The relationship between nutritional deficiencies in vitamins, including folate deficiency, and hearing loss has been explored in a variety of epidemiological studies (Houston et al., 1999; Cadoni et al., 2004; Lasisi et al., 2010; Attias et al., 2012; Karli et al., 2013). However, the data obtained have not always been consistent. This fact, led several authors to the evaluation of the putative contribution of human mutations to these disparities and, among them, the analysis of modifications in key genes of the one-carbon metabolism. Evaluation of the relationship between the polymorphism C677T in the methylenetetrahydrofolate reductase gene, a key player in folate metabolism, and hearing loss rendered contradictory results (Durga et al., 2006; Uchida et al., 2011; Fusconi et al., 2012). In contrast, animal studies have provided clues to the interplay between folate, Hcy and hearing loss, showing alterations in Hcy metabolism correlating with the onset of this impairment (Cohen-Salmon et al., 2007; Kundu et al., 2012; Martinez-Vega et al., 2015a). In this line of evidence, a previous study using the C57BL/6J mouse strain, known by its early onset of hearing loss, showed that a decrease in folate intake accelerates development of this sensory decline (Martinez-Vega et al., 2015a). A fact that correlated with a systemic decrease of the vitamin levels and concomitant hyperhomocysteinemia, as expected from the critical role of folate in Hcy remethylation (Pajares and Pérez-Sala, 2006). These systemic changes are also detected in the present study using CBA/Ca mice during long-term feeding with a folate deprived diet, following the same trend than in C57BL/6J mice after 2 months of FD diet (Martinez-Vega et al., 2015a). However, hyperhomocysteinemia was more severe in CBA/Ca mice after 8 months on the FD diet than in C57BL/6J mice after 2 months (Martinez-Vega et al., 2015a).