A Double Blind Randomized Trial Showing Probiotics to be Ineffective in Acute Diarrhea in Indonesian Children



To investigate the efficacy of probiotics added to oral rehydration solution and zinc in the treatment of acute infectious diarrhea in Indonesian children.


A prospective randomized double blind placebo-controlled trial was performed to test the efficacy of a probiotic food supplement in 112 children in the Kenari subdistrict, central Jakarta, aged 6–36 mo with acute infectious diarrhea and moderate dehydration. The supplemented group was given standard therapy (oral rehydration solution and zinc) and the probiotic strains Lactobacillus (L.) rhamnosus R0011 1.9 × 109 colony forming units (cfu) and L. acidophilus R0052 0.1 × 109 cfu/d for 7 d, while the control group was given standard therapy and placebo.


Median duration of diarrhea was 68.5 h (range 13–165) in the supplemented and 61.5 h (range 21–166) in the control group (P = 0.596). Median daily frequency of defecation until diarrhea stopped was 5.0 in the supplemented vs. 5.5 in the control group (P = 0.795).


This probiotic food supplement tested did not reduce the duration of acute infectious diarrhea as compared to oral rehydration and zinc.

This is a preview of subscription content, access via your institution.


  1. 1.

    The United Nations Children’s Fund/World Health Organization. WHO/UNICEF joint statement: clinical management of acute diarrhea. 2004. [cited 2008 April 1]. Available from http://www.mostproject.org/ZINC/WHO-UNICEF%20Statement.pdf

  2. 2.

    Dekate P, Jayashree M, Singhi SC. Management of acute diarrhea in emergency room. Indian J Pediatr. 2013;80:235–46.

    Article  PubMed  Google Scholar 

  3. 3.

    Hoque KM, Binder HJ. Zinc in the treatment of acute diarrhea: Current status and assessment. Gastroenterology. 2006;130:2201–5.

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Patro B, Golicki D, Szajewska H. Meta-analysis: Zinc supplementation for acute gastroenteritis in children. Aliment Pharmacol Ther. 2008;28:713–23.

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Salvatore S, Hauser B, Devreker T, Vieira MC, Luini C, Arrigo S, et al. Probiotics and zinc in acute infectious gastroenteritis in children: Are they effective? Nutrition. 2007;23:498–506.

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Pieścik-Lech M, Shamir R, Guarino A, Szajewska H. Review article: The management of acute gastroenteritis in children. Aliment Pharmacol Ther. 2013;37:289–303.

    Article  PubMed  Google Scholar 

  7. 7.

    Guarino A, Albano F, Ashkenazi S, Gendrel D, Hoekstra JH, Shamir R, et al. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe. J Pediatr Gastroenterol Nutr. 2008;46:S81–122.

    Article  PubMed  Google Scholar 

  8. 8.

    Heaton KW, Radvan J, Cripps H, Mountford RA, Braddon FE, Hughes AO. Defecation frequency and timing, and stool form in the general population: A prospective study. Gut. 1992;33:818–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. 9.

    Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32:920–4.

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Thomas DW, Greer FR; American Academy of Pediatrics Committee on Nutrition, American Academy of Pediatrics Section on Gastroenterology. Probiotics and prebiotics in pediatrics. Pediatrics. 2010;126:1217–31.

    Article  PubMed  Google Scholar 

  11. 11.

    Vandenplas Y, De Hert SG, PROBIOTICAL-study group. Randomised clinical trial: The synbiotic food supplement probiotical vs. Placebo for acute gastroenteritis in children. Aliment Pharmacol Ther. 2011;34:862–7.

  12. 12.

    Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev. 2010;11: CD003048.

    PubMed  Google Scholar 

  13. 13.

    Shamir R, Makhoul IR, Etzioni A, Shehadeh N. Original research: evaluation of a diet containing probiotics and zinc for the treatment of mild diarrheal illness in children younger than one year of age. J Am Coll Nutr. 2005;24:370–5.

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Dalgic N, Sancar M, Bayraktar B, Pullu M, Hasim O. Probiotic, zinc and lactose-free formula in children with rotavirus diarrhea: Are they effective? Pediatr Int. 2011;53:677–82.

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Sazawal S, Jalla S, Mazumder S, Sinha A, Black RE, Bhan MK. Effect of zinc supplementation on cell mediated immunity and lymphocyte subsets in preschool children. Indian Pediatr. 1997;34:689–97.

    Google Scholar 

  16. 16.

    Wadhwa N, Natchu UC, Sommerfelt H, Strand TA, Kapoor V, Saini S, et al. ORS containing zinc does not reduce duration or stool volume of acute diarrhea in hospitalized children. J Pediatr Gastroenterol Nutr. 2011;53:161–7.

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Passariello A, Terrin G, De Marco G, Cecere G, Ruotolos S, Marino A, et al. Effiacy of a new hypotonic oral rehydration solution containing zinc and prebiotics in the treatment of childhood acute diarrhea: A randomized controlled trial. J Pediatr. 2011;158:e1.

    PubMed  Google Scholar 

  18. 18.

    Agustina R, Kok FJ, van de Rest O, Fahmida U, Firmansyah A, Lukito W, et al. Randomized trial of probiotics and calcium on diarrhea and respiratory tract infections in Indonesian children. Pediatrics. 2012;129:1155–64.

    Article  Google Scholar 

  19. 19.

    Mcfarland LV, Elmer GW, Mcfarland M. Meta-analysis of probiotics for the prevention and treatment of acute pediatric diarrhea. Int J Probiotics Prebiotics. 2006;1:63–76.

    Google Scholar 

  20. 20.

    Riaz M, Alam S, Malik A, Ali SM. Efficacy and safety of Saccharomyces boulardii in acute childhood diarrhoea: A double blind randomised controlled trial. Indian J Pediatr. 2012;79:478–82.

    Article  PubMed  Google Scholar 

  21. 21.

    Narayanappa D. Randomized double blinded controlled trial to evaluate the efficacy and safety of Bifilac in patients with acute viral diarrhea. Indian J Pediatr. 2008;75:709–13.

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Alam S. Efficacy of a synbiotic BIFILAC: Questionable study. Indian J Pediatr. 2009;76:660.

    Article  PubMed  Google Scholar 

  23. 23.

    Salazar-Lindo E, Miranda- Langschwager P, Campos-Sanchez M, Woo Chea E, Sack RB. Lactobacillus casei strain GG in the treatment of infants with acute watery diarrhea: A randomized, double-blind, placebo controlled clinical trial [ISRCTN67363048]. BMC Pediatr. 2004;4:18.

  24. 24.

    Tlaskal P, Schramlova J, Kokesova A, Adamus J, Bubakova D, Kocnarova N. Probiotics in the treatment of diarrhoeal disease of children. NAFAS. 2005;3:25–8.

    Google Scholar 

  25. 25.

    Tlaskal P, Michkova E, Klayarova H, Jerabkova L, Nevoral J, Balackova J. Lactobacillus acidophilus in the treatment of children with gastrointestinal tract illness. Cesk Pediatr. 1995;51:615–9.

    Google Scholar 

  26. 26.

    Dianawati D, Shah NP. Survival, acid and bile tolerance, and surface hydrophobicity of microencapsulated B. animalis ssp. lactis Bb12 during storage at room temperature. J Food Sci. 2011;76:592–9.

    Article  Google Scholar 

  27. 27.

    Vanhee LM, Goemé F, Nelis HJ, Coenye T. Quality control of fifteen probiotic products containing Saccharomyces boulardii. J Appl Microbiol. 2010;109:1745–52.

    CAS  PubMed  Google Scholar 

  28. 28.

    Rerksuppaphol S, Rerksuppaphol L. Lactobacillus acidophilus and bifidobacterium bifidum stored at ambient temperature are effective in the treatment of acute diarrhoea. Ann Trop Paediatr. 2010;30:299–304.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. 29.

    Institut Rosell. M2 ctd Summaries, summary of information contained in the ctd registration file for the product lacidofil capsules. Supporting Information for the registration of the product lacidofil capsules in Indonesia. 2005.

  30. 30.

    Guarino A, Dupont C, Gorelov AV, Gottrand F, Lee JK, Lin Z, et al. The management of acute diarrhea in children in developed and developing areas: From evidence base to clinical practice. Expert Opin Pharmacother. 2012;13:17–26.

    Article  CAS  PubMed  Google Scholar 

Download references


BH, IMIW, HG and YV: Designed the study; IMIW, HG: Included the patients; BH and YV: Wrote the manuscript. YV will act as guarantor for this paper.

Conflict of Interest

YV is consultant for Biocodex and United Pharmaceuticals.

Role of Funding Source

Dexa Medica (Jakarta, Indonesia) provided the probiotics and Indofarma (Jakarta, Indonesia) zinc and ORS for free.

Author information



Corresponding author

Correspondence to Yvan Vandenplas.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hegar, B., Waspada, I.M.I., Gunardi, H. et al. A Double Blind Randomized Trial Showing Probiotics to be Ineffective in Acute Diarrhea in Indonesian Children. Indian J Pediatr 82, 410–414 (2015). https://doi.org/10.1007/s12098-014-1408-5

Download citation


  • Acute diarrhea
  • Acute gastroenteritis
  • Lactobacillus
  • Oral rehydration (solution)
  • Probiotic
  • Zinc