’ reply : Vitamins in the treatment of chronic Chagas disease : adjuvant antiparasitary or antioxidant therapy ?

[1]. Departamento de Patologia e Medicina Legal, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE. [2]. Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, CE. [3]. Departamento de Farmácia, Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, CE. [4]. Departamento de Saúde Comunitária, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE.


Dear Editor,
We would like to acknowledge the comments regarding our article Clinical and serological evolution in chronic Chagas disease patients in a 4-year pharmacotherapy follow-up: a preliminary study 1 , which are contained in the letter The role of benznidazole with cyanocobalamin and ascorbic acid in treating the chronic phase of Chagas disease 2 .
Although pharmacotherapy with benznidazole is associated with adverse reactions and limited effectiveness in the chronic phase of Chagas disease 1,3 , it has been used in the indeterminate phase of Chagas disease to reduce parasitemia, prevent visceral lesions and transmission.As well, observational studies have shown that benznidazole may even benefi t patients in the cardiac chronic stage of the disease 4 .Moreover, despite the large number of adverse reactions caused by benznidazole administration, it is considered safe when administered by a qualifi ed professional, as monitoring of the treatment can prevent complications 3 .
After reviewing the articles referenced in the letter, we have noticed that although benznidazole, when combined with both vitamins, has improved antiparasitic effects in the experimental acute phase 5 , this study was not designed to assess the outcomes of the chronic phase of the disease.Marim et al. 5 have recently reported that vitamin C administration reduced parasitemia, although no effect was observed regarding the number of amastigote nets in the other tissues 6 .This phenomenon might limit the effi cacy of the combined treatment in the chronic phase, as other researchers have reported no statistically signifi cant histopathological differences in chronically infected mice that were treated with vitamin C for 180 days 7 .
Although our group has never treated chagasic patients with benznidazole combined with cyanocobalamin and ascorbic acid, Ribeiro et al. 8 have conducted a study where they administered vitamins C and E for 6 months following the termination of benznidazole treatment.The authors concluded that supplementation with both vitamins reduced the oxidative stress produced by the disease itself, as well as that produced by the administration of benznidazole.
More conclusive results would be needed to demonstrate that there is a real improvement in the trypanocidal effect or clinical outcomes associated with the concomitant use of the vitamins and benznidazole in the chronic phase.Besides, vitamin C may exert prooxidant or antioxidant effects in a dosedependent manner 9,10 , and its cytotoxicity may be increased by concomitant use of vitamin B12 11 .In this way, vitamin C might either reduce or enhance the oxidative burst when simultaneously administered with benznidazole, and therefore concerns exist regarding this treatment's effi cacy and safety.On the other hand, the evidence provided by studies conducted in chronic chagasic patients may justify the use of vitamin C following termination of benznidazole treatment, in order to decrease the oxidative stress 8 .