With the progressive elimination of dietary protein-energy deficits, deficiencies of micronutrients are emerging as the limiting factors in ensuring children's optimal health. Data from several countries in Asia and Latin America indicate that deficiencies of vitamin C and zinc continue to be at alarming levels. This article reviews the roles of vitamin C and zinc in supporting children's growth and development, with a particular focus on the complementary roles they play in supporting immune functions and combating infections. The contemporary relevance of vitamin C and zinc deficiency in the Asian and Latin American regions, both undergoing a rapid nutritional transition, are also discussed. Overall, there is increasing evidence that deficiency of vitamin C and zinc adversely affects the physical and mental growth of children and can impair their immune defences. Nutrition should be the main vehicle for providing these essential nutrients; however, supplementation can represent a valid support method, especially in developing regions.
World Health Organization (WHO)/Food and Agriculture Organization: Diet, Nutrition and the Prevention of Chronic Diseases. WHO Technical Report Series, No. 916. Geneva: World Health Organization, 2003 (available at: http://whqlibdoc.who.int/trs/WHO_TRS_916.pdf).
2.
FairfieldKMFletcherRH: Vitamins for chronic disease prevention in adults: Scientific review. JAMA2002; 287: 3116–3126.
3.
FletcherRHFairfieldKM: Vitamins for chronic disease prevention in adults: Clinical applications. JAMA2002; 287: 3127–3129.
4.
UauyRKainJMericqV: Nutrition, child growth, and chronic disease prevention. Ann Med2008; 40: 11–20.
5.
FanjiangGKleinmanRE: Nutrition and performance in children. Curr Opin Clin Nutr Metab Care2007; 10: 342–347.
6.
KoletzkoB: Early nutrition and its later consequences: New opportunities. Adv Exp Med Biol2005; 569: 1–12.
7.
RamakrishnanUNguyenPMartorellR: Effects of micronutrients on growth of children under 5 y of age: Meta-analyses of single and multiple nutrient interventions. Am J Clin Nutr2009; 89: 191–203.
8.
SinghM: Role of micronutrients for physical growth and mental development. Indian J Pediatr2004; 71: 59–62.
9.
BellisleF: Effects of diet on behaviour and cognition in children. Br J Nutr2004; 92 (suppl 2): S227–S232.
10.
BourreJM: Effects of nutrients (in food) on the structure and function of the nervous system: Update on dietary requirements for brain. Part 1: Micronutrients. J Nutr Health Aging2006; 10: 377–385.
11.
ChandraRK: Nutrition and the immune system from birth to old age. Eur J Clin Nutr2002; 56 (suppl 3): S73–S76.
12.
MagginiSBeveridgeSSorbaraPJP: Feeding the immune system: The role of micronutrients in restoring resistance to infections. CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources2008; 3 (98): 1–21.
RickettsCD: Fat preferences, dietary fat intake and body composition in children. Eur J Clin Nutr1997; 51: 778–781.
25.
LiemDGZandstraLH: Children's liking and wanting of snack products: Influence of shape and flavour. Int J Behav Nutr Phys Act2009; 6: 38.
26.
StefanidouMMaraveliasCDonaA: Zinc: A multipurpose trace element. Arch Toxicol2006; 80: 1–9.
27.
DeruelleFBaronB: Vitamin C: Is supplementation necessary for optimal health?J Altern Complement Med2008; 14: 1291–1298.
28.
BhatnagarSNatchuUC: Zinc in child health and disease. Indian J Pediatr2004; 71: 991–995.
29.
CarrACFreiB: Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr1999; 69: 1086–1107.
30.
Institute of Medicine: VitaminC. In: Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000; pp 95–185.
31.
Institute of Medicine: Zinc. In: Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2001; pp 442–501.
32.
BrunoEJJrZiegenfussTNLandisJ: Vitamin C: Research update. Curr Sports Med Rep2006; 5: 177–181.
33.
ParkJBLevineM: Purification, cloning and expression of dehydroascorbic acid-reducing activity from human neutrophils: Identification as glutaredoxin. Biochem J1996; 315: 931–938.
34.
HimmelreichUDrewKNSerianniAS: 13C NMR studies of vitamin C transport and its redox cycling in human erythrocytes. Biochemistry1998; 37: 7578–7588.
35.
AtanassovaBDTzatchevKN: Ascorbic acid–important for iron metabolism. Folia Med (Plovdiv)2008; 50: 11–16.
36.
WintergerstESMagginiSHornigDH: Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab2006; 50: 85–94.
37.
JacobRAKelleyDSPianaltoFS: Immunocompetence and oxidant defense during ascorbate depletion of healthy men. Am J Clin Nutr1991; 54 (6 suppl): 1302S–1309S.
38.
HaaseHRinkL: Functional significance of zinc-related signaling pathways in immune cells. Annu Rev Nutr2009; 29: 133–152.
39.
PowellSR: The antioxidant properties of zinc. J Nutr2000; 130 (5S suppl): 1447S–1454S.
40.
SalgueiroMJZubillagaMLysionekA: Zinc status and immune system relationship: A review. Biol Trace Elem Res2000; 76: 193–205.
BrownKHRiveraJABhuttaZ: International Zinc Nutrition Consultative Group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull2004; 25 (1 suppl 2): S99–S203.
43.
SongYChungCSBrunoRS: Dietary zinc restriction and repletion affects DNA integrity in healthy men. Am J Clin Nutr2009; 90: 321–328.
44.
PrasadAS: Zinc and immunity. Mol Cell Biochem1998; 188: 63–69.
45.
PrasadAS: Zinc: Role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care2009; 12: 646–652.
46.
HessSYPeersonJMKingJC: Use of serum zinc concentration as an indicator of population zinc status. Food Nutr Bull2007; 28 (3 suppl): S403–S429.
47.
HessSYLönnerdalBHotzC: Recent advances in knowledge of zinc nutrition and human health. Food Nutr Bull2009; 30 (1 suppl): S5–S11.
48.
SandströmB: Micronutrient interactions: Effects on absorption and bioavailability. Br J Nutr2001; 85 (suppl 2): S181–S185.
49.
VitaleALa TorreFMartiniG: Arthritis and gum bleeding in two children. J Paediatr Child Health2009; 45: 158–160.
50.
Ratanachu-EkSSukswaiPJeerathanyasakunY: Scurvy in pediatric patients: A review of 28 cases. J Med Assoc Thai2003; 86 (suppl 3): S734–S740.
51.
WeinsteinMBabynPZlotkinS: An orange a day keeps the doctor away: Scurvy in the year 2000. Pediatrics2001; 108: E55.
52.
AkikusaJDGarrickDNashMC: Scurvy: Forgotten but not gone. J Paediatr Child Health2003; 39: 75–77.
53.
OlmedoJMYianniasJAWindgassenEB: Scurvy: A disease almost forgotten. Int J Dermatol2006; 45: 909–913.
54.
SiegenbergDBaynesRDBothwellTH: Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption. Am J Clin Nutr1991; 53: 537–541.
55.
HallbergLHulthénL: Prediction of dietary iron absorption: An algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr2000; 71: 1147–1160.
56.
TeucherBOlivaresMCoriH: Enhancers of iron absorption: Ascorbic acid and other organic acids. Int J Vitam Nutr Res2004; 74: 403–419.
57.
MaoXYaoG: Effect of vitamin C supplementations on iron deficiency anemia in Chinese children. Biomed Environ Sci1992; 5: 125–129.
58.
IannottiLLTielschJMBlackMM: Iron supplementation in early childhood: Health benefits and risks. Am J Clin Nutr2006; 84: 1261–1276.
59.
MillerJZNanceWENortonJA: Therapeutic effect of vitamin C. A co-twin control study. JAMA1977; 237: 248–251.
60.
PrasadASMialeAFaridZ: Biochemical studies on dwarfism, hypogonadism, and anemia. Arch Intern Med1963; 111: 407–428.
61.
PrasadASMialeAFaridZ: Zinc metabolism in patients with the syndrome of iron deficiency anemia, hepatosplenomegaly, dwarfism, and hypognadism. J Lab Clin Med1963; 61: 537–549.
62.
FergusonELGibsonRSOpare-ObisawC: The zinc nutriture of preschool children living in two African countries. J Nutr1993; 123: 1487–1496.
63.
RiveraJARuelMTSantizoMC: Zinc supplementation improves the growth of stunted rural Guatemalan infants. J Nutr1998; 128: 556–562.
64.
HambidgeKMWalravensPABrownRM: Zinc nutrition of preschool children in the Denver Head Start program. Am J Clin Nutr1976; 29: 734–738.
65.
WalravensPAHambidgeKM: Growth of infants fed a zinc supplemented formula. Am J Clin Nutr1976; 29: 1114–1121.
66.
WalravensPAChakarAMokniR: Zinc supplements in breastfed infants. Lancet1992; 340: 683–685.
67.
International Zinc Nutrition Consultative Group: Prevalence of Nutritional Stunting in Children Under 5 Years of Age. Dakar Yoff, Senegal: International Zinc Nutrition Consultative Group, 2006 (available at: http://www.izincg.org/stunt.php#).
68.
MaGLiYJinY: Assessment of intake inadequacy and food sources of zinc of people in China. Public Health Nutr2007; 10: 848–854.
69.
KhorGLSharifZM: Dual forms of malnutrition in the same households in Malaysia–a case study among Malay rural households. Asia Pac J Clin Nutr2003; 12: 427–437.
70.
ZalilahMSThamBL: Food security and child nutritional status among Orang Asli (Temuan) households in Hulu Langat, Selangor. Med J Malaysia2002; 57: 36–50.
World Health Organization (1995) Physical Status: The Use and Interpretation of Anthropometry 1995 WHO Geneva, Switzerland. Technical Report Series no. 854. (available at: http://whqlibdoc.who.int/trs/WHO_TRS_854.pdf).
73.
SandströmBCederbladALönnerdalB: Zinc absorption from human milk, cow's milk, and infant formulas. Am J Dis Child1983; 137: 726–729.
74.
LönnerdalB: Trace element absorption in infants as a foundation to setting upper limits for trace elements in infant formulas. J Nutr1989; 119: 1839–1844.
75.
LönnerdalBStanislowskiAGHurleyLS: Isolation of a low molecular weight zinc binding ligand from human milk. J Inorg Biochem1980; 12: 71–78.
76.
UmetaMWestCEVerhoefH: Factors associated with stunting in infants aged 5–11 months in the Dodota-Sire District, rural Ethiopia. J Nutr2003; 133: 1064–1069.
77.
DóreaJG: Zinc deficiency in nursing infants. J Am Coll Nutr2002; 21: 84–87.
78.
BrownKHPeersonJMRiveraJ: Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: A meta-analysis of randomized controlled trials. Am J Clin Nutr2002; 75: 1062–1071.
79.
YangYXHanJHShaoXP: Effect of micronutrient supplementation on the growth of preschool children in China. Biomed Environ Sci2002; 15: 196–202.
80.
PortoMA SayegOliveiraHPCunhaAJ: Linear growth and zinc supplementation in children with short stature. J Pediatr Endocrinol Metab2000; 13: 1121–1128.
81.
LindTLönnerdalBStenlundH: A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: Effects on growth and development. Am J Clin Nutr2004; 80: 729–736.
82.
SandsteadHHPenlandJGAlcockNW: Effects of repletion with zinc and other micronutrients on neuropsychologic performance and growth of Chinese children. Am J Clin Nutr1998; 68 (2 suppl): 470S–475S.
83.
RiceMERusso-MennaI: Differential compartmentalization of brain ascorbate and glutathione between neurons and glia. Neuroscience1998; 82: 1213–1223.
84.
TsukaguchiHTokuiTMackenzieB: A family of mammalian Na+-dependent l-ascorbic acid transporters. Nature1999; 399: 70–75.
85.
SotiriouSGispertSChengJ: Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. Nat Med2002; 8: 514–517.
86.
WilsonJX: Regulation of vitamin C transport. Annu Rev Nutr2005; 25: 105–125.
87.
Tveden-NyborgPLykkesfeldtJ: Does vitamin C deficiency result in impaired brain development in infants?Redox Rep2009; 14: 2–6.
88.
VenkataramanPMuthuvelRKrishnamoorthyG: PCB (Aroclor 1254) enhances oxidative damage in rat brain regions: Protective role of ascorbic acid. Neurotoxicology2007; 28: 490–498.
89.
LevineMMoritaKHeldmanE: Ascorbic acid regulation of norepinephrine biosynthesis in isolated chromaffin granules from bovine adrenal medulla. J Biol Chem1985; 260: 15598–15603.
90.
BermanSBZigmondMJHastingsTG: Modification of dopamine transporter function: Effect of reactive oxygen species and dopamine. J Neurochem1996; 67: 593–600.
91.
MieleMBoutelleMGFillenzM: The physiologically induced release of ascorbate in rat brain is dependent on impulse traffic, calcium influx and glutamate uptake. Neuroscience1994; 62: 87–91.
92.
ToddRDBauerPA: Ascorbate modulates 5-[3H]hydroxytryptamine binding to central 5-HT3 sites in bovine frontal cortex. J Neurochem1988; 50: 1505–1512.
93.
MajewskaMDBellJA: Ascorbic acid protects neurons from injury induced by glutamate and NMDA. Neuroreport1990; 1: 194–196.
94.
MajewskaMDBellJALondonED: Regulation of the NMDA receptor by redox phenomena: Inhibitory role of ascorbate. Brain Res1990; 537: 328–332.
95.
LevineMMoritaKPollardH: Enhancement of norepinephrine biosynthesis by ascorbic acid in cultured bovine chromaffin cells. J Biol Chem1985; 260: 12942–12947.
96.
PatersonIAHertzL: Sodium-independent transport of noradrenaline in mouse and rat astrocytes in primary culture. J Neurosci Res1989; 23: 71–77.
97.
LykkesfeldtJMoosT: Age-dependent change in vitamin C status: A phenomenon of maturation rather than of ageing. Mech Ageing Dev2005; 126: 892–898.
98.
Tveden-NyborgPJohansenLKRaidaZ: Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs. Am J Clin Nutr2009; 90: 540–546.
99.
FredericksonCJSuhSWSilvaD: Importance of zinc in the central nervous system: The zinc-containing neuron. J Nutr2000; 130 (5S suppl): 1471S–1483S.
100.
WallworkJC: Zinc and the central nervous system. Prog Food Nutr Sci1987; 11: 203–247.
101.
GeorgieffMK: Nutrition and the developing brain: Nutrient priorities and measurement. Am J Clin Nutr2007; 85: 614S–620S.
102.
FredericksonCJ: Neurobiology of zinc and zinc-containing neurons. Int Rev Neurobiol1989; 31: 145–238.
103.
SmartTG: Uncultured lobster muscle, cultured neurons and brain slices: The neurophysiology of zinc. J Pharm Pharmacol1990; 42: 377–387.
104.
XieXMSmartTG: A physiological role for endogenous zinc in rat hippocampal synaptic neurotransmission. Nature1991; 349: 521–524.
105.
PenlandJGSandsteadHHAlcockNW: A preliminary report: Effects of zinc and micronutrient repletion on growth and neuropsychological function of urban Chinese children. J Am Coll Nutr1997; 16: 268–272.
AshworthAMorrisSSLiraPI: Zinc supplementation, mental development and behaviour in low birth weight term infants in northeast Brazil. Eur J Clin Nutr1998; 52: 223–227.
108.
SazawalSBentleyMBlackRE: Effect of zinc supplementation on observed activity in low socioeconomic Indian preschool children. Pediatrics1996; 98: 1132–1137.
109.
BentleyMECaulfieldLERamM: Zinc supplementation affects the activity patterns of rural Guatemalan infants. J Nutr1997; 127: 1333–1338.
110.
DiGirolamoAMRamirez-ZeaM: Role of zinc in maternal and child mental health. Am J Clin Nutr2009; 89: 940S–945S.
111.
DelvesPJRoittIM: The immune system–first of two parts. N Engl J Med2000; 343: 37–49.
112.
DelvesPJRoittIM: The immune system–second of two parts. N Engl J Med2000; 343: 108–117.
113.
ParkinJCohenB: An overview of the immune system. Lancet2001; 357: 1777–1789.
114.
WebbALVillamorE: Update: Effects of antioxidant and non-antioxidant vitamin supplementation on immune function. Nutr Rev2007; 65: 181–217.
115.
StröhleAHahnA: Vitamin C and immune function. Med Monatsschr Pharm2009; 32: 49–54 [in German].
116.
ThomasWRHoltPG: Vitamin C and immunity: An assessment of the evidence. Clin Exp Immunol1978; 32: 370–379.
117.
AndersonROosthuizenRMaritzR: The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am J Clin Nutr1980; 33: 71–76.
118.
LevineMConry-CantilenaCWangY: Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc Natl Acad Sci USA1996; 93: 3704–3709.
119.
LevineMDhariwalKRWangY: Ascorbic acid in neutrophils. In: Natural Antioxidants in Health and Disease (FreiB, ed). San Diego: Academic Press, 1994; pp 469–488.
120.
PatroneFDallegriFBonviniE: Effects of ascorbic acid on neutrophil function. Studies on normal and chronic granulomatous disease neutrophils. Acta Vitaminol Enzymol1982; 4: 163–168.
121.
LevyRShrikerOPorathA: Vitamin C for the treatment of recurrent furunculosis in patients with impaired neutrophil functions. J Infect Dis1996; 173: 1502–1505.
122.
MeydaniSNWuDSantosMS: Antioxidants and immune response in aged persons: Overview of present evidence. Am J Clin Nutr1995; 62 (6 suppl): 1462S–1476S.
123.
KnightJA: Review: Free radicals, antioxidants, and the immune system. Ann Clin Lab Sci2000; 30: 145–158.
124.
HärtelCPuzikAGöpelW: Immunomodulatory effect of vitamin C on intracytoplasmic cytokine production in neonatal cord blood cells. Neonatology2007; 91: 54–60.
125.
HärtelCStrunkTBucskyP: Effects of vitamin C on intracytoplasmic cytokine production in human whole blood monocytes and lymphocytes. Cytokine2004; 27: 101–106.
126.
JohnstonCSRetrumKRSrilakshmiJC: Antihistamine effects and complications of supplemental vitamin C. J Am Diet Assoc1992; 92: 988–989.
127.
JohnstonCSMartinLJCaiX: Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis. J Am Coll Nutr1992; 11: 172–176.
128.
FlodinNW (ed): Vitamin C. In: Pharmacology of Micronutrients. New York: Alan R Liss, 1988; pp 201–244.
129.
MortolaEOkudaMOhnoK: Inhibition of apoptosis and virus replication in feline immunodeficiency virus-infected cells by N-acetylcysteine and ascorbic acid. J Vet Med Sci1998; 60: 1187–1193.
130.
BuccaCRollaGFarinaJC: Effect of vitamin C on transient increase of bronchial responsiveness in conditions affecting the airways. Ann NY Acad Sci1992; 669: 175–186.
131.
JariwallaRJHarakehS: Antiviral and immunomodulatory activities of ascorbic acid. In: Subcellular Biochemistry Ascorbic Acid: Biochemistry and Biomedical Cell Biology (HarrisJR, ed). New York: Plenum Press, 1996; pp 215–231.
132.
AndersonRSmitMJJooneGK: Vitamin C and cellular immune functions. Protection against hypochlorous acid-mediated inactivation of glyceraldehyde-3-phosphate dehydrogenase and ATP generation in human leukocytes as a possible mechanism of ascorbate-mediated immunostimulation. Ann NY Acad Sci1990; 587: 34–48.
133.
PanushRSDelafuenteJCKatzP: Modulation of certain immunologic responses by vitamin C. III. Potentiation of in vitro and in vivo lymphocyte responses. Int J Vitam Nutr Res Suppl1982; 23: 35–47.
134.
PrasadAS: Zinc in human health: Effect of zinc on immune cells. Mol Med2008; 14: 353–357.
135.
RinkLHaaseH: Zinc homeostasis and immunity. Trends Immunol2007; 28: 1–4.
136.
MocchegianiE: Zinc and ageing: Third Zincage conference. Immun Ageing2007; 4: 5.
137.
HaaseHRinkL: Signal transduction in monocytes: The role of zinc ions. Biometals2007; 20: 579–585.
138.
OverbeckSRinkLHaaseH: Modulating the immune response by oral zinc supplementation: A single approach for multiple diseases. Arch Immunol Ther Exp (Warsz)2008; 56: 15–30.
139.
TapieroHTewKD: Trace elements in human physiology and pathology: Zinc and metallothioneins. Biomed Pharmacother2003; 57: 399–411.
140.
PrasadAS: Effects of zinc deficiency on immune functions. J Trace Elem Exp Med2000; 13: 1–20.
141.
KeenCLGershwinME: Zinc deficiency and immune function. Annu Rev Nutr1990; 10: 415–431.
142.
RavagliaGFortiPMaioliF: Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged > 90 y. Am J Clin Nutr2000; 71: 590–598.
143.
AllenJIPerriRTMcClainCJ: Alterations in human natural killer cell activity and monocyte cytotoxicity induced by zinc deficiency. J Lab Clin Med1983; 102: 577–589.
144.
WellinghausenNKirchnerHRinkL: The immunobiology of zinc. Immunol Today1997; 18: 519–521.
145.
FrakerPJHaasSMLueckeRW: Effect of zinc deficiency on the immune response of the young adult A/J mouse. J Nutr1977; 107: 1889–1895.
146.
FrakerPJDePasquale-JardieuPZwicklCM: Regeneration of T-cell helper function in zinc-deficient adult mice. Proc Natl Acad Sci USA1978; 75: 5660–5664.
147.
DardenneMPléauJMNabarraB: Contribution of zinc and other metals to the biological activity of the serum thymic factor. Proc Natl Acad Sci USA1982; 79: 5370–5373.
148.
BachJFDardenneM: Thymulin, a zinc-dependent hormone. Med Oncol Tumor Pharmacother1989; 6: 25–29.
149.
PrasadAS: Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis2000; 182 (suppl 1): S62–S68.
150.
BeckFWPrasadASKaplanJ: Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. Am J Physiol1997; 272: E1002–E1007.
151.
YamasakiSSakata-SogawaKHasegawaA: Zinc is a novel intracellular second messenger. J Cell Biol2007; 177: 637–645.
152.
MagginiSWintergerstESBeveridgeS: Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses. Br J Nutr2007; 98 (suppl 1): S29–S35.
153.
BeveridgeSWintergerstESMagginiS: Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Proc Nutr Soc2008; 67: E83.
154.
MagginiSWintergerstESBeveridgeS: Contribution of selected vitamins and trace elements to immune function. Proc Nutr Soc2008; 67: E84.
155.
ShankarAHPrasadAS: Zinc and immune function: The biological basis of altered resistance to infection. Am J Clin Nutr1998; 68 (2 suppl): 447S–463S.
156.
HuseMEckMJHarrisonSC: A Zn2+ ion links the cytoplasmic tail of CD4 and the N-terminal region of Lck. J Biol Chem1998; 273: 18729–18733.
157.
LinRSRodriguezCVeilletteA: Zinc is essential for binding of p56lck to CD4 and CD8. J Biol Chem1998; 273: 32878–32882.
IbsKHRinkL: Zinc. In: Diet and Human Immune Function (HughesDADarlingtonLGBendichA, eds). Totowa, NJ: Humana Press, 2004; pp 241–259.
160.
FrakerPJKingLE: Reprogramming of the immune system during zinc deficiency. Annu Rev Nutr2004; 24: 277–298.
161.
WalkerC FischerBlackRE: Zinc and the risk for infectious disease. Annu Rev Nutr2004; 24: 255–275.
162.
FendrickAMMontoASNightengaleB: The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med2003; 163: 487–494.
163.
FuchsSCFischerGBBlackRE: The burden of pneumonia in children in Latin America. Paediatr Respir Rev2005; 6: 83–87.
164.
RomieuIManninoDMReddSC: Dietary intake, physical activity, body mass index, and childhood asthma in the Third National Health And Nutrition Survey (NHANES III). Pediatr Pulmonol2004; 38: 31–42.
165.
HumeRWeyersE: Changes in leucocyte ascorbic acid during the common cold. Scott Med J1973; 18: 3–7.
166.
RitzelG: Critical evaluation of vitamin C as a prophylactic and therapeutic agent in colds. Helv Med Acta1961; 28: 63–68 [in German].
167.
LudvigssonJHanssonLOTibblingG: Vitamin C as a preventive medicine against common colds in children. Scand J Infect Dis1977; 9: 91–98.
168.
BancalariASeguelCNeiraF: Prophylactic value of vitamin C in acute respiratory tract infections in schoolchildren. Rev Med Chil1984; 112: 871–876 [in Spanish].
169.
CohenHANeumanINahumH: Blocking effect of vitamin C in exercise-induced asthma. Arch Pediatr Adolesc Med1997; 151: 367–370.
170.
HatchGE: Asthma, inhaled oxidants, and dietary antioxidants. Am J Clin Nutr1995; 61 (3 suppl): 625S–630S.
171.
SchwartzJWeissST: Relationship between dietary vitamin C intake and pulmonary function in the First National Health and Nutrition Examination Survey (NHANES I). Am J Clin Nutr1994; 59: 110–114.
172.
AdereleWIEtteSIOduwoleO: Plasma vitamin C (ascorbic acid) levels in asthmatic children. Afr J Med Med Sci1985; 14: 115–120.
173.
RamFSRoweBHKaurB: Vitamin C supplementation for asthma. Cochrane Database Syst Rev2004: CD000993.
174.
BiltagiMABasetAABassiounyM: Omega-3 fatty acids, vitamin C and Zn supplementation in asthmatic children: A randomized self-controlled study. Acta Paediatr2009; 98: 737–742.
175.
AllenSBrittonJRLeonardi-BeeJA: Association between antioxidant vitamins and asthma outcome measures: Systematic review and meta-analysis. Thorax2009; 64: 610–619.
176.
PrestonAMRodriguezCRiveraCE: Influence of environmental tobacco smoke on vitamin C status in children. Am J Clin Nutr2003; 77: 167–172.
Health effects of outdoor air pollution. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society. Am J Respir Crit Care Med1996; 153: 3–50.
179.
RomieuISienra-MongeJJRamírez-AguilarM: Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Am J Respir Crit Care Med2002; 166: 703–709.
180.
PrasadAS: Zinc: Mechanisms of host defense. J Nutr2007; 137: 1345–1349.
181.
LarsonCPRoySKKhanAI: Zinc treatment to under-five children: Applications to improve child survival and reduce burden of disease. J Health Popul Nutr2008; 26: 356–365.
182.
BhuttaZABlackREBrownKH: Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomized controlled trials. Zinc Investigators’ Collaborative Group. J Pediatr1999; 135: 689–697.
183.
BhandariNBahlRTanejaS: Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: Randomised controlled trial in an urban slum. BMJ2002; 324: 1358.
184.
BrooksWAYunusMSantoshamM: Zinc for severe pneumonia in very young children: Double-blind placebo-controlled trial. Lancet2004; 363: 1683–1688.
185.
BlackRE: Zinc deficiency, infectious disease and mortality in the developing world. J Nutr2003; 133 (5 suppl 1): 1485S–1489S.
186.
BrownKHBakerSKIZiNCG Steering Committee: Galvanizing action: Conclusions and next steps for mainstreaming zinc interventions in public health programs. Food Nutr Bull2009; 30 (1 suppl): S179–S184.
187.
HaiderBABhuttaZA: The effect of therapeutic zinc supplementation among young children with selected infections: A review of the evidence. Food Nutr Bull2009; 30 (1 suppl): S41–S59.
188.
BrownKHPeersonJMBakerSK: Preventive zinc supplementation among infants, preschoolers, and older prepubertal children. Food Nutr Bull2009; 30 (1 suppl): S12–S40.
189.
BrownLM: Helicobacter pylori: Epidemiology and routes of transmission. Epidemiol Rev2000; 22: 283–297.
190.
PounderRENgD: The prevalence of Helicobacter pylori infection in different countries. Aliment Pharmacol Ther1995; 9 (suppl 2): 33–39.
191.
SalgueiroJZubillagaMGoldmanC: Review article: Is there a link between micronutrient malnutrition and Helicobacter pylori infection?Aliment Pharmacol Ther2004; 20: 1029–1034.
192.
AkyönY: Effect of antioxidants on the immune response of Helicobacter pylori. Clin Microbiol Infect2002; 8: 438–441.
193.
KimDSLeeMSKimYS: Effect modification by vitamin C on the relation between gastric cancer and Helicobacter pylori. Eur J Epidemiol2005; 20: 67–71.
194.
HahmKBLeeKJKimJH: Helicobacter pylori infection, oxidative DNA damage, gastric carcinogenesis, and reversibility by rebamipide. Dig Dis Sci1998; 43 (9 suppl): 72S–77S.
195.
BlanchardTGCzinnSJ: Review article: Immunological determinants that may affect the Helicobacter pylori cancer risk. Aliment Pharmacol Ther1998; 12 (suppl 1): 83–90.
196.
LindholmCQuiding-JärbrinkMLönrothH: Local cytokine response in Helicobacter pylori-infected subjects. Infect Immun1998; 66: 5964–5971.
197.
WoodwardMTunstall-PedoeHMcCollK: Helicobacter pylori infection reduces systemic availability of dietary vitamin C. Eur J Gastroenterol Hepatol2001; 13: 233–237.
198.
AnnibaleBCapursoGDelle FaveG: Consequences of Helicobacter pylori infection on the absorption of micronutrients. Dig Liver Dis2002; 34 (suppl 2): S72–S77.
199.
WangXWillénRWadströmT: Astaxanthin-rich algal meal and vitamin C inhibit Helicobacter pylori infection in BALB/cA mice. Antimicrob Agents Chemother2000; 44: 2452–2457.
200.
ChatterjeeABagchiDYasminT: Antimicrobial effects of antioxidants with and without clarithromycin on Helicobacter pylori. Mol Cell Biochem2005; 270: 125–130.
201.
ParkJHKimSYKimDW: Correlation between Helicobacter pylori infection and vitamin C levels in whole blood, plasma, and gastric juice, and the pH of gastric juice in Korean children. J Pediatr Gastroenterol Nutr2003; 37: 53–62.
202.
SasazukiSSasakiSTsubonoY: The effect of 5-year vitamin C supplementation on serum pepsinogen level and Helicobacter pylori infection. Cancer Sci2003; 94: 378–382.
203.
GoodmanKJCorreaPAuxHJ Tenganá: Nutritional factors and Helicobacter pylori infection in Colombian children. J Pediatr Gastroenterol Nutr1997; 25: 507–515.
204.
KikuchiS: Epidemiology of Helicobacter pylori and gastric cancer. Gastric Cancer2002; 5: 6–15.
205.
ZhangZWFarthingMJ: The roles of vitamin C in Helicobacter pylori associated gastric carcinogenesis. Chin J Dig Dis2005; 6: 53–58.
206.
JaroszMRychlikESiubaM: Dietary and socio-economic factors in relation to Helicobacter pylori re-infection. World J Gastroenterol2009; 15: 1119–1125.
207.
Boschi-PintoCVelebitLShibuyaK: Estimating child mortality due to diarrhoea in developing countries. Bull World Health Organ2008; 86: 710–717.
208.
BryceJBoschi-PintoCShibuyaK: WHO estimates of the causes of death in children. Lancet2005; 365: 1147–1152.
209.
KosekMBernCGuerrantRL: The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ2003; 81: 197–204.
210.
BrownKH: Diarrhea and malnutrition. J Nutr2003; 133: 328S–332S.
211.
LazzeriniMRonfaniL: Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev2008: CD005436.
212.
JonesGSteketeeRWBlackRE: How many child deaths can we prevent this year?Lancet2003; 362: 65–71.
213.
BhuttaZABirdSMBlackRE: Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: Pooled analysis of randomized controlled trials. Am J Clin Nutr2000; 72: 1516–1522.
214.
BrooksWASantoshamMNaheedA: Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: Randomised controlled trial. Lancet2005; 366: 999–1004.
215.
RahmanMMVermundSHWahedMA: Simultaneous zinc and vitamin A supplementation in Bangladeshi children: Randomised double blind controlled trial. BMJ2001; 323: 314–318.
216.
BaquiAHZamanKPerssonLA: Simultaneous weekly supplementation of iron and zinc is associated with lower morbidity due to diarrhea and acute lower respiratory infection in Bangladeshi infants. J Nutr2003; 133: 4150–4157.
217.
BahlRBhandariNSaksenaM: Efficacy of zinc-fortified oral rehydration solution in 6-to 35-month-old children with acute diarrhea. J Pediatr2002; 141: 677–682.
218.
GuptaDNMondalSKGhoshS: Impact of zinc supplementation on diarrhoeal morbidity in rural children of West Bengal, India. Acta Paediatr2003; 92: 531–536.
219.
BhatnagarSBahlRSharmaPK: Zinc with oral rehydration therapy reduces stool output and duration of diarrhea in hospitalized children: A randomized controlled trial. J Pediatr Gastroenterol Nutr2004; 38: 34–40.
220.
Al-SonboliNGurgelRQShenkinA: Zinc supplementation in Brazilian children with acute diarrhoea. Ann Trop Paediatr2003; 23: 3–8.
221.
World Health Organization (WHO)/United Nations Children's Fund (UNICEF): WHO/UNICEF Joint Statement. Clinical Management of Acute Diarrhoea (WHO/FCH/CAH/04.7 or UNICEF/PD/Diarrhoea/01). Geneva: WHO/New York: UNICEF, 2004 (available at: http://rehydrate.org/diarrhoea/pdf/acute-diarrhoea.pdf).
222.
GhishanFK: Transport of electrolytes, water, and glucose in zinc deficiency. J Pediatr Gastroenterol Nutr1984; 3: 608–612.
223.
PatrickJGoldenBEGoldenMH: Leucocyte sodium transport and dietary zinc in protein energy malnutrition. Am J Clin Nutr1980; 33: 617–620.
224.
PatrickJMichaelJGoldenMN: Effect of zinc on leucocyte sodium transport in vitro. Clin Sci Mol Med1978; 54: 585–587.
225.
BettgerWJO'DellBL: A critical physiological role of zinc in the structure and function of biomembranes. Life Sci1981; 28: 1425–1438.
226.
ElmesMEJonesJG: Ultrastructural changes in the small intestine of zinc deficient rats. J Pathol1980; 130: 37–43.
227.
MoranJRLewisJC: The effects of severe zinc deficiency on intestinal permeability: An ultrastructural study. Pediatr Res1985; 19: 968–973.
228.
RoySKBehrensRHHaiderR: Impact of zinc supplementation on intestinal permeability in Bangladeshi children with acute diarrhoea and persistent diarrhoea syndrome. J Pediatr Gastroenterol Nutr1992; 15: 289–296.
229.
GebhardRLKarouaniRPriggeWF: The effect of severe zinc deficiency on activity of intestinal disaccharidases and 3-hydroxy-3-methylglutaryl coenzyme A reductase in the rat. J Nutr1983; 113: 855–859.
230.
JonesPEPetersTJ: Oral zinc supplements in non-responsive coeliac syndrome: Effect on jejunal morphology, enterocyte production, and brush border disaccharidase activities. Gut1981; 22: 194–198.
231.
LueckeRWFrakerPJ: The effect of varying dietary zinc levels on growth and antibody-mediated response in two strains of mice. J Nutr1979; 109: 1373–1376.
232.
FrakerPJ: Zinc deficiency: A common immunodeficiency state. Surv Immunol Res1983; 2: 155–163.
233.
SazawalSJallaSMazumderS: Effect of zinc supplementation on cell-mediated immunity and lymphocyte subsets in preschool children. Indian Pediatr1997; 34: 589–597.
234.
WalkerCL FischerFontaineOYoungMW: Zinc and low osmolarity oral rehydration salts for diarrhoea: A renewed call to action. Bull World Health Organ2009; 87: 780–786.
235.
BatesCJEvansPHDardenneM: A trial of zinc supplementation in young rural Gambian children. Br J Nutr1993; 69: 243–255.
236.
GibsonRSHuddleJM: Suboptimal zinc status in pregnant Malawian women: Its association with low intakes of poorly available zinc, frequent reproductive cycling, and malaria. Am J Clin Nutr1998; 67: 702–709.
237.
Zinc Against Plasmodium Study Group: Effect of zinc on the treatment of Plasmodium falciparum malaria in children: A randomized controlled trial. Am J Clin Nutr2002; 76: 805–812.
238.
BakerEMHodgesREHoodJ: Metabolism of 14C- and 3H-labeled L-ascorbic acid in human scurvy. Am J Clin Nutr1971; 24: 444–454.
239.
LevineMKatzAPadayattySJ: Vitamin C. In: Modern Nutrition in Health and Disease, 10th edn (ShilsMEShikeMRossAC, eds). Baltimore: Lippincott Williams & Wilkins, 2006; pp 507–524.
240.
JacobRA: Vitamin C. In: Modern Nutrition in Health and Disease, 9th edn (ShilsMEOlsenJAShikeM, eds). Philadelphia: Lippincott Williams & Wilkins, 1999; pp 467–483.
241.
SchorahCJ: Vitamin C status in population groups. In: Vitamin C (Ascorbic Acid) (CounsellJNHornigDH, eds). London: Applied Science, 1981; pp 23–47.
242.
TribbleDLGiulianoLJFortmannSP: Reduced plasma ascorbic acid concentrations in nonsmokers regularly exposed to environmental tobacco smoke. Am J Clin Nutr1993; 58: 886–890.
243.
DietrichMBlockGBenowitzNL: Vitamin C supplementation decreases oxidative stress biomarker F2-isoprostanes in plasma of nonsmokers exposed to environmental tobacco smoke. Nutr Cancer2003; 45: 176–184.
244.
VillalpandoSMontalvo-VelardeIZambranoN: Vitamins A, and C and folate status in Mexican children under 12 years and women 12–49 years: A probabilistic national survey. Salud Publica Mex2003; 45 (suppl 4): S508–S519.
245.
RiveraJAAmorJ Sepúlveda: Conclusions from the Mexican National Nutrition Survey 1999: Translating results into nutrition policy. Salud Publica Mex2003; 45 (suppl 4): S565–S575.
246.
DeweyKG: Nutrition survey in Tabasco, Mexico: Nutritional status of preschool children. Am J Clin Nutr1983; 37: 1010–1019.
247.
Encuesta Nacional de Nutrición y Salud: Documento de Resultados. Buenos Aries: Ministerio de Salud de la Nacion, 2006 (available at: http://www.msal.gov.ar/htm/site/ennys/) [in Spanish].
248.
PerlasLAGibsonRSAdairLS: Macronutrient and selected vitamin intakes from complementary foods of infants and toddlers from Cebu, Philippines. Int J Food Sci Nutr2004; 55: 1–15.
249.
GibsonRSMangerMSKrittapholW: Does zinc deficiency play a role in stunting among primary school children in NE Thailand?Br J Nutr2007; 97: 167–175.
250.
LeungSSChanSMLuiS: Growth and nutrition of Hong Kong children aged 0–7 years. J Paediatr Child Health2000; 36: 56–65.
251.
Instituto Brasileiro de Geografia e Estatística (IBGE): Pesquisa de Orçamentos Familiares 2002–2003. Análise da Disponibilidade Domiciliar de Alimentos e do Estado Nutricional no Brasil. In: IBGE, Coordenação de Índices de Preços. Rio de Janeiro: IBGE, 2004 [in Portuguese].
252.
KingJCCousinsRJ: Zinc. In: Modern Nutrition in Health and Disease, 10th edn (ShilsMEShikeMRossAC, eds). Baltimore: Lippincott Williams & Wilkins, 2006; pp 271–285.
253.
HotzCPeersonJMBrownKH: Suggested lower cutoffs of serum zinc concentrations for assessing zinc status: Reanalysis of the second National Health and Nutrition Examination Survey data (1976–1980). Am J Clin Nutr2003; 78: 756–764.
254.
MaretWSandsteadHH: Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol2006; 20: 3–18.
255.
GibsonRSHessSYHotzC: Indicators of zinc status at the population level: A review of the evidence. Br J Nutr2008; 99 (suppl 3): S14–S23.
256.
PrasadAS: Discovery of human zinc deficiency: Impact on human health. Nutrition2001; 17: 685–687.
257.
HambidgeM: Human zinc deficiency. J Nutr2000; 130 (5S suppl): 1344S–1349S.
258.
AggettPJComerfordJG: Zinc and human health. Nutr Rev1995; 53: S16–S22.
259.
BahlRBhandariNHambidgeKM: Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting. Am J Clin Nutr1998; 68 (2 suppl): 414S–417S.
260.
BhandariNBahlRHambidgeKM: Increased diarrhoeal and respiratory morbidity in association with zinc deficiency a preliminary report. Acta Paediatr1996; 85: 148–150.
261.
WagstaffABustreoFBryceJ: Child health: Reaching the poor. Am J Public Health2004; 94: 726–736.
262.
Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO): Zinc: In Human Vitamin and Mineral Requirements. Report of a Joint FAO/WHO Expert Consultation. Rome: FAO/Geneva: WHO, 2002, pp 257–270.
263.
TeeESFlorentinoR: Recommended Dietary Allowances (RDA) Harmonization in Southeast Asia. Monograph Series. Singapore: International Life Sciences Institute, Southeast Asia Region, 2005.
264.
SandsteadHHPrasadASPenlandJG: Zinc deficiency in Mexican American children: Influence of zinc and other micronutrients on T cells, cytokines, and antiinflammatory plasma proteins. Am J Clin Nutr2008; 88: 1067–1073.
265.
DuqueXFlores-HernándezSFlores-HuertaS: Prevalence of anemia and deficiency of iron, folic acid, and zinc in children younger than 2 years of age who use the health services provided by the Mexican Social Security Institute. BMC Public Health2007; 7: 345.
266.
da CostaGAdo NascimentoMarreiro DEulálioJM: Erythrocytary zinc and the infant growth profile in northeast Brazil. Biol Trace Elem Res2008; 126 (suppl 1): S15–S20.
267.
FerreiraFidelis C MartinsOsórioMM: Dietary intake of macro and micronutrients by children under five years of age in the State of Pernambuco, Brazil. Rev Bras Saúde Matern Infant2007; 7: 63–74.
268.
GeKYChangSY: Dietary intake of some essential micronutrients in China. Biomed Environ Sci2001; 14: 318–324.
269.
MaGLiYJinY: Phytate intake and molar ratios of phytate to zinc, iron and calcium in the diets of people in China. Eur J Clin Nutr2007; 61: 368–374.
270.
QinYMelse-BoonstraAZhaoJ: Stunting and zinc deficiency among primary school children in rural areas with low soil zinc concentrations in Jiangsu Province, China. Asia Pac J Clin Nutr2009; 18: 15–21.
271.
ChenXCYinTAHeJS: Low levels of zinc in hair and blood, pica, anorexia, and poor growth in Chinese preschool children. Am J Clin Nutr1985; 42: 694–700.
272.
ShengXYHambidgeKMZhuXX: Major variables of zinc homeostasis in Chinese toddlers. Am J Clin Nutr2006; 84: 389–394.
273.
ZhaoXH: Nutritional situation of Beijing residents. Southeast Asian J Trop Med Public Health1992; 23 (suppl 3): 65–68.
274.
DijkhuizenMAWieringaFTWestCE: Concurrent micronutrient deficiencies in lactating mothers and their infants in Indonesia. Am J Clin Nutr2001; 73: 786–791.
275.
DijkhuizenMAWieringaFTWestCE: Micronutrient deficiency and supplementation in Indonesian infants. Interactions between micronutrients. Adv Exp Med Biol2003; 531: 359–368.
276.
ThuBDSchultinkWDillonD: Effect of daily and weekly micronutrient supplementation on micronutrient deficiencies and growth in young Vietnamese children. Am J Clin Nutr1999; 69: 80–86.
277.
Van NhienNKhanNCNinhNX: Micronutrient deficiencies and anemia among preschool children in rural Vietnam. Asia Pac J Clin Nutr2008; 17: 48–55.
278.
KrittapholWBaileyKBPongcharoenT: Low zinc, iron, and calcium intakes of Northeast Thai school children consuming glutinous rice-based diets are not exacerbated by high phytate. Int J Food Sci Nutr2006; 57: 520–528.
279.
ThurlowRAWinichagoonPPongcharoenT: Risk of zinc, iodine and other micronutrient deficiencies among school children in North East Thailand. Eur J Clin Nutr2006; 60: 623–632.
