Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment

The objective of the present study was to assess the toxicology of melatoni n (10 mg), administered for 28 days to 40 volunteers randomly assigned to g roups receiving either melatonin (N = 30) or placebo (N = 10) in a double-b lind fashion. The following measurements were performed: polysomnography (P SG), laboratory examinations, including complete blood count, urinalysis, s odium, potassium and calcium levels, total protein levels, albumin, blood g lucose, triglycerides, total cholesterol, high-density lipoprotein (HDL), l ow-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), urea , creatinine, uric acid, glutamic-oxalacetic transaminase (GOT), glutamic-p yruvate transaminase (GPT), bilirubin, alkaline phosphatase, gama-glutamic transaminase (GGT), T-3, T-4, TSH, LH/FSH, cortisol, and melatonin serum co ncentrations. In addition, the Epworth Somnolence Scale (ESS) and a sleep d iary (SD) were also applied to the volunteers 1 wk before each PSG. In addi tion, the volunteers were asked about possible side effects (SE) that appea red during the treatment. The study was carried out according to the follow ing timetable: Visit 0, filling out the term of consent and inclusion crite ria; Visit 1, PSG, laboratory examinations, ESS, SD, melatonin serum concen trations; Visit 2, SD, melatonin serum concentrations, SE; Visit 3, melaton in serum concentrations, PSG, ESS, SE; Visit 4, laboratory examinations, SE , melatonin serum concentrations, SD; and Visit 5, PSG, ESS, SE. Analysis o f the PSG showed a statistically significant reduction of stage 1 of sleep in the melatonin group. No other differences between the placebo and melato nin groups were obtained. In the present study we did not observe, accordin g to the parameters analyzed, any toxicological effect that might compromis e the use of melatonin at a dose of 10 mg for the period of time utilized i n this study.