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Melatonin

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Melatonin

  • See Also
  • Physiology
  1. Pineal gland synthesizes Melatonin
    1. Overall Pathway: Tryptophan to Serotonin to Melatonin
    2. May also affect adrenal and gonadal function
  2. Endogenous Melatonin physiology
    1. Secreted at night
    2. Normally highest levels during sleep
      1. Increases rapidly late evening
      2. Peaks after midnight
      3. Decreases in Morning
  3. Potential Effects on Sleep
    1. Improved Sleep Efficiency (Sleep Time/Time in bed)
    2. Decreased Nocturnal Awakenings
    3. Improved Sleep quality
    4. Does not Decrease sleep latency
    5. Does not Increase total sleep time
  4. As compared with Benzodiazepines
    1. Not addictive
    2. Does not suppress REM Sleep
    3. Does not increase morning Sleepiness
  5. Future Potential uses
    1. Chemotherapeutic
  • Pathophysiology
  1. Elderly with Insomnia
    1. Low levels of Melatonin
  2. Blind with irregular sleep cycles
    1. Free running Melatonin
    2. Exogenous Melatonin shown to normalize sleep rhythms
      1. Melatonin 5mg at bedtime for 3 weeks
  3. References
    1. Sack (1991) J Biol Rhythms 6:249 [PubMed]
  • Sources
  1. Marketed as a dietary supplement
    1. Not regulated by FDA
    2. No information on production, purity, manufacturer
  2. Risk of impurities
    1. Example: L-Tryptophan related deaths
    2. Consumers should purchase USP Verified products
  • Dosing
  1. General
    1. Effective doses are lower than package insert
    2. May be effective for promoting sleep onset
    3. Not effective for maintaining sleep (extending sleep duration)
    4. Does not require tapering
  2. Dosing by age
    1. Child: Start at 1 mg (maximum effective dose 3 mg)
    2. Adult: Start at 3 mg (maximum effective dose 6 mg)
  • Dosing
  • Specific Indications in Adults
  1. Night Shift Workers
    1. Start with 3 mg prior to daytime sleep (may increase to 5 mg)
  2. Sleep onset Insomnia
    1. Start with 3 mg at 30 to 60 minutes before bedtime (may increase to 5 mg)
  3. Jet Lag
    1. Melatonin 5 mg orally at bedtime on arrival at destination and for 2-6 nights after arrival
  1. Recent Cochrane review suggests effective at travel
    1. Indications
      1. Travel across 5 or more time zones
      2. May also be useful if 2 or more time zones crossed
      3. Most effective when traveling eastward
    2. Protocol
      1. Take 5 mg PO at bedtime on arrival at destination
      2. Continue for 2-5 days after arrival
    3. References
      1. Smucny (2002) Am Fam Physician 66(11):2087-8 [PubMed]
  2. Other small trials show benefit at travel time
    1. Petrie (1989) Br Med J 298:705
      1. Before travel: 5 mg PO at bedtime for 3 days
      2. After travel: 5 mg PO at bedtime for 3 days
    2. Petrie (1993) Biol Psychiatry 33:526
      1. After travel: 5 mg PO at bedtime for 5 days
    3. Claustrat (1992) Biol Psychiatry 32:705
      1. Before travel: 8 mg PO at bedtime for 1 day
      2. After travel: 8 mg PO at bedtime for 3 days
  3. Trials showing lack of Melatonin benefit in Jet Lag
    1. Hao (2000) J Clin Endocrinol Metab 85(10):3618-22
  1. Some small trials suggest benefit
    1. Garfinkel (1995) Lancet 346:541
      1. Melatonin 2 mg PO 2 hours before bedtime
    2. Dollins (1994) Proc Natl Acad Sci 91:1824
      1. Melatonin 0.3 to 1 mg PO 1-2 hours before bedtime
    3. Zhadanova (1995) Clin Pharmacol Ther 57:552
      1. Melatonin 0.3 to 1 mg PO 1-2 hours before bedtime
  • Safety
  1. Not recommended in pregnancy and Lactation due to insufficient safety data
  2. May effect growth in children on Melatonin longterm (hormonal suppression)
  • Adverse Effects
  • Standard dosing
  1. See Safety as above
  2. Drowsiness
    1. Onset 30 minutes after administered
    2. Duration: 1 hour
  3. Headache
  4. Gastrointestinal upset
  5. Major Depression
  • Adverse Effects
  • Higher doses (e.g. 10 mg, often mixed with other supplements)
  1. Hangover Sensation
  2. Lethargy
  3. Disorientation
  4. Amnesia
  • Myths
  • False Claims or myths without scientific support
  1. Anti-Aging effect
  2. Heart and Immune System Strengthening
  3. Improved Sexual Libido and Vitality
  4. Seasonal Affective Disorder treatment
  • References