{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:47:33Z","timestamp":1785433653527,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Health Management of Castilla y Le\u00f3n (GRS)","award":["GRS 2320\/A\/21"],"award-info":[{"award-number":["GRS 2320\/A\/21"]}]},{"name":"University of Salamanca","award":["PIC-2022-12"],"award-info":[{"award-number":["PIC-2022-12"]}]},{"award":["PIC-2022-12"],"award-info":[{"award-number":["PIC-2022-12"]}],"id":[{"id":"https:\/\/ror.org\/02f40zc51","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Institute of Biomedical Research of Salamanca (IBSAL) 2025","award":["IBOA25\/0003"],"award-info":[{"award-number":["IBOA25\/0003"]}]},{"award":["IBOA25\/0003"],"award-info":[{"award-number":["IBOA25\/0003"]}],"id":[{"id":"https:\/\/ror.org\/02zz52s52","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to examine plasma melatonin levels, seasonal variation, and their association with sleep quality in adults aged 25\u201365 years using both the Pittsburgh Sleep Quality Index and actigraphy. A cross-sectional study was conducted in a stratified random sample of 500 adults from Salamanca and \u00c1vila (Spain). Plasma melatonin was quantified by HPLC-DAD-MS\/MS, and sleep quality was assessed using the Pittsburgh Sleep Quality Index and a 5-day wrist actigraphy protocol (ActiGraph GT3X+). Participants were stratified by age and sex, and seasonal variation was evaluated. Multivariable analyses were adjusted for relevant confounders. A total of 334 participants with valid melatonin measurements were included (mean age 43 years). Mean plasma melatonin concentration was 14.5 \u00b1 15.9 pg\/mL, with higher levels observed in men than women and a decreasing trend with age. A trend toward higher melatonin levels during winter was observed, although the differences were not statistically significant. No significant association was found between plasma melatonin levels and Pittsburgh Sleep Quality Index scores. However, higher melatonin levels were associated with slightly greater sleep efficiency measured by actigraphy. Participants reporting melatonin supplement use showed higher Pittsburgh Sleep Quality Index scores and lower total sleep time compared with non-users. Overall, plasma melatonin levels varied by sex, age, and season but showed no association with subjective sleep quality, while a modest relationship was observed with objective sleep efficiency, suggesting that melatonin alone is not a strong determinant of perceived sleep quality and highlighting the multifactorial nature of sleep regulation in adults.<\/jats:p>","DOI":"10.3390\/ijms27146320","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:23:14Z","timestamp":1784193794000},"page":"6320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Melatonin Levels, Seasonal Variation, and Sleep Quality: A Stratified Analysis of Adults Aged 25\u201365 Years Using the Pittsburgh Sleep Quality Index and Actigraphy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2292-3802","authenticated-orcid":false,"given":"Irene A.","family":"Garcia-Yu","sequence":"first","affiliation":[{"name":"Facultad de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Crespo-Sedano","sequence":"additional","affiliation":[{"name":"Complejo Asistencial Universitario de Palencia, 34005 Palencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-0131","authenticated-orcid":false,"given":"C\u00e9sar","family":"Jim\u00e9nez-Vaquero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Escuela Universitaria de Enfermer\u00eda de \u00c1vila, Universidad de Salamanca, 05003 \u00c1vila, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5453-2510","authenticated-orcid":false,"given":"Jes\u00fas","family":"Gonzalez-Sanchez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Facultad de Enfermer\u00eda y Fisioterapia, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Alonso-Dominguez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Facultad de Enfermer\u00eda y Fisioterapia, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5816-1494","authenticated-orcid":false,"given":"Natalia","family":"Sanchez-Aguadero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Facultad de Enfermer\u00eda y Fisioterapia, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3772-8746","authenticated-orcid":false,"given":"Jose I.","family":"Recio-Rodriguez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Facultad de Enfermer\u00eda y Fisioterapia, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","unstructured":"Arendt, J., and Aulinas, A. (2022). Physiology of the Pineal Gland and Melatonin. Endotext, MDText.com, Inc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1111\/j.1742-4658.2006.05322.x","article-title":"Melatonin: Nature\u2019s most versatile biological signal?","volume":"273","author":"Srinivasan","year":"2006","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.neuchi.2015.03.002","article-title":"Melatonin: Physiological effects in humans","volume":"61","author":"Claustrat","year":"2015","journal-title":"Neurochirurgie"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1210\/jcem-66-3-648","article-title":"Alterations in nocturnal serum melatonin levels in humans with growth and aging","volume":"66","author":"Waldhauser","year":"1988","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1210\/jcem-55-1-27","article-title":"Age-dependent reduction in serum melatonin concentrations in healthy human subjects","volume":"55","author":"Iguchi","year":"1982","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"B293","DOI":"10.1093\/gerona\/53A.4.B293","article-title":"Endogenous Melatonin Levels and the Fate of Exogenous Melatonin: Age Effects","volume":"53A","author":"Zhdanova","year":"1998","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3109\/07420528.2015.1112396","article-title":"Sex differences in the circadian profiles of melatonin and cortisol in plasma and urine matrices under constant routine conditions","volume":"33","author":"Gunn","year":"2016","journal-title":"Chronobiol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1177\/0748730410374943","article-title":"Sex Differences in Phase Angle of Entrainment and Melatonin Amplitude in Humans","volume":"25","author":"Cain","year":"2010","journal-title":"J. Biol. Rhythm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0165-1781(89)90047-4","article-title":"The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research [\u00cdndice de calidad del sue\u00f1o de Pittsburgh: Un nuevo instrumento para la pr\u00e1ctica y la investigaci\u00f3n psiqui\u00e1trica]","volume":"28","author":"Buysse","year":"1989","journal-title":"Psychiatry Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1093\/sleep\/26.3.342","article-title":"The role of actigraphy in the study of sleep and circadian rhythms","volume":"26","author":"Cole","year":"2003","journal-title":"Sleep"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kov\u00e1\u010dov\u00e1, K., and Stebelov\u00e1, K. (2021). Sleep Characteristics According to Gender and Age Measured by Wrist Actigraphy. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph182413213"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4103\/ijd.ijd_31_21","article-title":"The Association between Melatonin Levels and Sleep Quality in Patients with Pruritus: A Potential Biomarker on a Candidate Future Treatment","volume":"66","author":"Erdem","year":"2021","journal-title":"Indian J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Evans, A.T., Vanden Brink, H., Lim, J.S., Jarrett, B.Y., Lin, A.W., Lujan, M.E., and Hoeger, K. (2023). Overnight Melatonin Concentration and Sleep Quality Are Associated with the Clinical Features of Polycystic Ovary Syndrome. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102763"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.jsmc.2015.08.002","article-title":"Aging and circadian rhythms","volume":"10","author":"Duffy","year":"2015","journal-title":"Sleep. Med. Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13731","DOI":"10.1038\/s41598-020-70750-3","article-title":"Sex and race influence objective and self-report sleep and circadian measures in emerging adults independently of risk for bipolar spectrum disorder","volume":"10","author":"Titone","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101926","DOI":"10.1016\/j.smrv.2024.101926","article-title":"Sex differences in sleep, circadian rhythms, and metabolism: Implications for precision medicine","volume":"75","author":"Lok","year":"2024","journal-title":"Sleep Med. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1210\/er.2018-00084","article-title":"Melatonin as a Hormone: New Physiological and Clinical Insights","volume":"39","author":"Amaral","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40101-016-0103-9","article-title":"Annual variation in daily light exposure and circadian change of melatonin and cortisol concentrations at a northern latitude with large seasonal differences in photoperiod length","volume":"36","author":"Adamsson","year":"2016","journal-title":"J. Physiol. Anthropol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nogueira, L.M., Sampson, J.N., Chu, L.W., Yu, K., Andriole, G., Church, T., Stanczyk, F.Z., Koshiol, J., and Hsing, A.W. (2013). Individual Variations in Serum Melatonin Levels through Time: Implications for Epidemiologic Studies. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083208"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1158\/1055-9965.EPI-10-0004","article-title":"Measuring Serum Melatonin in Epidemiologic Studies","volume":"19","author":"Hsing","year":"2010","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"R52","DOI":"10.1186\/cc6871","article-title":"Melatonin therapy to improve nocturnal sleep in critically ill patients: Encouraging results from a small randomised controlled trial","volume":"12","author":"Bourne","year":"2008","journal-title":"Crit. Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00228-015-1873-4","article-title":"Clinical pharmacokinetics of melatonin: A systematic review","volume":"71","author":"Andersen","year":"2015","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"bvaf155","DOI":"10.1210\/jendso\/bvaf155","article-title":"Sex and Seasonal Variations in Melatonin Suppression and Alerting Response to Light","volume":"9","author":"Fazlali","year":"2025","journal-title":"J. Endocr. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e12936","DOI":"10.1111\/jpi.12936","article-title":"Greater sensitivity of the circadian system of women to bright light, but not dim-to-moderate light","volume":"76","author":"Vidafar","year":"2024","journal-title":"J. Pineal Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Paj\u0117dien\u0117, E., Urbonavi\u010di\u016bt\u0117, V., Ramanauskait\u0117, V., Strazdauskas, L., and Stefani, A. (2024). Sex Differences in Insomnia and Circadian Rhythm Disorders: A Systematic Review. Medicina, 60.","DOI":"10.3390\/medicina60030474"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1081\/CBI-120015958","article-title":"AGING AND THE CIRCADIAN RHYTHM OF MELATONIN: A CROSS-SECTIONAL STUDY OF CHINESE SUBJECTS 30\u2013110 YR OF AGE","volume":"19","author":"Zhao","year":"2002","journal-title":"Chronobiol. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S0531-5565(01)00120-6","article-title":"Human aging and melatonin. Clinical relevance","volume":"36","author":"Touitou","year":"2001","journal-title":"Exp. Gerontol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/j.1600-079X.2006.00365.x","article-title":"Seasonality of psychopathology and circannual melatonin rhythm","volume":"41","author":"Morera","year":"2006","journal-title":"J. Pineal Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s00415-020-10381-w","article-title":"Effect of melatonin supplementation on sleep quality: A systematic review and meta-analysis of randomized controlled trials","volume":"269","author":"Fatemeh","year":"2022","journal-title":"J. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"105799","DOI":"10.1016\/j.msard.2024.105799","article-title":"Impact of oral melatonin supplementation on urine and serum melatonin concentrations and quality-of-life measures in persons with relapsing multiple sclerosis","volume":"90","author":"Smoot","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_31","first-page":"20552173211048756","article-title":"Effects of melatonin on sleep disturbances in multiple sclerosis: A randomized, controlled pilot study","volume":"7","author":"Hsu","year":"2021","journal-title":"Mult. Scler. J. Exp. Transl. Clin."},{"key":"ref_32","unstructured":"Agencia Espa\u00f1ola de Seguridad Alimentaria y Nutrici\u00f3n (AESAN) (2026). Gu\u00eda Para el Control Oficial del Etiquetado y Composici\u00f3n de Complementos Alimenticios, Agencia Espa\u00f1ola de Seguridad Alimentaria y Nutrici\u00f3n (AESAN). Available online: https:\/\/www.aesan.gob.es\/AECOSAN\/docs\/documentos\/seguridad_alimentaria\/interpretaciones\/nutricionales\/Guia_etiquetado_composicion_CA_CI_15_marzo_2023.pdf."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Thanawala, S., Abiraamasundari, R., and Shah, R. (2024). Comparative Pharmacokinetics of Sustained-Release versus Immediate-Release Melatonin Capsules in Fasting Healthy Adults: A Randomized, Open-Label, Cross-Over Study. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16101248"},{"key":"ref_34","first-page":"575","article-title":"Melatonin in sleep disorders","volume":"37","author":"Poza","year":"2022","journal-title":"Neurol. (Engl. Ed.)"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sohrabi, M., Gholami, A., Hassanzadeh, P., Hatami, S., Ajdarkosh, H., Zamani, F., and Doustmohammadian, A. (2024). Examining the factor structure of the Pittsburgh Sleep Quality Index and its determinants among GI cancer patients. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-13347-7"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e29393","DOI":"10.1002\/pbc.29393","article-title":"A randomized double-blind placebo-controlled trial of the effectiveness of melatonin on neurocognition and sleep in survivors of childhood cancer","volume":"69","author":"Lubas","year":"2022","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1093\/sleep\/26.7.893","article-title":"A Multicenter, Placebo-controlled Trial of Melatonin for Sleep Disturbance in Alzheimer\u2019s Disease","volume":"26","author":"Singer","year":"2003","journal-title":"Sleep"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e069444","DOI":"10.1136\/bmjopen-2022-069444","article-title":"Analysis of the determinants of sleep quality in a Spanish population: A study protocol for a cross-sectional study","volume":"13","year":"2023","journal-title":"BMJ Open"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e012073","DOI":"10.1136\/bmjopen-2016-012073","article-title":"Nurses\u2019 sleep quality, work environment and quality of care in the Spanish National Health System: Observational study among different shifts","volume":"6","author":"Madrid","year":"2016","journal-title":"BMJ Open"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.jad.2013.05.017","article-title":"Psychometric properties of the List of Threatening Experiences\u2014LTE and its association with psychosocial factors and mental disorders according to different scoring methods","volume":"150","author":"Motrico","year":"2013","journal-title":"J. Affect. Disord."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.3945\/jn.110.135566","article-title":"A Short Screener Is Valid for Assessing Mediterranean Diet Adherence among Older Spanish Men and Women123","volume":"141","author":"Estruch","year":"2011","journal-title":"J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2147\/NSS.S151085","article-title":"Actigraphy-based sleep estimation in adolescents and adults: A comparison with polysomnography using two scoring algorithms","volume":"10","author":"Quante","year":"2018","journal-title":"Nat. Sci. Sleep"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/sleep\/15.5.461","article-title":"Automatic Sleep\/Wake Identification from Wrist Activity","volume":"15","author":"Cole","year":"1992","journal-title":"Sleep"},{"key":"ref_45","first-page":"53","article-title":"Fully automated waist-worn accelerometer algorithm for detecting children\u2019s sleep-period time separate from 24-h physical activity or sedentary behaviors","volume":"39","author":"Barreira","year":"2013","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_46","unstructured":"ActiGraph Support (2026, May 13). What Does the Detect Sleep Periods Button Do and How Does It Work. Available online: https:\/\/actigraphcorp.my.site.com\/support\/s\/article\/What-does-the-Detect-Sleep-Periods-button-do-and-how-does-it-work."},{"key":"ref_47","first-page":"81","article-title":"Propiedades clinim\u00e9tricas de la versi\u00f3n castellana del cuestionario de Pittsburgh","volume":"9","author":"Royuela","year":"1997","journal-title":"Vigilia-Sue\u00f1o"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"206","DOI":"10.31083\/ph.2019.8225","article-title":"An HPLC-DAD validated method for the detection and quantification of cortisol, corticosterone and melatonin in plasma samples of two different animal species","volume":"74","author":"Viljoen","year":"2019","journal-title":"Pharmazie"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6320\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:24:22Z","timestamp":1784193862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":48,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146320"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146320","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]}}}