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 diarrhea, but the impact of therapeutic doses given during diarrhea on biochemical and clinical outcomes is less clear. We investigated these potential therapeutic benefits within a study of the optimum time for vitamin A supplementation 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 had resolved, usually after 5 to 8 days. Either during acute diarrhea or after its resolution, children not receiving vitamin A were given identical placebo. On Days 0 and 3 we measured urinary neopterin, plasma retinol and acute phase proteins and intestinal permeability by the lactulose/mannitol test. Eight weeks after discharge children returned to hospital for a modified 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 retinol concentrations of children receiving vitamin A during acute diarrhea, compared with those receiving it in early convalescence [0.67 (95% confidence interval, 0.58 to 0.76) micromol/l vs. 0.68 (95% confidence interval, 0.59 to 0.79) micromol/l], and the proportion of children with deficient vitamin A stores (7 of 34 vs. 8 of 34) did not differ. Clinical features, lactulose/mannitol tests and urinary neopterin concentrations on Day 3 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 in a population in whom vitamin A deficiency is a public health problem. Vitamin A did not significantly improve early clinical or biochemical recovery from severe diarrhea.