A cross-sectional report on the use of high doses of melatonin in humans.

The administration of melatonin in chronobiotic doses (≤10 mg daily) is a common procedure in clinics. In addition, research in animals has led to greater awareness on the potentiality of melatonin as an antioxidant, immunological and mitochondrial regulator and anti-inflammatory compound. Doses allometrically derived from animal studies correspond to 75 to 112.5 mg daily range for a 75 kg human adult. In view of the absence of toxicity of melatonin in phase 1 pharmacological studies with doses up to 100 mg in normal volunteers, we regularly use melatonin in this dose range to treat sleep disorders in aged patients to prevent age-related comorbidities. In an observational, analytical, retrospective, cross-sectional study of clinical history data from a closed population of patients taking melatonin in doses equal to or greater than 40 mg/day of melatonin for various sleep disorders, 80 patients (74.2 % female, mean age 74 years ± 9.26) were included. The indication of melatonin doses varied between 40 and 200 mg per day, with a mean of 76.56 mg ± 33.58 mg daily. The main reason for indication was complaints of disorders in falling asleep or maintaining sleep with melatonin doses varying depending on the comorbidities clinically detected. The 59 % of patients received treatment for more than 4 years. Laboratory variables related to liver function remain within the normal range after melatonin administration regardless of the dose employed. No relation was also found between melatonin dose and concomitant pharmacological treatment. The results advocate for the safe use of melatonin in higher doses than those commonly employed.