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In this study, we determined whether 5-aminolevulinic acid (5-ALA) supplementation alleviates the feeling of fatigue in healthy subjects who feel chronic physical tiredness. Males and females between ages of 20 and 64 who felt physical fatigue on a daily basis, with a visual analogue scale (VAS) for fatigue\u2009\u2265\u200940\u00a0mm, a T-score of Fatigue-Inertia in the Profile of Mood States\u2014Second Edition\u2014Adult (POMS2-A)\u2009\u2265\u200950, and a T-score of Vigor-Activity in POMS2-A\u2009\u2264\u200960 were recruited. Seventy eligible participants were randomly assigned to either a 5-ALA or a placebo group. During the 8\u00a0weeks of consumption, the subjects completed VAS questionnaires for fatigue and POMS2-A at 4-week intervals. The VAS values for overall feeling of fatigue and feeling of work-related fatigue, and the Anger-Hostility subscale of POMS2-A were decreased by 5-ALA with significant time\u2009\u00d7\u2009group interaction effects (<jats:italic>p<\/jats:italic>\u2009=\u20090.040, 0.020, and 0.045, respectively). Besides, the 5-ALA group showed significant differences in Fatigue-Inertia, Depression-Dejection and Total Mood Disturbance scores, when compared between pre- and post-intervention, while the placebo group did not. In conclusion, the oral administration of 5-ALA improves fatigue and negative mood in subjects who constantly feel physical fatigue.<\/jats:p><jats:p>This clinical trial was registered with University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as UMIN000031528 on 2\/3\/2018.<\/jats:p>","DOI":"10.1038\/s41598-020-72763-4","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T10:03:40Z","timestamp":1601373820000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Reduction of fatigue and anger-hostility by the oral administration of 5-aminolevulinic acid phosphate: a randomized, double-blind, placebo-controlled, parallel study"],"prefix":"10.1038","volume":"10","author":[{"given":"Fumiko","family":"Higashikawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishi","family":"Kanno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Ogata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"72763_CR1","doi-asserted-by":"publisher","first-page":"e027070","DOI":"10.1136\/bmjopen-2018-027070","volume":"9","author":"C Galland-Decker","year":"2019","unstructured":"Galland-Decker, C., Marques-Vidal, P. & Vollenweider, P. 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