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Open AccessArticle

Melatonin Pharmacological Blood Levels Increase Total Antioxidant Capacity in Critically Ill Patients

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20142 Milano, Italy
Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, San Paolo University Hospital, 20142 Milano, Italy
Department of Health Science, Università degli Studi di Milano, 20142 Milano, Italy
Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
Department of Cellular and Structural Biology, University of Texas Health Science Centre, San Antonio, TX 78229-3900, USA
Author to whom correspondence should be addressed.
Academic Editor: Rosa M. Lamuela-Raventós
Int. J. Mol. Sci. 2017, 18(4), 759;
Received: 21 February 2017 / Revised: 22 March 2017 / Accepted: 30 March 2017 / Published: 3 April 2017
(This article belongs to the Special Issue Melatonin and Its Analogues: Experimental and Clinical Aspects)
In this study, the aim was to test the biochemical effects of melatonin supplementation in Intensive Care Unit (ICU) patients, since their blood levels are decreased. Sixty-four patients were enrolled in the study. From the evening of the 3rd ICU day, patients were randomized to receive oral melatonin (3 mg, group M) or placebo (group P) twice daily, at 20:00 and 24:00, until discharged. Blood was taken (at 00:00 and 14:00), on the 3rd ICU day to assess basal nocturnal melatonin values, and then during the treatment period on the 4th and 8th ICU days. Melatonin, total antioxidant capacity, and oxidative stress were evaluated in serum. Melatonin circadian rhythm before treatment was similar in the two groups, with a partial preservation of the cycle. Four hours from the 1st administration (4th ICU day, 00:00), melatonin levels increased to 2514 (982.3; 7148) pg·mL−1 in group M vs. 20.3 (14.7; 62.3) pg·mL−1 in group P (p < 0.001). After five treatment days (8th ICU day), melatonin absorption showed a repetitive trend in group M, while in group P nocturnal secretion (00:00) was impaired: 20 (11.5; 34.5) pg·mL−1 vs. 33.8 (25.0; 62.2) on the 3rd day (p = 0.029). Immediately from the beginning of treatment, the total antioxidant capacity was significantly higher in melatonin treated subjects at 00:00; a significant correlation was found between total antioxidant capacity and blood melatonin values (ρ = 0.328; p < 0.001). The proposed enteral administration protocol was adequate, even in the early phase, to enhance melatonin blood levels and to protect the patients from oxidative stress. The antioxidant effect of melatonin could play a meaningful role in the care and well-being of these patients. View Full-Text
Keywords: melatonin; oxidative stress; critical illness; antioxidants; dietary supplements melatonin; oxidative stress; critical illness; antioxidants; dietary supplements
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Mistraletti, G.; Paroni, R.; Umbrello, M.; D’Amato, L.; Sabbatini, G.; Taverna, M.; Formenti, P.; Finati, E.; Favero, G.; Bonomini, F.; Rezzani, R.; Reiter, R.J.; Iapichino, G. Melatonin Pharmacological Blood Levels Increase Total Antioxidant Capacity in Critically Ill Patients. Int. J. Mol. Sci. 2017, 18, 759.

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