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Effect of vitamin D3 supplementation upon the metabolic and DNA methylation profile of cystic fibrosis patients

Maria Paula de Paiva, Dayanna Joyce Marques Queiroz, Celso Costa da Silva Junior, Constantino Giovanni Braga Cartaxo, Marina de Castro Coelho, Rafaella Cristhine Luna Pordeus, Rafaela Lira Formiga Cavalcanti de Lima, Darlene Camati Persuhn, Alexandre Sergio Silva, Naila Francis Paulo de Oliveira, Maria da Conceicao Rodrigues Goncalves.


Background: Cystic fibrosis (CF) is a genetic disease that affects the transmembrane conductance regulator gene responsible for modulating chloride ion transportation in the cell membrane. Hypovitaminosis D is frequently observed among fibrocystic disease patients. Therefore, this study was aimed to evaluate the effect of vitamin D3 supplementation in patients with CF concerning their metabolic and deoxyribonucleic acid (DNA) methylation profiles.
Methodology: A clinical trial involving 12 CF patients was carried out in Joao Pessoa. After assessment of hypovitaminosis D prevalence in the studied population, four patients with vitamin D3 insufficiency/deficiency were administered cholecalciferol megadose supplementation in addition to biochemical examinations and analysis of inflammatory and epigenetic indicators. The DNA methylation profile of the studied genes' promoter regions was determined through a qualitative methylation restriction enzyme technique. Data were analyzed using the Statistical Package for the Social Sciences 25.0 software for T-tests, Mann-Whitney, and Wilcoxon test calculations.
Results: Hypovitaminosis D was observed in 58%, 33% of the studied individuals. Patients with hypovitaminosis D reported blood sugar, glutamic-pyruvic transaminase (ALT), and uric acid levels significantly higher (p = 0.02; p = 0.05; p = 0.02, respectively) compared to individuals with sufficient 25-hydroxyvitamin D (25(OH)D), as well as elevated inflammatory values. Supplementation did not influence epigenetic nor metabolic parameters significantly, although the mean 25(OH)D serum concentration value increased from 18.3 ng/dl to 34.1 ng/dl (p = 0.06).
Conclusion: Cholecalciferol megadose elevated 25(OH)D serum levels, although it did not alter inflammatory, glycemic, or epigenetic parameters. This encourages future studies on the matter since significant differences were found in blood sugar, uric acid, and ALT serum levels for the vitamin D3 insufficiency/deficiency group despite this study’s small sample size.

Key words: Epigenetics, cystic fibrosis, supplementation, vitamin D, DNA methylation

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