{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T21:45:22Z","timestamp":1770414322950,"version":"3.49.0"},"reference-count":27,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2013,5,8]],"date-time":"2013-05-08T00:00:00Z","timestamp":1367971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>To compare the efficacy of a diet rich in natural  folate and of two different folic acid supplementation protocols in subjects with \u201cmoderate\u201d hyperhomocysteinemia, also taking into account C677T polymorphism of  5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Subjects\/Methods: We performed a 13 week open, randomized, double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia, with daily 200 \u03bcg from a natural folate-rich diet, 200 \u03bcg [6S]5-methyltetrahydrofolate (5-MTHF), 200 \u03bcg folic acid or placebo. Participants were stratified according to their MTHFR genotype. Results: Homocysteine (Hcy) levels were reduced after folate enriched diet, 5-MTHF or folic acid supplementation respectively by 20.1% (p &lt; 0.002), 19.4% (p &lt; 0.001) and 21.9% (p &lt; 0.001), as compared to baseline levels and significantly as compared to placebo (p &lt; 0.001, p &lt; 0.002 and p &lt; 0.001, respectively for enriched diet, 5-MTHF and folic acid). After this enriched diet and the folic acid supplementation, Hcy in both genotype groups decreased approximately to the same level, with higher percentage decreases observed for the TT group because of their higher pre-treatment value. Similar results were not seen by genotype for 5-MTHF. A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations, as compared to placebo. Conclusions: Supplementation with natural folate-rich foods, folic acid and 5-MTHF reached a similar reduction in  Hcy concentrations.<\/jats:p>","DOI":"10.3390\/nu5051531","type":"journal-article","created":{"date-parts":[[2013,5,8]],"date-time":"2013-05-08T11:26:23Z","timestamp":1368012383000},"page":"1531-1543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Homocysteine Lowering by Folate-Rich Diet or  Pharmacological Supplementations in Subjects with  Moderate Hyperhomocysteinemia"],"prefix":"10.3390","volume":"5","author":[{"given":"Bruno","family":"Zappacosta","sequence":"first","affiliation":[{"name":"Department of Laboratory, Foundation of Research and Care, \"John Paul II\", Catholic University of Sacred Heart, Campobasso 86100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierpaolo","family":"Mastroiacovo","sequence":"additional","affiliation":[{"name":"ICBD, Alessandra Lisi International Centre on Birth Defects and Prematurity, Rome 00100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Persichilli","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Policlinico A. Gemelli, Catholic University of Sacred Heart, Rome 00168, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Pounis","sequence":"additional","affiliation":[{"name":"Research Laboratories, Foundation of Research and Care, \"John Paul II\", Catholic University of Sacred Heart, Campobasso 86100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Ruggeri","sequence":"additional","affiliation":[{"name":"National Institute of Research for Foods and Nutrition (Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione), Rome 00178, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Minucci","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Policlinico A. Gemelli, Catholic University of Sacred Heart, Rome 00168, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"Carnovale","sequence":"additional","affiliation":[{"name":"National Institute of Research for Foods and Nutrition (Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione), Rome 00178, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Generoso","family":"Andria","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Federico II University, Neaples 81100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Catholic University of Sacred Heart, Rome 00168, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Scala","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Federico II University, Neaples 81100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orazio","family":"Genovese","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Catholic University of Sacred Heart, Rome 00168, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aida","family":"Turrini","sequence":"additional","affiliation":[{"name":"National Institute of Research for Foods and Nutrition (Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione), Rome 00178, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenza","family":"Mistura","sequence":"additional","affiliation":[{"name":"National Institute of Research for Foods and Nutrition (Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione), Rome 00178, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Giardina","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Policlinico A. Gemelli, Catholic University of Sacred Heart, Rome 00168, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Licia","family":"Iacoviello","sequence":"additional","affiliation":[{"name":"Research Laboratories, Foundation of Research and Care, \"John Paul II\", Catholic University of Sacred Heart, Campobasso 86100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s10545-010-9235-y","article-title":"Homocysteine and vascular disease: Review of published results of the homocysteine-lowering trials","volume":"34","author":"Clarke","year":"2011","journal-title":"J. Inherit. Metab. 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