{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:58:53Z","timestamp":1790744333405,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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>The clinical relevance of a proposed relationship between vitamin D status and homocysteine remains uncertain. This narrative review integrates mechanistic, observational, Mendelian randomization (MR), and trial evidence. A documented supplementary search of PubMed and Europe PMC was executed on 21 September 2026 for publications through 31 July 2026; no formal risk-of-bias assessment or quantitative synthesis was performed. Experimental studies support vitamin D-dependent regulation of homocysteine metabolism and homocysteine-related suppression of vitamin D signaling, but reciprocal regulation has not been established in humans. Human biomarker associations and supplementation effects on homocysteine are heterogeneous; two frequently cited intervention publications report the same trial. Additional longitudinal and multibiomarker studies provide preliminary outcome associations, without externally validating the proposed four-category classification or its treatment utility. Homocysteine MR signals are more consistent for stroke than coronary disease, subject to validity and multiplicity concerns. Vitamin D MR is predominantly null, including the republished stratified analysis, and large supplementation trials have not demonstrated consistent cardiovascular benefit. A combined folate\u2013vitamin D cognitive trial did not demonstrate its primary intention-to-treat benefit and does not validate vascular treatment selection. Clinical outcome trials carry greater weight for treatment decisions than molecular plausibility or biomarker co-occurrence. The proposed classification and explanatory models remain hypothesis-generating: a clinically meaningful reciprocal axis and differential benefit from phenotype-guided combined nutritional intervention are unproven.<\/jats:p>","DOI":"10.3390\/nu18193167","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:31:14Z","timestamp":1790353874000},"page":"3167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Proposed Vitamin D\u2013Homocysteine Relationship in Cardiometabolic Health: A Narrative Review of Mechanisms, Evidence, and Research Phenotypes"],"prefix":"10.3390","volume":"18","author":[{"given":"Yun-Ah","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Family Medicine, St. Vincent\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 16247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Goo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, St. Vincent\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 16247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D Deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. 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