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Phase advance with separate and combined melatonin and light treatment

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Abstract

Introduction

Melatonin and light treatment are recommended for hastening adaptation to time zone change. We evaluated an afternoon regimen of 3 mg sustained release (SR) melatonin with and without next morning green light treatment for circadian phase advance. Effects of melatonin and light were tested separately and then combined to determine if the total phase change is additive or synergistic.

Material and methods

For each condition (melatonin, placebo, light, melatonin plus light), 11 subjects spent from Tuesday evening until Friday afternoon in the laboratory. For all four conditions, the following sleep schedule was maintained: night 1, 2345 to 0630 hours, night 2, 1600 to 0530 hours, and night 3, 2345 to 0700 hours. For the light-only condition, light treatment was administered between 0700 and 0800 hours on Thursday. For melatonin-only or placebo conditions, capsules were administered at 1600 hours on Wednesday. For the combined condition, melatonin was administered at 1600 hours on Wednesday with light treatment between 0600 and 0700 hours on Thursday. Circadian phase was assessed by calculating dim light melatonin onset (DLMO) from salivary melatonin, using a mean baseline +2 standard deviations (BL + 2 SD) threshold. For all four conditions, pre-treatment and post-treatment DLMO assessments were on Tuesday and Thursday evenings, respectively.

Results

Phase advances were: melatonin at 1600 hours, 0.72 h p < 0.005, light treatment from 0700 to 0800 hours, 0.31 h, non-significant, and the combined treatment, 1.04 h p < 0.0002.

Conclusion

The phase advance from the combination of afternoon melatonin with next morning light is additive.

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References

  • Arendt J (2009) Managing jet lag: some of the problems and possible new solutions. Sleep Med Rev 13:249–256

    Article  PubMed  Google Scholar 

  • Arendt J, Skene DJ (2005) Melatonin as a chronobiotic. Sleep Med Rev 9:25–39

    Article  PubMed  Google Scholar 

  • Arendt J, Aldhous M, Marks V (1986) Alleviation of jet lag by melatonin: preliminary results of controlled double blind trial. Br Med J 92:1170 (Clin Res Ed)

    Article  Google Scholar 

  • Benloucif S, Burgess HJ, Klerman EB, Lewy AJ, Middleton B, Murphy PJ, Parry BL, Revell VL (2008) Measuring melatonin in humans. J Clin Sleep Med 4:1542–1551

    Google Scholar 

  • Bjorvatn B, Pallesen S (2009) A practical approach to circadian rhythm sleep disorders. Sleep Med Rev 13:47–60

    Article  PubMed  Google Scholar 

  • Boivin DB, Duffy JR, Kronauer RE, Czeisler CA (1996) Dose-response relationships for resetting of human circadian clock by light. Nature 379:540–542

    Article  PubMed  CAS  Google Scholar 

  • Burgess HJ, Crowley SJ, Gazda CJ, Fogg LF, Eastman CI (2003) Preflight adjustment to eastward travel: 3 days of advancing sleep with and without morning bright light. J Biol Rhythms 18:318–328

    Article  PubMed  Google Scholar 

  • Burgess HJ, Revell VL, Eastman CI (2008) A three pulse phase response curve to three milligrams of melatonin in humans. J Physiol 586(2):639–647

    Article  PubMed  CAS  Google Scholar 

  • Burgess HJ, Revell VL, Molina TA, Eastman CI (2010) Human phase response curves to 3 days of daily melatonin: 0.5 mg versus 3.0 mg. J Clin Endocrinol Metab 95:3325–3331. doi:10.1210/jc.2009-2590

    Article  PubMed  CAS  Google Scholar 

  • Caldwell JA, Mallis MM, Caldwell JL, Paul MA, Miller JC, Neri DF (2009) Fatigue countermeasures in aviation. Aviat Space Environ Med 80:20–59

    Article  Google Scholar 

  • Cole RJ, Kripke DF, Gruen W, Mullaney DJ, Gillin JC (1992) Automatic sleep/wake identification from wrist activity. Sleep 15:461–469

    PubMed  CAS  Google Scholar 

  • Crowley SJ, Lee C, Tseng CY, Fogg LF, Eastman CI (2003) Combinations of bright light, scheduled dark, sunglasses, and melatonin to facilitate entrainment to night shift work. J Biol Rhythms 18:513–523

    Article  PubMed  Google Scholar 

  • Deacon S, Arendt J (1996) Adapting to phase shifts. I. An experimental model for jet lag and shift work. Physiol Behav 59:665–673

    Article  PubMed  CAS  Google Scholar 

  • Doljansky JT, Kannety H, Dagan Y (2005) Working under daylight intensity lamp: an occupational risk for developing circadian rhythm sleep disorder? Chronobiol Int 22:596–605

    Article  Google Scholar 

  • Eastman CI, Burgess HJ (2009) How to travel the world without jetlag. Sleep Med Clin 4(2):241–255

    Article  PubMed  Google Scholar 

  • Gibbs M, Hampton S, Morgan L, Arendt J (2007) Predicting circadian reponse to an abrupt phase shift: 6-sulphatoxymelatonin rhythms in rotating shift workers offshore. J Biol Rjhythms 22(4):368–370

    Article  CAS  Google Scholar 

  • Horne JA, Ostberg O (1976) A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol 4:97–110

    PubMed  CAS  Google Scholar 

  • Khalsa SB, Jewett ME, Cajochen C, Czeisler CA (2003) A phase response curve to single bright light pulses in human subjects. J Physiol 549:945–952

    Article  PubMed  CAS  Google Scholar 

  • Lewy AJ, Sack RL (1989) The dim light melatonin onset as a marker for circadian phase position. Chronobiol Int 6:93–102

    Article  PubMed  CAS  Google Scholar 

  • Lewy AJ, Sack RL (1996) The role of melatonin and light in the human circadian system. In: Buijs RM, Kalsbeek A, Romijn HJ, Pennartz CMA, Mirmiran M (eds) Progress in brain research, vol 111. Elsevier Science BV, Amsterdam

    Google Scholar 

  • Lewy AJ, Bauer VK, Ahmed S, Thomas KH, Cutler NL, Singer CM, Moffit MT, Sack RL (1998) The human phase response curve (PRC) to melatonin is about 12 hours out of phase with the PRC to light. Chronobiol Int 15:71–83

    Article  PubMed  CAS  Google Scholar 

  • Murphy PJ, Myers BL, Badia P (1996) Nonsteroidal anti-inflammatory drugs alter body temperature and suppress melatonin in humans. Physiol Behav 59:133–139

    Article  PubMed  CAS  Google Scholar 

  • Ozguner F, Koyu A, Cesur G (2005) Active smoking causes oxidative stress and decreases blood melatonin levels. Toxicol Ind Health 21:21–26

    Article  PubMed  CAS  Google Scholar 

  • Paul MA, Miller JC, Gray GW, Buick F, Blazeski S, Arendt J (2007) Phototherapy for circadian phase delay: a comparison of 4 phototherapeutic devices. Aviat Space Environ Med 78:645–652

    PubMed  Google Scholar 

  • Paul MA, Miller JC, Love RJ, Lieberman HR, Blazeski S, Arendt J (2009) Timing light treatment for eastward and westward travel preparation. Chronobiol Int 26:867–890

    Article  PubMed  CAS  Google Scholar 

  • Paul MA, Miller JC, Gray GW, Love RJ, Lieberman HR, Arendt J (2010) Melatonin treatment for eastward and westward travel preparation. Psychopharmacology 208:377–387

    Article  PubMed  CAS  Google Scholar 

  • Revell VL, Eastman CI (2005) How to trick mother nature into letting you fly around or stay up all night. J Biol Rhythms 20:353–365

    Article  PubMed  Google Scholar 

  • Revell VL, Burgess HJ, Gazda CJ, Smith MR, Fogg LF, Eastman CI (2006) Advancing human circadian rhythms with afternoon melatonin and morning intermittent bright light. J Clin Endocrinol Metab 91:54–59

    Article  PubMed  CAS  Google Scholar 

  • Samel A, Wegmann HM, Vejvoda M, Maass H, Gundel A, Schutz M (1991) Influence of melatonin treatment on human circadian rhythmicity before and after a simulated 9-hr time shift. J Biol Rhythms 6:235–248

    Article  PubMed  CAS  Google Scholar 

  • Spencer MB, Rogers AS, Pascoe PA (1995) The effect of a large eastward time zone change on sleep, performance and circadian rhythms. DRA, Farnborough, Report No.: CHS/A&N/CR/95/001

    Google Scholar 

  • Takahashi T, Sasaki M, Itoh H, Sano H, Yamadera W, Ozone M, Obuchi K, Nishimura H, Matsunaga N (1999) Re-entrainment of circadian rhythm of plasma melatonin on an 8-h eastward flight. Psychiatry Clin Neurosci 53:257–260

    Article  PubMed  CAS  Google Scholar 

  • Takahashi T, Sasaki M, Itoh H, Yamadera W, Ozone M, Obuchi K, Matsunaga N, Sano H, Hayashida KI (2001) Re-entrainment of the circadian rhythms of plasma melatonin in an 11-h eastward bound flight. Psychiatry Clin Neurosci 55:275–276

    Article  PubMed  CAS  Google Scholar 

  • Takahashi T, Sasaki M, Itoh H et al (2002) Melatonin alleviates jet lag symptoms caused by an 11-hour eastward flight. Psychiatry Clin Neurosci 56:301–302

    Article  PubMed  CAS  Google Scholar 

  • Voultsios A, Kennaway DJ, Dawson D (1997) Salivary melatonin as a circadian phase marker: validation and comparison to plasma melatonin. J Biol Rhythms 12:457–466

    PubMed  CAS  Google Scholar 

  • Waterhouse J, Reilly T, Atkinson G, Edwards B (2007) Jet lag: trends and coping strategies. Lancet 369:1117–1120

    Article  PubMed  Google Scholar 

  • Wirz-Justice A, Krauchi K, Cajochen C, Danilenko KV, Renz C, Weber JM (2004) Evening melatonin and bright light administration induce additive phase shifts in dim light melatonin onset. J Pineal Res 36:192–194

    Article  PubMed  CAS  Google Scholar 

  • Wright HR, Lack LC, Partridge KJ (2001) Light emitting diodes can be used to phase delay the melatonin rhythm. J Pineal Res 31:350–355

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The views, opinions, and/or findings in this report are those of the authors and should not be construed as an official Defence Research & Development Canada (DRDC), Department of National Defence (DND) Canada, or U.S. Department of Defense (DoD) position, policy or decisions, unless so designated by other official documentation. Citations of commercial organizations and trade names in this report do not constitute an official DRDC, DND Canada, or U.S. DoD endorsement or approval of the products or services of these organizations. Funding for this research was provided by the Canadian Forces.

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Correspondence to Michel A. Paul.

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Paul, M.A., Gray, G.W., Lieberman, H.R. et al. Phase advance with separate and combined melatonin and light treatment. Psychopharmacology 214, 515–523 (2011). https://doi.org/10.1007/s00213-010-2059-5

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  • DOI: https://doi.org/10.1007/s00213-010-2059-5

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