{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:15:21Z","timestamp":1790082921838,"version":"4.0.1"},"reference-count":24,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2026-1304_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Serum total homocysteine (tHcy) is interpreted against fixed reference intervals and a decision limit. Whether the month of blood collection is a material source of variation, and whether it reflects the seasonal cycle of 25-hydroxyvitamin D [25(OH)D], is unresolved because earlier studies were cross-sectional or\u00a0small.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-1304_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed 268,877\u00a0health-screening examinations from 69,131 adults between January 2014 and December 2025 at a single Korean centre. Because no participant was examined twice in a calendar year, within-person seasonal contrasts span years; all models therefore combined person with calendar-year fixed effects. Seasonality was quantified by cosinor regression with cluster-robust standard errors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-1304_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The crude amplitude of tHcy (0.473\u202f\u03bcmol\/L) fell to 0.255\u202f\u03bcmol\/L under person fixed effects, so about half of the\u00a0apparent seasonality reflected who attended. After the secular trend was also removed the within-person amplitude was 0.301\u202f\u03bcmol\/L (95\u202f% CI 0.281\u20130.324), peaking in early November, and was unchanged by time-varying covariates. The 25(OH)D acrophase was in August, 2.6\u00a0months away, and adjustment for 25(OH)D did not attenuate the tHcy amplitude (retention 108.0\u202f%); the rhythm persisted where within-person 25(OH)D barely varied. Spring examinations carried lower within-person odds of exceeding 15\u202f\u03bcmol\/L (odds ratio 0.699, 95\u2009% CI 0.654\u20130.748).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-1304_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Month of sampling is a small but reproducible systematic source of within-person variation in tHcy that is not explained by 25(OH)D. It is modest relative to within-subject biological variation, but sufficient to alter classification near the decision limit and to bias reference intervals derived from seasonally unbalanced\u00a0data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2026-1304","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:55:54Z","timestamp":1790081754000},"source":"Crossref","is-referenced-by-count":0,"title":["Season of sampling and the interpretation of serum homocysteine results: a within-person analysis of 268,877\u00a0health-screening examinations"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5898-6517","authenticated-orcid":false,"given":"Seung-Hwan","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Neurosurgery , Samsung Changwon Hospital, Sungkyunkwan University School of Medicine , Changwon , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7074-6495","authenticated-orcid":false,"given":"Jeong-Hwan","family":"Chae","sequence":"additional","affiliation":[{"name":"Bio-Convergence Integrative Science and Engineering Division, Underwood International College, Yonsei University , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8448-6340","authenticated-orcid":false,"given":"Chang-Ho","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Medicine , Samsung Changwon Hospital, Sungkyunkwan University School of Medicine , Changwon , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"2026092212554522210_j_cclm-2026-1304_ref_001","doi-asserted-by":"crossref","unstructured":"Refsum, H, Ueland, PM, Nyg\u00e5rd, O, Vollset, SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998;49:31\u201362. https:\/\/doi.org\/10.1146\/annurev.med.49.1.31.","DOI":"10.1146\/annurev.med.49.1.31"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_002","doi-asserted-by":"crossref","unstructured":"Smith, AD, Refsum, H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr 2016;36:211\u201339. https:\/\/doi.org\/10.1146\/annurev-nutr-071715-050947.","DOI":"10.1146\/annurev-nutr-071715-050947"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_003","doi-asserted-by":"crossref","unstructured":"Wald, DS, Law, M, Morris, JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002;325:1202. https:\/\/doi.org\/10.1136\/bmj.325.7374.1202.","DOI":"10.1136\/bmj.325.7374.1202"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_004","doi-asserted-by":"crossref","unstructured":"Selhub, J. Homocysteine metabolism. Annu Rev Nutr 1999;19:217\u201346. https:\/\/doi.org\/10.1146\/annurev.nutr.19.1.217.","DOI":"10.1146\/annurev.nutr.19.1.217"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_005","doi-asserted-by":"crossref","unstructured":"Selhub, J, Jacques, PF, Rosenberg, IH, Rogers, G, Bowman, BA, Gunter, EW, et al.. Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey [1991\u20131994]: population reference ranges and contribution of vitamin status to high serum concentrations. Ann Intern Med 1999;131:331\u20139. https:\/\/doi.org\/10.7326\/0003-4819-131-5-199909070-00003.","DOI":"10.7326\/0003-4819-131-5-199909070-00003"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_006","doi-asserted-by":"crossref","unstructured":"Clarke, R, Woodhouse, P, Ulvik, A, Frost, C, Sherliker, P, Refsum, H, et al.. Variability and determinants of total homocysteine concentrations in plasma in an elderly population. Clin Chem 1998;44:102\u20137. https:\/\/doi.org\/10.1093\/clinchem\/44.1.102.","DOI":"10.1093\/clinchem\/44.1.102"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_007","doi-asserted-by":"crossref","unstructured":"Jacques, PF, Bostom, AG, Wilson, PW, Rich, S, Rosenberg, IH, Selhub, J. Determinants of plasma total homocysteine concentration in the framingham offspring cohort. Am J Clin Nutr 2001;73:613\u201321. https:\/\/doi.org\/10.1093\/ajcn\/73.3.613.","DOI":"10.1093\/ajcn\/73.3.613"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_008","doi-asserted-by":"crossref","unstructured":"Kim, HJ, Kim, MK, Kim, JU, Ha, HY, Choi, BY. Major determinants of serum homocysteine concentrations in a Korean population. J\u00a0Kor Med Sci 2010;25:509\u201316. https:\/\/doi.org\/10.3346\/jkms.2010.25.4.509.","DOI":"10.3346\/jkms.2010.25.4.509"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_009","doi-asserted-by":"crossref","unstructured":"McKinley, MC, Strain, JJ, McPartlin, J, Scott, JM, McNulty, H. Plasma homocysteine is not subject to seasonal variation. Clin Chem 2001;47:1430\u20136. https:\/\/doi.org\/10.1093\/clinchem\/47.8.1430.","DOI":"10.1093\/clinchem\/47.8.1430"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_010","doi-asserted-by":"crossref","unstructured":"Holick, MF. Vitamin D deficiency. N\u00a0Engl J Med 2007;357:266\u201381. https:\/\/doi.org\/10.1056\/nejmra070553.","DOI":"10.1056\/NEJMra070553"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_011","doi-asserted-by":"crossref","unstructured":"Wacker, M, Holick, MF. Sunlight and vitamin D: a global perspective for health. Dermatoendocrinol 2013;5:51\u2013108. https:\/\/doi.org\/10.4161\/derm.24494.","DOI":"10.4161\/derm.24494"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_012","doi-asserted-by":"crossref","unstructured":"Amer, M, Qayyum, R. The relationship between 25-hydroxyvitamin D and homocysteine in asymptomatic adults. J\u00a0Clin Endocrinol Metab 2014;99:633\u20138. https:\/\/doi.org\/10.1210\/jc.2013-3262.","DOI":"10.1210\/jc.2013-3262"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_013","doi-asserted-by":"crossref","unstructured":"Lee, YA, Kang, SG, Song, SW, Kim, SH. Association between homocysteine and vitamin D levels in asymptomatic Korean adults. Nutrients 2024;16:1155. https:\/\/doi.org\/10.3390\/nu16081155.","DOI":"10.3390\/nu16081155"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_014","doi-asserted-by":"crossref","unstructured":"Kriebitzsch, C, Verlinden, L, Eelen, G, van Schoor, NM, Swart, K, Lips, P, et al.. 1,25-dihydroxyvitamin D3 influences cellular homocysteine levels in murine preosteoblastic MC3T3-E1 cells by direct regulation of cystathionine \u03b2-synthase. J\u00a0Bone Miner Res 2011;26:2991\u20133000. https:\/\/doi.org\/10.1002\/jbmr.493.","DOI":"10.1002\/jbmr.493"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_015","doi-asserted-by":"crossref","unstructured":"Holick, MF, Binkley, NC, Bischoff-Ferrari, HA, Gordon, CM, Hanley, DA, Heaney, RP, et al.. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J\u00a0Clin Endocrinol Metab 2011;96:1911\u201330. https:\/\/doi.org\/10.1210\/jc.2011-0385.","DOI":"10.1210\/jc.2011-0385"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_016","doi-asserted-by":"crossref","unstructured":"Cornelissen, G. Cosinor-based rhythmometry. Theor Biol Med Model 2014;11:16. https:\/\/doi.org\/10.1186\/1742-4682-11-16.","DOI":"10.1186\/1742-4682-11-16"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_017","doi-asserted-by":"crossref","unstructured":"Homocysteine Lowering Trialists\u2019 Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr 2005;82:806\u201312. https:\/\/doi.org\/10.1093\/ajcn\/82.4.806.","DOI":"10.1093\/ajcn\/82.4.806"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_018","doi-asserted-by":"crossref","unstructured":"Cuskelly, GJ, McNulty, H, Scott, JM. Effect of increasing dietary folate on red-cell folate: implications for prevention of neural-tube defects. Lancet 1996;347:657\u20139. https:\/\/doi.org\/10.1016\/s0140-6736(96)91205-2.","DOI":"10.1016\/S0140-6736(96)91205-2"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_019","doi-asserted-by":"crossref","unstructured":"Bailey, LB, Stover, PJ, McNulty, H, Fenech, MF, Gregory, JF3rd, Mills, JL, et al.. Biomarkers of nutrition for development\u00a0\u2013\u00a0folate review. J\u00a0Nutr 2015;145:1636S\u201380S. https:\/\/doi.org\/10.3945\/jn.114.206599.","DOI":"10.3945\/jn.114.206599"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_020","doi-asserted-by":"crossref","unstructured":"Kim, YN, Cho, YO. Folate food source, usual intake, and folate status in Korean adults. Nutr Res Prac 2018;12:47\u201351. https:\/\/doi.org\/10.4162\/nrp.2018.12.1.47.","DOI":"10.4162\/nrp.2018.12.1.47"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_021","doi-asserted-by":"crossref","unstructured":"Song, S, Song, BM, Park, HY. Folate, vitamin B12, and homocysteine status in the Korean population: data from the 2013\u20132015 Korea National Health and Nutrition Examination Survey. Epidemiol Health 2024;46:e2024007. https:\/\/doi.org\/10.4178\/epih.e2024007.","DOI":"10.4178\/epih.e2024007"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_022","doi-asserted-by":"crossref","unstructured":"Fraser, WD, Tang, JCY, Dutton, JJ, Schoenmakers, I. Vitamin D measurement, the debates continue, new analytes have emerged, developments have variable outcomes. Calcif Tissue Int 2020;106:3\u201313. https:\/\/doi.org\/10.1007\/s00223-019-00620-2.","DOI":"10.1007\/s00223-019-00620-2"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_023","doi-asserted-by":"crossref","unstructured":"Jones, KS, Assar, S, Harnpanich, D, Bouillon, R, Lambrechts, D, Prentice, A, et al.. 25(OH)D2\u00a0half-life is shorter than 25 (OH) D3\u00a0half-life and is influenced by DBP concentration and genotype. J\u00a0Clin Endocrinol Metab 2014;99:3373\u201381. https:\/\/doi.org\/10.1210\/jc.2014-1714.","DOI":"10.1210\/jc.2014-1714"},{"key":"2026092212554522210_j_cclm-2026-1304_ref_024","doi-asserted-by":"crossref","unstructured":"Asif, M, Groboske, SE, Leung, EKY, Yeo, KTJ, van Wijk, XMR. Evaluation of a new generation automated assay for 25-hydroxy vitamin D based on competitive protein binding. J\u00a0Appl Lab Med 2019;4:247\u201353. https:\/\/doi.org\/10.1373\/jalm.2018.028415.","DOI":"10.1373\/jalm.2018.028415"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2026-1304\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2026-1304\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:56:05Z","timestamp":1790081765000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2026-1304\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":24,"alternative-id":["10.1515\/cclm-2026-1304"],"URL":"https:\/\/doi.org\/10.1515\/cclm-2026-1304","relation":{},"ISSN":["1434-6621","1437-4331"],"issn-type":[{"value":"1434-6621","type":"print"},{"value":"1437-4331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]}}}