Effect of Melatonin on Serum Levels of INF-1β and Vitamin B12 in Patients With Multiple Sclerosis: A Randomized Controlled Trial

Abstract

Background: Multiple Sclerosis (MS) is a chronic autoimmune disease due to the demyelination of axons in the central nervous system. Melatonin, as a hormone with potential anti-inflammatory effects, can reduce the MS symptoms by altering the levels of inflammatory mediators. Methods: In this study, 50 MS patients referred to the MS Society in Markazi Province were randomly selected. Each patient completed and signed a consent form and was referred to the MS Center at Vali-Asr Hospital in Arak, Iran. All patients who were routinely receiving interferon, were divided into two groups of 25 each. Group 1 (control) received placebo, and Group 2 (treatment) received one dose of melatonin (3mg) per day for 24 weeks. Patients’ recorded anthropometric data included height, weight, and age. Fasting blood samples were collected and the serum levels of INF-1β and VitB12 determined. The blood samples were immediately centrifuged to separate sera, which were kept in a freezer at -80° C. The serum levels of INF-1β and Vitamin B12 were determined, using ELISA kits. Results: The data showed that there were significant differences in the serum levels of INF-1β and Vitamin B12 between the control and treatment groups. The levels were significantly increased in the treatment group compared to those in the controls, suggesting that melatonin might have induced the changes. Conclusion: Based on the results, the application of melatonin might be a valuable strategy in the treatment of patients with MS.

Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action

“…Describe the overexpression of the melatonin effector/receptor system in peripheral blood mononuclear cells from patients with MS Sánchez-López et al ( 2018 ) Male (10)/Female (26) 18–55 years RRMS 25 mg/day (orally, 6 months) Melatonin administration for 6 month period is effective in reducing levels of serum pro-inflammatory cytokines and oxidative stress markers in patients with RRMS Yosefi-Fard et al ( 2019 ) Male (5)/Female (45) 18–50 years RRMS 3 mg/day (orally, 24 weeks) There were no significant differences between the control groups and the melatonin-treated group in terms of serum TNF-α levels. However, melatonin significantly reduced IL-1β levels Yosefi-Fard et al ( 2020 ) Male (5)/Female (45) 18–50 years RRMS 3 mg/day (orally, 24 weeks) The serum melatonin levels were associated with increases in the levels of IFN1β Chang et al ( 2020 ) Male (23)/Female (20) 40.2 ± 17.439 Myasthenia gravis 8 μg/ml PHA with 10 –4 M melatonin (in vitro) Melatonin exerts immunoregulatory activity by balancing effector and regulatory Th cell populations as well as by suppressing proinflammatory cytokine production Ding et al ( 2020 ) – – Epithelial–Mesenchymal Transition 0–3200 μM (in vitro) Melatonin can protect human alveolar epithelial cells against oxidative stress by effectively inhibiting LPS-induced EMT, which was mostly dependent on upregulation of the Nrf2 Das et al ( 2020 ) – – Alzheimer’s disease 0.1 to 100 μM (in vitro) Melatonin alleviated oxidative stress via Nrf2 nuclear translocation Palmer et al ( 2020 ) …”

“…Similarly, Spelman et al ( 2014 ), determine that relapse onset in MS followed an annual cyclical sinusoidal pattern with peaks in early spring (Spelman et al 2014 ). Among the reasons for which it is believed that MS patients exhibit a lower level of melatonin is that it is due to the deposition of calcium in the pineal gland (Akpinar et al 2008 ; Tan et al 2018 ; Yosefi-Fard et al 2020 ) or to hypothalamic dysfunction in the regulation of the oscillatory secretion of the melatonin (Akpinar et al 2008 ).…”

“…These doses range from 3 to 25 mg, all administered once a day. In four of the articles, this dose is administered orally (Adamczyk-Sowa et al 2016a ; Sánchez-López et al 2018 ; Yosefifard et al 2019 ; Yosefi-Fard et al 2020 ), while in two of them, the route of melatonin administration is not specified (Miller et al 2013 ; Roostaei et al 2021 ). Similarly, the duration of the treatment varies considerably from article to article, the shortest duration being 1 month (Miller et al 2013 ) and the longest 1 year (Roostaei et al 2015 ).…”

“…It also offers a more protective microenvironment for cytokines (Álvarez-Sánchez et al 2017 ). In addition, Yosefi-Fard et al 2020 show in their study that melatonin levels are associated with an increase in IFN-β, which is beneficial against relapses in MS (Yosefi-Fard et al 2020 ).…”

The Role of Sleep in Multiple Sclerosis

“…Melatonin seems to reduce pathogenic inflammation also decreasing Th17 cells and IL-17 cytokines increasing anti-inflammatory cytokines, such as IL-10 and T regulatory cells [190]. It is possible that melatonin could provide a more protective microenvironment for cytokines [191].…”