The association of serum choline with linear growth failure in young children from rural Malawi.
Choline is an essential nutrient for cell structure, cell signaling, neurotransmission, lipid transport, and bone formation. Choline can be irreversibly converted to betaine, a major source of methyl groups. Trimethylene N-oxide (TMAO), a proatherogenic molecule, is produced from the metabolism of dietary choline by the gut microbiome. The relation between serum choline and its closely related metabolites with linear growth in children is unknown.



The aim was to characterize the relation between serum choline and its closely related metabolites, betaine and TMAO, with linear growth and stunting in young children.



We measured serum choline, betaine, and TMAO concentrations by using liquid chromatography isotopic dilution tandem mass spectrometry in a cross-sectional study in 325 Malawian children, aged 12-59 mo, of whom 62% were stunted.



Median (25th, 75th percentile) serum choline, betaine, and TMAO concentrations were 6.4 (4.8, 8.3), 12.4 (9.1, 16.3), and 1.2 (0.7, 1.8) μmol/L, respectively. Spearman correlation coefficients of age with serum choline, betaine, and TMAO were -0.57 (P < 0.0001), -0.26 (P < 0.0001), and -0.10 (P = 0.07), respectively. Correlation coefficients of height-for-age z score with serum choline, betaine-to-choline ratio, and TMAO-to-choline ratio were 0.31 (P < 0.0001), -0.24 (P < 0.0001), and -0.29 (P < 0.0001), respectively. Serum choline concentrations were strongly and significantly associated with stunting. Children with and without stunting had median (25th, 75th percentile) serum choline concentrations of 5.6 (4.4, 7.4) and 7.3 (5.9, 9.1) μmol/L (P < 0.0001).



Linear growth failure in young children is associated with low serum choline and elevated betaine-to-choline and TMAO-to-choline ratios. Further work is needed to understand whether low dietary choline intake explains low circulating choline among stunted children living in low-income countries and whether increasing choline intake may correct choline deficiency and improve growth and development. This trial was registered in the ISRCTN registry (www.isrctn.com) as ISRCTN14597012.
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD; rdsemba@jhmi.edu.
Richard D
RD
Semba
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD;
Pingbo
P
Zhang
National Institute on Aging, NIH, Baltimore, MD;
Marta
M
Gonzalez-Freire
National Institute on Aging, NIH, Baltimore, MD;
Ruin
R
Moaddel
Department of Pediatrics, Washington University in St. Louis, St. Louis, MO; and Departments of Community Health and Pediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi.
Indi
I
Trehan
Community Health and Pediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi.
Kenneth M
KM
Maleta
Department of Pediatrics, Washington University in St. Louis, St. Louis, MO; and Departments of.
M Isabel
MI
Ordiz
National Institute on Aging, NIH, Baltimore, MD;
Luigi
L
Ferrucci
Department of Pediatrics, Washington University in St. Louis, St. Louis, MO; and Departments of Community Health and Pediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi.
Mark J
MJ
Manary
D001622:Betaine / Q000097:blood*; D002675:Child, Preschool; D002794:Choline / Q000097:blood*; D002853:Chromatography, Liquid; D003430:Cross-Sectional Studies; D004032:Diet; D005260:Female; D006128:Growth; D006130:Growth Disorders / Q000097:blood / Q000209:etiology*; D006801:Humans; D007223:Infant; D008295:Malawi; D008297:Male; D013058:Mass Spectrometry; D008744:Methylamines / Q000097:blood*; D009752:Nutritional Status; D012307:Risk Factors; D012424:Rural Population
D008744:Methylamines; D001622:Betaine; C005855:trimethyloxamine; D002794:Choline
betaine; children; choline; linear growth; malnutrition; stunting; trimethylene-N-oxide; undernutrition