“For the first time, our research provides precise guidelines on how to effectively use melatonin to promote sleep,” says Professor Ugo Faraguna (pictured) from the University of Pisa, who coordinated the work. “Previous studies have yielded inconsistent results; our hypothesis is that this was due to the administration schedule, a non-physiological combination of timing and dosage.”

The analysis involved 26 randomized studies published between 1987 and 2020, with a total of 1689 observations on patients with insomnia and healthy volunteers, evaluating the effect of melatonin administration on sleep.

“Compared to the commonly used clinical practice of 2 mg taken 30 minutes before bedtime,” Faraguna continues, “our results suggest that to optimize the effect of melatonin, it is important to administer it three hours before bedtime and increase the dose to 4 mg daily. In addition to being earlier, the timing of administration should be personalized based on each patient’s sleep/wake rhythm to mimic the natural production of melatonin in humans. In fact, when melatonin is administered according to the treatment regimen we propose, it achieves its maximum effectiveness precisely when melatonin naturally produced by the human body is released into the bloodstream.”

Along with Ugo Faraguna, Associate Professor at the Department of Translational Research and New Technologies in Medicine and Surgery, the first co-authors of the article are Francy Cruz Sanabria and Simone Bruno, both former PhD students at the University of Pisa. Francy Cruz Sanabria currently works as a research fellow between the University of Pisa and the Stella Maris Foundation in Pisa, while Simone is now in the United States as a Research Associate at the University of Wisconsin-Madison.

“In addition to colleagues from our university, Professors Scarselli and Frumento,” Faraguna concludes, “I would like to highlight the presence among the co-authors of Professor Debra Skene from the University of Surrey, the world’s leading expert on melatonin, who wanted to be involved after we sent her the first draft of the article for her opinion; and Dr. Alessio Crippa, the statistician from the Karolinska Institutet in Stockholm, who first developed the analysis technique we chose for this work.”