{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:38:34Z","timestamp":1788266314559,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kuhnil Pharmacy, Seoul, Korea","award":["YUHS 4-2016-0418"],"award-info":[{"award-number":["YUHS 4-2016-0418"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Melatonin is a hormone produced in the pineal gland that controls sleep and circadian rhythm. Some studies have reported antioxidant and anti-inflammatory effects of melatonin that could benefit cardiometabolic function; however, there is a lack of evidence to support these assertions. The aim of this study was to investigate whether melatonin has beneficial effects on arterial stiffness and mitochondrial deoxyribonucleic acid (DNA) in humans. Methods: This study was designed as a double-blind randomized controlled study. Thirty-eight healthy women aged 55 years and older were enrolled. All had insomnia (Pittsburgh Sleep Quality Index (PSQI) \u2265 5), not treated with any medications, for at least three months before enrollment. Subjects were divided into a melatonin and a placebo group according to melatonin supplementation. The melatonin group took 2 mg melatonin every night for six weeks. The cardio\u2013ankle vascular index (CAVI) was used as an indicator of arterial stiffness. After six weeks, CAVI, mitochondrial DNA (mtDNA) copy number in white blood cells (WBCs), and other metabolic indices, such as homeostasis model assessment of insulin resistance (HOMA-IR), were checked. Results: Sleep quality index using PSQI was improved in the melatonin group from a score of 11 to 8 (p = 0.01), but did not change significantly in the control group. However, there was no significant intergroup difference in PSQI. Systolic blood pressure (SBP) decreased in the melatonin group from 135 to 128 mmHg (p = 0.015), while remaining stable in the placebo group. Right CAVI, mitochondrial DNA copy number, and HOMA-IR were not altered in either group. There were no intergroup differences in CAVI, mtDNA, HOMA-IR, or SBP between baseline and week six. Conclusions: We found no evidence that melatonin supplementation improved cardiometabolic parameters like arterial stiffness, mtDNA, or insulin resistance compared to the placebo between baseline and week six. Sleep quality was improved in the melatonin group. Further research, including longer-term studies with higher doses of melatonin, is warranted.<\/jats:p>","DOI":"10.3390\/ijerph18052561","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T21:58:07Z","timestamp":1614895087000},"page":"2561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Melatonin Supplementation for Six Weeks Had No Effect on Arterial Stiffness and Mitochondrial DNA in Women Aged 55 Years and Older with Insomnia: A Double-Blind Randomized Controlled Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9965-675X","authenticated-orcid":false,"given":"Yonghwan","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Family Medicine, Chungbuk National University Hospital, Cheongju 28644, Korea"},{"name":"Department of Medicine, Graduate School, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8048-6247","authenticated-orcid":false,"given":"Hee-Taik","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Chungbuk National University Hospital, Cheongju 28644, Korea"},{"name":"Department of Family Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duk-Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"995","DOI":"10.2165\/00023210-200721120-00004","article-title":"Role of the melatonin system in the control of sleep","volume":"21","author":"Srinivasan","year":"2007","journal-title":"CNS Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"228","DOI":"10.2174\/157015910792246155","article-title":"Antiinflammatory activity of melatonin in central nervous system","volume":"8","author":"Esposito","year":"2010","journal-title":"Curr. Neuropharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18388\/abp.2007_3264","article-title":"Melatonin and its metabolites: New findings regarding their production and their radical scavenging actions","volume":"54","author":"Reiter","year":"2007","journal-title":"Acta Biochim. Pol. Engl. Ed."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.phrs.2012.01.003","article-title":"New perspectives in melatonin uses","volume":"65","author":"Carpentieri","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.18388\/abp.2003_3637","article-title":"Melatonin as an antioxidant: Biochemical mechanisms and pathophysiological implications in humans","volume":"50","author":"Reiter","year":"2003","journal-title":"Acta Biochim. Pol. Engl. Ed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1159\/000324699","article-title":"Melatonin and the metabolic syndrome: Physiopathologic and therapeutical implications","volume":"93","author":"Cardinali","year":"2011","journal-title":"Neuroendocrinology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/j.clnu.2017.11.003","article-title":"Effects of melatonin supplementation on blood lipid concentrations: A systematic review and meta-analysis of randomized controlled trials","volume":"37","author":"Ghorbani","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1600-079X.2010.00835.x","article-title":"Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome","volume":"50","author":"Poliwczak","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1748-1716.2012.02410.x","article-title":"Melatonin and the metabolic syndrome: A tool for effective therapy in obesity-associated abnormalities?","volume":"205","author":"Nduhirabandi","year":"2012","journal-title":"Acta Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1600-079X.2011.00928.x","article-title":"Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats","volume":"52","author":"Agil","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_11","first-page":"577","article-title":"Effect of melatonin on nocturnal blood pressure: Meta-analysis of randomized controlled trials","volume":"7","author":"Grossman","year":"2011","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s11154-009-9117-5","article-title":"Role of melatonin in metabolic regulation","volume":"10","author":"Korkmaz","year":"2009","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"947","DOI":"10.2741\/2116","article-title":"Melatonin role in the mitochondrial function","volume":"12","author":"Escames","year":"2007","journal-title":"Front. Biosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.lfs.2004.03.003","article-title":"Melatonin and mitochondrial function","volume":"75","author":"Leon","year":"2004","journal-title":"Life Sci."},{"key":"ref_15","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","volume":"28","author":"Buysse","year":"1989","journal-title":"Psychiatry Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101","DOI":"10.5551\/jat.13.101","article-title":"A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI)","volume":"13","author":"Shirai","year":"2006","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wong, A., and Cortopassi, G. (2002). Reproducible Quantitative PCR of Mitochondrial and Nuclear DNA Copy Number Using the LightCycler\u2122. Mitochondrial DNA, Springer.","DOI":"10.1385\/1-59259-284-8:129"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/j.1365-2869.2007.00613.x","article-title":"Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects","volume":"16","author":"Lemoine","year":"2007","journal-title":"J. Sleep Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1161\/01.HYP.0000113293.15186.3b","article-title":"Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension","volume":"43","author":"Scheer","year":"2004","journal-title":"Hypertension"},{"key":"ref_22","first-page":"669","article-title":"The effect of melatonin on circadian blood pressure in patients with type 2 diabetes and essential hypertension","volume":"10","author":"Wojdan","year":"2014","journal-title":"Arch. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1600-079X.2007.00518.x","article-title":"Cardiovascular diseases: Protective effects of melatonin","volume":"44","author":"Tengattini","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/j.1600-079X.2007.00490.x","article-title":"Melatonin protects against common deletion of mitochondrial DNA-augmented mitochondrial oxidative stress and apoptosis","volume":"43","author":"Jou","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1210\/jc.2014-1262","article-title":"Association between urinary 6-sulfatoxymelatonin excretion and arterial stiffness in the general elderly population: The HEIJO-KYO cohort","volume":"99","author":"Obayashi","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.maturitas.2014.03.010","article-title":"Urine 6-sulfatoxymelatonin levels are inversely associated with arterial stiffness in post-menopausal women","volume":"78","author":"Lee","year":"2014","journal-title":"Maturitas"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Namekata, T., Suzuki, K., Ishizuka, N., and Shirai, K. (2011). Establishing baseline criteria of cardio-ankle vascular index as a new indicator of arteriosclerosis: A cross-sectional study. BMC Cardiovasc. Disord., 11.","DOI":"10.1186\/1471-2261-11-51"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"924","DOI":"10.5551\/jat.7716","article-title":"Cardio-ankle vascular index (CAVI) as a novel indicator of arterial stiffness: Theory, evidence and perspectives","volume":"18","author":"Shirai","year":"2011","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1185\/030079907X233098","article-title":"Efficacy of prolonged release melatonin in insomnia patients aged 55\u201380 years: Quality of sleep and next-day alertness outcomes","volume":"23","author":"Wade","year":"2007","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1161\/HYPERTENSIONAHA.109.148254","article-title":"Effects of melatonin and Pycnogenol on small artery structure and function in spontaneously hypertensive rats","volume":"55","author":"Rezzani","year":"2010","journal-title":"Hypertension"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ferracioli-Oda, E., Qawasmi, A., and Bloch, M.H. (2013). Meta-analysis: Melatonin for the treatment of primary sleep disorders. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063773"},{"key":"ref_32","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":"53","author":"Zhdanova","year":"1998","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med Sci."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/5\/2561\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:32:49Z","timestamp":1760160769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/5\/2561"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,4]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijerph18052561"],"URL":"https:\/\/doi.org\/10.3390\/ijerph18052561","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,4]]}}}