Supplementation with Apple Juice Can Compensate for Folate Deficiency in a Mouse Model Deficient in Methylene Tetra Hydrofoate Reductase Activity

Folate insufficiency promotes developmental as well as age-related disorders of the nervous system. The C677T variant of 5′,10′ methylene tetrahydrofolate reductase (MTHFR; which utilizes folate to regenerate methionine from homocysteine) displays reduced activity, and therefore promotes functional folate deficiency. Mice heterozygously lacking this gene (MTHFR+/− mice) represent a useful model for analysis of the impact of MTHFR deficiency and potential compensatory approaches. Since consumption of apple products has benefited mouse models subjected to dietary and/or genetically-induced folate deficiency, we compared the impact of supplementation with apple juice on cognitive and neuromuscular performance of mice MTHFR+/+ and +/− mice with and without dietary folate deficiency. Mice were maintained for 1 month on a standard, complete diet, or a challenge diet lacking folate, and vitamin E and containing a 50g iron/500g total diet as a pro-oxidant. Additional groups received apple juice concentrate (AJC) diluted to 0.5% (vol/vol) in their sole source of drinking water. MTHFR+/− mice demonstrated significantly impaired cognitive performance in standard reward-based T maze and the non-reward-based Y maze tests as compared to MTHFR+/+ when maintained on the complete diet; supplementation with AJC improved the performance of MTHFR+/− to the level observed for MTHFR+/+ mice. Maintenance for 1 month on the deficient diet reduced the performance of both genotypes in both tests, but supplementation with AJC prevented these reductions. MTHFR+/+ and +/− displayed virtually identical neuromuscular performance in the standard paw grip endurance test when maintained on the complete diet, and displayed similar, non-significant declines in performance when maintained on the deficient diet. Supplementation of either diet with AJC dramatically improved the performance of both genotypes. The findings presented herein indicate that supplementation with AJCs can compensate for genetic as well as dietary insufficiency in folate in a murine model of genetic folate compromise, and support the notion that dietary supplementation may be more critical under conditions of latent genetic compromise.