The Epigenetic Role of Vitamin C in Health and Disease

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2016 Feb 6

PMID 26846695

Citations 85

Authors

Vladimir Camarena

Gaofeng Wang

Affiliations

Soon will be listed here.

Abstract

Recent advances have uncovered a previously unknown function of vitamin C in epigenetic regulation. Vitamin C exists predominantly as an ascorbate anion under physiological pH conditions. Ascorbate was discovered as a cofactor for methylcytosine dioxygenases that are responsible for DNA demethylation, and also as a likely cofactor for some JmjC domain-containing histone demethylases that catalyze histone demethylation. Variation in ascorbate bioavailability thus can influence the demethylation of both DNA and histone, further leading to different phenotypic presentations. Ascorbate deficiency can be presented systematically, spatially and temporally in different tissues at the different stages of development and aging. Here, we review how ascorbate deficiency could potentially be involved in embryonic and postnatal development, and plays a role in various diseases such as neurodegeneration and cancer through epigenetic dysregulation.

Citing Articles

Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.

Smith-Diaz C, Das A, Jurkowski T, Hore T, Vissers M J Med Chem. 2025; 68(3):2219-2237.

PMID: 39883951 PMC: 11831678. DOI: 10.1021/acs.jmedchem.4c02342.

A Guinea Pig Model of Pediatric Metabolic Dysfunction-Associated Steatohepatitis: Poor Vitamin C Status May Advance Disease.

Pedersen K, Poojari A, Colberg S, Mechernsee S, Iversen J, Barres R Nutrients. 2025; 17(2).

PMID: 39861421 PMC: 11767659. DOI: 10.3390/nu17020291.

Vitamin C Supplementation in the Treatment of Autoimmune and Onco-Hematological Diseases: From Prophylaxis to Adjuvant Therapy.

Isola S, Gammeri L, Furci F, Gangemi S, Pioggia G, Allegra A Int J Mol Sci. 2024; 25(13).

PMID: 39000393 PMC: 11241675. DOI: 10.3390/ijms25137284.

DNA methylation modification in Idiopathic pulmonary fibrosis.

Ren L, Chang Y, Jiang S, Li X, Cheng H Front Cell Dev Biol. 2024; 12:1416325.

PMID: 38915445 PMC: 11194555. DOI: 10.3389/fcell.2024.1416325.

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers.

Shen X, Wang J, Deng B, Zhao Z, Chen S, Kong W Antioxidants (Basel). 2024; 13(5).

PMID: 38790722 PMC: 11118910. DOI: 10.3390/antiox13050617.

References

Krasner N, Dymock I . Ascorbic acid deficiency in malignant diseases: a clinical and biochemical study. Br J Cancer. 1974; 30(2):142-5. PMC: 2009278. DOI: 10.1038/bjc.1974.125. View

Tveden-Nyborg P, Johansen L, Raida Z, Villumsen C, Larsen J, Lykkesfeldt J . Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs. Am J Clin Nutr. 2009; 90(3):540-6. DOI: 10.3945/ajcn.2009.27954. View

Maiti A, Drohat A . Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites. J Biol Chem. 2011; 286(41):35334-35338. PMC: 3195571. DOI: 10.1074/jbc.C111.284620. View

Huang Y, Tang X, Xie W, Zhou Y, Li D, Zhou Y . Vitamin C enhances in vitro and in vivo development of porcine somatic cell nuclear transfer embryos. Biochem Biophys Res Commun. 2011; 411(2):397-401. DOI: 10.1016/j.bbrc.2011.06.160. View

Kere M, Siriboon C, Lo N, Nguyen N, Ju J . Ascorbic acid improves the developmental competence of porcine oocytes after parthenogenetic activation and somatic cell nuclear transplantation. J Reprod Dev. 2012; 59(1):78-84. PMC: 3943238. DOI: 10.1262/jrd.2012-114. View

Gess B, Rohr D, Fledrich R, Sereda M, Kleffner I, Humberg A . Sodium-dependent vitamin C transporter 2 deficiency causes hypomyelination and extracellular matrix defects in the peripheral nervous system. J Neurosci. 2011; 31(47):17180-92. PMC: 6623846. DOI: 10.1523/JNEUROSCI.3457-11.2011. View

Wang C, Lee J, Cho Y, Xiao Y, Jin Q, Liu C . UTX regulates mesoderm differentiation of embryonic stem cells independent of H3K27 demethylase activity. Proc Natl Acad Sci U S A. 2012; 109(38):15324-9. PMC: 3458330. DOI: 10.1073/pnas.1204166109. View

Mamede A, Tavares S, Abrantes A, Trindade J, Maia J, Botelho M . The role of vitamins in cancer: a review. Nutr Cancer. 2011; 63(4):479-94. DOI: 10.1080/01635581.2011.539315. View

Wang T, Chen K, Zeng X, Yang J, Wu Y, Shi X . The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner. Cell Stem Cell. 2011; 9(6):575-87. DOI: 10.1016/j.stem.2011.10.005. View

10.

Corpe C, Tu H, Eck P, Wang J, Faulhaber-Walter R, Schnermann J . Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice. J Clin Invest. 2010; 120(4):1069-83. PMC: 2847422. DOI: 10.1172/JCI39191. View

11.

Mellen M, Ayata P, Dewell S, Kriaucionis S, Heintz N . MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell. 2012; 151(7):1417-30. PMC: 3653293. DOI: 10.1016/j.cell.2012.11.022. View

12.

Bradley-Whitman M, Lovell M . Epigenetic changes in the progression of Alzheimer's disease. Mech Ageing Dev. 2013; 134(10):486-95. PMC: 3857018. DOI: 10.1016/j.mad.2013.08.005. View

13.

Schjoldager J, Tveden-Nyborg P, Lykkesfeldt J . Prolonged maternal vitamin C deficiency overrides preferential fetal ascorbate transport but does not influence perinatal survival in guinea pigs. Br J Nutr. 2013; 110(9):1573-9. DOI: 10.1017/S0007114513000913. View

14.

Tsukada Y, Fang J, Erdjument-Bromage H, Warren M, Borchers C, Tempst P . Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2005; 439(7078):811-6. DOI: 10.1038/nature04433. View

15.

Lykkesfeldt J, Christen S, Wallock L, Chang H, Jacob R, Ames B . Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes. Am J Clin Nutr. 2000; 71(2):530-6. DOI: 10.1093/ajcn/71.2.530. View

16.

Lykkesfeldt J . Ascorbate and dehydroascorbic acid as reliable biomarkers of oxidative stress: analytical reproducibility and long-term stability of plasma samples subjected to acidic deproteinization. Cancer Epidemiol Biomarkers Prev. 2007; 16(11):2513-6. DOI: 10.1158/1055-9965.EPI-07-0639. View

17.

Xu Y, Wu F, Tan L, Kong L, Xiong L, Deng J . Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol Cell. 2011; 42(4):451-64. PMC: 3099128. DOI: 10.1016/j.molcel.2011.04.005. View

18.

Schleicher R, Carroll M, Ford E, Lacher D . Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). Am J Clin Nutr. 2009; 90(5):1252-63. DOI: 10.3945/ajcn.2008.27016. View

19.

Blaschke K, Ebata K, Karimi M, Zepeda-Martinez J, Goyal P, Mahapatra S . Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature. 2013; 500(7461):222-6. PMC: 3893718. DOI: 10.1038/nature12362. View

20.

Hering T, Kollar J, Huynh T, Varelas J, Sandell L . Modulation of extracellular matrix gene expression in bovine high-density chondrocyte cultures by ascorbic acid and enzymatic resuspension. Arch Biochem Biophys. 1994; 314(1):90-8. DOI: 10.1006/abbi.1994.1415. View