Case report of sudden death in a twin infant given melatonin supplementation: A challenging interpretation of postmortem toxicology.

Melatonin (MEL) is a neurohormone in humans produced in a number of locations. Starting with the amino acid tryptophan, MEL is produced through a number of enzymatic steps that includes serotonin as an intermediate compound. The primary production of MEL is in the pineal gland located in the brain. It is directly associated with the the suprachiasmatic nucleus (SCN) located in the hypothalamus. In young and adult humans, the blood levels of MEL are typically in the picogram levels and produced in a cyclic schedule highly regulated by light detected in the retina by intrinsically photosensitive retinal ganglion cells (ipRGCs), resulting in production primarily during periods of darkness. During periods of light, MEL levels are typically very low or undetectable. Basal levels of MEL in infants have been observed to be either undetectable or also in the picogram levels, although some medical treatment has involved administration of exogenous MEL resulting in peak levels in the nanogram range. MEL is considered to be well tolerated and there have been limited reports of toxicity. In this case, an infant was found unresponsive and cause of death was ruled as Undetermined. Melatonin was detected in the peripheral blood at a concentration of 1,400ng/mL.

Melatonin exposures reported to Texas poison centers in 1998-2003.

Melatonin regulates circadian rhythms, and although widely used in the US, information on the public use of melatonin and patterns of reported adverse effects associated with the substance is limited. To describe the patterns of melatonin calls to poison centers in Texas during 1998-2003, data on all melatonin calls reported to the Texas Poison Center Network were analyzed. During 1998-2003, there were 779 identified human exposures to melatonin identified. Of those patients with a known age, 59.1% were < 6 y. Males accounted for 54.1% of preschool-age patients while more of the older patients were female. Melatonin exposures were unintentional in 99.3% of the cases among children less than 6y and unintentional in < 41% among the older age groups. While 92.4% of exposures involving theyoungest age group were managed outside of a health care facility, 42% or less of the exposures occurring to patients > age 6 years were managed outside of a health care facility. Of those cases with a known outcome, the proportion of cases with at least minor effects rose with increasing age. The majority of melatonin exposures reported to Texas poison centers involved children < 6 y. Younger patients were more likely to be male, have unintentional exposures, have no clinical effect, and to not require management at health care facilities. The observed clinical effects and treatment methods were consistent with the literature.

Problems in assessment of acute melatonin overdose.

Melatonin is sold in the United States as a dietary supplement and is promoted primarily as an aid for insomnia, stress, jet lag, and aging. Cases of acute poisoning have not been reported, partially because of problems in assessment of toxicity. We report the case of a 66-year-old man who became lethargic and disoriented after taking 24 mg melatonin to aid relaxation and sleep the evening before prostate surgery. He recovered uneventfully, and after the scheduled surgery he resumed his regular practice of taking 6 mg melatonin with prescription sedative drugs. Although melatonin is not regulated as a drug, it may interact with benzodiazepines, be antagonized by naloxone and flumazenil, and interact with melatonin receptors in the central nervous system and elsewhere in the body. Melatonin appears to be pharmacologically active and should not be considered a benign agent on overdose.