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 Immune Health and Autoimmunity


Promising, emerging research indicates that melatonin supplementation may have therapeutic benefits for autoimmune conditions, such as multiple sclerosis (MS) and perhaps Hashimoto’s thyroiditis, most likely due to its involvement in anti-inflammatory mechanisms, oxidative stress reduction, and modulation of the gut microbiota (1). Melatonin is linked to the seasonal relapse rate in patients with MS (2). Clinical data investigating melatonin supplementation in individuals with MS have reported better quality of life with lower doses (3) and reduced oxidative stress and inflammatory markers (4,5) in this patient population. Anderson, Rodriguez, and Reiter (6) conducted a systematic review of the correlation between the gut microbiome, gut permeability, and the possible pathophysiology of MS. An overall gut dysbiosis in patients with MS was identified as a result of increased ceramide production. The suppression of melatonin is suspected to cause this metabolic shift directly or indirectly, further complicating the circadian dysregulation that is evident in MS patients.


While not extensively studied in clinical trials, vitamin D and melatonin have been suggested to be part of a nutritional protocol for individuals with Hashimoto’s thyroiditis due to their molecular actions (7).


Currently, there is an ongoing scientific discussion regarding the use of melatonin for COVID-19. With its ability to impact mechanisms that modify immune regulation, melatonin has been included as one of the top recommendations as a preventive and therapeutic option for COVID-19, along with zinc, selenium, vitamin C, and vitamin D (8-10). Scientific evidence is not definitive, though it is emerging suggesting there are some indications that melatonin could be beneficial and is also considered to be safe (9,11). One systematic review and meta-analysis included eleven studies that revealed lower mortality rates, improved recovery time, shorter hospital stays, and a shorter duration of mechanical ventilation use when melatonin was administered as an adjuvant therapy (12). Moreover, studies have found a variation in several doses of melatonin and length of use to be effective for COVID-19, with additional clinical trials underway (10,13–15).


Authors: Deanna Minich, Ph.D., Melanie Henning, ND, Catherine Darley, ND, Mona Fahoum, ND, Corey B. Schuler, DC, James Frame

Reviewer: Peer-review in Nutrients Journal

Last updated: October 2, 2023




1. Muñoz-Jurado A, Escribano BM, Caballero-Villarraso J, Galván A, Agüera E, Santamaría A, et al. Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action. Vol. 30, Inflammopharmacology. Springer Science and Business Media Deutschland GmbH; 2022. p. 1569–96.

2. Farez MF, Mascanfroni ID, Méndez-Huergo SP, Yeste A, Murugaiyan G, Garo LP, et al. Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses. Cell. 2015;162(6).

3.  Adamczyk-Sowa M, Pierzchala K, Sowa P, Polaniak R, Kukla M, Hartel M. Influence of melatonin supplementation on serum antioxidative properties and impact of the quality of life in multiple sclerosis patients. Journal of Physiology and Pharmacology. 2014;65(4).

4. Sánchez-López AL, Ortiz GG, Pacheco-Moises FP, Mireles-Ramírez MA, Bitzer-Quintero OK, Delgado-Lara DLC, et al. Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis. Arch Med Res. 2018;49(6).

5. Yosefifard M, Vaezi G, Malekirad AA, Faraji F, Hojati V. A randomized control trial study to determine the effect of melatonin on serum levels of IL-1β and TNF-α in patients with multiple sclerosis. Iran J Allergy Asthma Immunol. 2019;18(6).

6. Anderson G, Rodriguez M, Reiter RJ. Multiple sclerosis: Melatonin, orexin, and ceramide interact with platelet activation coagulation factors and gut-microbiome-derived butyrate in the circadian dysregulation of mitochondria in glia and immune cells. Vol. 20, International Journal of Molecular Sciences. 2019.

7. Danailova Y, Velikova T, Nikolaev G, Mitova Z, Shinkov A, Gagov H, et al. Nutritional Management of Thyroiditis of Hashimoto. Vol. 23, International Journal of Molecular Sciences. MDPI; 2022.

8. Giovane RA, di Giovanni-Kinsley S, Keeton E. Micronutrients for potential therapeutic use against COVID-19; a review. Vol. 46, Clinical Nutrition ESPEN. 2021.

9.  Molina-Carballo A, Palacios-López R, Jerez-Calero A, Augustín-Morales MC, Agil A, Muñoz-Hoyos A, et al. Protective effect of melatonin administration against sars-cov-2 infection: A systematic review. Vol. 44, Current Issues in Molecular Biology. 2022.

10. Borges L, Gennari-Felipe M, Dias BB, Hatanaka E. Melatonin, Zinc, and Vitamin C: Potential Adjuvant Treatment for COVID-19 Patients. Vol. 8, Frontiers in Nutrition. 2022.

11. Corrao S, Mallaci Bocchio R, lo Monaco M, Natoli G, Cavezzi A, Troiani E, et al. Does evidence exist to blunt inflammatory response by nutraceutical supplementation during covid-19 pandemic? An overview of systematic reviews of vitamin d, vitamin c, melatonin, and zinc. Vol. 13, Nutrients. 2021.

12. Mohamed Taha A, Adel Abdelkader Saed S, Hossam-Eldin Moawad M, Abd El-Tawab Moawad W, Al-hejazi T, Mousa Y, et al. Safety and efficacy of melatonin as an adjuvant therapy in COVID-19 patients: Systematic review and meta-analysis. Adv Med Sci. 2023 Sep;68(2):341–52.

13. Menczel Schrire Z, Phillips CL, Chapman JL, Duffy SL, Wong G, D’Rozario AL, et al. Safety of higher doses of melatonin in adults: A systematic review and meta-analysis. Vol. 72, Journal of Pineal Research. 2022.

14. Tan DX, Hardeland R. Estimated doses of melatonin for treating deadly virus infections: focus on COVID-19. Melatonin Research. 2020 Jun 3;3(3):276–96.

15. Bahrampour Juybari K, Pourhanifeh MH, Hosseinzadeh A, Hemati K, Mehrzadi S. Melatonin potentials against viral infections including COVID-19: Current evidence and new findings. Vol. 287, Virus Research. 2020.

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