{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:17:36Z","timestamp":1789154256500,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2015,2,6]],"date-time":"2015-02-06T00:00:00Z","timestamp":1423180800000},"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>Elevated circulating total homocysteine (tHcy) concentrations (hyperhomocysteinemia) have been regarded as an independent risk factor for cardiovascular disease (CVD). However, several large clinical trials to correct hyperhomocysteinemia using B-vitamin supplements (particularly folic acid) have largely failed to reduce the risk of CVD. There is no doubt that a large segment of patients with CVD have hyperhomocysteinemia; therefore, it is reasonable to postulate that circulating tHcy concentrations are in part a surrogate marker for another, yet-to-be-identified risk factor(s) for CVD. We found  that iron catalyzes the formation of Hcy from methionine, S-adenosylhomocysteine  and cystathionine. Based on these findings, we propose that an elevated amount of  non-protein-bound iron (free Fe) increases circulating tHcy. Free Fe catalyzes the formation of oxygen free radicals, and oxidized low-density lipoprotein is a well-established risk factor for vascular damage. In this review, we discuss our findings on iron-catalyzed formation of Hcy from thioethers as well as recent findings by other investigators on this issue. Collectively, these support our hypothesis that circulating tHcy is in part a surrogate marker for free Fe, which is one of the independent risk factors for CVD.<\/jats:p>","DOI":"10.3390\/nu7021108","type":"journal-article","created":{"date-parts":[[2015,2,6]],"date-time":"2015-02-06T10:51:12Z","timestamp":1423219872000},"page":"1108-1118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Homocysteine, Iron and Cardiovascular Disease: A Hypothesis"],"prefix":"10.3390","volume":"7","author":[{"given":"Joseph","family":"Baggott","sequence":"first","affiliation":[{"name":"Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsunenobu","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/0955-2863(90)90070-2","article-title":"Methionine metabolism in mammals","volume":"1","author":"Finkelstein","year":"1990","journal-title":"J. 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