Effects of wheat-flour biscuits fortified with iron and EDTA, alone and in combination, on blood lead concentration, iron status, and cognition in children: A double-blind randomized controlled trial1

American Journal of Clinical Nutrition

Volumn 104, Issue 5, 2016, Pages 1318-1326

  Bouhouch, Raschida R ^a   El Fadeli, Sana ^b   Andersson, Maria ^a   Aboussad, Abdelmounaim ^c   Chabaa, Laila ^c   Zeder, Christophe ^a   Kippler, Maria ^d   Baumgartner, Jeannine ^e   Sedki, Azzedine ^b   Zimmermann, Michael B ^a  

^a ETH ZURICH   (Switzerland)

^b CADI AYYAD UNIVERSITY   (Morocco)

^c CHU Mohammed VI   (Morocco)

^d KAROLINSKA INSTITUTE   (Sweden)

^e NORTH WEST UNIVERSITY   (South Africa)

Author keywords

Cognition; Fortification; Iron; Lead; NaFeEDTA

Indexed keywords

EDETATE SODIUM; EDETIC ACID; FERROUS SULFATE; IRON; LEAD; PLACEBO; FE(III)-EDTA; FERRIC ION; FERROUS ION;

ARTICLE; BISCUIT; CHILD; COGNITION; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; FACTORIAL DESIGN; FEMALE; FOOD INTAKE; HOPKINS VERBAL LEARNING TEST; HUMAN; INTENTION TO TREAT ANALYSIS; KAUFMAN ASSESSMENT BATTERY FOR CHILDREN; LEAD BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; MOROCCAN; RANDOMIZED CONTROLLED TRIAL; SCHOOL; WHEAT FLOUR; ANALYSIS; ANEMIA, IRON-DEFICIENCY; BLOOD; BODY MASS; BODY WEIGHT; DRUG EFFECTS; FLOUR; FORTIFIED FOOD; PRESCHOOL CHILD; STATISTICAL MODEL; WHEAT;

ANEMIA, IRON-DEFICIENCY; BODY MASS INDEX; BODY WEIGHT; CHILD; CHILD, PRESCHOOL; COGNITION; DOUBLE-BLIND METHOD; EDETIC ACID; FEMALE; FERRIC COMPOUNDS; FERROUS COMPOUNDS; FLOUR; FOOD, FORTIFIED; HUMANS; IRON; LEAD; LOGISTIC MODELS; MALE; TRITICUM;

EID: 84994318681     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.115.129346     Document Type: Article

References (53)

1. Lanphear BP, Hornung R, Khoury J, Yolton K, Baghurst P, Bellinger DC, Canfield RL, Dietrich KN, Bornschein R, Greene T, et al. Lowlevel environmental lead exposure and children's intellectual function: an international pooled analysis. Environ Health Perspect 2005;113:894-9.
2. EFSA Panel on Contaminants in the Food Chain. Scientific opinion on lead in food. Parma (Italy): European Food Safety Authority; 2013.
3. Budtz-Jørgensen E, Bellinger D, Lanphear B, Grandjean P; International Pooled Lead Study Investigators. An international pooled analysis for obtaining a benchmark dose for environmental lead exposure in children. Risk Anal 2013;33:450-61.
4. Joint FAO/WHO Expert Committee on Food Additives. Evaluation of certain food additives and contaminants. Seventy-third report of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organ Tech Rep Ser 2011;(966):1-136.
5. Evens A, Hryhorczuk D, Lanphear BP, Rankin KM, Lewis DA, Forst L, Rosenberg D. The impact of low-level lead toxicity on school performance among children in the Chicago public schools: a population-based retrospective cohort study. Environ Health 2015;14:21.
6. Joint FAO/WHO Expert Committee on Food Additives. Joint FAO/WHO Expert Committee on Food Additives (JECFA) meeting. Fiftythird meeting. Rome (Italy): FAO; 1999. [cited 2016 Sep 21]. Available from: ftp://ftp.fao.org/es/esn/jecfa/jecfa61sc.pdf.
7. American Academy of Pediatrics Committee on Environmental Health. Lead exposure in children: prevention, detection, and management. Pediatrics 2005;116:1036-46.
8. Watson WS, Morrison J, Bethel MI, Baldwin NM, Lyon DT, Dobson H, Moore MR, Hume R. Food iron and lead absorption in humans. Am J Clin Nutr 1986;44:248-56.
9. Flanagan PR, Chamberlain MJ, Valberg LS. The relationship between iron and lead absorption in humans. Am J Clin Nutr 1982;36:823-9.
10. Bannon Di, Abounader R, Lees PS, Bressler JP. Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells. Am J Physiol Cell Physiol 2003;284:C44-50.
11. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 1997;388:482-8.
12. Barton JC, Conrad ME, Nuby S, Harrison L. Effects of iron on the absorption and retention of lead. J Lab Clin Med 1978;92:536-47.
13. Kwong WT, Friello P, Semba RD. Interactions between iron deficiency and lead poisoning: epidemiology and pathogenesis. Sci Total Environ 2004;330:21-37.
14. Wright RO, Tsaih SW, Schwartz J, Wright RJ, Hu H. Association between iron deficiency and blood lead level in a longitudinal analysis of children followed in an urban primary care clinic. J Pediatr 2003; 142:9-14.
15. Rosado JL, Lopez P, Kordas K, Garcia-Vargas G, Ronquillo D, Alatorre J, Stoltzfus RJ. Iron and/or zinc supplementation did not reduce blood lead concentrations in children in a randomized, placebocontrolled trial. J Nutr 2006;136:2378-83.
16. Centers for Disease Control and Prevention. Managing elevated blood lead levels among young children: recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention. Atlanta (GA): CDC; 2002.
17. Bothwell TH, MacPhail AP. The potential role of NaFeEDTA as an iron fortificant. Int J Vitam Nutr Res 2004;74:421-34.
18. Bradberry S, Vale A. A comparison of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning. Clin Toxicol (Phila) 2009;47:841-58.
19. James HM, Hilburn ME, Blair JA. Effects of meals and meal times on uptake of lead from the gastrointestinal tract in humans. Hum Toxicol 1985;4:401-7.
20. Foreman H, Trujillo TT. The metabolism of C14 labeled ethylenediaminetetraacetic acid in human beings. J Lab Clin Med 1954;43:566-71.
21. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Scientific opinion on the use of ferric sodium EDTA as a source of iron added for nutritional purposes to foods for the general population (including food supplements) and to foods for particular nutritional uses. EFSA J 2010;8(1):1414-46.
22. Andersson M, Theis W, Zimmermann MB, Foman JT, Jakel M, Duchateau GS, Frenken LG, Hurrell RF. Random serial sampling to evaluate efficacy of iron fortification: a randomized controlled trial of margarine fortification with ferric pyrophosphate or sodium iron edetate. Am J Clin Nutr 2010;92:1094-104.
23. Lu Y, Kippler M, Harari F, Grander M, Palm B, Nordqvist H, Vahter M. Alkali dilution of blood samples for high throughput ICP-MS analysiscomparison with acid digestion. Clin Biochem 2015;48:140-7.
24. Centers for Disease Control. CDC response to Advisory Committee on Childhood Lead Poisoning Prevention recommendations. Low level lead exposure harms children: a renewed call for primary prevention. Atlanta (GA): CDC; 2012 (updated 7 June). (updated 2012 Jun 7). [cited 2016 Sep 21]. Available from: http://www.cdc.gov/nceh/lead/acclpp/final-document-030712.pdf.
25. Baumgartner J, Smuts CM, Malan L, Kvalsvig J, van Stuijvenberg ME, Hurrell RF, Zimmermann MB. Effects of iron and n-3 fatty acid supplementation, alone and in combination, on cognition in school children: a randomized, double-blind, placebo-controlled intervention in South Africa. Am J Clin Nutr 2012;96:1327-38.
26. Eisinger J, Blumberg WE, Fischbein A, Lilis R, Selikoff IJ. Zinc protoporphyrin in blood as a biological indicator of chronic lead intoxication. J Environ Pathol Toxicol 1978;1:897-910.
27. Grantham-McGregor S. Early child development in developing countries. Lancet 2007;369:824.
28. World Health Organization. Serum ferritin concentrations for the assessment of iron status and iron deficiency in populations. Geneva (Switzerland): World Health Organization; 2011.
29. Thurnham Di, McCabe LD, Haldar S, Wieringa FT, Northrop-Clewes CA, McCabe GP. Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis. Am J Clin Nutr 2010;92:546-55.
30. Thurnham Di, Northrop-Clewes CA, Knowles J. The use of adjustment factors to address the impact of inflammation on Vitamin a and iron status in humans. J Nutr 2015;145:1137S-43S.
31. World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva (Switzerland): World Health Organization; 2011.
32. Baumgartner J. Interactions between iron and omega-3 fatty acids: effects of deficiency and repletion on brain monoamines and cognition [dissertation]. Zurich (Switzerland): Swiss Federal Institute of Technology; 2012.
33. Kaufman AS, Lichtenberger EO, Fletscher-Janzen E, Kaufman LN. Essentials of KABC-II assessment. 2nd ed. Hoboken (NJ): John Wiley & Sons; 2005.
34. Brandt J. The Hopkins Verbal Learning Test: development of a new memory test with six equivalent forms. Clin Neuropsychol 1991;5:125-42.
35. Ogunlade AO, Kruger HS, Jerling JC, Smuts CM, Covic N, Hanekom SM, Mamabolo RL, Kvalsvig J. Point-of-use micronutrient fortification: lessons learned in implementing a preschool-based pilot trial in South Africa. Int J Food Sci Nutr 2011;62:1-16.
36. Dalton A, Wolmarans P, Witthuhn RC, van Stuijvenberg ME, Swanevelder SA, Smuts CM. A randomised control trial in schoolchildren showed improvement in cognitive function after consuming a bread spread, containing fish flour from a marine source. Prostaglandins Leukot Essent Fatty Acids 2009;80:143-9.
37. Muthayya S, Eilander A, Transler C, Thomas T, van der Knaap HC, Srinivasan K, van Klinken BJ, Osendarp SJ, Kurpad AV. Effect of fortification with multiple micronutrients and n-3 fatty acids on growth and cognitive performance in Indian schoolchildren: the CHAMPION (Children's Health and Mental Performance Influenced by Optimal Nutrition) study. Am J Clin Nutr 2009;89:1766-75.
38. Zimmermann MB, Muthayya S, Moretti D, Kurpad A, Hurrell RF. Iron fortification reduces blood lead levels in children in Bangalore, India. Pediatrics 2006;117:2014-21.
39. Robertson IK, Worwood M. Lead and iron absorption from rat small intestine: the effect of dietary Fe deficiency. Br J Nutr 1978; 40:253-60.
40. Leong WI, Bowlus CL, Tallkvist J, Lonnerdal B. Iron supplementation during infancy-effects on expression of iron transporters, iron absorption, and iron utilization in rat pups. Am J Clin Nutr 2003;78:1203-11.
41. Elsenhans B, Janser H, Windisch W, Schümann K. Does lead use the intestinal absorptive pathways of iron? Impact of iron status on murine 210Pb and 59Fe absorption in duodenum and ileum in vivo. Toxicology 2011;284:7-11.
42. Foreman H, Vier M, Magee M. The metabolism of C14-labeled ethylenediaminetetraacetic acid in the rat. J Biol Chem 1953;203:1045-53.
43. Ruff HA, Bijur PE, Markowitz M, Ma YC, Rosen JF. Declining blood lead levels and cognitive changes in moderately lead-poisoned children. JAMA 1993;269:1641-6.
44. Angle CRSK, McIntire MS. Lead and iron deficiencies. In: Hemphil DD, editor. Trace substances in environmental health. Columbia (MO): University of Missouri, 1975.
45. Wolf AW, Jimenez E, Lozoff B. Effects of iron therapy on infant blood lead levels. J Pediatr 2003;143:789-95.
46. Choi JW, Kim SK. Association between blood lead concentrations and body iron status in children. Arch Dis Child 2003;88:791-2.
47. Lynch SR. The impact of iron fortification on nutritional anaemia. Best Pract Res Clin Haematol 2005;18:333-46.
48. Chen A, Dietrich KN, Ware JH, Radcliffe J, Rogan WJ. IQ and blood lead from 2 to 7 years of age: are the effects in older children the residual of high blood lead concentrations in 2-year-olds? Environ Health Perspect 2005;113:597-601.
49. Hornung RW, Lanphear BP, Dietrich KN. Age of greatest susceptibility to childhood lead exposure: a new statistical approach. Environ Health Perspect 2009;117:1309-12.
50. Rischitelli G, Nygren P, Bougatsos C, Freeman M, Helfand M. Screening for elevated lead levels in childhood and pregnancy: an updated summary of evidence for the US Preventive Services Task Force. Pediatrics 2006;118:e1867-95.
51. Kordas K. Iron, lead, and children's behavior and cognition. Annu Rev Nutr 2010;30:123-48.
52. Wasserman G, Graziano JH, Factor-Litvak P, Popovac D, Morina N, Musabegovic A, Vrenezi N, Capuni-Paracka S, Lekic V, Preteni-Redjepi E, et al. Independent effects of lead exposure and iron deficiency anemia on developmental outcome at age 2 years. J Pediatr 1992;121:695-703.
53. Goering PL. Lead-protein interactions as a basis for lead toxicity. Neurotoxicology 1993;14:45-60.