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Review
. 2020 Apr 27;12(5):1234.
doi: 10.3390/nu12051234.

Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery

Maria Cappuccilli  1 , Camilla Bergamini  2 , Floriana A Giacomelli  2 , Giuseppe Cianciolo  1 , Gabriele Donati  1 , Diletta Conte  1 , Teresa Natali  1 , Gaetano La Manna  1 , Irene Capelli  1
Affiliations
Review

Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery

Maria Cappuccilli et al. Nutrients. .

Abstract

Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo- or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection.

Keywords: DNA methylation; chronic kidney disease; cobalamin; epigenetic; folic acid; methyl donors; vitamin B12 sublingual formulation; vitamin B6.

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Conflict of interest statement

M.C., G.C., G.D., T.N., G.L.M., I.C. declare no competing interest. C.B. is a Pharmaelle S.r.l. employee; F.A.G. is a Pharmaelle S.r.l. employee.

Figures

Figure 1
Figure 1
Hyperhomocysteinemia in the atherosclerotic process. HHcy, hyperhomocysteinemia, LDL, low density lipoproteins.
Figure 2
Figure 2
Effects of DNA hypermethylation (upper) and hypomethylation (lower) on transcriptional activity. DNMT, DNA methyltransferase; TET, Ten-eleven translocation enzymes.
Figure 3
Figure 3
Schematic representation of one-carbon metabolism. DHF, dihydrofolate; DMG, N,N-dimethylglycine betaine; Met, methionine; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; THF, tetrahydrofolate.
See this image and copyright information in PMC

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