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.

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.