Individual Differences in the Amount and Timing of Salivary Melatonin Secretion

Background The aim of this study was to examine individual differences in a large sample of complete melatonin profiles not suppressed by light and search for possible associations between the amount and timing of melatonin secretion and a multitude of lifestyle variables. The melatonin profiles were derived from saliva samples collected every 30 minutes in dim light from 85 healthy women and 85 healthy men aged 18–45 years. There was a large individual variability in the amount of melatonin secreted with peak values ranging from 2 to 84 pg/ml. The onset of melatonin secretion ranged from 18:13 to 00:26 hours. The use of hormonal birth control, reduced levels of employment, a smaller number of days on a fixed sleep schedule, increased day length and lower weight were associated with an increased amplitude of melatonin secretion. The use of hormonal birth control, contact lenses, a younger age, and lower ratings of mania and paranoia were associated with a longer duration of melatonin secretion. An earlier occurrence of the onset of melatonin secretion was associated with an earlier wake time, more morningness and the absence of a bed partner. Lifestyle and behavioral variables were only able to explain about 15% of the individual variability in the amount of melatonin secretion, which is likely because of a substantial genetic influence on the levels of melatonin secretion.

[1]  G. Barbato,et al.  Conservation of photoperiod-responsive mechanisms in humans. , 1993, The American journal of physiology.

[2]  O. Vakkuri,et al.  Ethanol inhibits melatonin secretion in healthy volunteers in a dose-dependent randomized double blind cross-over study. , 1993, The Journal of clinical endocrinology and metabolism.

[3]  G. Sassolas,et al.  A Once‐Repeated Study of Nocturnal Plasma Melatonin Patterns and Sleep Recordings in Six Normal Young Men , 1986, Journal of pineal research.

[4]  M. Wheeler,et al.  Neurohypophysial hormone and melatonin secretion over the natural and suppressed menstrual cycle in premenopausal women , 1998, Clinical endocrinology.

[5]  Francine Laden,et al.  Night work and breast cancer risk: a systematic review and meta-analysis. , 2005, European journal of cancer.

[6]  R. Wurtman,et al.  The circadian rhythm of plasma melatonin during the normal menstrual cycle and in amenorrheic women. , 1988, The Journal of clinical endocrinology and metabolism.

[7]  T. Paparrigopoulos,et al.  Normative melatonin excretion: a multinational study , 1999, Psychoneuroendocrinology.

[8]  C. Eastman,et al.  How to Trick Mother Nature into Letting You Fly Around or Stay Up All Night , 2005, Journal of biological rhythms.

[9]  B. Hoffman,et al.  Light and exercise and melatonin production in women. , 2005, American journal of epidemiology.

[10]  M. Dowsett,et al.  Urinary 6‐sulfatoxymelatonin levels and their correlations with lifestyle factors and steroid hormone levels , 2006, Journal of pineal research.

[11]  P. Badia,et al.  Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation , 1999, Behavioural Brain Research.

[12]  C. Eastman,et al.  Phase advancing the human circadian clock with blue-enriched polychromatic light. , 2009, Sleep medicine.

[13]  C. M. Singer,et al.  Human Melatonin Production Decreases With Age , 1986, Journal of pineal research.

[14]  M. Bourdages,et al.  Effects of electric and magnetic fields from high-power lines on female urinary excretion of 6-sulfatoxymelatonin. , 2001, American journal of epidemiology.

[15]  C. Eastman,et al.  The effects of prior light history on the suppression of melatonin by light in humans , 2002, Journal of pineal research.

[16]  D. Dijk,et al.  Plasma melatonin rhythms in young and older humans during sleep, sleep deprivation, and wake. , 2007, Sleep.

[17]  M. Johns,et al.  A new method for measuring daytime sleepiness: the Epworth sleepiness scale. , 1991, Sleep.

[18]  W. Kaune,et al.  Alcohol Consumption and Urinary Concentration of 6-Sulfatoxymelatonin in Healthy Women , 2000, Epidemiology.

[19]  J. Carrier,et al.  Challenging sleep in aging: the effects of 200 mg of caffeine during the evening in young and middle‐aged moderate caffeine consumers , 2006, Journal of sleep research.

[20]  C. Eastman,et al.  FAILURE OF EXTRAOCULAR LIGHT TO FACILITATE CIRCADIAN RHYTHM REENTRAINMENT IN HUMANS , 2000, Chronobiology international.

[21]  H. Babkoff,et al.  Single-dose bright light and/or caffeine effect on nocturnal performance. , 2002, Aviation, space, and environmental medicine.

[22]  A. Lewy,et al.  The Endogenous Melatonin Profile as a Marker for Circadian Phase Position , 1999, Journal of biological rhythms.

[23]  S. Berga,et al.  Circadian pattern of plasma melatonin concentrations during four phases of the human menstrual cycle. , 1990, Neuroendocrinology.

[24]  C. Shapiro,et al.  Blocking low-wavelength light prevents nocturnal melatonin suppression with no adverse effect on performance during simulated shift work. , 2005, The Journal of clinical endocrinology and metabolism.

[25]  A. Locatelli,et al.  Bilateral Lesions of the Suprachiasmatic Nuclei Alter the Nocturnal Melatonin Secretion in Sheep , 1995, Journal of neuroendocrinology.

[26]  Till Roenneberg,et al.  The human circadian clock entrains to sun time , 2007, Current Biology.

[27]  S. Berga,et al.  Plasma Melatonin Circadian Rhythms during the Menstrual Cycle and after Light Therapy in Premenstrual Dysphoric Disorder and Normal Control Subjects , 1997, Journal of biological rhythms.

[28]  F. Magkos,et al.  Caffeine Use in Sports, Pharmacokinetics in Man, and Cellular Mechanisms of Action , 2005, Critical reviews in food science and nutrition.

[29]  K. Sharkey,et al.  Melatonin phase shifts human circadian rhythms in a placebo-controlled simulated night-work study. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[30]  Shadab A. Rahman,et al.  Altered sleep architecture and higher incidence of subsyndromal depression in low endogenous melatonin secretors , 2010, European Archives of Psychiatry and Clinical Neuroscience.

[31]  Richard E Kronauer,et al.  Comparisons of the Variability of Three Markers of the Human Circadian Pacemaker , 2002, Journal of biological rhythms.

[32]  J. Arendt,et al.  Annual changes in 6-sulphatoxymelatonin excretion in man. , 1988, Acta endocrinologica.

[33]  Sato Honma,et al.  Repeated exposures to daytime bright light increase nocturnal melatonin rise and maintain circadian phase in young subjects under fixed sleep schedule. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[34]  M. Hakel,et al.  Caffeine and light effects on nighttime melatonin and temperature levels in sleep-deprived humans , 1997, Brain Research.

[35]  Trevor R. Norman,et al.  The heritability of melatonin secretion and sensitivity to bright nocturnal light in twins , 2006, Psychoneuroendocrinology.

[36]  J. Horne,et al.  A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. , 1976, International journal of chronobiology.

[37]  J. Graham,et al.  MMPI-2 : Assessing Personality and Psychopathology , 1990 .

[38]  D. Kunz,et al.  Normative data on the daily profile of urinary 6-sulfatoxymelatonin in healthy subjects between the ages of 20 and 84 , 2006, Psychoneuroendocrinology.

[39]  C. Eastman,et al.  A late wake time phase delays the human dim light melatonin rhythm , 2006, Neuroscience Letters.

[40]  P. Zvolský,et al.  The circadian rhythm in plasma melatonin concentration of the urbanized man: the effect of summer and winter time , 1985, Brain Research.

[41]  D. Dawson,et al.  Urinary 6‐sulfatoxymelatonin excretion and aging: New results and a critical review of the literature , 1999, Journal of pineal research.

[42]  S. Hathaway,et al.  MMPI-2 : Minnesota Multiphasic Personality Inventory-2 : manual for administration and scoring , 1989 .

[43]  B. Malpaux,et al.  Genetic variability in melatonin concentrations in ewes originates in its synthesis, not in its catabolism. , 1998, American journal of physiology. Endocrinology and metabolism.

[44]  P. Badia,et al.  Nonsteroidal anti-inflammatory drugs alter body temperature and suppress melatonin in humans , 1996, Physiology & Behavior.

[45]  D. Dawson,et al.  Salivary Melatonin as a Circadian Phase Marker: Validation and Comparison to Plasma Melatonin , 1997, Journal of biological rhythms.

[46]  T. Wehr,et al.  Suppression of men's responses to seasonal changes in day length by modern artificial lighting. , 1995, The American journal of physiology.

[47]  M. Hébert,et al.  Blue blocker glasses impede the capacity of bright light to suppress melatonin production , 2006, Journal of pineal research.

[48]  Daniel J Buysse,et al.  The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research , 1989, Psychiatry Research.

[49]  Susan E Hankinson,et al.  Urinary melatonin levels and breast cancer risk. , 2005, Journal of the National Cancer Institute.

[50]  D A Newsome,et al.  Light suppresses melatonin secretion in humans. , 1980, Science.

[51]  Saturnino L. Salas Calculus : one and several variables with analytic geometry / Saturnino L. Salas , 1974 .

[52]  Till Roenneberg,et al.  The Human Circadian Clock's Seasonal Adjustment Is Disrupted by Daylight Saving Time , 2007, Current Biology.

[53]  R. Chervin Epworth sleepiness scale? , 2003, Sleep medicine.

[54]  J. Wikner,et al.  Caffeine raises the serum melatonin level in healthy subjects: An indication of melatonin metabolism by cytochrome P450(CYP)1A2 , 2003, Journal of endocrinological investigation.

[55]  J. Baskett,et al.  Melatonin in older people with age-related sleep maintenance problems: a comparison with age matched normal sleepers. , 2001, Sleep.

[56]  I. Fentiman,et al.  Melatonin and breast cancer: a prospective study. , 2004, Journal of the National Cancer Institute.

[57]  C. Eastman,et al.  A Compromise Phase Position for Permanent Night Shift Workers: Circadian Phase after Two Night Shifts with Scheduled Sleep and Light/Dark Exposure , 2006, Chronobiology international.

[58]  W. Herrmann,et al.  A New Concept for Melatonin Deficit: On Pineal Calcification and Melatonin Excretion , 1999, Neuropsychopharmacology.

[59]  D. Skene,et al.  An action spectrum for melatonin suppression: evidence for a novel non‐rod, non‐cone photoreceptor system in humans , 2001, The Journal of physiology.

[60]  D. Cardinali,et al.  Neuroendocrine integrative mechanisms in mammalian pineal gland: effects of steroid and adenohypophysial hormones on melatonin synthesis in vitro. , 1987, Journal of steroid biochemistry.

[61]  C. Eastman,et al.  Circadian phase determined from melatonin profiles is reproducible after 1 wk in subjects who sleep later on weekends , 2005, Journal of pineal research.

[62]  H. Tokura,et al.  Bright light exposure during the daytime affects circadian rhythms of urinary melatonin and salivary immunoglobulin A. , 1999, Chronobiology international.

[63]  H. Taylor,et al.  The effect of prescription eyewear on ocular exposure to ultraviolet radiation. , 1986, American journal of public health.

[64]  M. Terman,et al.  A circadian signal of change of season in patients with seasonal affective disorder. , 2001, Archives of general psychiatry.

[65]  R. Kronauer,et al.  Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression , 2000, The Journal of physiology.

[66]  B. Malpaux,et al.  Genetic variability in melatonin secretion originates in the number of pinealocytes in sheep. , 2002, The Journal of endocrinology.

[67]  M. Dubocovich,et al.  Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats. , 2005, Cancer research.

[68]  W Gruen,et al.  Seasonal Variation in Human Illumination Exposure at Two Different Latitudes , 1995, Journal of biological rhythms.

[69]  G. Cornelissen,et al.  Do plasma melatonin concentrations decline with age? , 2000, The American journal of medicine.

[70]  G. Brainard,et al.  Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor , 2001, The Journal of Neuroscience.