{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T15:02:47Z","timestamp":1789570967768,"version":"build-2803163510"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Sleep"],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Non-restorative sleep is frequently associated with disturbances in circadian regulation, impaired sleep quality, and reduced daytime functioning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This randomized, double-blind, active-controlled, cross over study compared black cumin oil extract (TD; 200 mg) with synthetic melatonin (s-Mel; 5 mg\/day) in 24 individuals with non-restorative sleep. Participants received each intervention for 7 nights separated by a 7-day washout period. Plasma melatonin was measured at fixed nighttime intervals under dim light to determine dim-light melatonin onset (DLMO), while sleep parameters were assessed using actigraphy. DLMO serves as an important physiological marker of circadian timing. Daytime sleepiness was evaluated with the Epworth Sleepiness Scale (ESS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both interventions significantly increased nocturnal plasma melatonin concentration under dim-light conditions (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). TD was associated with an earlier attainment of the predefined plasma melatonin threshold of 10 pg\/mL.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The interpretation of the corresponding threshold timing in the s-Mel arm was limited due to exogenous melatonin administration. s-Mel induced a rapid early rise in melatonin followed by a sharp decline, whereas TD demonstrated a more sustained nocturnal profile. Actigraphy outcomes were generally comparable; sleep latency and total sleep time improved more with s-Mel, while TD significantly reduced cortisol levels and daytime sleepiness. Overall, TD showed earlier threshold attainment, cortisol reduction, and improved daytime alertness, supporting its potential as a natural alternative for circadian disruption and non-restorative sleep.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/ctri.nic.in\/Clinicaltrials\/pmaindet2.php?EncHid=MTExNTY4&amp;amp;Enc=&amp;amp;userName=<\/jats:ext-link>\n                      CTRI\/2024\/11\/077454 dated 28\/11\/2024.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/frsle.2026.1879110","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:33:49Z","timestamp":1789101229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Responsiveness of ThymoDream\u00ae as a natural modulator of the circadian axis: a comparative RCT with melatonin supplementation employing melatonin profiling and actigraphy"],"prefix":"10.3389","volume":"5","author":[{"given":"C. S.","family":"Harshith","sequence":"first","affiliation":[{"name":"BGS Global Institute of Medical Sciences, Bangalore","place":["Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas V.","family":"Jestin","sequence":"additional","affiliation":[{"name":"Leads Clinical Research and Bio Services Pvt. Ltd, Bangalore","place":["Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Das S.","family":"Syam","sequence":"additional","affiliation":[{"name":"Akay Natural Ingredients Private Limited, Kochi","place":["Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhakaran","family":"Prathibha","sequence":"additional","affiliation":[{"name":"Akay Natural Ingredients Private Limited, Kochi","place":["Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithyanandam","family":"Allimuthu","sequence":"additional","affiliation":[{"name":"Tamil Nadu Government Multi Super Specialty Hospital","place":["Chennai, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Abhirami","sequence":"additional","affiliation":[{"name":"Translational Nanomedicine and Lifestyle Disease Research Laboratory, Department of Biochemistry, University of Kerala, Thiruvananthapuram","place":["Kerala, India"]},{"name":"Department of Biochemistry, University of Kerala, Thiruvananthapuram","place":["Kerala, India"]},{"name":"Centre for Advanced Cancer Research, Department of Biochemistry, University of Kerala, Thiruvananthapuram","place":["Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Radhika","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Government Arts and Science College, Kulathoor, Thiruvananthapuram","place":["Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. 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