title: Nutrition, infection and stunting: the roles of deficiencies of individual nutrients and foods, and of inflammation, as determinants of reduced linear growth of children.
abstract: The regulation of linear growth by nutritional and inflammatory influences is examined in terms of growth-plate endochondral ossification, in order to better understand stunted growth in children. Linear growth is controlled by complex genetic, physiological, and nutrient-sensitive endocrine/paracrine/autocrine mediated molecular signalling mechanisms, possibly including sleep adequacy through its influence on growth hormone secretion. Inflammation, which accompanies most infections and environmental enteric dysfunction, inhibits endochondral ossification through the action of mediators including proinflammatory cytokines, the activin A-follistatin system, glucocorticoids and fibroblast growth factor 21 (FGF21). In animal models linear growth is particularly sensitive to dietary protein as well as Zn intake, which act through insulin, insulin-like growth factor-1 (IGF-1) and its binding proteins, triiodothyronine, amino acids and Zn2+ to stimulate growth-plate protein and proteoglycan synthesis and cell cycle progression, actions which are blocked by corticosteroids and inflammatory cytokines. Observational human studies indicate stunting to be associated with nutritionally poor, mainly plant-based diets. Intervention studies provide some support for deficiencies of energy, protein, Zn and iodine and for multiple micronutrient deficiencies, at least during pregnancy. Of the animal-source foods, only milk has been specifically and repeatedly shown to exert an important influence on linear growth in both undernourished and well-nourished children. However, inflammation, caused by infections, environmental enteric dysfunction, which may be widespread in the absence of clean water, adequate sanitation and hygiene (WASH), and endogenous inflammation associated with excess adiposity, in each case contributes to stunting, and may explain why nutritional interventions are often unsuccessful. Current interventions to reduce stunting are targeting WASH as well as nutrition.
authors.affiliation: Department of Nutritional Sciences,School of Biosciences and Medicine, Faculty of Health and Medical Sciences,University of Surrey,Guildford GU2 7XH,UK.
authors.forename: D Joe
authors.initials: DJ
authors.lastname: Millward
mesh_terms: D000818:Animals; D002648:Child; D002657:Child Development; D002664:Child Nutritional Physiological Phenomena; D004044:Dietary Proteins / Q000008:administration & dosage; D004703:Endocrine System / Q000503:physiopathology; D002149:Energy Intake; D005260:Female; D006130:Growth Disorders; D006801:Humans; D007239:Infections; D007249:Inflammation / Q000503:physiopathology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007455:Iodine / Q000172:deficiency; D018977:Micronutrients / Q000172:deficiency; D009752:Nutritional Status / Q000502:physiology*; D010012:Osteogenesis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011488:Protein Deficiency; D015032:Zinc / Q000172:deficiency
chemical_list: D004044:Dietary Proteins; C583557:IGF1 protein, human; D018977:Micronutrients; D007334:Insulin-Like Growth Factor I; D007455:Iodine; D015032:Zinc
keywords:  1;  ASF animal-source food;  CRP C-reactive protein;  FGF fibroblast growth factor;  GH growth hormone;  HA height-for-age;  IGF insulin-like growth factor;  IGFBP insulin-like growth factor binding protein;  LNS lipid-based nutrient supplement;  PTH parathyroid hormone;  PTHrP parathyroid-hormone-related protein;  QPM quality protein maize;  T3 triiodothyronine;  T4 thyroxine;  TGF transforming growth factor;  TSH thyroid-stimulating hormone;  WA weight-for-age;  WASH clean water;  WH weight-for-height;  ZD Zn deficient;  adequate sanitation and hygiene;  mTORC1 mammalian target of rapamycin complex 1; 25(OH)2D 1; 25-dihydroxyvitamin D; Endochondral ossification; Environmental enteric dysfunction; Iodine; Micronutrients; Milk; Protein; Zinc