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Folic acid excess: effects on vitamins B2 and B6 metabolism, tryptophan catabolism and immune response


In Brazil, most folic acid (FA)-containing drugs are manufactured at dosage of 5 mg. Besides Ministry of Health recommend daily use of this dosage for healthy childbearing women planning pregnancy, it contradicts a World Health Organization guidance, which recommend only 400 µg daily use. Consumption of high amounts of FA by Brazilian people worries us, since it has been associated with adverse effects as increased inflammatory cytokines expression and reduced natural killer (NK) cell cytotoxicity, as shown by our research group. We hypothesize that, since FA and vitamins B6 and B2 co-participate in one carbon metabolism, FA excess could influence vitamins B6 and B2 metabolism. Once these both vitamins are co-factors of kynurenine pathway of tryptophan catabolism, we believe these alterations on vitamins levels could affect this pathway, leading to a T helper (Th)1 and Th2 immune response imbalance and reduced regulatory T cell (Treg) proliferation. Here, we propose two studies: 1- in vivo, a 5 mg/day of folic acid intervention study with 80 healthy subjects for 90 days will be carried out; blood collections will be performed at baseline and after 45 and 90 days of intervention start; 2- in vitro, cell culture of lymphocytes isolated from healthy subjects will be submitted to different FA and vitamin B6 levels by up to 72 hours. In both studies, folate, vitamin B12 and B6, kynurenine pathway catabolites, Th1 and Th2 cytokines levels and mRNA expression and lymphocytes T, B and NK activation will be assessed. In in vivo study, vitamin B2 levels will be assessed, as well as the Treg cell ratio in the in vitro study. (AU)

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