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

Richard David Semba, Indi Trehan, Ximin Li, Norman Salem, Ruin Moaddel, M. Isabel Ordiz, Kenneth M. Maleta, Klaus Kraemer, Mark J. Manary

Research output: Contribution to journalArticle

Abstract

Background: Stunting affects ∼25% 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) ω-3 (n-3) and ω-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) γ-glutamyl amino acids, which represent an altered γ-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 ω-3 and ω-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 β-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.

Original languageEnglish (US)
Pages (from-to)1490-1499
Number of pages10
JournalThe American journal of clinical nutrition
Volume106
Issue number6
DOIs
StatePublished - Dec 1 2017

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Malawi
Growth Disorders
Unsaturated Fatty Acids
Carnitine
Growth
Serum
Glutathione
Neurotransmitter Agents
Tobacco Smoke Pollution
Essential Fatty Acids
Metabolomics
Brain
Tandem Mass Spectrometry
Metabolic Networks and Pathways
Growth and Development
Smoke
Tobacco Products
Liquid Chromatography
Tobacco
Fatty Acids

Keywords

  • arachidonic acid
  • carnitine
  • dehydroepiandrosterone
  • docosahexaenoic acid
  • malnutrition
  • pregnenolone sulfate
  • stunting

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Low serum ω-3 and ω-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi. / Semba, Richard David; Trehan, Indi; Li, Ximin; Salem, Norman; Moaddel, Ruin; Ordiz, M. Isabel; Maleta, Kenneth M.; Kraemer, Klaus; Manary, Mark J.

In: The American journal of clinical nutrition, Vol. 106, No. 6, 01.12.2017, p. 1490-1499.

Research output: Contribution to journalArticle

Semba, Richard David ; Trehan, Indi ; Li, Ximin ; Salem, Norman ; Moaddel, Ruin ; Ordiz, M. Isabel ; Maleta, Kenneth M. ; Kraemer, Klaus ; Manary, Mark J. / Low serum ω-3 and ω-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi. In: The American journal of clinical nutrition. 2017 ; Vol. 106, No. 6. pp. 1490-1499.
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abstract = "Background: Stunting affects ∼25{\%} 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) ω-3 (n-3) and ω-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) γ-glutamyl amino acids, which represent an altered γ-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 ω-3 and ω-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 β-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.",
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T1 - Low serum ω-3 and ω-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi

AU - Semba, Richard David

AU - Trehan, Indi

AU - Li, Ximin

AU - Salem, Norman

AU - Moaddel, Ruin

AU - Ordiz, M. Isabel

AU - Maleta, Kenneth M.

AU - Kraemer, Klaus

AU - Manary, Mark J.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background: Stunting affects ∼25% 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) ω-3 (n-3) and ω-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) γ-glutamyl amino acids, which represent an altered γ-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 ω-3 and ω-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 β-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.

AB - Background: Stunting affects ∼25% 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) ω-3 (n-3) and ω-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) γ-glutamyl amino acids, which represent an altered γ-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 ω-3 and ω-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 β-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.

KW - arachidonic acid

KW - carnitine

KW - dehydroepiandrosterone

KW - docosahexaenoic acid

KW - malnutrition

KW - pregnenolone sulfate

KW - stunting

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U2 - 10.3945/ajcn.117.164384

DO - 10.3945/ajcn.117.164384

M3 - Article

C2 - 29070563

AN - SCOPUS:85038130250

VL - 106

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JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

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