{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T08:29:00Z","timestamp":1773476940554,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"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>Hyperhomocysteinemia is recognized as risk factor for cardiovascular and age-associated diseases. Folic acid supplementation efficiently lowers plasma homocysteine (Hcy) levels, but high intake may negatively affect health because of unnatural levels of unmetabolized folic acid in the systemic circulation. Oxoproline (Oxo) provides by glutamic acid production an increase of intracellular folic acid trapping. Aim of this study was to compare the efficacy of three supplementation protocols: (1) traditional therapy (5-methyl-tetrahydrofolate: 15 mg\/day); (2) 5 mL\/day of Oxo with 300 \u03bcg folic acid (oxifolic); (3) 5 mL\/day of Oxo alone (magnesio+) in a 90 days randomized trial on thirty-two moderate hyperhomocysteinemic (18.6 \u00b1 2.4 \u03bcmol\u00b7L\u22121) patients (age 48 \u00b1 14 years). Thiols: cysteine (Cys), cysteinylglycine (Cys\u2013Gly) and glutathione levels were assessed too. Every supplementation induced significant (p range &lt;0.05\u20130.0001) reductions of Hcy level and Cys concentration after the three protocols adopted. Otherwise glutathione concentration significantly increased after oxifolic (p &lt; 0.01) and traditional (p &lt; 0.05) supplementation. The integration of Oxo resulted an interesting alternative to traditional therapy because absence or minimal number of folates in the integrator eliminates any chance of excess that can constitute a long-term risk.<\/jats:p>","DOI":"10.3390\/nu12071957","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T09:04:59Z","timestamp":1593507899000},"page":"1957","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Influence of Dietary Supplementation for Hyperhomocysteinemia Treatments"],"prefix":"10.3390","volume":"12","author":[{"given":"Alessandra","family":"Vezzoli","sequence":"first","affiliation":[{"name":"Institute of Clinical Physiology, National Council of Research (IFC-CNR), ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Dellanoce","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Council of Research (IFC-CNR), ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Maria Caimi","sequence":"additional","affiliation":[{"name":"S.S Emostasi, S.C. Ematologia ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Vietti","sequence":"additional","affiliation":[{"name":"Driatec srl, Cassina de\u2019 Pecchi, 20060 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5152-761X","authenticated-orcid":false,"given":"Michela","family":"Montorsi","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-2690","authenticated-orcid":false,"given":"Simona","family":"Mrakic-Sposta","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Council of Research (IFC-CNR), ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Accinni","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Council of Research (IFC-CNR), ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.3390\/nu7021108","article-title":"Homocysteine, iron and cardiovascular disease: A hypothesis","volume":"7","author":"Baggott","year":"2015","journal-title":"Nurients"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1191\/1358863x02vm428ra","article-title":"Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia","volume":"7","author":"Weiss","year":"2002","journal-title":"Vasc. 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