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Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases

OBJECTIVE: The use of folic acid (FA) has been discouraged in cerebral folate deficiency (CFD) because, theoretically, it could inhibit the transport of 5‐methyltetrahydrofolic acid (5MTHF) across the blood–cerebrospinal fluid (CSF) barrier. We present the clinical biochemical data of two cases with...

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Autores principales: Akiyama, Tomoyuki, Kuki, Ichiro, Kim, Kiyohiro, Yamamoto, Naohiro, Yamada, Yumi, Igarashi, Kazuya, Ishihara, Tomohiko, Hatano, Yuya, Kobayashi, Katsuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626660/
https://www.ncbi.nlm.nih.gov/pubmed/36341171
http://dx.doi.org/10.1002/jmd2.12321
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author Akiyama, Tomoyuki
Kuki, Ichiro
Kim, Kiyohiro
Yamamoto, Naohiro
Yamada, Yumi
Igarashi, Kazuya
Ishihara, Tomohiko
Hatano, Yuya
Kobayashi, Katsuhiro
author_facet Akiyama, Tomoyuki
Kuki, Ichiro
Kim, Kiyohiro
Yamamoto, Naohiro
Yamada, Yumi
Igarashi, Kazuya
Ishihara, Tomohiko
Hatano, Yuya
Kobayashi, Katsuhiro
author_sort Akiyama, Tomoyuki
collection PubMed
description OBJECTIVE: The use of folic acid (FA) has been discouraged in cerebral folate deficiency (CFD) because, theoretically, it could inhibit the transport of 5‐methyltetrahydrofolic acid (5MTHF) across the blood–cerebrospinal fluid (CSF) barrier. We present the clinical biochemical data of two cases with CFD to support this hypothesis. METHODS: We measured CSF and serum 5MTHF concentrations in a patient with Kearns‐Sayre syndrome (KSS) and a patient homozygous for MTHFR C677T polymorphism before and during folate supplementation therapy. To evaluate these 5MTHF concentrations, we also analyzed CSF and serum samples in pediatric patients without folate supplementation. RESULTS: Both patients had low CSF 5MTHF before treatment and high‐dose FA therapy did not normalize CSF 5MTHF. There was a dissociation between serum total folate and 5MTHF concentrations during FA therapy, which was considered to be due to the appearance of unmetabolized FA. The addition of folinic acid did not improve low CSF 5MTHF in the KSS patient and the cessation of FA resulted in the normalization of CSF 5MTHF. In the patient homozygous for MTHFR C677T, minimization of the FA dosage resulted in the normalization of CSF 5MTHF and an increased CSF‐to‐serum 5MTHF ratio. CONCLUSIONS: Our data suggest that excess supplementation of FA impaired 5MTHF transport across the blood–CSF barrier. In the treatment of CFD, supplementation of folinic acid or 5MTHF (in cases of impaired 5MTHF synthesis) is preferred over the use of FA. The reference values of CSF 5MTHF concentration based on 600 pediatric cases were also provided.
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spelling pubmed-96266602022-11-03 Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases Akiyama, Tomoyuki Kuki, Ichiro Kim, Kiyohiro Yamamoto, Naohiro Yamada, Yumi Igarashi, Kazuya Ishihara, Tomohiko Hatano, Yuya Kobayashi, Katsuhiro JIMD Rep Case Reports OBJECTIVE: The use of folic acid (FA) has been discouraged in cerebral folate deficiency (CFD) because, theoretically, it could inhibit the transport of 5‐methyltetrahydrofolic acid (5MTHF) across the blood–cerebrospinal fluid (CSF) barrier. We present the clinical biochemical data of two cases with CFD to support this hypothesis. METHODS: We measured CSF and serum 5MTHF concentrations in a patient with Kearns‐Sayre syndrome (KSS) and a patient homozygous for MTHFR C677T polymorphism before and during folate supplementation therapy. To evaluate these 5MTHF concentrations, we also analyzed CSF and serum samples in pediatric patients without folate supplementation. RESULTS: Both patients had low CSF 5MTHF before treatment and high‐dose FA therapy did not normalize CSF 5MTHF. There was a dissociation between serum total folate and 5MTHF concentrations during FA therapy, which was considered to be due to the appearance of unmetabolized FA. The addition of folinic acid did not improve low CSF 5MTHF in the KSS patient and the cessation of FA resulted in the normalization of CSF 5MTHF. In the patient homozygous for MTHFR C677T, minimization of the FA dosage resulted in the normalization of CSF 5MTHF and an increased CSF‐to‐serum 5MTHF ratio. CONCLUSIONS: Our data suggest that excess supplementation of FA impaired 5MTHF transport across the blood–CSF barrier. In the treatment of CFD, supplementation of folinic acid or 5MTHF (in cases of impaired 5MTHF synthesis) is preferred over the use of FA. The reference values of CSF 5MTHF concentration based on 600 pediatric cases were also provided. John Wiley & Sons, Inc. 2022-08-06 /pmc/articles/PMC9626660/ /pubmed/36341171 http://dx.doi.org/10.1002/jmd2.12321 Text en © 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Case Reports
Akiyama, Tomoyuki
Kuki, Ichiro
Kim, Kiyohiro
Yamamoto, Naohiro
Yamada, Yumi
Igarashi, Kazuya
Ishihara, Tomohiko
Hatano, Yuya
Kobayashi, Katsuhiro
Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases
title Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases
title_full Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases
title_fullStr Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases
title_full_unstemmed Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases
title_short Folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: Clinical biochemical data from two cases
title_sort folic acid inhibits 5‐methyltetrahydrofolate transport across the blood–cerebrospinal fluid barrier: clinical biochemical data from two cases
topic Case Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626660/
https://www.ncbi.nlm.nih.gov/pubmed/36341171
http://dx.doi.org/10.1002/jmd2.12321
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