vs. Δ PG (₋1.04 ± 1.00), p  = 0.0003] comparatively with placebo. Caregivers may recommend 12-week nocturnal melatonin intake to attenuate cardiac autonomic dysfunction, oxidative stress and sleep disorders in MS patients. Clinical registration This study was prospectively registered in the Pan African Clinical Trial Registry database (PACTR202007465309582) on 23 July 2020 ( https://pactr.samrc.ac.za/ .). Graphical abstract Highlights • 12-week melatonin supplementation (3 mg per night) alleviated cardiac autonomic dysfunction (i.e., it increased heart rate variability) in multiple sclerosis patients. • Exogenous me