DNA methylation and one-carbon metabolism related nutrients and polymorphisms: analysis after mandatory flour fortification with folic acid

There is a growing research interest in determining whether changes in the global status of DNA methylation are related to the environment, in particular, to one-carbon metabolism. So, our aim was to investigate the effect of dietary methyl-group donor intake (methionine, folate, choline, betaine, vitamins B 2 , B 6 and B 12 ), biomarkers (total folate, unmetabolised folic acid (FA), 5-methyltetrahydrofolate, homocysteine, vitamins B 6 and B 12 concentrations) and genetic variants (polymorphisms involved in one-carbon metabolism) on global DNA methylation in a population exposed to mandatory flour fortification with FA. A cross-sectional study of health and living conditions was conducted among a representative sample of residents in Sao Paulo, Brazil. The mean of global DNA methylation was lower in young people than in adults and the elderly ( P = 0·049). No differences between genotypes of polymorphism and global DNA methylation mean were identified. We observed that the increase in betaine intake led to an absolute change in percentage of DNA methylation ( β = 0·0005, P = 0·024) using multiple regression. Betaine intake alone was associated with an absolute change in percentage of global DNA methylation. The study did not find an association between global DNA methylation and folate status even in a population exposed to mandatory flour fortification with FA.