{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:02:20Z","timestamp":1784869340422,"version":"3.55.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"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. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background\/objectives<\/jats:title>\n                    <jats:p>\n                      Coping strategies for menstruation-related symptoms are required to support women\u2019s health-related quality of life (QoL) and the continued social advancement of women. Previous studies have reported that short-term intake of\n                      <jats:italic>\u03b1<\/jats:italic>\n                      -lactalbumin (aLA) alleviates physical symptoms during menstruation. In this study, we investigated the effects of long-term intake of aLA on menstruation-related symptoms and QoL in healthy Japanese women.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A randomized, double-blind, placebo-controlled study was conducted. Participants were 140 healthy women aged 20\u201339\u202fyears and were randomly assigned to receive aLA (900\u202fmg\/day) or placebo for three menstrual cycles. Premenstrual and intramenstrual symptoms were assessed at each cycle. The primary outcome was subjective symptoms on the Menstrual Distress Questionnaire (MDQ), and secondary outcomes were the 36-Item Short Form Health Survey (SF-36), subjective symptoms on the Visual Analog Scale, and urinary prostaglandins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The primary outcome, the MDQ, showed no significant differences in the total score or the six factor scores between groups, either premenstrually or during menstruation. In exploratory analyses, aLA intake significantly alleviated the premenstrual MDQ sub-scores \u201cWeight gain\u201d and \u201cLowered motor coordination\u201d compared with placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05 for each). Among the secondary outcomes, aLA intake significantly improved the premenstrual role-related and social QoL scores on the SF-36 compared with placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). No significant group differences were observed for other items.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this trial, long-term aLA supplementation did not improve overall menstruation-related symptoms as assessed by the primary outcome. However, secondary outcomes indicated potential benefits in role-related and social aspects of premenstrual QoL. These findings are exploratory, requiring further studies for confirmation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/center6.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000063507<\/jats:ext-link>\n                      , UMIN-CTR UMIN000055576\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1892605","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:24:39Z","timestamp":1784867079000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of long-term intake of \u03b1-lactalbumin on menstruation-related symptoms and quality of life in healthy Japanese women: a randomized, double-blind, placebo-controlled study"],"prefix":"10.3389","volume":"13","author":[{"given":"Kentaro","family":"Ito","sequence":"first","affiliation":[{"name":"Division of Research and Development, Meiji Co., Ltd.","place":["Hachioji, Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kae","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Division of Research and Development, Meiji Co., Ltd.","place":["Hachioji, Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Natori","sequence":"additional","affiliation":[{"name":"Division of Research and Development, Meiji Co., Ltd.","place":["Hachioji, Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/s0306-4530(03)00099-4","article-title":"Premenstrual syndrome and premenstrual dysphoric disorder: definitions and diagnosis","volume":"28","author":"Freeman","year":"2003","journal-title":"Psychoneuroendocrinology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1093\/humrep\/deae081","article-title":"Global, regional, and National Burden of premenstrual syndrome, 1990-2019: an analysis based on the global burden of disease study 2019","volume":"39","author":"Liu","year":"2024","journal-title":"Hum Reprod"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"569.e1","DOI":"10.1016\/j.ajog.2019.02.048","article-title":"The impact of menstrual symptoms on everyday life: a survey among 42,879 women","volume":"220","author":"Schoep","year":"2019","journal-title":"Am J Obstet Gynecol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1258\/mi.2012.012014","article-title":"Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder","volume":"18","author":"Rapkin","year":"2012","journal-title":"Menopause 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Gynaecol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/s0002-9378(84)80039-3","article-title":"Prostaglandin synthetase inhibitors in the treatment of primary dysmenorrhea. 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Further validation of the Sds","volume":"13","author":"Zung","year":"1965","journal-title":"Arch Gen Psychiatry"},{"key":"ref30","first-page":"97","article-title":"Research on instrument development. Commentary: a discriminative chart as a screening test of neurotics by cmi (Cornell medical index)","volume":"17","author":"Fukamachi","year":"1984","journal-title":"Kango Kenkyu"},{"key":"ref31","first-page":"72","article-title":"Investigation on stress-induced condition of healthy people","volume":"1","author":"Murakami","year":"1989","journal-title":"Psychosom Ther"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1097\/00006842-196811000-00006","article-title":"The development of a menstrual distress questionnaire","volume":"30","author":"Moos","year":"1968","journal-title":"Psychosom Med"},{"key":"ref33","first-page":"33","article-title":"Menstrual symptoms and life style of the nursing students","volume":"17","author":"Hattori","year":"1997","journal-title":"Annu Rep Coll Med Technol Kyoto Univ"},{"key":"ref34","first-page":"524","article-title":"Menstrual symptoms and depression of female nursing students","volume":"16","author":"Hattori","year":"1998","journal-title":"Adolescentology"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1260645","DOI":"10.3389\/fgwh.2023.1260645","article-title":"Menstruation-related symptoms are associated with physical activity and midpoint of sleep: a pilot study","volume":"4","author":"Masuda","year":"2023","journal-title":"Front Glob Womens Health"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1007\/s12325-022-02118-0","article-title":"Menstrual symptoms, health-related quality of life, and work productivity in Japanese women with dysmenorrhea receiving different treatments: prospective observational study","volume":"39","author":"Yoshino","year":"2022","journal-title":"Adv Ther"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1016\/s0895-4356(98)00095-x","article-title":"Translation, adaptation, and validation of the sf-36 health survey for use in Japan","volume":"51","author":"Fukuhara","year":"1998","journal-title":"J Clin Epidemiol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/s0895-4356(98)00096-1","article-title":"Psychometric and clinical tests of validity of the Japanese sf-36 health survey","volume":"51","author":"Fukuhara","year":"1998","journal-title":"J Clin Epidemiol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.jclinepi.2010.04.017","article-title":"Validation testing of a three-component model of Short Form-36 scores","volume":"64","author":"Suzukamo","year":"2011","journal-title":"J Clin Epidemiol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.jad.2011.06.058","article-title":"The premenstrual tension syndrome rating scales: an updated version","volume":"135","author":"Steiner","year":"2011","journal-title":"J Affect Disord"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s00737-006-0137-9","article-title":"Prevalence of premenstrual syndrome and premenstrual dysphoric disorder in Japanese women","volume":"9","author":"Takeda","year":"2006","journal-title":"Arch Womens Ment Health"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"S298","DOI":"10.1016\/j.gaceta.2021.10.039","article-title":"The influence of macronutrient intake, stress and prostaglandin levels (PGF2\u03b1) of urine with the incidence of dysmenorrhea in adolescents","volume":"35","author":"Tahir","year":"2021","journal-title":"Gac Sanit"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1111\/jog.15914","article-title":"The influence of physical activity, body mass index and urinary levels of prostaglandin (PGF2\u03b1) with the incidence of primary dysmenorrhea in adolescents","volume":"50","author":"Jusuf","year":"2024","journal-title":"J Obstet Gynaecol Res"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1194\/jlr.D090571","article-title":"Quantitative metabolic profiling of urinary eicosanoids for clinical phenotyping","volume":"60","author":"G\u00f3mez","year":"2019","journal-title":"J Lipid Res"},{"key":"ref45","volume-title":"Sample Sizes for Clinical, Laboratory and Epidemiology Studies","author":"Machin","year":"2022"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1176\/ajp.156.9.1403","article-title":"Characteristics of placebo responses in medical treatment of premenstrual syndrome","volume":"156","author":"Freeman","year":"1999","journal-title":"Am J Psychiatry"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e202907","DOI":"10.1001\/jamanetworkopen.2020.2907","article-title":"Effect of treatment expectation on placebo response and analgesic efficacy: a secondary aim in a randomized clinical 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