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dc.contributor.authorBobrowski-Khoury, Natasha
dc.contributor.authorSequeira, Jeffrey M
dc.contributor.authorArning, Erland
dc.contributor.authorBottiglieri, Teodoro
dc.contributor.authorQuadros, Edward V
dc.date.accessioned2023-03-01T18:02:57Z
dc.date.available2023-03-01T18:02:57Z
dc.date.issued2022-06-09
dc.identifier.citationBobrowski-Khoury N, Sequeira JM, Arning E, Bottiglieri T, Quadros EV. Absorption and Tissue Distribution of Folate Forms in Rats: Indications for Specific Folate Form Supplementation during Pregnancy. Nutrients. 2022 Jun 9;14(12):2397. doi: 10.3390/nu14122397. PMID: 35745126; PMCID: PMC9228663.en_US
dc.identifier.eissn2072-6643
dc.identifier.doi10.3390/nu14122397
dc.identifier.pmid35745126
dc.identifier.urihttp://hdl.handle.net/20.500.12648/8413
dc.description.abstractFood 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 (FRαAb)-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. FRαAb 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 FRα. In the presence of FRαAb, 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.
dc.language.isoenen_US
dc.relation.urlhttps://www.mdpi.com/2072-6643/14/12/2397en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectfetal uptake of folatesen_US
dc.subjectfolate deficiencyen_US
dc.subjectfolate receptor antibodiesen_US
dc.subjectfolate transporten_US
dc.subjectpregnancyen_US
dc.titleAbsorption and Tissue Distribution of Folate Forms in Rats: Indications for Specific Folate Form Supplementation during Pregnancy.en_US
dc.typeArticle/Reviewen_US
dc.source.journaltitleNutrientsen_US
dc.source.volume14
dc.source.issue12
dc.source.countrySwitzerland
dc.description.versionVoRen_US
refterms.dateFOA2023-03-01T18:02:57Z
html.description.abstractFood 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 (FRαAb)-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. FRαAb 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 FRα. In the presence of FRαAb, 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.
dc.description.institutionSUNY Downstateen_US
dc.description.departmentGraduate Studiesen_US
dc.description.degreelevelN/Aen_US
dc.identifier.journalNutrients


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