Are melatonin doses employed clinically adequate for melatonin-induced cytoprotection?

Abstract

Abstract: This review article discusses the special role that melatonin, a molecule with chronobiotic/cytoprotective properties, may have in prevention and treatment of the metabolic syndrome (MS), ischemic and non-ischemic cardiovascular diseases and Alzheimer ́s disease (AD). Prevention of these diseases is a major goal for governmental and non-governmental organizations, and melatonin, an unusual phylogenetically conserved molecule present in all aerobic organisms, merits consideration in this respect. In humans, circulating melatonin levels are consistently reduced in MS, ischemic and non-ischemic cardiovascular diseases and AD, the potential therapeutic value of melatonin being suggested by a limited number of clinical trials generally employing melatonin in the 2-5 mg/day range. In animal model studies of MS, ischemic and non-ischemic cardiovascular diseases and AD melatonin was very effective to curtail symptomatology. However, calculations derived from animal studies indicate projected cytoprotective melatonin doses for humans in the 40-100 mg/day range, doses that are rarely employed clinically. Hence, controlled studies employing melatonin doses in this range are urgently needed. Since the pharmaceutical industry is refractive to support them because of the lack of protective patents for a natural compound, only the involvement of governmental and non-profit organizations can achieve that goal. Within this prospect, the off-label use of melatonin is discussed.