MR1-dependence of unmetabolized folic acid side-effects
The fortification of flour with folic acid for the prevention of neural tube defects (NTD) is currently mandated in over eighty countries worldwide, hence compelling its consumption by the greater part of the world’s population. Notwithstanding its beneficial impact on rates of NTD, pervasive folic...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.946713/full |
| _version_ | 1811309202422890496 |
|---|---|
| author | Jeffry S. Tang Jeffry S. Tang Alissa Cait Reuben M. White Homayon J. Arabshahi David O’Sullivan David O’Sullivan Olivier Gasser Olivier Gasser |
| author_facet | Jeffry S. Tang Jeffry S. Tang Alissa Cait Reuben M. White Homayon J. Arabshahi David O’Sullivan David O’Sullivan Olivier Gasser Olivier Gasser |
| author_sort | Jeffry S. Tang |
| collection | DOAJ |
| description | The fortification of flour with folic acid for the prevention of neural tube defects (NTD) is currently mandated in over eighty countries worldwide, hence compelling its consumption by the greater part of the world’s population. Notwithstanding its beneficial impact on rates of NTD, pervasive folic acid supplementation has invariably led to additive daily intakes reaching well beyond their original target, resulting in the circulation of unmetabolized folic acid. Associated idiopathic side-effects ranging from allergies to cancer have been suggested, albeit inconclusively. Herein, we hypothesize that their inconsistent detection and elusive etiology are linked to the in vivo generation of the immunosuppressive folic acid metabolite 6-formylpterin, which interferes with the still emerging and varied functions of Major Histocompatibility Complex-related molecule 1 (MR1)-restricted T cells. Accordingly, we predict that fortification-related adverse health outcomes can be eliminated by substituting folic acid with the bioequivalent folate vitamer 5-methyltetrahydrofolate, which does not break down into 6-formylpterin. |
| first_indexed | 2024-04-13T09:36:53Z |
| format | Article |
| id | doaj.art-b7181680fa474a9daea9dc248560b206 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T09:36:53Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b7181680fa474a9daea9dc248560b2062022-12-22T02:52:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.946713946713MR1-dependence of unmetabolized folic acid side-effectsJeffry S. Tang0Jeffry S. Tang1Alissa Cait2Reuben M. White3Homayon J. Arabshahi4David O’Sullivan5David O’Sullivan6Olivier Gasser7Olivier Gasser8Malaghan Institute of Medical Research, Wellington, New ZealandHigh-Value Nutrition National Science Challenge, Auckland, New ZealandMalaghan Institute of Medical Research, Wellington, New ZealandSchool of Chemical Sciences, University of Auckland, Auckland, New ZealandSchool of Chemical Sciences, University of Auckland, Auckland, New ZealandMalaghan Institute of Medical Research, Wellington, New ZealandHigh-Value Nutrition National Science Challenge, Auckland, New ZealandMalaghan Institute of Medical Research, Wellington, New ZealandHigh-Value Nutrition National Science Challenge, Auckland, New ZealandThe fortification of flour with folic acid for the prevention of neural tube defects (NTD) is currently mandated in over eighty countries worldwide, hence compelling its consumption by the greater part of the world’s population. Notwithstanding its beneficial impact on rates of NTD, pervasive folic acid supplementation has invariably led to additive daily intakes reaching well beyond their original target, resulting in the circulation of unmetabolized folic acid. Associated idiopathic side-effects ranging from allergies to cancer have been suggested, albeit inconclusively. Herein, we hypothesize that their inconsistent detection and elusive etiology are linked to the in vivo generation of the immunosuppressive folic acid metabolite 6-formylpterin, which interferes with the still emerging and varied functions of Major Histocompatibility Complex-related molecule 1 (MR1)-restricted T cells. Accordingly, we predict that fortification-related adverse health outcomes can be eliminated by substituting folic acid with the bioequivalent folate vitamer 5-methyltetrahydrofolate, which does not break down into 6-formylpterin.https://www.frontiersin.org/articles/10.3389/fimmu.2022.946713/fullMR1MAIT cellfolatefolic acid (B9)unmetabolized folic acid |
| spellingShingle | Jeffry S. Tang Jeffry S. Tang Alissa Cait Reuben M. White Homayon J. Arabshahi David O’Sullivan David O’Sullivan Olivier Gasser Olivier Gasser MR1-dependence of unmetabolized folic acid side-effects Frontiers in Immunology MR1 MAIT cell folate folic acid (B9) unmetabolized folic acid |
| title | MR1-dependence of unmetabolized folic acid side-effects |
| title_full | MR1-dependence of unmetabolized folic acid side-effects |
| title_fullStr | MR1-dependence of unmetabolized folic acid side-effects |
| title_full_unstemmed | MR1-dependence of unmetabolized folic acid side-effects |
| title_short | MR1-dependence of unmetabolized folic acid side-effects |
| title_sort | mr1 dependence of unmetabolized folic acid side effects |
| topic | MR1 MAIT cell folate folic acid (B9) unmetabolized folic acid |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.946713/full |
| work_keys_str_mv | AT jeffrystang mr1dependenceofunmetabolizedfolicacidsideeffects AT jeffrystang mr1dependenceofunmetabolizedfolicacidsideeffects AT alissacait mr1dependenceofunmetabolizedfolicacidsideeffects AT reubenmwhite mr1dependenceofunmetabolizedfolicacidsideeffects AT homayonjarabshahi mr1dependenceofunmetabolizedfolicacidsideeffects AT davidosullivan mr1dependenceofunmetabolizedfolicacidsideeffects AT davidosullivan mr1dependenceofunmetabolizedfolicacidsideeffects AT oliviergasser mr1dependenceofunmetabolizedfolicacidsideeffects AT oliviergasser mr1dependenceofunmetabolizedfolicacidsideeffects |