Long-chain PUFA supplementation in rural African infants: A randomized controlled trial of effects on gut integrity, growth, and cognitive development

Medical Research Council and Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 12/2012; 97(1). DOI: 10.3945/ajcn.112.042267
Source: PubMed


Background: Intestinal damage and malabsorption caused by chronic environmental enteropathy are associated with growth faltering seen in infants in less-developed countries. Evidence has suggested that supplementary omega-3 (n−3) long-chain PUFAs (LC-PUFAs) might ameliorate this damage by reducing gastrointestinal inflammation. LC-PUFA supplementation may also benefit cognitive development.
Objective: We tested whether early n−3 LC-PUFA supplementation improves infant intestinal integrity, growth, and cognitive function.
Design: A randomized, double-blind, controlled trial [200 mg DHA and 300 mg EPA or 2 mL olive oil/d for 6 mo] was conducted in a population of 172 rural Gambian infants aged 3–9 mo. The primary endpoints were anthropometric measures and gut integrity [assessed by using urinary lactulose:mannitol ratios (LMRs)]. Plasma fatty acid status, intestinal mucosal inflammation (fecal calprotectin), daily morbidity, and cognitive development (2-step means-end test and an attention assessment) were secondary endpoints.
Results: PUFA supplementation resulted in a significant increase in plasma n−3 LC-PUFA concentrations (P < 0.001 for both DHA and EPA) and midupper arm circumference (MUAC) (effect size: 0.31 z scores; 95% CI: 0.06, 0.56; P = 0.017) at 9 mo of age. At 12 mo, MUAC remained greater in the intervention group, and we observed significant increases in skinfold thicknesses (P ≤ 0.022 for all). No other significant differences between treatment groups were detected for growth or LMRs at 9 mo or for secondary outcomes.
Conclusions: Fish-oil supplementation successfully increased plasma n−3 fatty acid status. However, in young, breastfed Gambian infants, the intervention failed to improve linear growth, intestinal integrity, morbidity, or selected measures of cognitive development. The trial was registered at as ISRCTN66645725.

13 Reads
  • Source
    • "There is no established therapy to reverse the changes of EE. Antibiotics [8], probiotics [9], glutamine supplementation [10] and long chain fatty acid supplements [11] have been tried without success. Multiple micronutrient (MM) supplementation is an attractive potential therapy as micronutrients such as zinc [12,13] and vitamin A [14] have previously been shown to reduce morbidity and mortality from infectious diarrhoeal illnesses, hinting at an immunological role in the intestine. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Environmental enteropathy (EE) is an asymptomatic abnormality of small bowel structure and function, which may underlie vaccine inefficacy in the developing world. HIV infection co-exists in many of these populations. There is currently no effective treatment. We conducted a secondary analysis of a randomised controlled trial of high dose multiple micronutrient (MM) supplementation on small bowel architecture in EE in participants with or without HIV infection. In a double-blind parallel-group trial of the effect of MM on innate immune responses to oral vaccines, consenting Zambian adults were randomised to receive 6 weeks of 24 micronutrients as a daily capsule or placebo. HIV status was established after randomisation. Proximal jejunal biopsies were obtained after the supplementation period. Villous height, crypt depth, villous width, villous perimeter per 100 mum muscularis mucosa (a measure of epithelial surface area), and villous cross sectional area per 100 mum muscularis mucosa (a measure of villous compartment volume) were measured in orientated biopsy sections using semi-automated image analysis. Analysis was by intention to treat. 18 patients received MM and 20 placebo. 6/18 MM and 9/20 placebo patients had HIV. In HIV negative patients given MM compared to placebo, mean villous height was 24.0% greater (293.3 v. 236.6 mum; 95% CI of difference 17.7-95.9 mum; P = 0.006), mean villous area was 27.6% greater (27623 v. 21650 mum2/100 mum; 95% CI of difference 818-11130 mum2/100 mum; P = 0.03), and median villous perimeter was 29.7% greater (355.0 v. 273.7 mum/100 mum; 95% CI of difference 16.3-146.2 mum/100 mum; P = 0.003). There was no significant effect on crypt depth or villous width. No effect was observed in HIV positive patients. There were no adverse events attributable to MM. MM improved small bowel villous height and absorptive area, but not crypt depth, in adults with EE without HIV. Nutritional intervention may therefore selectively influence villous compartment remodelling. In this small study, there was a clear difference in response depending on HIV status, suggesting that EE with superimposed HIV enteropathy may be a distinct pathophysiological condition.
    BMC Gastroenterology 01/2014; 14(1):15. DOI:10.1186/1471-230X-14-15 · 2.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Enteric infections are common during the first years of life in low-income countries and contribute to growth faltering with long-term impairment of health and development. Water quality, sanitation, handwashing and nutritional interventions can independently reduce enteric infections and growth faltering. There is little evidence that directly compares the effects of these individual and combined interventions on diarrhoea and growth when delivered to infants and young children. The objective of the WASH Benefits study is to help fill this knowledge gap. WASH Benefits includes two cluster-randomised trials to assess improvements in water quality, sanitation, handwashing and child nutrition-alone and in combination-to rural households with pregnant women in Kenya and Bangladesh. Geographically matched clusters (groups of household compounds in Bangladesh and villages in Kenya) will be randomised to one of six intervention arms or control. Intervention arms include water quality, sanitation, handwashing, nutrition, combined water+sanitation+handwashing (WSH) and WSH+nutrition. The studies will enrol newborn children (N=5760 in Bangladesh and N=8000 in Kenya) and measure outcomes at 12 and 24 months after intervention delivery. Primary outcomes include child length-for-age Z-scores and caregiver-reported diarrhoea. Secondary outcomes include stunting prevalence, markers of environmental enteropathy and child development scores (verbal, motor and personal/social). We will estimate unadjusted and adjusted intention-to-treat effects using semiparametric estimators and permutation tests. Study protocols have been reviewed and approved by human subjects review boards at the University of California, Berkeley, Stanford University, the International Centre for Diarrheal Disease Research, Bangladesh, the Kenya Medical Research Institute, and Innovations for Poverty Action. Independent data safety monitoring boards in each country oversee the trials. This study is funded by a grant from the Bill & Melinda Gates Foundation to the University of California, Berkeley. Trial registration identifiers ( NCT01590095 (Bangladesh), NCT01704105 (Kenya).
    BMJ Open 08/2013; 3(8):e003476. DOI:10.1136/bmjopen-2013-003476 · 2.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine whether DHA supplementation improves the behavior of children with autism. 3 to 10 year old children with autism were randomized in a double-blind fashion to receive a supplement containing 200 mg of DHA or a placebo for 6 months. Parent and investigator Clinical Global Impressions-Improvement (CGI-I) scales were completed to rate changes in core symptoms of autism after 3 and 6 months. Parents completed the Child Development Inventory (CDI) and Aberrant Behavior Checklist (ABC), and both parents and teachers completed the Behavior Assessment Scale for Children (BASC) at enrollment and after 6 months. 48 children (40 [83%] male; mean age [SD] = 6.1 [2.0] years) were enrolled; 24 received DHA and 24 placebo. Despite a median 431% increase in total plasma DHA levels after 6 months, the DHA group was not rated as improved in core symptoms of autism compared to the placebo group on the CGI-I. Based on analysis of covariance models adjusted for the baseline rating scores, parents (but not teachers) provided a higher average rating of social skills on the BASC for the children in the placebo group compared to the DHA group (p = 0.04), and teachers (but not parents) provided a higher average rating of functional communication on the BASC for the children in the DHA group compared to the placebo group (p = 0.02). Dietary DHA supplementation of 200 mg per day for 6 months does not improve the core symptoms of autism. Our results may have been limited by inadequate sample size.
    Journal of pediatric gastroenterology and nutrition 12/2013; DOI:10.1097/MPG.0000000000000260 · 2.63 Impact Factor
Show more

Similar Publications


13 Reads
Available from