ArticleProceedings of the National Academy of Sciences of the United States of America2020
Vitamin B12 and folic acid alleviate symptoms of nutritional deficiency by antagonizing aryl hydrocarbon receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Cobinamide, a Vitamin BToxics · 2026Article
- Monocytes from inflammatory arthritis patients accumulate methotrexate and their transcriptome predicts methotrexate clinical response.Cellular and molecular life sciences : CMLS · 2026Article
- Reimagining AHR in Cancer: From Environmental Sensor to Novel Immunomodulatory Therapeutic Target.International journal of biological sciences · 2026Review
- Cobamide metabolism, regulation, and adaptation inJournal of bacteriology · 2025Review
- From Nutrient to Nanocarrier: The Multifaceted Role of Vitamin B12 in Drug Delivery.International journal of molecular sciences · 2025Review
- Ratiometric fluorescence quantification of folic acid utilizing D-penicillamine-based carbon dots in conjunction with glutathione S-transferase-Au nanoclusters.Mikrochimica acta · 2025Article
- The Significance of Genetically Determined Methylation and Folate Metabolism Disorders in the Pathogenesis of Coronary Artery Disease: A Target for New Therapies?International journal of molecular sciences · 2024Review
- Uremic toxins mediate kidney diseases: the role of aryl hydrocarbon receptor.Cellular & molecular biology letters · 2024Review
- Review
- Ah receptor, vitamin B12 and itaconate: how localized decrease of vitamin B12 prevents survival of macrophage-ingested bacteria.Frontiers in toxicology · 2024Article
- Transcobalamin 2 orchestrates monocyte proliferation and TLR4-driven inflammation in systemic lupus erythematosus via folate one-carbon metabolism.Frontiers in immunology · 2024Article
- The complex biology of aryl hydrocarbon receptor activation in cancer and beyond.Biochemical pharmacology · 2023Review
- Bacteroides ovatus accelerates metformin-induced vitamin B12 deficiency in type 2 diabetes patients by accumulating cobalamin.NPJ biofilms and microbiomes · 2023Article
- UVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR- and SP1-dependent manner.JCI insight · 2022Article
- Structural biology of SARS-CoV-2: open the door for novel therapies.Signal transduction and targeted therapy · 2022Review
- Aryl hydrocarbon receptor (AHR) functions in infectious and sterile inflammation and NADArchives of toxicology · 2021Review
- Kynurenic acid may underlie sex-specific immune responses to COVID-19.Science signaling · 2021Article
- Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways.Cell host & microbe · 2021Article
- Drug Mimicry: Promiscuous Receptors PXR and AhR, and Microbial Metabolite Interactions in the Intestine.Trends in pharmacological sciences · 2020Review
- What's eating you? An update on Giardia, the microbiome and the immune response.Current opinion in microbiology · 2020Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Despite broad appreciation of their clinical utility, it has been unclear how vitamin B12 and folic acid (FA) function at the molecular level to directly prevent their hallmark symptoms of deficiency like anemia or birth defects. To this point, B12 and FA have largely been studied as cofactors for enzymes in the one-carbon (1C) cycle in facilitating the de novo generation of nucleotides and methylation of DNA and protein. Here, we report that B12 and FA function as natural antagonists of aryl hydrocarbon receptor (AhR). Our studies indicate that B12 and FA bind AhR directly as competitive antagonists, blocking AhR nuclear localization, XRE binding, and target gene induction mediated by AhR agonists like 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 6-formylindolo[3,2-b]carbazole (FICZ). In mice, TCDD treatment replicated many of the hallmark symptoms of B12/FA deficiency and cotreatment with aryl hydrocarbon portions of B12/FA rescued mice from these toxic effects. Moreover, we found that B12/FA deficiency in mice induces AhR transcriptional activity and accumulation of erythroid progenitors and that it may do so in an AhR-dependent fashion. Consistent with these results, we observed that human cancer samples with deficient B12/FA uptake demonstrated higher transcription of AhR target genes and lower transcription of pathways implicated in birth defects. In contrast, there was no significant difference observed between samples with mutated and intact 1C cycle proteins. Thus, we propose a model in which B12 and FA blunt the effect of natural AhR agonists at baseline to prevent the symptoms that arise with AhR overactivation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.