title: Optimal dosages for melatonin supplementation therapy in older adults: a systematic review of current literature.
abstract: BACKGROUND
  Melatonin is a hormone that regulates circadian rhythm, and its levels decline with age. As melatonin levels decrease, older adults are prone to develop disorders related to an altered circadian rhythm. The effective dose of melatonin supplementation in these disorders remains unclear.
  
  
  OBJECTIVE
  Our objective was to define the optimal dosage of exogenous melatonin administration in disorders related to altered melatonin levels in older adults aged 55 years and above by determining the dose-response effect of exogenous administered melatonin on endogenous levels.
  
  
  METHODS
  We conducted a systematic review through PubMed/MEDLINE and Embase, both from 1980 until November 2013. Included articles studied the effect of exogenous melatonin administration on endogenous melatonin levels in either serum, urine, or saliva in humans aged 55 years and above.
  
  
  RESULTS
  We included 16 articles, nine of which were randomized controlled trials (RCTs). The mean age varied from 55.3 to 77.6 years. Melatonin dosage varied from 0.1 mg to 50 mg/kg and was administered orally in all studies. Pre- and post-intervention levels revealed a significant elevation of the post-intervention melatonin levels in a dose-dependent fashion. The maximum concentrations measured in serum and urine were all elevated compared with placebo, and a higher elevation in older adults than in younger adults was demonstrated. Even though there were no differences between times to reach maximum concentration in serum and urine, melatonin levels with higher doses were maintained longer above a certain threshold than were lower doses.
  
  
  CONCLUSIONS
  In older adults, we advise the use of the lowest possible dose of immediate-release formulation melatonin to best mimic the normal physiological circadian rhythm of melatonin and to avoid prolonged, supra-physiological blood levels.
authors.affiliation: Department of Internal Medicine, Section of Geriatric Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, e.vural@vumc.nl.
authors.forename: Esmée M S
authors.initials: EM
authors.lastname: Vural
authors.forename: Barbara C
authors.initials: BC
authors.lastname: van Munster
authors.forename: Sophia E
authors.initials: SE
authors.lastname: de Rooij
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008550:Melatonin / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use / Q000652:urine; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy / Q000378:metabolism
chemical_list: D008550:Melatonin