Advertisement

Current Treatment Options in Neurology

, Volume 5, Issue 3, pp 225–229 | Cite as

Melatonin, circadian rhythms, and sleep

  • Irina V. Zhdanova
  • Valter Tucci
Article

Opinion statement

Experimental data show a close relationship among melatonin, circadian rhythms, and sleep. Low-dose melatonin treatment, increasing circulating melatonin levels to those normally observed at night, promotes sleep onset and sleep maintenance without changing sleep architecture. Melatonin treatment can also advance or delay the phase of the circadian clock if administered in the evening or in the morning, respectively. If used in physiologic doses and at appropriate times, melatonin can be helpful for those suffering from insomnia or circadian rhythm disorders. This may be especially beneficial for individuals with low melatonin production, which is established by measuring individual blood or saliva melatonin levels. However, high melatonin doses (over 0.3 mg) may cause side effects and disrupt the delicate mechanism of the circadian system, dissociating mutually dependent circadian body rhythms. A misleading labeling of the hormone melatonin as a “food supplement” and lack of quality control over melatonin preparations on the market continue to be of serious concern.

Keywords

Melatonin Circadian Rhythm Circadian Clock Pineal Gland Melatonin Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Tzischinsky O, Shlitner A, Lavie P: The association between the nocturnal sleep gate and nocturnal onset of urinary 6-sulfatoxymelatonin. J Biol Rhythms 1993, 8:199–209.PubMedCrossRefGoogle Scholar
  2. 2.
    Zhdanova IV, Wurtman RJ, Morabito C, et al.: Effects of low oral doses of melatonin, given 2 to 4 hours before habitual bedtime, on sleep in normal young humans. Sleep 1996, 19:423–431. The results of the study provide evidence that physiologic melatonin doses promote earlier sleep onset in healthy young individuals, treated several hours before their habitual bedtime, without significantly altering their sleep architecturePubMedGoogle Scholar
  3. 3.
    Zhdanova IV, Wurtman RJ, Lynch HJ, et al.: Sleepinducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther 1995, 57:552–558.PubMedCrossRefGoogle Scholar
  4. 4.
    Zhdanova IV, Wurtman RJ, Regan MM, et al.: Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab 2001, 86:4727–4730.PubMedCrossRefGoogle Scholar
  5. 5.
    Stone BM, Turner C, Mills SL, Nicholson AN: Hypnotic activity of melatonin. Sleep 2000, 23:663–669.PubMedGoogle Scholar
  6. 6.
    Zhdanova IV, Piotrovskaya VR: Melatonin reduces symptoms of acute nicotine withdrawal in humans. Pharm Biochem Behav 2000, 67:131–135. Oral 0.3-mg dose of melatonin administered to habitual smokers 3.5 hours after the nicotine withdrawal, and increasing circulating melatonin concentrations within the physiologic range, attenuates the acute effects of smoking cessation on mood and reduces cigarette craving.CrossRefGoogle Scholar
  7. 7.
    Lewy AJ, Bauer VK, Hasler BP, et al.: Capturing the circadian rhythms of free-running blind people with 0.5 mg melatonin. Brain Res 2001, 918:96–100. Daily treatment using low-dose (0.5 mg) melatonin can entrain circadian rhythms in blind people suffering from free-running circadian rhythms.PubMedCrossRefGoogle Scholar
  8. 8.
    Wiechmann AF, O’Steen WK: Melatonin increases photoreceptor susceptibility to light-induced damage. Invest Ophthalmol Vis Sci 1992, 33:1894–1902.PubMedGoogle Scholar
  9. 9.
    Arushanian EB, Ovanesov KB: Melatonin lowers the threshold of light sensitivity of the human retina. Eksp Klin Farmakol 1999, 62:58–60. Chronic melatonin treatment can significantly decrease retinal sensitivity threshold in older individuals. The authors suggest a connection between the retinal light sensitivity and the direct effect of the melatonin on photoreceptors.PubMedGoogle Scholar
  10. 10.
    Stoschitzky K, Sakotnik A, Lercher P, et al.: Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol 1999, 55:111–115.PubMedCrossRefGoogle Scholar
  11. 11.
    Palazidou E, Papadopoulos A, Sitsen A, et al.: An alpha 2 adrenoceptor antagonist, Org 3770, enhances nocturnal melatonin secretion in man. Psychopharmacology (Berl) 1989, 97:115–117.CrossRefGoogle Scholar
  12. 12.
    Ferini-Strambi L, Zucconi M, Biella G, et al.: Effect of melatonin on sleep microstructure: preliminary results in healthy subjects. Sleep 1993, 16:744–777. The authors showed that a combination of melatonin and low benzodiazepine doses could avoid the residual, dose-related benzodiazepine effects.PubMedGoogle Scholar
  13. 13.
    Hartter S, Grozinger M, Weigmann H, et al.: Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000, 67:1–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Childs PA, Rodin I, Martin NJ, et al.: Effect of fluoxetine on melatonin in patients with seasonal affective disorder and matched controls. Br J Psychiatry 1995, 166:196–198. This study showed that effect of fluoxetine differs from tricyclic antidepressants and fluvoxamine, which increase melatonin.PubMedCrossRefGoogle Scholar
  15. 15.
    Demisch L, Demisch K, Nickelsen T: Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res 1987, 5:317–322.CrossRefGoogle Scholar
  16. 16.
    Hughes RJ, Sack RL, Lewy AJ: The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement. Sleep 1998, 21:52–68. The study assessed sleep-promoting effects of fast- and slowrelease melatonin preparations administered at different times to patients with age-related sleep-maintenance insomnia. Melatonin treatments shortened latencies to sleep, demonstrating that high physiologic doses of melatonin can promote sleep in this population.PubMedGoogle Scholar
  17. 17.
    Middleton B, Arendt J, Stone BM: Complex effects of melatonin on human circadian rhythms in constant dim light. J Biol Rhythms 1997, 12:467–477.PubMedGoogle Scholar
  18. 18.
    Zhdanova IV, Wurtman RJ, Wagstaff J: Effects of low dose of melatonin on sleep in children with Angelman syndrome. J Pediatr Endocrinol Metab 1999, 12:57–67. The authors studied the effects of low-dose (0.3 mg) melatonin therapy on sleep and serum melatonin levels in 13 Angelman syndrome children suffering from insomnia, and found that a moderate overnight increase in circulating melatonin levels can promote sleep and reduce motor activity during sleep in these patients.PubMedGoogle Scholar
  19. 19.
    Dollins AB, Zhdanova IV, Wurtman RJ, et al.: Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci U S A 1994, 91:1824–1822.PubMedCrossRefGoogle Scholar
  20. 20.
    Galvan Manso M, Campistol J, et al.: Angelman syndrome: physical characteristics and behavioral phenotype in 37 patients with confirmed genetic diagnosis. Rev Neurol 2002, 35:425–429. The authors reviewed data on multiple physiologic, behavioral, and sociologic parameters collected from 37 patients with a positive genetic diagnosis of Angelman syndrome. The sleep disorders were present in 48% of the patients and required medication. The most effective treatment for the sleep disorders was melatonin.Google Scholar

Copyright information

© Current Science Inc 2003

Authors and Affiliations

  • Irina V. Zhdanova
    • 1
  • Valter Tucci
  1. 1.Department of Anatomy and NeurobiologyBoston University Medical SchoolBostonUSA

Personalised recommendations