Effectiveness of Zinc Supplementation in Nutritional Catch-Up Growth Management for Stunted Toddlers: A Systematic Review of Randomized Controlled Trials and Primary Studies
Keywords:
zinc supplementation, stunting, catch-up growth, linear growth, IGF-1Abstract
Introduction: Stunting affects 148.1 million children under five globally, with zinc deficiency mechanistically implicated through impaired IGF-1 signaling and cellular proliferation. This systematic review evaluates the effectiveness of zinc supplementation on linear growth, ponderal growth, biomarkers, and morbidity outcomes in stunted toddlers.
Methods: The study strictly adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines from inception to June 2025. Included studies comprised RCTs, cluster-RCTs, or primary studies enrolling children aged 0–72 months receiving oral zinc supplementation with at least one anthropometric or morbidity outcome. Risk of bias was assessed using Cochrane RoB 2.0. Narrative synthesis was employed with pooled estimates derived from included meta-analyses.
Results: Zinc supplementation significantly improved linear growth in stunted children (effect size 0.13–0.50 SD), with the most pronounced effect in Ethiopian infants (7.0 cm vs 2.8 cm placebo, p<0.001). Weight gain showed consistent positive effects (ES 0.309, 95% CI 0.178–0.439). Serum zinc responded robustly (ES 0.820). Zinc reduced diarrhea (OR 0.82, 95% CI 0.72–0.93) and pneumonia (OR 0.59, 0.41–0.83). All-cause mortality was reduced by 16% (SRR 0.84). However, stunting prevalence was not consistently reduced, with attenuation observed in settings with high environmental enteric dysfunction or iron co-supplementation.
Discussion: Zinc demonstrates significant benefit for linear growth velocity in zinc-deficient stunted toddlers, mediated through IGF-1 upregulation, improved appetite, and reduced infectious morbidity. Contextual heterogeneity is driven by baseline zinc status, co-existing deficiencies, EED burden, and iron co-supplementation.
Conclusion: Zinc supplementation at 10 mg/day for ≥24 weeks is effective for improving linear growth velocity and reducing morbidity in stunted toddlers with zinc deficiency, though insufficient as monotherapy for reversing stunting prevalence. Integrated approaches addressing multifactorial etiology are recommended.
References
UNICEF, WHO, World Bank. Levels and trends in child malnutrition: UNICEF/WHO/World Bank Group Joint Child Malnutrition Estimates. Key findings of the 2023 edition. Geneva: World Health Organization; 2023. Available from: https://www.who.int/publications/i/item/9789240073791
Victora CG, Christian P, Vidaletti LP, et al. Revisiting maternal and child undernutrition in low-income and middle-income countries: variable progress towards an unfinished agenda. Lancet. 2021;397(10282):1388–1399. doi:10.1016/S0140-6736(21)00394-9. Available from: https://consensus.app/papers/details/bafbafe4337f541587035f690b842da5/
Wessells KR, Brown KH. Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting. PLoS ONE. 2012;7(11):e50568. doi:10.1371/journal.pone.0050568. Available from: https://consensus.app/papers/details/116a0519d7d75830a7c4e6e381517438/
Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2013;382(9890):427–451. doi:10.1016/S0140-6736(13)60937-X. Available from: https://consensus.app/papers/details/16b23f92b0f1573ea7d762ac93ee4f6d/
Brown KH, Peerson JM, Rivera J, Allen LH. Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2002;75(6):1062–1071. doi:10.1093/ajcn/75.6.1062. Available from: https://consensus.app/papers/details/2c37b64de1c0555e876f9f220c4553fb/
Liu E, Pimpin L, Shulkin M, Kranz S, Duggan CP, Mozaffarian D, Fawzi WW. Effect of Zinc Supplementation on Growth Outcomes in Children under 5 Years of Age. Nutrients. 2018 Mar 20;10(3):377. doi: 10.3390/nu10030377. PMID: 29558383; PMCID: PMC5872795. https://pmc.ncbi.nlm.nih.gov/articles/PMC5872795/
Imdad A, Bhutta ZA. Effect of preventive zinc supplementation on linear growth in children under 5 years of age in developing countries: a meta-analysis of studies for input to the Lives Saved Tool. BMC Public Health. 2011;11(Suppl 3):S22. doi:10.1186/1471-2458-11-S3-S22. Available from: https://consensus.app/papers/details/593a340a3d415e09918f835fe2830235/
Umeta M, West CE, Haider J, Deurenberg P, Hautvast JGAJ. Zinc supplementation and stunted infants in Ethiopia: a randomised controlled trial. Lancet. 2000;355(9220):2021–2026. doi:10.1016/S0140-6736(00)02355-4. Available from: https://consensus.app/papers/details/cb5a630a208c554486b205f157ec3b90/
Bhutta ZA, Black RE, Brown KH, et al. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. J Pediatr. 1999;135(6):689–697. doi:10.1016/S0022-3476(99)70086-7. Available from: https://consensus.app/papers/details/dd0642e8de915edbbcfc3511f1e8b2b5/
Rouhani P, Rezaei Kelishadi M, Saneei P. Effect of zinc supplementation on mortality in under 5-year children: a systematic review and meta-analysis of randomized clinical trials. Eur J Nutr. 2021;60(2):981–996. doi:10.1007/s00394-020-02206-z. Available from: https://consensus.app/papers/details/5b17cbf67d1d5e08bf4f031c7ee9089d/
Wang AZ, Shulman RJ, Crocker AH, et al. A combined intervention of zinc, multiple micronutrients, and albendazole does not ameliorate environmental enteric dysfunction or stunting in rural Malawian children. J Nutr. 2016;146(10):2132–2138. doi:10.3945/jn.116.236406. Available from: https://consensus.app/papers/details/74fd50f2426a5e3bafba8b97aef70648/
Barffour MA, Hinnouho GM, Wessells KR, et al. Effects of daily zinc, daily multiple micronutrient powder, or therapeutic zinc supplementation for diarrhea prevention on physical growth, anemia, and micronutrient status in rural Laotian children: a randomized controlled trial. J Pediatr. 2019;214:67–75.e4. doi:10.1016/j.jpeds.2019.07.063. Available from: https://consensus.app/papers/details/60acf07447a550679bda7f3dc7b0fe3f/
Prasad AS. Discovery of human zinc deficiency: its impact on human health and disease. Adv Nutr. 2013;4(2):176–190. doi:10.3945/an.112.003210. Available from: https://consensus.app/papers/details/d9af39a82e0450418f53eb8e6257fdd0/
Macdonald RS. The role of zinc in growth and cell proliferation. J Nutr. 2000;130(5S Suppl):1500S–1508S. doi:10.1093/jn/130.5.1500S. Available from: https://consensus.app/papers/details/6bd334ad976856e0aecbdc7302ba2d55/
Millward DJ. Nutrition, infection and stunting: the roles of deficiencies of individual nutrients and foods, and of inflammation, as determinants of reduced linear growth of children. Nutr Res Rev. 2017;30(1):50–72. doi:10.1017/S0954422416000238. Available from: https://consensus.app/papers/details/846dfdefab1e5508814e2e34e18f0fc7/
Lowe NM, et al. Preventing and controlling zinc deficiency across the life course: a call to action. Adv Nutr. 2024;15(1):100-116. doi:10.1016/j.advnut.2023.10.001. Available from: https://consensus.app/papers/details/30df75cea68f50c2891f729032950805/
Liu E, Pimpin L, Shulkin M, et al. Effect of zinc supplementation on growth outcomes in children under 5 years of age. Nutrients. 2018;10(3):377. doi:10.3390/nu10030377. Available from: https://consensus.app/papers/details/3331f9c801945ae98053e1b2b1d64825/
Rivera JA, Ruel MT, Santizo MC, Lonnerdal B, Brown KH. Zinc supplementation improves the growth of stunted rural Guatemalan infants. J Nutr. 1998;128(3):556–562. doi:10.1093/jn/128.3.556. Available from: https://consensus.app/papers/details/8455575323945793ba98920cb6d19163/
Ninh NX, Thissen JP, Collette L, Gerard G, Khoi HH, Ketelslegers JM. Zinc supplementation increases growth and circulating insulin-like growth factor I (IGF-I) in growth-retarded Vietnamese children. Am J Clin Nutr. 1996;63(4):514–519. doi:10.1093/ajcn/63.4.514. Available from: https://consensus.app/papers/details/8a020b0433a45209834800d2fcda6831/
Müller O, Becher H, Baltussen A, et al. Effect of zinc supplementation on growth in West African children: a randomized double-blind placebo-controlled trial in rural Burkina Faso. Int J Epidemiol. 2003;32(6):1098–1102. doi:10.1093/ije/dyg178. Available from: https://consensus.app/papers/details/4db6a3f6fd0b50f88b7410d753e126dd/
Barffour MA, Hinnouho GM, Wessells KR, et al. Effects of daily zinc, daily multiple micronutrient powder, or therapeutic zinc supplementation for diarrhea prevention on physical growth, anemia, and micronutrient status in rural Laotian children: a randomized controlled trial. J Pediatr. 2019;214:67–75.e4. (As ref 12 above)
Locks LM, Manji KP, McDonald CM, et al. Effect of zinc and multivitamin supplementation on the growth of Tanzanian children aged 6–84 wk: a randomized, placebo-controlled, double-blind trial. Am J Clin Nutr. 2016;103(2):910–918. doi:10.3945/ajcn.115.118224. Available from: https://consensus.app/papers/details/204b2c3ea2555b4bacdba61c7219bc8d/
Barffour MA, Hinnouho GM, Wessells KR, et al. Insulin-like growth factor 1 (IGF1), IGF binding protein-3 (IGFBP3) and growth response to daily zinc supplementation: a randomized trial in rural Laotian children. Nutrients. 2023;15(1):1–15. doi:10.3390/nu15010178. Available from: https://consensus.app/papers/details/5edf9e2ac6f853c099336670d79bc763/
Sazawal S, Black RE, Bhan MK, Bhandari N, Sinha A, Jalla S. Zinc supplementation in young children with acute diarrhea in India. N Engl J Med. 1995;333(13):839–844. doi:10.1056/NEJM199509283331304. Available from: https://consensus.app/papers/details/2f182ae5aeef5a35aaef7fb2dce41d40/
Ruel MT, Rivera JA, Santizo MC, Lönnerdal B, Brown KH. Impact of zinc supplementation on morbidity from diarrhea and respiratory infections among rural Guatemalan children. Pediatrics. 1997;99(6):808–813. doi:10.1542/peds.99.6.808. Available from: https://consensus.app/papers/details/fec550bd917852a18bbc8e33f234198e/
Baqui AH, Black RE, El Arifeen S, et al. Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ. 2002;325(7372):1059. doi:10.1136/bmj.325.7372.1059. Available from: https://consensus.app/papers/details/aecb3b0fdae55b03b8a151fe1aabaf51/
Brooks WA, Santosham M, Naheed A, et al. 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(9490):999–1004. doi:10.1016/S0140-6736(05)67221-8. Available from: https://consensus.app/papers/details/8fdd724b796d5c74973a10d03bb3f036/
Mayo-Wilson E, Junior JA, Imdad A, et al. Preventive zinc supplementation for children, and the effect of additional iron: a systematic review and meta-analysis. BMJ Open. 2014;4(6):e004647. doi:10.1136/bmjopen-2013-004647. Available from: https://consensus.app/papers/details/9274d23f343a548e875503b466101707/
Dhingra U, Kisenge R, Sudfeld CR, et al. Lower-dose zinc for childhood diarrhea — a randomized, multicenter trial. N Engl J Med. 2020;383(13):1231–1241. doi:10.1056/NEJMoa2004773. Available from: https://consensus.app/papers/details/951820e6325054bf81bca8d4a683f974/
McDonald CM, Manji KP, Kupka R, et al. Daily zinc but not multivitamin supplementation reduces diarrhea and upper respiratory infections in Tanzanian infants: a randomized, double-blind, placebo-controlled clinical trial. J Nutr. 2015;145(9):2153–2160. doi:10.3945/jn.115.212985. Available from: https://consensus.app/papers/details/8afd85ca096352f680333aeaba425701/
Mayén AL, Bell Z, Turner T, et al. Childhood stunting and micronutrient status unaffected by RCT of micronutrient fortified drink. Matern Child Nutr. 2021;17(3):e13164. doi:10.1111/mcn.13164. Available from: https://consensus.app/papers/details/e9deba7de2195233a949c4038adf56ea/
Wang AZ, Shulman RJ, Crocker AH, et al. A combined intervention of zinc, multiple micronutrients, and albendazole does not ameliorate environmental enteric dysfunction or stunting in rural Malawian children. J Nutr. 2016. (As ref 11 above)
Hess SY, Abbeddou S, Jimenez EY, et al. Small-quantity lipid-based nutrient supplements, regardless of their zinc content, increase growth and reduce the prevalence of stunting and wasting in young Burkinabe children: a cluster-randomized trial. PLoS ONE. 2015;10(3):e0120260. doi:10.1371/journal.pone.0120260. Available from: https://consensus.app/papers/details/8e978d8691c557dea52d7e30081c37ae/
Kikafunda JK, Walker AF, Collett D, Tumwine JK. Effect of zinc supplementation on growth and body composition of Ugandan preschool children: a randomized, controlled, intervention trial. Am J Clin Nutr. 1998;68(6):1261–1266. doi:10.1093/ajcn/68.6.1261. Available from: https://consensus.app/papers/details/d64910fa15e650a5883505e18f466b48/
Lind T, Lönnerdal B, Stenlund H, et al. A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development. Am J Clin Nutr. 2004;80(3):729–736. doi:10.1093/ajcn/80.3.729. Available from: https://consensus.app/papers/details/77a1b6d46fca5c34937450e73ac809c1/
Raqib R, Roy SK, Rahman MJ, et al. Effect of zinc supplementation on immune and inflammatory responses in pediatric patients with shigellosis. Am J Clin Nutr. 2004;79(3):444–450. doi:10.1093/ajcn/79.3.444. Available from: https://consensus.app/papers/details/3157e00a350e59c78081f81fcc1348d3/
Bobat R, Coovadia H, Stephen C, et al. Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial. Lancet. 2005;366(9500):1862–1867. doi:10.1016/S0140-6736(05)67756-8. Available from: https://consensus.app/papers/details/162d22ad26995815a27f87ffd0d8f456/
Islam MM, Ahmed T, Mahfuz M, et al. Different doses, forms, and frequencies of zinc supplementation for the prevention of diarrhea and promotion of linear growth among young Bangladeshi children: a six-arm, randomized, community-based efficacy trial. J Nutr. 2022;152(6):1571–1582. doi:10.1093/jn/nxac077. Available from: https://consensus.app/papers/details/70bc57d2a26f52cdad9a0b68e0d96b91/
Tam E, Keats EC, Rind F, Das JK, Bhutta AZA. Micronutrient supplementation and fortification interventions on health and development outcomes among children under-five in low- and middle-income countries: a systematic review and meta-analysis. Nutrients. 2020;12(2):289. doi:10.3390/nu12020289. Available from: https://consensus.app/papers/details/915602737aa15f34a835f9d26f230cac/
Wastney ME, House WA, Greger JL. A dynamic model for predicting growth in zinc-deficient stunted infants given supplemental zinc. Am J Clin Nutr. 2018;107(2):216–222. doi:10.1093/ajcn/nqx048. Available from: https://consensus.app/papers/details/c9ce1f69991952d1aabcb6e1910a9e6f/
Stammers AL, Lowe NM, Medina MW, et al. The relationship between zinc intake and growth in children aged 1–8 years: a systematic review and meta-analysis. Eur J Clin Nutr. 2014;68(2):164–170. doi:10.1038/ejcn.2013.253. Available from: https://consensus.app/papers/details/c0228cce2dc257b5b872c42a99a1a0c5/
Jongstra R, Rietman JL, Herkert D, et al. The effect of zinc-biofortified rice on zinc status of Bangladeshi preschool children: a randomized, double-masked, household-based, controlled trial. Am J Clin Nutr. 2021;113(5):1271–1281. doi:10.1093/ajcn/nqaa414. Available from: https://consensus.app/papers/details/07a0f61ecfb157fcb8109cefb867c0dd/
Barffour MA, Wessells KR, Hinnouho GM, et al. Daily preventive zinc supplementation decreases lymphocyte and eosinophil concentrations in rural Laotian children. J Nutr. 2020;150(5):1307–1315. doi:10.1093/jn/nxaa006. Available from: https://consensus.app/papers/details/ede1ece4b655509eb061c2764a1a93a6/
Nemati K, Hemsworth J, Pendergast C, et al. Catch-up growth following early-life stunting in a low-resource area in rural Tanzania: the MAL-ED Metabolic study. BMJ Open. 2025;15(3):e088734. doi:10.1136/bmjopen-2025-088734. Available from: https://consensus.app/papers/details/a289e6241fd85136add53c12d680d225/
World Health Organization. WHO Child Growth Standards: Length/Height-for-Age, Weight-for-Age, Weight-for-Length, Weight-for-Height and Body Mass Index-for-Age: Methods and Development. Geneva: WHO; 2006. Available from: https://www.who.int/tools/child-growth-standards/
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Kartika Dewi (Author)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors publishing here keep copyright but grant the journal first publication rights, under a Creative Commons Attribution-NonCommercial 4.0 License. They can distribute their work non-exclusively elsewhere with an acknowledgment of its first publication in this journal. Posting the work online before and during submission for earlier and greater citation is encouraged, reflecting Open Access benefits.
