Skip to main content
Top
Published in: BMC Medicine 1/2009

Open Access 01-12-2009 | Research article

Zinc and copper supplementation in acute diarrhea in children: a double-blind randomized controlled trial

Authors: Archana Patel, Michael J Dibley, Manju Mamtani, Neetu Badhoniya, Hemant Kulkarni

Published in: BMC Medicine | Issue 1/2009

Login to get access

Abstract

Background

Diarrhea causes an estimated 2.5 million child deaths in developing countries each year, 35% of which are due to acute diarrhea. Zinc and copper stores in the body are known to be depleted during acute diarrhea. Our objectives were to evaluate the efficacy of zinc and copper supplementation when given with standard treatment to children with acute watery or bloody diarrhea.

Methods

We conducted a double-blind randomized controlled clinical trial in the Department of Pediatrics at Indira Gandhi Government Medical College Nagpur, India. Eight hundred and eight children aged 6 months to 59 months with acute diarrhea were individually randomized to placebo (Pl), zinc (Zn) only, and zinc and copper (Zn+Cu) together with standard treatment for acute diarrhea.

Results

The mean duration of diarrhea from enrolment and the mean stool weight during hospital stay were 63.7 hours and 940 grams, respectively, and there were no significant differences in the adjusted means across treatment groups. Similarly, the adjusted means of the amount of oral rehydration solution or intravenous fluids used, the proportion of participants with diarrhea more than 7 days from onset, and the severity of diarrhea indicated by more than three episodes of some dehydration or any episode of severe dehydration after enrolment, did not differ across the three groups.

Conclusion

The expected beneficial effects of zinc supplementation for acute diarrhea were not observed. Therapeutic Zn or Zn and Cu supplementation may not have a universal beneficial impact on the duration of acute diarrhea in children.

Trial registration

The study was registered as an International Standard Randomized Controlled Trial (ISRCTN85071383).
Appendix
Available only for authorised users
Literature
1.
go back to reference Kosek M, Bern C, Guerrant RL: The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ. 2003, 81: 197-204.PubMedPubMedCentral Kosek M, Bern C, Guerrant RL: The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ. 2003, 81: 197-204.PubMedPubMedCentral
2.
go back to reference Arora R, Kulshreshtha S, Mohan G, Singh M, Sharma P: Estimation of serum zinc and copper in children with acute diarrhea. Biol Trace Elem Res. 2006, 114: 121-126. 10.1385/BTER:114:1:121.CrossRefPubMed Arora R, Kulshreshtha S, Mohan G, Singh M, Sharma P: Estimation of serum zinc and copper in children with acute diarrhea. Biol Trace Elem Res. 2006, 114: 121-126. 10.1385/BTER:114:1:121.CrossRefPubMed
3.
go back to reference Tomkins A, Behrens R, Roy S: The role of zinc and vitamin A deficiency in diarrhoeal syndromes in developing countries. Proc Nutr Soc. 1993, 52: 131-142. 10.1079/PNS19930045.CrossRefPubMed Tomkins A, Behrens R, Roy S: The role of zinc and vitamin A deficiency in diarrhoeal syndromes in developing countries. Proc Nutr Soc. 1993, 52: 131-142. 10.1079/PNS19930045.CrossRefPubMed
4.
go back to reference Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A: Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr. 2000, 72: 1516-1522.PubMed Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A: Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr. 2000, 72: 1516-1522.PubMed
5.
go back to reference Lazzerini M, Ronfani L: Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2008, 3: CD005436-DOI: 10.1002/14651858.CD005436.pub2.PubMed Lazzerini M, Ronfani L: Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2008, 3: CD005436-DOI: 10.1002/14651858.CD005436.pub2.PubMed
6.
go back to reference Bhatnagar S, Lodha R, Choudhury P, Sachdev HP, Shah N, Narayan S, Wadhwa N, Makhija P, Kunnekel K, Ugra D, Indian Academy of Pediatrics: IAP Guidelines 2006 on management of acute diarrhea. Indian Pediatr. 2007, 44: 380-389.PubMed Bhatnagar S, Lodha R, Choudhury P, Sachdev HP, Shah N, Narayan S, Wadhwa N, Makhija P, Kunnekel K, Ugra D, Indian Academy of Pediatrics: IAP Guidelines 2006 on management of acute diarrhea. Indian Pediatr. 2007, 44: 380-389.PubMed
7.
go back to reference Brooks WA, Santosham M, Roy SK, Faruque AS, Wahed MA, Nahar K, Khan AI, Khan AF, Fuchs GJ, Black RE: Efficacy of zinc in young infants with acute watery diarrhea. Am J Clin Nutr. 2005, 82: 605-610.PubMed Brooks WA, Santosham M, Roy SK, Faruque AS, Wahed MA, Nahar K, Khan AI, Khan AF, Fuchs GJ, Black RE: Efficacy of zinc in young infants with acute watery diarrhea. Am J Clin Nutr. 2005, 82: 605-610.PubMed
8.
go back to reference Long KZ, Montoya Y, Hertzmark E, Santos JI, Rosado JL: A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico. Am J Clin Nutr. 2006, 83: 693-700.PubMed Long KZ, Montoya Y, Hertzmark E, Santos JI, Rosado JL: A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico. Am J Clin Nutr. 2006, 83: 693-700.PubMed
9.
go back to reference Bhandari N, Taneja S, Mazumder S, Bahl R, Fontaine O, Bhan MK: Adding zinc to supplemental iron and folic acid does not affect mortality and severe morbidity in young children. J Nutr. 2007, 137: 112-117.PubMed Bhandari N, Taneja S, Mazumder S, Bahl R, Fontaine O, Bhan MK: Adding zinc to supplemental iron and folic acid does not affect mortality and severe morbidity in young children. J Nutr. 2007, 137: 112-117.PubMed
10.
go back to reference Sazawal S, Black RE, Ramsan M, Chwaya HM, Dutta A, Dhingra U, Stoltzfus RJ, Othman MK, Kabole FM: Effect of zinc supplementation on mortality in children aged 1–48 months: a community-based randomised placebo-controlled trial. Lancet. 2007, 369: 927-934. 10.1016/S0140-6736(07)60452-8.CrossRefPubMed Sazawal S, Black RE, Ramsan M, Chwaya HM, Dutta A, Dhingra U, Stoltzfus RJ, Othman MK, Kabole FM: Effect of zinc supplementation on mortality in children aged 1–48 months: a community-based randomised placebo-controlled trial. Lancet. 2007, 369: 927-934. 10.1016/S0140-6736(07)60452-8.CrossRefPubMed
11.
go back to reference Tielsch JM, Khatry SK, Stoltzfus RJ, Katz J, LeClerq SC, Adhikari R, Mullany LC, Black R, Shresta S: Effect of daily zinc supplementation on child mortality in southern Nepal: a community-based, cluster randomised, placebo-controlled trial. Lancet. 2007, 370: 1230-1239. 10.1016/S0140-6736(07)61539-6.CrossRefPubMedPubMedCentral Tielsch JM, Khatry SK, Stoltzfus RJ, Katz J, LeClerq SC, Adhikari R, Mullany LC, Black R, Shresta S: Effect of daily zinc supplementation on child mortality in southern Nepal: a community-based, cluster randomised, placebo-controlled trial. Lancet. 2007, 370: 1230-1239. 10.1016/S0140-6736(07)61539-6.CrossRefPubMedPubMedCentral
12.
go back to reference Cousins RJ: Zinc. Present Knowledge in Nutrition. 1990, Washington, DC: International Life Sciences Institute, Nutrition Foundation Cousins RJ: Zinc. Present Knowledge in Nutrition. 1990, Washington, DC: International Life Sciences Institute, Nutrition Foundation
13.
go back to reference WHO: The treatment of diarrhea: a manual for physicians and other senior health workers. Vol. WHO/CDD/SER/80.2. 2005, Geneva, Switzerland: World Health Organization WHO: The treatment of diarrhea: a manual for physicians and other senior health workers. Vol. WHO/CDD/SER/80.2. 2005, Geneva, Switzerland: World Health Organization
14.
go back to reference Bland M: ClinStat: Simple statistical software. London. 1996 Bland M: ClinStat: Simple statistical software. London. 1996
15.
go back to reference HemoCue: Operating manual. Angelholm Sweden: HemaCue AB HemoCue: Operating manual. Angelholm Sweden: HemaCue AB
16.
go back to reference Filmer DPL, Pritchett L: Estimating wealth effects without expenditure data or tears: An application to educational enrolments in States of India. Demography. 2001, 38: 115-132.PubMed Filmer DPL, Pritchett L: Estimating wealth effects without expenditure data or tears: An application to educational enrolments in States of India. Demography. 2001, 38: 115-132.PubMed
17.
go back to reference WHO: WHO Anthro. 2005, Geneva, Switzerland: World Health Organization WHO: WHO Anthro. 2005, Geneva, Switzerland: World Health Organization
18.
go back to reference Black RE, Allen LH, Bhutta ZA, Caulfield LE, de Onis M, Ezzati M, Mathers C, Rivera J, Maternal and Child Undernutrition Study Group: Maternal and child undernutrition: global and regional exposures and health consequences. Lancet. 2008, 371: 243-260. 10.1016/S0140-6736(07)61690-0.CrossRefPubMed Black RE, Allen LH, Bhutta ZA, Caulfield LE, de Onis M, Ezzati M, Mathers C, Rivera J, Maternal and Child Undernutrition Study Group: Maternal and child undernutrition: global and regional exposures and health consequences. Lancet. 2008, 371: 243-260. 10.1016/S0140-6736(07)61690-0.CrossRefPubMed
19.
go back to reference Bahl R, Bhandari N, Saksena M, Strand T, Kumar GT, Bhan MK, Sommerfelt H: Efficacy of zinc-fortified oral rehydration solution in 6- to 35-month-old children with acute diarrhea. J Pediatr. 2002, 141: 677-682. 10.1067/mpd.2002.128543.CrossRefPubMed Bahl R, Bhandari N, Saksena M, Strand T, Kumar GT, Bhan MK, Sommerfelt H: Efficacy of zinc-fortified oral rehydration solution in 6- to 35-month-old children with acute diarrhea. J Pediatr. 2002, 141: 677-682. 10.1067/mpd.2002.128543.CrossRefPubMed
20.
go back to reference Brooks WA, Santosham M, Naheed A, Goswami D, Wahed MA, Diener-West M, Faruque AS, Black RE: 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. Lancet. 2005, 366: 999-1004. 10.1016/S0140-6736(05)67109-7.CrossRefPubMed Brooks WA, Santosham M, Naheed A, Goswami D, Wahed MA, Diener-West M, Faruque AS, Black RE: 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. Lancet. 2005, 366: 999-1004. 10.1016/S0140-6736(05)67109-7.CrossRefPubMed
21.
go back to reference Bhatnagar S, Bahl R, Sharma PK, Kumar GT, Saxena SK, Bhan MK: Zinc with oral rehydration therapy reduces stool output and duration of diarrhea in hospitalized children: a randomized controlled trial. J Pediatr Gastroenterol Nutr. 2004, 38: 34-40. 10.1097/00005176-200401000-00010.CrossRefPubMed Bhatnagar S, Bahl R, Sharma PK, Kumar GT, Saxena SK, Bhan MK: Zinc with oral rehydration therapy reduces stool output and duration of diarrhea in hospitalized children: a randomized controlled trial. J Pediatr Gastroenterol Nutr. 2004, 38: 34-40. 10.1097/00005176-200401000-00010.CrossRefPubMed
22.
go back to reference Polat TB, Uysalol M, Cetinkaya F: Efficacy of zinc supplementation on the severity and duration of diarrhea in malnourished Turkish children. Pediatr Int. 2003, 45: 555-559. 10.1046/j.1442-200X.2003.01772.x.CrossRefPubMed Polat TB, Uysalol M, Cetinkaya F: Efficacy of zinc supplementation on the severity and duration of diarrhea in malnourished Turkish children. Pediatr Int. 2003, 45: 555-559. 10.1046/j.1442-200X.2003.01772.x.CrossRefPubMed
23.
go back to reference Roy SK, Raqib R, Khatun W, Azim T, Chowdhury R, Fuchs GJ, Sack DA: Zinc supplementation in the management of shigellosis in malnourished children in Bangladesh. Eur J Clin Nutr. 2007 Roy SK, Raqib R, Khatun W, Azim T, Chowdhury R, Fuchs GJ, Sack DA: Zinc supplementation in the management of shigellosis in malnourished children in Bangladesh. Eur J Clin Nutr. 2007
24.
go back to reference Roy SK, Tomkins AM, Akramuzzaman SM, Behrens RH, Haider R, Mahalanabis D, Fuchs G: Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea. Arch Dis Child. 1997, 77: 196-200. 10.1136/adc.77.3.196.CrossRefPubMedPubMedCentral Roy SK, Tomkins AM, Akramuzzaman SM, Behrens RH, Haider R, Mahalanabis D, Fuchs G: Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea. Arch Dis Child. 1997, 77: 196-200. 10.1136/adc.77.3.196.CrossRefPubMedPubMedCentral
25.
go back to reference Sachdev HP, Mittal NK, Mittal SK, Yadav HS: A controlled trial on utility of oral zinc supplementation in acute dehydrating diarrhea in infants. J Pediatr Gastroenterol Nutr. 1988, 7: 877-881.CrossRefPubMed Sachdev HP, Mittal NK, Mittal SK, Yadav HS: A controlled trial on utility of oral zinc supplementation in acute dehydrating diarrhea in infants. J Pediatr Gastroenterol Nutr. 1988, 7: 877-881.CrossRefPubMed
26.
go back to reference Strand TA, Chandyo RK, Bahl R, Sharma PR, Adhikari RK, Bhandari N, Ulvik RJ, Mølbak K, Bhan MK, Sommerfelt H: Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children. Pediatrics. 2002, 109: 898-903. 10.1542/peds.109.5.898.CrossRefPubMed Strand TA, Chandyo RK, Bahl R, Sharma PR, Adhikari RK, Bhandari N, Ulvik RJ, Mølbak K, Bhan MK, Sommerfelt H: Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children. Pediatrics. 2002, 109: 898-903. 10.1542/peds.109.5.898.CrossRefPubMed
27.
go back to reference Gibson RS, Hess S, Hotz C, Brown KH: Indicators of zinc status at the population level: a review of the evidence. Br J Nutr. 2008, 99 (Suppl 3): S14-S23.PubMed Gibson RS, Hess S, Hotz C, Brown KH: Indicators of zinc status at the population level: a review of the evidence. Br J Nutr. 2008, 99 (Suppl 3): S14-S23.PubMed
28.
go back to reference Fischer Walker CL, Bhutta ZA, Bhandari N, Teka T, Shahid F, Taneja S, Black RE, Zinc Study Group: Zinc supplementation for the treatment of diarrhea in infants in Pakistan, India and Ethiopia. J Pediatr Gastroenterol Nutr. 2006, 43: 357-363. 10.1097/01.mpg.0000232018.40907.00.CrossRefPubMed Fischer Walker CL, Bhutta ZA, Bhandari N, Teka T, Shahid F, Taneja S, Black RE, Zinc Study Group: Zinc supplementation for the treatment of diarrhea in infants in Pakistan, India and Ethiopia. J Pediatr Gastroenterol Nutr. 2006, 43: 357-363. 10.1097/01.mpg.0000232018.40907.00.CrossRefPubMed
29.
go back to reference Al-Sonboli N, Gurgel RQ, Shenkin A, Hart CA, Cuevas LE: Zinc supplementation in Brazilian children with acute diarrhoea. Ann Trop Paediatr. 2003, 23: 3-8. 10.1179/000349803125002797.CrossRefPubMed Al-Sonboli N, Gurgel RQ, Shenkin A, Hart CA, Cuevas LE: Zinc supplementation in Brazilian children with acute diarrhoea. Ann Trop Paediatr. 2003, 23: 3-8. 10.1179/000349803125002797.CrossRefPubMed
30.
go back to reference Baqui AH, Black RE, El Arifeen S, Yunus M, Chakraborty J, Ahmed S, Vaughan JP: Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ. 2002, 325: 1059-10.1136/bmj.325.7372.1059.CrossRefPubMedPubMedCentral Baqui AH, Black RE, El Arifeen S, Yunus M, Chakraborty J, Ahmed S, Vaughan JP: Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ. 2002, 325: 1059-10.1136/bmj.325.7372.1059.CrossRefPubMedPubMedCentral
31.
go back to reference Dutta P, Mitra U, Datta A, Niyogi SK, Dutta S, Manna B, Basak M, Mahapatra TS, Bhattacharya SK: Impact of zinc supplementation in malnourished children with acute watery diarrhoea. J Trop Pediat. 2000, 46: 259-263. 10.1093/tropej/46.5.259.CrossRef Dutta P, Mitra U, Datta A, Niyogi SK, Dutta S, Manna B, Basak M, Mahapatra TS, Bhattacharya SK: Impact of zinc supplementation in malnourished children with acute watery diarrhoea. J Trop Pediat. 2000, 46: 259-263. 10.1093/tropej/46.5.259.CrossRef
32.
go back to reference Canani RB, Cirillo P, Buccigrossi V, Ruotolo S, Passariello A, De Luca P, Porcaro F, De Marco G, Guarino A: Zinc inhibits cholera toxin-induced, but not Escherichia coli heat-stable enterotoxin-induced, ion secretion in human enterocytes. J Infect Dis. 2005, 191: 1072-1077. 10.1086/428504.CrossRefPubMed Canani RB, Cirillo P, Buccigrossi V, Ruotolo S, Passariello A, De Luca P, Porcaro F, De Marco G, Guarino A: Zinc inhibits cholera toxin-induced, but not Escherichia coli heat-stable enterotoxin-induced, ion secretion in human enterocytes. J Infect Dis. 2005, 191: 1072-1077. 10.1086/428504.CrossRefPubMed
33.
go back to reference Crane JK, Naeher T, Shulgina I, Zhu C, Boedeker EC: Effect of zinc in enteropathogenic Escherichia coli infection. Infect Immun. 2007, 75: 5974-5984. 10.1128/IAI.00750-07.CrossRefPubMedPubMedCentral Crane JK, Naeher T, Shulgina I, Zhu C, Boedeker EC: Effect of zinc in enteropathogenic Escherichia coli infection. Infect Immun. 2007, 75: 5974-5984. 10.1128/IAI.00750-07.CrossRefPubMedPubMedCentral
34.
go back to reference Long KZ, Rosado JL, Fawzi W: The comparative impact of iron, the B-complex vitamins, vitamins C and E, and selenium on diarrheal pathogen outcomes relative to the impact produced by vitamin A and zinc. Nutr Rev. 2007, 65: 218-232. 10.1111/j.1753-4887.2007.tb00299.x.CrossRefPubMed Long KZ, Rosado JL, Fawzi W: The comparative impact of iron, the B-complex vitamins, vitamins C and E, and selenium on diarrheal pathogen outcomes relative to the impact produced by vitamin A and zinc. Nutr Rev. 2007, 65: 218-232. 10.1111/j.1753-4887.2007.tb00299.x.CrossRefPubMed
35.
go back to reference Long KZ, Rosado JL, Montoya Y, de Lourdes Solano M, Hertzmark E, DuPont HL, Santos JI: Effect of vitamin A and zinc supplementation on gastrointestinal parasitic infections among Mexican children. Pediatrics. 2007, 120: e846-855. 10.1542/peds.2006-2187.CrossRefPubMed Long KZ, Rosado JL, Montoya Y, de Lourdes Solano M, Hertzmark E, DuPont HL, Santos JI: Effect of vitamin A and zinc supplementation on gastrointestinal parasitic infections among Mexican children. Pediatrics. 2007, 120: e846-855. 10.1542/peds.2006-2187.CrossRefPubMed
36.
go back to reference Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A: Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. J Pediatr. 1999, 135: 689-697. 10.1016/S0022-3476(99)70086-7.CrossRefPubMed Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A: Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. J Pediatr. 1999, 135: 689-697. 10.1016/S0022-3476(99)70086-7.CrossRefPubMed
37.
go back to reference Faruque AS, Mahalanabis D, Haque SS, Fuchs GJ, Habte Dl: Double-blind, randomized, controlled trial of zinc or vitamin A supplementation in young children with acute diarrhoea. Acta Paediatr. 1999, 88: 154-160. 10.1080/08035259950170312.CrossRefPubMed Faruque AS, Mahalanabis D, Haque SS, Fuchs GJ, Habte Dl: Double-blind, randomized, controlled trial of zinc or vitamin A supplementation in young children with acute diarrhoea. Acta Paediatr. 1999, 88: 154-160. 10.1080/08035259950170312.CrossRefPubMed
38.
go back to reference Bhan MK, Bhandari N: The role of zinc and vitamin A in persistent diarrhea among infants and young children. J Pediatr Gastroenterol Nutr. 1998, 26: 446-453. 10.1097/00005176-199804000-00016.CrossRefPubMed Bhan MK, Bhandari N: The role of zinc and vitamin A in persistent diarrhea among infants and young children. J Pediatr Gastroenterol Nutr. 1998, 26: 446-453. 10.1097/00005176-199804000-00016.CrossRefPubMed
39.
go back to reference Boron B, Hupert J, Barch DH, Fox CC, Friedman H, Layden TJ, Mobarhan S: Effect of zinc deficiency on hepatic enzymes regulating vitamin A status. J Nutr. 1988, 118: 995-1001.PubMed Boron B, Hupert J, Barch DH, Fox CC, Friedman H, Layden TJ, Mobarhan S: Effect of zinc deficiency on hepatic enzymes regulating vitamin A status. J Nutr. 1988, 118: 995-1001.PubMed
40.
go back to reference Christian P, West KP: Interactions between zinc and vitamin A: an update. Am J Clin Nutr. 1998, 68 (2 Suppl): 435S-441S.PubMed Christian P, West KP: Interactions between zinc and vitamin A: an update. Am J Clin Nutr. 1998, 68 (2 Suppl): 435S-441S.PubMed
41.
go back to reference Fuchs GJ: Possibilities for zinc in the treatment of acute diarrhea. Am J Clin Nutr. 1998, 68 (2 Suppl): 480S-483S.PubMed Fuchs GJ: Possibilities for zinc in the treatment of acute diarrhea. Am J Clin Nutr. 1998, 68 (2 Suppl): 480S-483S.PubMed
42.
go back to reference Castillo-Duran C, Vial P, Uauy R: Oral copper supplementation: effect on copper and zinc balance during acute gastroenteritis in infants. Am J Clin Nutr. 1990, 51: 1088-1092.PubMed Castillo-Duran C, Vial P, Uauy R: Oral copper supplementation: effect on copper and zinc balance during acute gastroenteritis in infants. Am J Clin Nutr. 1990, 51: 1088-1092.PubMed
43.
go back to reference Bhandari N, Bahl R, Taneja S, Strand T, Mølbak K, Ulvik RJ, Sommerfelt H, Bhan MK: Substantial reduction in severe diarrheal morbidity by daily zinc supplementation in young north Indian children. Pediatrics. 2002, 109: e86-10.1542/peds.109.6.e86.CrossRefPubMed Bhandari N, Bahl R, Taneja S, Strand T, Mølbak K, Ulvik RJ, Sommerfelt H, Bhan MK: Substantial reduction in severe diarrheal morbidity by daily zinc supplementation in young north Indian children. Pediatrics. 2002, 109: e86-10.1542/peds.109.6.e86.CrossRefPubMed
44.
go back to reference Abdel-Mageed AB, Oehme FW: The effect of various dietary zinc concentrations on the biological interactions of zinc, copper, and iron in rats. Biol Trace Elem Res. 1991, 29: 239-256. 10.1007/BF03032681.CrossRefPubMed Abdel-Mageed AB, Oehme FW: The effect of various dietary zinc concentrations on the biological interactions of zinc, copper, and iron in rats. Biol Trace Elem Res. 1991, 29: 239-256. 10.1007/BF03032681.CrossRefPubMed
45.
go back to reference Hedemann MS, Jensen BB, Poulsen HD: Influence of dietary zinc and copper on digestive enzyme activity and intestinal morphology in weaned pigs. J Anim Sci. 2006, 84: 3310-3320. 10.2527/jas.2005-701.CrossRefPubMed Hedemann MS, Jensen BB, Poulsen HD: Influence of dietary zinc and copper on digestive enzyme activity and intestinal morphology in weaned pigs. J Anim Sci. 2006, 84: 3310-3320. 10.2527/jas.2005-701.CrossRefPubMed
Metadata
Title
Zinc and copper supplementation in acute diarrhea in children: a double-blind randomized controlled trial
Authors
Archana Patel
Michael J Dibley
Manju Mamtani
Neetu Badhoniya
Hemant Kulkarni
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2009
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-7-22

Other articles of this Issue 1/2009

BMC Medicine 1/2009 Go to the issue