Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring hormone found in animals, plants, and microbes. In humans, it is produced primarily by the pineal gland, located in the center of the brain. Melatonin forms part of the system that regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature. Production of melatonin by the pineal gland is inhibited by light and permitted by darkness. Secretion of melatonin, as well as its level in the blood, peaks in the middle of the night and gradually falls during the second half of the night, with normal variations in timing according to an individual’s chronotype. (1,2) Melatonin is also important for its ability to scavenge free radicals and to regulate the activity and expression of antioxidant and pro-oxidant enzymes. (3,4,5) In human plasma 61-85% of melatonin is weakly bound to proteins, and there is a close relationship between circulating free and salivary melatonin levels. (6) Melatonin enters saliva from blood either by passive diffusion or active transport. (7) Melatonin is measurable in saliva, and the acrophases of saliva and plasma melatonin rhythms are significantly correlated. (8,9) Plasma and salivary melatonin concentrations increase when moving from a supine to a standing position, and decrease when these positions are reversed, due to changes in plasma volume. (10) Inflammatory processes such as periodontitis trigger an increase in plasma melatonin, which then increases melatonin levels in the oral cavity, where it may increase antioxidant protection. (11)

DLMO & Melatonin Onset Analysis

With saliva as a biological sample, researchers can non-invasively monitor melatonin levels without an overnight sleep clinic stay (polysomnogram). This eliminates the rhythm perturbation caused by a clinical sleep center laboratory, can be performed in 4-6 hrs (as opposed to 24 hrs), and offers the convenience of collecting samples at home. Salivary DLMO is determined by measuring salivary melatonin levels over several time-points prior to and just after habitual sleeptime. Calculating the time that the nocturnal melatonin concentration is significantly elevated from daytime samples (+/- 2 deviations from baseline levels)- DMLO is the most sensitive and direct index for identifying an individual’s biorhythm which may be entrained (synchronized) to a 24 hr light/dark cycle or can be in a free-running state. A misaligned DMLO may indicate delayed sleep phase syndrome (DSPS) or advanced sleep phase disorder (ASPD) and its relationship to various metabolic conditions, diseases, disorders and genetic and environmental components are of significant interest in current research.