The epigenetic role of vitamin C in health and disease

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.

Modulating Epigenetic Memory through Vitamins and TET: Implications for Regenerative Medicine and Cancer Treatment

“…The benefit of high doses of ascorbate in broad-spectrum cancer treatment was initially reported by Cameron and Pauling [77]; however, subsequent trials have either shown promising benefits in certain circumstances, or have provided no detectable advantages at all [78][79][80][81][82][83][84]. Nevertheless, it remains possible that vitamin C supplementation can reverse global loss of 5hmC [6] and hypermethylation of tumor-suppressor genes [75,76]. In support of this proposition, it has been found that a high proportion of cancer patients are actually deficient in vitamin C [84].…”

“…One of the most recently discovered fields that vitamins A and C impact upon is epigenetics [5][6][7]. New research has shown that both vitamins drive active removal of DNA methylation in embryonic stem cells (ESCs) by enhancing the same family of ten-eleven translocation (TET) enzymes, and in doing so, help erase DNA methylation and the epigenetic memory encoded by it to improve the reprogramming of differentiated cells to an embryonic-like state.…”

“…Eventual isolation of the respective compounds underlying both vitamins led to Nobel Prizes in Chemistry and Medicine in 1937 [4]. Since this time, a considerable amount of scientific progress (and at times conjecture) has been associated with vitamins A and C, and their respective biological effects touch disciplines as divergent as development and dermatology.One of the most recently discovered fields that vitamins A and C impact upon is epigenetics [5][6][7]. New research has shown that both vitamins drive active removal of DNA methylation in embryonic stem cells (ESCs) by enhancing the same family of ten-eleven translocation (TET) enzymes, and in doing so, help erase DNA methylation and the epigenetic memory encoded by it to improve the reprogramming of differentiated cells to an embryonic-like state.…”

Protective Activity of Ascorbic Acid at Influenza Infection

“…In addition, AA is also a cofactor of enzymes that carry out methylation of histones, which also provides epigenetic regulation of gene activity, in particular by changing the concentration and bioavailability of AA in different sites of organs and tissues. This activity is important in the development of pathologies such as neurodegenerative and oncological diseases in the absence of AA [10].…”

Anticancer Effects of Curcumin, Artemisinin, Genistein, and Resveratrol, and Vitamin C: Free Versus Liposomal Forms

“…For example, vitamin C has been shown to be a cofactor for methylcytosine dioxygenases, which are enzymes for DNA demethylation, an important crossroad in epigenetic regulation [37] [38]. Curcumin is a complementary therapy that may be helpful for the treatment of a variety of diseases because of its anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative effects [39] [40] [41].…”