Vitamin A supplementation of South African children with severe diarrhea: optimum timing for improving biochemical and clinical recovery and subsequent vitamin A status

Background. Vitamin A has well-recognized benefits for prevention of diarrh ea, but the impact of therapeutic doses given during diarrhea on biochemica l and clinical outcomes Is less clear. We investigated these potential ther apeutic benefits within a study of the optimum time for vitamin A supplemen tation to promote vitamin A status. Methods. Young children with severe diarrhea were randomized to receive 60 mg of retinol as retinyl palmitate during acute diarrhea or once symptoms h ad resolved, usually after 5 to 8 days. Either during acute diarrhea or aft er its resolution, children not receiving vitamin A were given identical pl acebo. On Days 0 and 3 we measured urinary neopterin, plasma retinol and ac ute phase proteins and intestinal permeability by the lactulose/mannitol te st. Eight weeks after discharge children returned to hospital for a modifie d dose response test of vitamin A stores, Results. Most children presented with watery diarrhea and grossly abnormal intestinal permeability and immune activation markers. At 8 weeks plasma re tinol concentrations of children receiving vitamin A during acute diarrhea, compared with those receiving it in early convalescence [0.67 (95% confide nce interval, 0.58 to 0.76) mu mol/l vs. 0.68 (95% confidence interval, 0.5 9 to 0.79) mu mol/l], and the proportion of children with deficient vitamin A stores (7 of 34 vs. 8 of 34) did not differ. Clinical features, lactulos e/mannitol tests and urinary neopterin concentrations on Day 8 also did not differ significantly when vitamin A was given early or late. Conclusions. Even when it was given during severe diarrhea, a large dose of vitamin A improved vitamin A stores inn a population in whom vitamin A def iciency is a public health problem. Vitamin A did not significantly improve early clinical or biochemical recovery from severe diarrhea.