Low serum v-3 and v-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi

Background: Stunting affects w25% of children,5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood. Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting. Design: We measured 677 serum metabolites using liquid chromatography–tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12–59 mo, of whom 62% were stunted. Results: A low height-for-age z score (HAZ) was associated with lower serum concentrations of 1) v-3 (n–3) and v-6 (n–6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a role in brain development, 3) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and 4) g-glutamyl amino acids, which represent an altered g-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure. Conclusions: This metabolomics study shows a cross-sectional association between stunting and low serum v-3 and v-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for b-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. This trial was registered at www.controlled-trials.com as ISRCTN14597012.