The appropriate and inappropriate uses of saliva melatonin measurements.

Melatonin is produced in the pineal gland under very tight control through the influences of light and the suprachiasmatic nucleus. As such, melatonin circulates in the blood at levels <3 pg/ml during the day and is only actively secreted at night reaching levels of approximately 100 pg/ml. As a consequence of binding to plasma proteins, free melatonin appears in saliva at approximately one third the plasma concentration. Measurement of melatonin is technically challenging because of these very low concentrations and while a number of commercial immunoassay kits are available and mass spectrometry assay methods have been published, not all are fit for purpose and can lead to unreliable conclusions. In this review I discuss the aspects of pineal melatonin production that saliva melatonin reflects, the factors influencing melatonin production or metabolism, saliva collection and analysis methods. Examples are provided of the appropriate use of saliva melatonin measurements; Dim Light Melatonin Onset (DLMO) assessment, impact of light on melatonin and the monitoring of rhythms prior to specific treatments. Examples of inappropriate use of saliva melatonin measurements are also provided including the use of poorly validated assays, morning saliva collections, attempts to stimulate melatonin, and linking specific illnesses to saliva melatonin levels.