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Introduction
Kwashiorkor is a form of severe childhood malnutrition defined by oedema and characterised by anorexia, irritability, ulcerating dermatosis, and fatty infiltration of the liver. 1 2 The hypothesis that kwashiorkor is a consequence of dietary protein deficiency and hypoalbuminemia has been advanced widely. 3 However, this hypothesis has been challenged by data showing that oedema resolves before serum albumin concentrations change, 4 children with kwashiorkor do not ingest any less protein than children with marasmus, 5 and oedema dissipates while the children are being fed a low protein diet. 6
Golden and Ramdath proposed that kwashiorkor results from an imbalance between the production of free radicals and their safe disposal. 7 This theory is supported by the observations that blood concentrations of vitamin E derivatives, glutathione, and red cell antioxidant enzymes are lower in children with kwashiorkor than in marasmic children. 8 â[euro]" 10 There is biochemical evidence of excessive lipid peroxidation in kwashiorkor, 11 as well as excessive quantities of oxidised amino acids. 12 In a small clinical trial, the administration of N-acetylcysteine, a glutathione precursor, resulted in more rapid resolution of oedema in kwashiorkor. 13 These associations between oxidative stress and kwashiorkor indicate that antioxidant depletion may cause kwashiorkor, and the onset of kwashiorkor may therefore be prevented with antioxidant supplementation.
Malawi is a rural country in Africa where 56% of childhood deaths are attributed to malnutrition and kwashiorkor is the predominant form of severe malnutrition. A large population survey of more than 25 000 children conducted in 1994 found the prevalence of kwashiorkor to be 2.5% in healthy children aged 1-3 years. 14
This study tested the hypothesis that antioxidant supplementation would prevent kwashiorkor in children in Malawi.
Methods
We conducted our study from November 2003 to March 2004 in eight villages in the Machinga district of southern Malawi. We chose this district because it was found to have the highest prevalence of kwashiorkor in southern Malawi. 14 The habitual diet of people in this region is based on maize and is supplemented with fish. Most villagers are subsistence farmers, but they have difficulties growing crops in the sandy soil surrounding the lake. About half of the villagers have access to a source of clean water. Almost everyone in this area...