Child Stunting is Associated with Low Circulating Essential Amino Acids

Abstract

Background: Stunting affects about one-quarter of children under five worldwide. The pathogenesis of stunting is poorly understood. Nutritional interventions have had only modest effects in reducing stunting. We hypothesized that insufficiency in essential amino acids may be limiting the linear growth of children.

Methods: We used a targeted metabolomics approach to measure serum amino acids, glycerophospholipids, sphingolipids, and other metabolites using liquid chromatography-tandem mass spectrometry in 313 children, aged 12-59months, from rural Malawi. Children underwent anthropometry.

Findings: Sixty-two percent of the children were stunted. Children with stunting had lower serum concentrations of all nine essential amino acids (tryptophan, isoleucine, leucine, valine, methionine, threonine, histidine, phenylalanine, lysine) compared with nonstunted children (p<0.01). In addition, stunted children had significantly lower serum concentrations of conditionally essential amino acids (arginine, glycine, glutamine), non-essential amino acids (asparagine, glutamate, serine), and six different sphingolipids compared with nonstunted children. Stunting was also associated with alterations in serum glycerophospholipid concentrations.

Interpretation: Our findings support the idea that children with a high risk of stunting may not be receiving an adequate dietary intake of essential amino acids and choline, an essential nutrient for the synthesis of sphingolipids and glycerophospholipids.

Keywords: Amino acids; Children; Glycerophospholipids; Malnutrition; Sphingolipids; Stunting.

Fig. 1

Heat map showing the relationship of the fifty most significant serum metabolites by HAZ, adjusted by age and gender. HAZ divided into deciles. Metabolites are ordered by p-values, with the lowest p-values on the left side. Standard three-letter abbreviations used for amino acids. Abbreviations for lipid nomenclature are described in the methods section. Other abbreviation: carnitine (C0).

Fig. 2

Volcano plot showing the relationship of partial Spearman correlations, adjusted for age and gender, between HAZ and serum metabolites using Bonferroni-adjusted p-values. Horizontal line indicates p-value cut-off for Bonferroni-adjusted p-value of 0.05/5 (p < 0.01).

Fig. 3

Scatterplots and fitted regression curves using natural cubic splines for the 20 serum metabolites with the most significant correlations. Abbreviations for lipid nomenclature are described in the methods section. Standard three-letter abbreviations used for amino acids.