{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T11:12:40Z","timestamp":1773745960673,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"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>Background\/Objectives: Fatigue and reduced motivation impair daily functioning and quality of life. Homocysteine (Hcy) has been implicated in oxidative stress and one\u2013carbon metabolism, but its relationship with fatigue\u2013related outcomes remains unclear. We explored associations between plasma Hcy and fatigue-related measures in healthy adults. Methods: We analyzed cross\u2013sectional data from 602 community\u2013dwelling adults. Plasma Hcy concentrations were categorized into sex\u2212specific tertiles. Fatigue and motivation were assessed using the Chalder Fatigue Scale and a visual analog scale (VAS). Sex\u2212stratified multivariable linear models adjusted for lifestyle and biochemical covariates were used to examine associations. Sensitivity analyses additionally modeled Hcy as a continuous variable. Results: Higher Hcy tertiles were associated with lower serum folate and vitamin B12 concentrations in both sexes (p &lt; 0.001). In men, the lowest Hcy tertile was associated with lower Chalder physical fatigue scores, whereas in women the highest Hcy tertile was associated with lower VAS motivation scores in multivariable analyses. Pairwise contrasts indicated higher physical fatigue in men in the highest tertile compared with the lowest (T3\u2013T1: 1.55; 95% CI 0.24\u20132.86; p = 0.022) and lower motivation in women (T3\u2013T1: \u22125.62; 95% CI \u221210.65 to \u22120.59; p = 0.029). However, no significant associations were observed when Hcy was modeled as a continuous variable. Conclusions: In this exploratory cross\u2212sectional analysis, plasma Hcy showed associations with fatigue\u2212related outcomes in sex\u2212stratified analyses. These findings should be interpreted cautiously and considered hypothesis\u2013generating. Longitudinal and mechanistic studies are needed to clarify potential causal relationships.<\/jats:p>","DOI":"10.3390\/nu18060941","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T10:21:41Z","timestamp":1773742901000},"page":"941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations of Plasma Homocysteine Reflecting Vitamin B12 and Folate Status with Fatigue-Related Outcomes in Healthy Adults"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-1502","authenticated-orcid":false,"given":"Hiroaki","family":"Kanouchi","sequence":"first","affiliation":[{"name":"Department of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan University, Osaka 536-8525, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan University, Osaka 536-8525, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Kuwabara","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan University, Osaka 536-8525, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2519-9549","authenticated-orcid":false,"given":"Shigeo","family":"Takenaka","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan University, Osaka 536-8525, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Nishikubo","sequence":"additional","affiliation":[{"name":"Alinamin Pharmaceutical Co., Ltd., Tokyo 100-0005, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihiro","family":"Nomura","sequence":"additional","affiliation":[{"name":"Alinamin Pharmaceutical Co., Ltd., Tokyo 100-0005, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiro","family":"Naruto","sequence":"additional","affiliation":[{"name":"Alinamin Pharmaceutical Co., Ltd., Tokyo 100-0005, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6261-5690","authenticated-orcid":false,"given":"Kyosuke","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Kobe University Graduate School of Science, Technology and Innovation, Osaka 530-0011, Japan"},{"name":"Center for Health Science Innovation, Osaka Metropolitan University, Osaka 558-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Kobe University Graduate School of Science, Technology and Innovation, Osaka 530-0011, Japan"},{"name":"Center for Health Science Innovation, Osaka Metropolitan University, Osaka 558-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyoshi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Kobe University Graduate School of Science, Technology and Innovation, Osaka 530-0011, Japan"},{"name":"Center for Health Science Innovation, Osaka Metropolitan University, Osaka 558-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.brainresrev.2008.07.001","article-title":"Mental fatigue: Costs and benefits","volume":"59","author":"Boksem","year":"2008","journal-title":"Brain Res. 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