{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:01:54Z","timestamp":1792101714996,"version":"4.4.0"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brain Foundation"},{"name":"Vembu Srinivasan family fund"},{"name":"NY City-funded Institute for Basic Science Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Food fortification and folic acid supplementation during pregnancy have been implemented as strategies to prevent fetal malformations during pregnancy. However, with the emergence of conditions where folate metabolism and transport are disrupted, such as folate receptor alpha autoantibody (FR\u03b1Ab)-induced folate deficiency, it is critical to find a folate form that is effective and safe for pharmacologic dosing for prolonged periods. Therefore, in this study, we explored the absorption and tissue distribution of folic acid (PGA), 5-methyl-tetrahydrofolate (MTHF), l-folinic acid (levofolinate), and d,l-folinic acid (Leucovorin) in adult rats. During absorption, all forms are converted to MTHF while some unconverted folate form is transported into the blood, especially PGA. The study confirms the rapid distribution of absorbed folate to the placenta and fetus. FR\u03b1Ab administered, also accumulates rapidly in the placenta and blocks folate transport to the fetus and high folate concentrations are needed to circumvent or overcome the blocking of FR\u03b1. In the presence of FR\u03b1Ab, both Leucovorin and levofolinate are absorbed and distributed to tissues better than the other forms. However, only 50% of the leucovorin is metabolically active whereas levofolinate is fully active and generates higher tetrahydrofolate (THF). Because levofolinate can readily incorporate into the folate cycle without needing methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) in the first pass and is relatively stable, it should be the folate form of choice during pregnancy, other disorders where large daily doses of folate are needed, and food fortification.<\/jats:p>","DOI":"10.3390\/nu14122397","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T23:55:24Z","timestamp":1655078124000},"page":"2397","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Absorption and Tissue Distribution of Folate Forms in Rats: Indications for Specific Folate Form Supplementation during Pregnancy"],"prefix":"10.3390","volume":"14","author":[{"given":"Natasha","family":"Bobrowski-Khoury","sequence":"first","affiliation":[{"name":"The School of Graduate Studies, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Sequeira","sequence":"additional","affiliation":[{"name":"Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erland","family":"Arning","sequence":"additional","affiliation":[{"name":"Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott & White Research Institute, Dallas, TX 75204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodoro","family":"Bottiglieri","sequence":"additional","affiliation":[{"name":"Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott & White Research Institute, Dallas, TX 75204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward V.","family":"Quadros","sequence":"additional","affiliation":[{"name":"Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8613","DOI":"10.1007\/s00253-018-9266-0","article-title":"Formation of folates by microorganisms: Towards the biotechnological production of this vitamin","volume":"102","author":"Revuelta","year":"2018","journal-title":"Appl. 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