Supplementary vitamin E, selenium, cysteine and riboflavin for preventing kwashiorkor in preschool children in developing countries.

BACKGROUND: Protein Energy Malnutrition is an important cause of child morbidity and mortality in middle- and low-income countries. It has been suggested that excessive free radical activity may be responsible for the clinical manifestation of kwashiorkor. Antioxidants may be able to curb excessive free radical activity and prevent the development of kwashiorkor in susceptible children. OBJECTIVES: To evaluate the benefits of supplementation of vitamin E, selenium, cysteine and riboflavin (alone or in combination) in preventing kwashiorkor. SEARCH STRATEGY: We conducted searches of CENTRAL 2009 (The Cochrane Library 2009 Issue 2), MEDLINE 1966 to 2009, EMBASE 1980 to 2009, CINAHL 1982 to 2009, LILACS 1982 to 2009, Meta register of Controlled trials, Open Sigle, African Index Medicus. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating vitamin E, selenium, cysteine and riboflavin alone or in combination in healthy pre-school children in middle- and low-income countries. DATA COLLECTION AND ANALYSIS: Two authors extracted and independently analysed data. MAIN RESULTS: One cluster-RCT including 2372 children met our inclusion criteria. Children were randomised, based on household, either to a supplement containing all four micronutrients or to placebo. No statistically significant difference in the incidence of kwashiorkor between the intervention and control groups could be demonstrated at 20 weeks (RR 1.70; 95% CI 0.98 to 2.42). Nor could any statistically significant difference in all-cause mortality be demonstrated (RR 0.75; 95% CI 0.17 to 3.36). AUTHORS' CONCLUSIONS: Based on the one available trial, we could draw no firm conclusion for the effectiveness of supplementary antioxidant micronutrients for the prevention of kwashiorkor in pre-school children.

Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi.

BACKGROUND: Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS: We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765. FINDINGS: Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION: In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies. FUNDING: Department for International Development (DfID).

Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial.

OBJECTIVE: To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor. DESIGN: Prospective, double blind, placebo controlled trial randomised by household. SETTING: 8 villages in rural southern Malawi. PARTICIPANTS: 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial. INTERVENTION: Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks. MAIN OUTCOME MEASURES: The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms. RESULTS: 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea. CONCLUSIONS: Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor.

Malnutrition in South Africa: some thoughts on the problem.

With special reference to pellagra and kwahiorkor, malnutirtion in South Africa is discussed in relation to the depth in which it is necessary to study malnutrition before action programmes are instituted; the time lag between research and adequate programmes for action; the importance of taking cultural factors into account in health education and in other applications of research; the importance of dealing with nutritional problems holistically and the limits of the researcher's responsibility. Suggestions regarding the responsibilities of various groups that should be involved in eradicating malnutrition are made.