Objective: This study aims to evaluate the neuroprotective action of exogenous melatonin in Parkinson disease patients and its impact on daily routine.

Background: Parkinson Disease (PD) is considered a multifactorial disease and has been associated with oxide-reduction processes. It has been suggested that elevated oxidative stress and pro-inflammatory processes influence the severity of PD and can contribute to exacerbate the nigro-striatal degeneration. Decreased secretion of melatonin was associated with abnormal sleep-wake cycles as well as motor and non-motor symptom (NMS) fluctuations in PD.

Method: A search was performed in the PubMed database, using the keywords “melatonin”, “parkinson’s disease”, “sleep disorder” and their equivalents. Articles published in English were selected. Case reports, systematic reviews, meta-analysis or studies that did not approach EM were excluded. After title and abstract analysis, duplicates were excluded and all studies evaluating the action of exogenous melatonin (EM) in PD patients or its impact on daily routine were included.

Results: 16 articles were found; 8 met the inclusion criteria. Sample sizes varied from 112 to 13 participants. Among those evaluated, 3 focused on biochemical effects. EM intake had favorable effects on the UPDRS part I score, Pittsburgh Sleep Quality Index (PSQI), BDI, BAI, high-sensitivity C-reactive protein, GSH, insulin levels, LDL, and gene expression of TNF-α, PPAR-γ and LDLR. Activity of mitochondrial complex I and the RCR were significantly lower in PD patients, characterizing the use of EM as an effective antioxidant. Analyzing quality of life, 6 showed reduction of PD motor or NMS. Lack of efficacy in ameliorating REM Behavior Disorder was reported once. An association was found between COX-2 activity, EM consumption and decreased UPDRS values. The interaction of antioxidant reactive EM plays an important role in immunomodulation of pro-inflammatory factors to prevent neuronal death.

Conclusion: Having elevated generation of ROS linked to PD makes the use of EM to reduce oxidative stress an alternative treatment. Besides, the benefits of its use, mainly towards sleep behaviors, may improve the UPDRS part I score, anxiety, depression and fatigue. However, more studies are required to evaluate the extension EM use in the reduction of PD symptoms.

References: Gilat, M., Coeytaux Jackson, A., Marshall, N.S., Hammond, D., Mullins, A.E., Hall, J.M., Fang, B.A.M., Yee, B.J., Wong, K.K.H., Grunstein, R.R. and Lewis, S.J.G. (2020), Melatonin for Rapid Eye Movement Sleep Behavior Disorder in Parkinson’s disease: A Randomised Controlled Trial. Mov Disord, 35: 344-349. https://doi.org/10.1002/mds.27886
Hadi, F., Agah, E., Tavanbakhsh, S. et al. Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson’s disease and sleep disorders: a randomized, double-blind trial. Neurol Sci 43, 6141–6148 (2022). https://doi.org/10.1007/s10072-022-06188-4
Jong Hyeon Ahn, Minkyeong Kim, Suyeon Park, Wooyoung Jang, Jinse Park, Eungseok Oh, Jin Whan Cho, Ji Sun Kim, Jinyoung Youn, Prolonged-release melatonin in Parkinson’s disease patients with a poor sleep quality: A randomized trial, Parkinsonism & Related Disorders, Volume 75, 2020, Pages 50-54, ISSN 1353-8020, https://doi.org/10.1016/j.parkreldis.2020.03.029.
Reza Daneshvar Kakhaki, Vahidreza Ostadmohammadi, Ebrahim Kouchaki, Esmat Aghadavod, Fereshteh Bahmani, Omid Reza Tamtaji, Russel J.Reiter, Mohammad Ali Mansournia, Zatollah Asemi, Melatonin supplementation and the effects on clinical and metabolic status in Parkinson’s disease: A randomized, double-blind, placebo-controlled trial, Clinical Neurology and Neurosurgery, Volume 195, 2020, 105878, ISSN 0303-8467, https://doi.org/10.1016/j.clineuro.2020.105878.
Alicia Jiménez-Delgado, Genaro Gabriel Ortiz, Daniela L. Delgado-Lara, Hector Alberto González-Usigli, Luis Javier González-Ortiz, Margarita Cid-Hernández, José Antonio Cruz-Serrano, Fermín Paul Pacheco-Moisés, “Effect of Melatonin Administration on Mitochondrial Activity and Oxidative Stress Markers in Patients with Parkinson’s Disease”, Oxidative Medicine and Cellular Longevity, vol. 2021, Article ID 5577541, 7 pages, 2021. https://doi.org/10.1155/2021/5577541
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Ortiz GG, Moráles-Sánchez EW, Pacheco-Moisés FP, et al. Efecto de la administración de melatonina sobre la actividad de la ciclooxigenasa-2, la concentración sérica de metabolitos del óxido nítrico, los lipoperóxidos y la actividad de la glutatión peroxidasa en pacientes con enfermedad de Parkinson [Effect of melatonin administration on cyclooxygenase-2 activity, serum levels of nitric oxide metabolites, lipoperoxides and glutathione peroxidase activity in patients with Parkinson’s disease]. Gac Med Mex. 2017;153(Supl. 2):S72-S81. doi:10.24875/GMM.M000008
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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroprotective-action-of-exogenous-melatonin-in-parkinson-disease-patients-and-its-impact-on-daily-routine-a-systematic-review/