{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:29:59Z","timestamp":1777364999166,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T00:00:00Z","timestamp":1519776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Severe fatigue can negatively affect quality of life, and oxidative stress may play a role in its mechanism. The aim of this study was to evaluate the effect of dietary supplementation of astaxanthin and sesamin (AS), strong food-derived antioxidants, on fatigue. Twenty-four healthy volunteers were supplemented with AS and placebo, each for four weeks. After each supplementation period, participants underwent tasks inducing mental and physical fatigue (visual display terminal task and ergometer task, respectively). Subjective fatigue was evaluated using a visual analogue scale during and after the mental and physical tasks, and daily subjective fatigue was evaluated by the Chalder fatigue questionnaire. Secondary outcomes included other subjective feelings, work efficiency, autonomic nerve activity, levels of an oxidative stress marker (plasma phosphatidylcholine hydroperoxide (PCOOH)) and safety. AS supplementation was associated with significantly improved recovery from mental fatigue compared with placebo. Increased PCOOH levels during mental and physical tasks were attenuated by AS supplementation. No differences between AS and placebo were detected in secondary outcomes, and no adverse effects of AS supplementation were observed. In conclusion, AS supplementation may be a candidate to promote recovery from mental fatigue which is experienced by many healthy people.<\/jats:p>","DOI":"10.3390\/nu10030281","type":"journal-article","created":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T12:54:12Z","timestamp":1519822452000},"page":"281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Effects of Dietary Supplementation of Astaxanthin and Sesamin on Daily Fatigue: A Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study"],"prefix":"10.3390","volume":"10","author":[{"given":"Ayano","family":"Imai","sequence":"first","affiliation":[{"name":"Pharmaceutical and Healthcare Research Laboratories, Research and Development Management Headquarters, FUJIFILM Corporation, 577, Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuriko","family":"Oda","sequence":"additional","affiliation":[{"name":"Pharmaceutical and Healthcare Research Laboratories, Research and Development Management Headquarters, FUJIFILM Corporation, 577, Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-8494","authenticated-orcid":false,"given":"Naoki","family":"Ito","sequence":"additional","affiliation":[{"name":"Pharmaceutical and Healthcare Research Laboratories, Research and Development Management Headquarters, FUJIFILM Corporation, 577, Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinobu","family":"Seki","sequence":"additional","affiliation":[{"name":"Pharmaceutical and Healthcare Research Laboratories, Research and Development Management Headquarters, FUJIFILM Corporation, 577, Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyotaka","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 980-0845, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruo","family":"Miyazawa","sequence":"additional","affiliation":[{"name":"Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 980-0845, Japan"},{"name":"New Industry Creation Hatchery Center (NICHe), Tohoku University, Sendai 980-8579, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumitaka","family":"Ueda","sequence":"additional","affiliation":[{"name":"Pharmaceutical and Healthcare Research Laboratories, Research and Development Management Headquarters, FUJIFILM Corporation, 577, Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1139\/y91-043","article-title":"Free radicals may contribute to oxidative skeletal muscle fatigue","volume":"69","author":"Barclay","year":"1991","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1080\/10253890400012685","article-title":"Oxidative stress in university students during examinations","volume":"7","year":"2004","journal-title":"Stress"},{"key":"ref_3","first-page":"450","article-title":"Chronic fatigue syndrome: Oxidative stress and dietary modifications","volume":"6","author":"Logan","year":"2001","journal-title":"Altern. Med. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1016\/S0024-3205(01)01001-3","article-title":"Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome","volume":"68","author":"Moorkens","year":"2001","journal-title":"Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0304-3940(02)01058-3","article-title":"Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome","volume":"335","author":"Vecchiet","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1017\/S0007114510005398","article-title":"Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes","volume":"105","author":"Nakagawa","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1093\/clinchem\/41.12.1819","article-title":"Lipid-peroxidation and antioxidants as biomarkers of tissue-damage","volume":"41","author":"Gutteridge","year":"1995","journal-title":"Clin. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1080\/15421406.2013.804380","article-title":"Anti-oxidative properties of astaxanthin and related compounds","volume":"580","author":"Mori","year":"2013","journal-title":"Mol. Cryst. Liq. Cryst."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1021\/jf991106k","article-title":"Antioxidant activities of astaxanthin and related carotenoids","volume":"48","author":"Naguib","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_10","first-page":"7146","article-title":"Anti-inflammatory compounds of macro algae origin: A review","volume":"5","author":"Jaswir","year":"2011","journal-title":"J. Med. Plants Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.18388\/abp.2012_2168","article-title":"Cosmetic benefits of astaxanthin on humans subjects","volume":"59","author":"Tominaga","year":"2012","journal-title":"Acta Biochim. Pol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1743-7075-7-18","article-title":"Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans","volume":"7","author":"Park","year":"2010","journal-title":"Nutr. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1248\/bpb.28.47","article-title":"Antihypertensive and neuroprotective effects of astaxanthin in experimental animals","volume":"28","author":"Hussein","year":"2005","journal-title":"Biol. Pharm. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1194\/jlr.D004564","article-title":"LC-MS\/MS analysis of carboxymethylated and carboxyethylated phosphatidylethanolamines in human erythrocytes and blood plasma","volume":"51","author":"Shoji","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1590\/S0104-66322012000200020","article-title":"Extraction, fatty acid profile and antioxidant activity of sesame extract (Sesamum Indicum L.)","volume":"29","author":"Carvalho","year":"2012","journal-title":"Braz. J. Chem. Eng."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.foodchem.2007.05.023","article-title":"Ghafoorunissa Sesame lignans enhance the thermal stability of edible vegetable oils","volume":"105","author":"Hemalatha","year":"2007","journal-title":"Food Chem."},{"key":"ref_17","first-page":"61","article-title":"Daily fatigue-reducing effect of astaxathin\u2014A randomized, placebo-controlled, double-blind, parallel-group study","volume":"45","author":"Hongo","year":"2017","journal-title":"Jpn. Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5539\/gjhs.v7n6p1","article-title":"Sesame lignans and vitamin E supplementation improve subjective statuses and anti-oxidative capacity in healthy humans with feelings of daily fatigue","volume":"7","author":"Takemoto","year":"2015","journal-title":"Glob. J. Health Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0928-0987(03)00135-0","article-title":"Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations","volume":"19","author":"Odebarg","year":"2003","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/S0955-2863(00)00104-2","article-title":"Plasma appearance and distribution of astaxanthin E\/Z and R\/S isomers in plasma lipoproteins of men after single dose administration of astaxanthin","volume":"11","author":"Osterlie","year":"2000","journal-title":"J. Nutr. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1600844","DOI":"10.1002\/mnfr.201600844","article-title":"Absorption, distribution, metabolism, and excretion of [14 C]sesamin in rats","volume":"61","author":"Tomimori","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_22","first-page":"733","article-title":"Development of guideline of clinical evaluation of anti-fatigue","volume":"228","author":"Hirayama","year":"2009","journal-title":"J. Clin. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0022-3999(93)90081-P","article-title":"Development of a fatigue scale","volume":"37","author":"Chalder","year":"1993","journal-title":"J. Psychosom. Res."},{"key":"ref_24","unstructured":"Yokoyama, K., and Watanabe, K. (2015). Japanese Translation of POMS 2: Profile of Mood States Second Edition, Kaneko Shobo."},{"key":"ref_25","first-page":"401","article-title":"Standardization of revised version of OSA sleep inventory for middle age and aged","volume":"10","author":"Yamamoto","year":"1999","journal-title":"Brain Sci. Ment. Disord."},{"key":"ref_26","first-page":"199","article-title":"Effect of CBEX-Dr-containing drink on physical fatigue in healthy volunteers","volume":"36","author":"Tanaka","year":"2008","journal-title":"Jpn. Pharmacol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.nut.2007.12.002","article-title":"Effects of oral administration of caffeine and D-ribose on mental fatigue","volume":"24","author":"Ataka","year":"2008","journal-title":"Nutrition"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1002\/art.1780290714","article-title":"The face scale: A brief, nonverbal method for assessing patient mood","volume":"29","author":"Lorish","year":"1986","journal-title":"Arthritis Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"373","DOI":"10.7143\/jhep.35.373","article-title":"The acceleration plethysmography system as a new physiological technology for evaluating autonomic modulations","volume":"35","author":"Takada","year":"2008","journal-title":"Health Eval. Promot."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1037\/h0043688","article-title":"Age differences in short-term retention of rapidly changing information","volume":"55","author":"Kirchner","year":"1958","journal-title":"J. Exp. Psychol."},{"key":"ref_31","unstructured":"Mizuno, K., and Watanabe, Y. (2008). Utility of an advanced trail making test as a neuropsychological tool for an objective evaluation of work efficiency during mental fatigue. Fatigue Science for Human Health, Springer."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/02640418508729750","article-title":"Determination of the peak power output during maximal brief pedalling bouts","volume":"3","author":"Nakamura","year":"1985","journal-title":"J. Sports Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"547","DOI":"10.7143\/jhep.31.547","article-title":"An evaluation method for heart rate variability, by using acceleration plethysmography","volume":"31","author":"Takada","year":"2004","journal-title":"Health Eval. Promot."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart rate variability: Standards of measurement, physiological interpretation, and clinical use","volume":"17","author":"Malik","year":"1996","journal-title":"Eur. Heart J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipids from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ab.2014.10.017","article-title":"Liquid chromatography-tandem mass spectrometry determination of human plasma 1-palmitoyl-2-hydroperoxyoctadecadienoyl-phosphatidylcholine isomers via promotion of sodium adduct formation","volume":"471","author":"Kato","year":"2015","journal-title":"Anal. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2486\/indhealth.37.157","article-title":"Occupational stress in human computer interaction","volume":"37","author":"Smith","year":"1999","journal-title":"Ind. Health"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1096\/fj.08-123281","article-title":"Astaxanthin reduces ischemic brain injury in adult rats","volume":"23","author":"Shen","year":"2009","journal-title":"FASEB J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jss.2014.05.029","article-title":"Astaxanthin offers neuroprotection and reduces neuroinflammation in experimental subarachnoid hemorrhage","volume":"192","author":"Zhang","year":"2014","journal-title":"J. Surg. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3171\/2014.2.JNS13730","article-title":"Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage","volume":"121","author":"Zhang","year":"2014","journal-title":"J. Neurosurg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.fct.2010.10.029","article-title":"Astaxanthin protects against MPTP\/MPP+-induced mitochondrial dysfunction and ROS production in vivo and in vitro","volume":"49","author":"Lee","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Katakura, Y., Totsuka, M., Imabayashi, E., Matsuda, H., and Hisatsune, T. (2017). Anserine\/carnosine supplementation suppresses the expression of the inflammatory chemokine CCL24 in peripheral blood mononuclear cells from elderly people. Nutrients, 9.","DOI":"10.3390\/nu9111199"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"540","DOI":"10.12659\/MSM.883971","article-title":"Effects of chicken essence on recovery from mental fatigue in healthy males","volume":"19","author":"Yamano","year":"2013","journal-title":"Med. Sci. Monit."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1007\/s11926-007-0078-y","article-title":"Chronic fatigue syndrome: Inflammation, immune function, and neuroendocrine interactions","volume":"9","author":"Klimas","year":"2007","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1248\/bpb.29.2106","article-title":"Effects of astaxanthin supplementation on exercise-induced fatigue in mice","volume":"29","author":"Ikeuchi","year":"2006","journal-title":"Biol. Pharm. Bull."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.bbrc.2007.12.019","article-title":"Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPT I modification","volume":"366","author":"Aoi","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1055\/s-2003-42010","article-title":"Protective effect of sesamin administration on exercise-induced lipid peroxidation","volume":"24","author":"Ikeda","year":"2003","journal-title":"Int. J. Sports Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/biof.552210139","article-title":"Antioxidative roles of sesamin, a functional lignan in sesame seed, and it\u2019s effect on lipid- and alcohol-metabolism in the liver: A DNA microarray study","volume":"21","author":"Kiso","year":"2004","journal-title":"Biofactors"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1021\/jf0258961","article-title":"Novel antioxidative metabolites in rat liver with ingested sesamin","volume":"51","author":"Nakai","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0952-3278(98)90112-0","article-title":"Dietary \u03b1-linolenic acid increases TNF-\u03b1, and decreases IL-6, IL-10 in response to LPS: Effects of sesamin on the \u0394-5 desaturation of \u03c96 and \u03c93 fatty acids in mice","volume":"58","author":"Chavali","year":"1998","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1097\/00001756-200310060-00011","article-title":"Effect of sesame antioxidants on LPS-induced NO production by BV2 microglial cells","volume":"14","author":"Hou","year":"2003","journal-title":"Neuroreport"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"284","DOI":"10.59566\/IJBS.2006.2284","article-title":"Neuroprotective effects of sesamin and sesamolin on gerbil brain in cerebral ischemia","volume":"2","author":"Cheng","year":"2006","journal-title":"Int. J. Biomed. Sci."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/3\/281\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:56:54Z","timestamp":1760194614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/3\/281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,28]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["nu10030281"],"URL":"https:\/\/doi.org\/10.3390\/nu10030281","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,28]]}}}