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Physiological melatonin levels in healthy older people: A systematic review
Abstract
Objective Melatonin plays a major role in maintaining circadian rhythm. Previous studies showed that its secretion pattern and levels could be disturbed in persons with dementia, psychiatric disorders, sleep disorders or with cancer. Also ageing is a factor that could alter melatonin levels, although previous research provides contradicting results. As melatonin supplementation is increasingly applied in older persons as sleep medication, it is important to know if melatonin levels decrease in healthy ageing and/or secretion patterns change. The objective of this study is to determine physiological levels and secretion patterns of melatonin in healthy older people.Methods We performed a systematic review and searched PubMed and Embase for studies published between January 1st 1980 and October 5th 2015 that measured melatonin in healthy persons aged ≥65years.Results Nineteen studies were retrieved. The number of participants ranged from 5 to 60 per study. Melatonin was mostly measured by radioimmunoassay (RIA) and the number of measurements per 24hours varied from 1 to 96. Sixteen studies showed a secretion pattern with a clear peak concentration, mostly at 0200h or 0300h. Maximum concentrations varied greatly from 11.2 to 91.3pgml(-1). Maximum melatonin level in studies with participants mean aged 65-70years was 49.3pgml(-1) and in studies with participants mean aged ≥75years 27.8pgml(-1), p-value <0.001.Conclusion Total melatonin production in 24hours seems not to change in healthy ageing, but the maximal nocturnal peak concentration of melatonin might decline. It is important to take this into account when prescribing melatonin supplementation to older people.
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“Since the average human adult produces between 0.1 mg and 0.9 mg of melatonin daily [277], this range is known as physiological doses.”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [277]
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Cites
(2014) · Medical Entomology and Zoology · Cited by 17,633
Brzezinski, A. (1997) · New England Journal of Medicine · doi:10.1056/nejm199701163360306 · Cited by 1,549
The basic physiology and pathophysiology of melatonin
Claustrat, B., Brun, J., & Chazot, G. (2004) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2004.08.001 · Cited by 951
Benloucif, S., Burgess, H. J., Klerman, E. B., Lewy, A. J., Middleton, B., Murphy, P. J., Parry, B. L., & Revell, V. L. (2008) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.27083 · Cited by 532
Differences between Human Plasma and Serum Metabolite Profiles
Yu, Z., Kastenmüller, G., He, Y., Belcredi, P., Möller, G., Prehn, C. P., Mendes, J., Wahl, S., Roemisch‐Margl, W., Ceglarek, U., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021230 · Cited by 523
Putative Melatonin Receptors in a Human Biological Clock
Reppert, S. M., Weaver, D. R., Rivkees, S. A., & Stopa, E. G. (1988) · Science · doi:10.1126/science.2845576 · Cited by 504
Melatonin, hydroxyl radical‐mediated oxidative damage, and aging: A hypothesis
Pöeggeler, B., Reiter, R. J., Tan, D. X., Chen, L., & Manchester, L. C. (1993) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1993.tb00498.x · Cited by 502
Age-Dependent Reduction in Serum Melatonin Concentrations in Healthy Human Subjects
Iguchi, H., Kato, K., & Ibayashi, H. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-55-1-27 · Cited by 381
Melatonin, human aging, and age-related diseases
Karasek, M. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.04.012 · Cited by 380
Melatonin and sleep in aging population
Pandi-Perumal, S. R., Zisapel, N., Srinivasan, V. J., & Cardinali, D. P. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.08.009 · Cited by 367
Neuroendocrine rhythms and sleep in aging men
van Coevorden, A., Mockel, J., Laurent, E., Kerkhofs, M., L'Hermite-Baleriaux, M., Decoster, C., Neve, P., & Van Cauter, E. (1991) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1991.260.4.e651 · Cited by 336
Srinivasan, V., Smits, M., Spence, W., Lowe, A. D., Kayumov, L., Pandi-Perumal, S. R., Parry, B., & Cardinali, D. P. (2006) · The World Journal of Biological Psychiatry · doi:10.1080/15622970600571822 · Cited by 292
Hardeland, R. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12090 · Cited by 290
Melatonin rhythmicity: effect of age and Alzheimer's disease
Skene, D. J. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00198-5 · Cited by 273
Do plasma melatonin concentrations decline with age?
Zeitzer, J. M., Daniels, J. E., Duffy, J. F., Klerman, E. B., Shanahan, T. L., Dijk, D.-J., & Czeisler, C. A. (1999) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00266-1 · Cited by 239
Arendt, J. (1988) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1988.tb00263.x · Cited by 226
Diminished Melatonin Secretion in the Elderly Caused by Insufficient Environmental Illumination1
Mishima, K., Okawa, M., Shimizu, T., & Hishikawa, Y. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.1.7097 · Cited by 218
Human aging and melatonin. Clinical relevance
Touitou, Y. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00120-6 · Cited by 187
Dijk, D., & Duffy, J. F. (1999) · Annals of Medicine · doi:10.3109/07853899908998789 · Cited by 155
Daily rhythm of serum melatonin in patients with dementia of the degenerate type
Uchida, K., Okamoto, N., Ohara, K., & Morita, Y. (1996) · Brain Research · doi:10.1016/0006-8993(96)00086-8 · Cited by 138
Plasma melatonin—An index of brain aging in humans?
Nair, N. P. V., Hariharasubramanian, N., Pilapil, C., Isaac, I., & Thavundayil, J. (1986) · Biological Psychiatry · doi:10.1016/0006-3223(86)90141-1 · Cited by 135
Ohashi, Y., Okamoto, N., Uchida, K., Iyo, M., Mori, N., & Morita, Y. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00255-8 · Cited by 133
Melatonin secretion after surgery
Cronin, A. J., Keifer, J. C., Davies, M. F., King, T. S., & Bixler, E. O. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02795-1 · Cited by 122
Changes in Endocrine Orcadian Rhythms as Markers of Physiological and Pathological Brain Aging
Magri, F., Locatelli, M., Balza, G., Molla, G., Cuzzoni, G., Fioravanti, M., Solerte, S. B., & Ferrari, E. (1997) · Chronobiology International · doi:10.3109/07420529709001459 · Cited by 111
Bartsch, C., Bartsch, H., Schmidt, A., Ilg, S., Bichler, K., & Flüchter, S. (1992) · Clinica Chimica Acta · doi:10.1016/0009-8981(92)90164-l · Cited by 102
Magri, F., Sarra, S., Cinchetti, W., Guazzoni, V., Fioravanti, M., Cravello, L., & Ferrari, E. (2004) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2004.00125.x · Cited by 102
Delirium: A disturbance of circadian integrity?
Fitzgerald, J., Adamis, D., Trzepacz, P. T., O’Regan, N., Timmons, S., Dunne, C. P., & Meagher, D. J. (2013) · Medical Hypotheses · doi:10.1016/j.mehy.2013.06.032 · Cited by 100
Biological rhythms and melatonin in mood disorders and their treatments
Lanfumey, L., Mongeau, R., & Hamon, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.005 · Cited by 98
Endocrine and immune effects of melatonin therapy in metastatic cancer patients
Lissoni, P., Barni, S., Crispino, S., Tancini, G., & FRASCHINI, F. (1989) · European Journal of Cancer and Clinical Oncology · doi:10.1016/0277-5379(89)90122-3 · Cited by 95
Koch, B. C. P., van der Putten, K., Someren, E. J. W. V., Wielders, J. P. M., ter Wee, P. M., Nagtegaal, J. E., & Gaillard, S. (2009) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfp493 · Cited by 94
Karasek, M., & Reiter, R. J. (2002) · PubMed · Cited by 90
Zhao, Z., Xie, Y., Fu, Y.-R., Bogdan, A., & Touitou, Y. (2002) · Chronobiology International · doi:10.1081/cbi-120015958 · Cited by 89
Effects of Melatonin on Nervous System Aging: Neurogenesis and Neurodegeneration
Sarlak, G., Jenwitheesuk, A., Chetsawang, B., & Govitrapong, P. (2013) · Journal of Pharmacological Sciences · doi:10.1254/jphs.13r01sr · Cited by 88
Kędziora–Kornatowska, K., Szewczyk‐Golec, K., Kozakiewicz, M., Pawluk, H., Czuczejko, J., Kornatowski, T., Bartosz, G., & Kędziora, J. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2009.00666.x · Cited by 87
Melatonin secretion occurs at a constant rate in both young and older men and women
Fourtillan, J. B., Brisson, A. M., Fourtillan, M., Ingrand, I., Decourt, J., & Girault, J. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.1.e11 · Cited by 76
Treatment with beta‐adrenoceptor blockers reduces plasma melatonin concentration.
Cowen, P. J., Bevan, J., Gosden, B., & Elliott, S. (1985) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1985.tb02640.x · Cited by 74
Bartsch, C., Bartsch, H., Flüchter, S., Attanasio, A. F., & Gupta, D. (1985) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1985.tb00633.x · Cited by 73
Reiter, R. J. (1994) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-1994-1050 · Cited by 69
Shiraki, M., Enterline, H. T., Brooks, J. J. S., Cooper, N. S., Hirschl, S., Roth, J. A., Rao, U. N. M., Enzinger, F. M., Amato, D. A., & Borden, E. C. (1989) · Cancer · doi:10.1002/1097-0142(19890715)64:2 · Cited by 68
Biochemical and body composition analysis of nocturia in the elderly
Sugaya, K., Nishijima, S., Oda, M., Owan, T., Miyazato, M., & Ogawa, Y. (2007) · Neurourology and Urodynamics · doi:10.1002/nau.20492 · Cited by 55
Measurement of Melatonin and 6-Sulphatoxymelatonin
Middleton, B. (2006) · Humana Press eBooks · doi:10.1385/1-59259-986-9:235 · Cited by 46
Effect of melatonin on the oxidative stress in erythrocytes of healthy young and elderly subjects*
Kędziora–Kornatowska, K., Szewczyk‐Golec, K., Czuczejko, J., de Lumen, K. V. M., Pawluk, H., Motyl, J., Karasek, M., & Kędziora, J. (2006) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00394.x · Cited by 46
Melatonin and cortisol serum levels in lung cancer patients at different stages of disease.
Mazzoccoli, G., Carughi, S., Cata, A. D., Viola, M. L., & Vendemiale, G. (2005) · PubMed · Cited by 42
Direct enzyme-linked immunosorbent assay and a radioimmunoassay for melatonin compared
Chegini, S., HOFFMANN-EHRHART, B., Kaider, A., & Waldhauser, F. (1995) · Clinical Chemistry · doi:10.1093/clinchem/41.3.381 · Cited by 38
Individual Variations in Serum Melatonin Levels through Time: Implications for Epidemiologic Studies
Nogueira, L., Sampson, J. N., Chu, L. W., Yu, K. F., Andriole, G. L., Church, T. R., Stanczyk, F. Z., Koshiol, J. E., & Hsing, A. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083208 · Cited by 38
Nocturnal plasma melatonin levels after flunitrazepam administration in healthy subjects
Hajak, G., Rodenbeck, A., Bandelow, B., Friedrichs, S., Huether, G., & Rüther, E. (1996) · European Neuropsychopharmacology · doi:10.1016/0924-977x(96)00005-3 · Cited by 38
Tozawa, T., Mishima, K., Satoh, K., Echizenya, M., Shimizu, T., & Hishikawa, Y. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030147 · Cited by 38
Melatonin Deficiency Hypothesis in Delirium: A Synthesis of Current Evidence
de Rooij, S. E., & Munster, B. C. V. (2013) · Rejuvenation Research · doi:10.1089/rej.2012.1405 · Cited by 35
Thomas, D. R., & Miles, A. (1989) · Biological Psychiatry · doi:10.1016/0006-3223(89)90187-x · Cited by 34
Melatonin Levels in Hospitalized Elderly Patients: A Comparison with Community Based Volunteers
BASKETT, J. J., Cockrem, J. F., & Todd, M. (1991) · Age and Ageing · doi:10.1093/ageing/20.6.430 · Cited by 32
Ohashi, Y., Okamoto, N., Uchida, K., Iyo, M., Mori, N., & Morita, Y. (1997) · Neurosignals · doi:10.1159/000109141 · Cited by 28
Measurement of Melatonin and 6-Sulphatoxymelatonin
Middleton, B. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-616-0_11 · Cited by 25
Olbrich, D., & Dittmar, M. (2011) · Chronobiology International · doi:10.3109/07420528.2011.599904 · Cited by 22
Neuroendocrine-immune interactions in healthy aging
Mazzoccoli, G., Inglese, M., Cata, A. D., Carughi, S., Dagostino, M. P., Marzulli, N., Damato, M., Grilli, M., Giuliani, F., & Greco, A. (2010) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2010.00628.x · Cited by 19
Feasibility and Functionality of OROS® Melatonin in Healthy Subjects
Shah, J. A., Langmuir, V. K., & Gupta, S. K. (1999) · The Journal of Clinical Pharmacology · doi:10.1177/00912709922008218 · Cited by 10
Research works printed but not linked: 1
- Lissoni, 1996, Physiopathology and therapeutic role of the epiphysis in human neoplasms, Med. Biol. Environ., 24, 1996
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Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease
Chitimus, D. M., Popescu, M. R., Voiculescu, S. E., Panaitescu, A. M., Pavel, B., Zagrean, L., & Zagrean, A.-M. (2020) · Biomolecules · doi:10.3390/biom10091211 · Cited by 354
Melatonin as an anti-inflammatory agent modulating inflammasome activation
Favero, G., Franceschetti, L., Bonomini, F., Rodella, L. F., & Rezzani, R. (2017) · International Journal of Endocrinology · doi:10.1155/2017/1835195 · Cited by 233
Is Melatonin the Cornucopia of the 21st Century?
Ferlazzo, N., Andolina, G., Cannata, A., Costanzo, M. G., Rizzo, V., Currò, M., Ientile, R., & Caccamo, D. (2020) · Antioxidants · doi:10.3390/antiox9111088 · Cited by 189
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Metadata
- Authors
- Scholtens, R. M., van Munster, B. C., van Kempen, M. F., & de Rooij, S. E. J. A.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Scholtens, Rikie M.
- Venue
- Journal of Psychosomatic Research
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 86
- Pages
- 20-27
- ISSN
- 0022-3999 (ISSN-L)
- OpenAlex
- W2394482042
- Cited by
- 132
- References
- 55
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 16 · 2023: 18 · 2022: 10 · 2021: 18 · 2020: 13 · 2019: 12 · 2018: 9 · 2017: 9 · 2016: 2
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychosomatic Research (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- melatonin, healthy aging, older adults, circadian rhythm, melatonin levels, melatonin supplementation, sleep medication
- MeSH terms
- Aged, Aged, 80 and over, Aging, Circadian Rhythm, Dementia, Female, Health Status, Humans, Male, Melatonin, Sleep, Sleep Wake Disorders, Dietary Supplements, Observational Studies as Topic
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