Zinc for Childhood Diarrhoea: What the Trials and WHO Say

Table of Contents

1. Why Diarrhoea Matters for Young Children
2. Zinc Deficiency Where Diarrhoea Is Common
3. How Zinc Is Thought to Work in the Gut
4. The Early Trials in India and Bangladesh
5. What the Cochrane Review Found
6. Persistent Diarrhoea and Malnourished Children
7. Children Where Zinc Deficiency Is Rare
8. Vomiting and the Lower-Dose Trial
9. What WHO's 2024 Guidance States
10. Oral Rehydration Solution Remains the Core Treatment
11. Zinc Given to Prevent Diarrhoea
12. What Is Still Not Known
13. Key Research Papers
14. Connections
15. Featured Videos

Why Diarrhoea Matters for Young Children

The Global Burden of Disease Study 2016 estimated that diarrhoea was the eighth leading cause of death across all ages that year, with about 1,656,000 deaths, and the fifth leading cause of death in children younger than 5 years, with about 446,000 deaths (GBD 2016 Diarrhoeal Disease Collaborators, 2018). The background section of the 2016 Cochrane review of zinc gives a similar figure: in developing countries, diarrhoea causes around 500,000 child deaths each year (Lazzerini 2016).

The same Global Burden of Disease analysis looked at causes and risk factors:

• Rotavirus was the leading cause of diarrhoea deaths in children younger than 5, with about 128,500 deaths in 2016 (see the Rotavirus page). In the 1992 Bangladesh zinc study described below, the germs found in the children's stools included rotavirus, Escherichia coli, Vibrio cholerae (cholera), Shigella and Campylobacter jejuni (Roy 1992). The parasite Cryptosporidium is covered on its own page.
• Childhood wasting (low weight for height) was the leading risk factor, responsible for an estimated 80.4% of diarrhoea deaths in children under 5.
• Unsafe water accounted for an estimated 72.1% and unsafe sanitation for 56.4% of those deaths. The percentages overlap because one death can have several risk factors at once.
• The authors estimated that preventing wasting in about 1,762 children could avert one death from diarrhoea.

The authors also reported substantial progress in reducing the burden of diarrhoea worldwide, driven by falls in several of the main risk factors, but the progress was not equal from place to place. Rehydration, not zinc, is the centre of treatment (see below).

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Zinc Deficiency Where Diarrhoea Is Common

The places with the most child deaths from diarrhoea are often the same places where zinc deficiency is widespread. In a 2009 review, Ananda Prasad, the physician who first described human zinc deficiency, wrote that zinc deficiency, causing growth retardation, hypogonadism, immune dysfunction and cognitive impairment, affects nearly 2 billion people in the developing world. He attributed much of this to cereal-based diets high in phytate, a plant compound that binds zinc and lowers how much of it the gut can absorb (Prasad 2009). The same review lists acute diarrhoea in children among the conditions where zinc supplements produced beneficial responses.

The link runs both ways. Sazawal and colleagues noted in 1995 that diarrhoea is common in children with severe zinc deficiency and responds quickly to zinc, and that the longest and most severe bouts of diarrhoea occur in young children who are malnourished and have weaker immune defences, two conditions that may go along with zinc deficiency (Sazawal 1995). The 2023 Cochrane review of zinc for prevention describes zinc deficiency as common in low- and middle-income countries and as a significant risk factor for illness, death and poor growth (Imdad 2023).

Signs, causes and testing of zinc deficiency are covered on the Zinc Deficiency page.

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How Zinc Is Thought to Work in the Gut

How zinc shortens diarrhoea is not settled. A 2006 review in Gastroenterology stated that only limited information is known about the mechanism or mechanisms by which zinc reduces diarrhoea (Hoque and Binder 2006). The ideas below are proposed mechanisms, based on laboratory work and a few studies in children.

• Less fluid pumped into the gut. In many forms of watery diarrhoea, the lining of the intestine pushes chloride, and water with it, into the gut. In strips of rat intestine (rat ileum) in the laboratory, zinc added on the blood side of the lining markedly reduced chloride secretion driven by the signalling molecule cyclic AMP, by blocking potassium channels on that side of the cells. In the same rat tissue zinc did not change glucose-driven sodium absorption, which is the process oral rehydration solution relies on, and did not change chloride secretion driven by calcium signals (Hoque, Rajendran and Binder 2005). The 2006 review summarised this as zinc acting as a potassium-channel blocker of cyclic AMP-driven chloride secretion, and called for more detailed physiological studies (Hoque and Binder 2006).
• A tighter gut lining. In a 1992 trial in Bangladesh, 111 children with acute diarrhoea and 190 with persistent diarrhoea, aged 3 to 24 months, were randomly given zinc or a placebo in a multivitamin syrup for 2 weeks (the trial gave 5 mg of elemental zinc per kilogram of body weight a day). At the start, the children's guts let through more of a test sugar (lactulose) than those of healthy children of the same age, a sign of a leaky lining. Two weeks of zinc significantly reduced lactulose passage in both groups, and the largest reduction was in children who were underweight, thin, undernourished or had low blood zinc (Roy 1992). The authors noted that zinc had already been shown to help the gut lining repair itself in acrodermatitis enteropathica, the inherited zinc-absorption disorder described on the history page.
• Immune defence. The 2006 review mentions zinc's beneficial effects in other infections, including pneumonia, as part of the reason it was tried in diarrhoea (Hoque and Binder 2006). Zinc's roles in immune cells are covered on the immune function page.

The rat findings were made in isolated tissue, at concentrations set in a laboratory chamber, so they show a possible route and do not prove that this is what happens in a sick child.

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The Early Trials in India and Bangladesh

Three studies from the 1990s and early 2000s did much to put zinc into treatment guidance.

• New Delhi, 1995. A double-blind randomised trial in 937 children aged 6 to 35 months with acute diarrhoea gave either zinc (the trial gave 20 mg of elemental zinc a day) or a placebo. All the children also received oral rehydration therapy and vitamins. Children given zinc had a 23% lower risk of continued diarrhoea. The effect was small in the first three days (7%, not statistically clear) and larger after day 3 (38%). When zinc was started within three days of the diarrhoea beginning, the share of episodes lasting more than seven days fell by 39%. Zinc also cut the mean number of watery stools a day by 39% and the number of days with watery diarrhoea by 21%. The reductions were greater in children with stunted growth than in children of normal growth (Sazawal 1995).
• Pooled analysis, 2000. Researchers pooled the randomised trials of zinc given with oral rehydration therapy to children under 5 in developing countries. In the acute-diarrhoea trials, children given zinc had a 15% lower chance of still having diarrhoea on any given day. In the persistent-diarrhoea trials they had a 24% lower chance of continuing diarrhoea and a 42% lower rate of treatment failure or death (Bhutta 2000).
• Matlab, Bangladesh, 2002. A community trial randomised whole clusters of villages rather than single children: 8,070 children aged 3 to 59 months were followed for two years. In the intervention clusters, children with diarrhoea were given zinc (the trial gave 20 mg a day for 14 days); all children with diarrhoea received oral rehydration therapy. Children in the zinc clusters had shorter diarrhoea (hazard ratio 0.76) and less diarrhoea overall (rate ratio 0.85), and were admitted to hospital for diarrhoea less often (0.76). The rate of non-injury deaths in the zinc clusters was considerably lower (0.49, confidence interval 0.25 to 0.94). Use built up over time: about 40% of episodes were treated with zinc in the first four months, rising to more than 80% by month 7 (Baqui 2002).

The Bangladesh death finding comes from one cluster trial. The later Cochrane review, which pooled many trials, judged that there is not enough evidence to say whether zinc during acute diarrhoea reduces deaths (see below).

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What the Cochrane Review Found

The most complete summary of zinc as a treatment is the 2016 Cochrane review by Lazzerini and Wanzira. It included 33 randomised trials with 10,841 children aged one month to five years with acute or persistent diarrhoea, including dysentery (bloody diarrhoea). Most trials were run in Asian countries at high risk of zinc deficiency. Each finding came with a certainty grade, which says how confident the reviewers were.

The authors concluded that, where zinc deficiency or malnutrition is common, zinc may be of benefit in children aged six months or more. They also wrote that the current evidence does not support zinc supplements for children younger than six months, for well-nourished children, or in settings where children are at low risk of zinc deficiency (Lazzerini 2016).

Half a day sounds small. For a child at risk of dehydration, a shorter illness and fewer children still sick at one week are what the trials measured as the benefit; the review did not find evidence on whether that translates into fewer deaths.

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Persistent Diarrhoea and Malnourished Children

Persistent diarrhoea is diarrhoea that goes on for weeks rather than days. Several findings point the same way: zinc's effect appears larger in the children who are worst off.

• In the Cochrane review, the reduction in diarrhoea length in children with signs of malnutrition (around a day, high certainty) was about twice the reduction in children older than 6 months as a whole (around half a day, low certainty), and zinc probably shortened persistent diarrhoea by around 16 hours (Lazzerini 2016).
• In the 2000 pooled analysis, the persistent-diarrhoea trials showed a 42% lower rate of treatment failure or death with zinc. The subgroup comparisons did not differ significantly, but in persistent diarrhoea the effect tended to be greater in children under 12 months, in boys, and in children with wasting or lower starting blood zinc (Bhutta 2000).
• In the New Delhi trial, the benefit was greater in stunted children (Sazawal 1995), and in the Bangladesh permeability study the gut lining improved most in the most undernourished children (Roy 1992).

These findings are consistent with the idea that zinc helps most where it corrects a real shortage, though the trials did not test that idea directly.

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Children Where Zinc Deficiency Is Rare

Nearly all the trials were done in low- and middle-income countries, so the question of whether zinc helps children in high-income countries has been studied much less.

• A 2008 meta-analysis of 18 randomised trials (11,180 children, mainly from developing countries) found zinc shortened diarrhoea by a weighted mean of 0.69 day and reduced the risk of diarrhoea lasting more than 7 days (relative risk 0.71). It found no significant reduction in stool volume, and zinc increased the chance of vomiting (relative risk 1.2). The authors wrote that the role of zinc in children in developed countries needed further evaluation (Patro 2008).
• The same research group then ran a randomised, double-blind, placebo-controlled trial in Poland in children aged 3 to 48 months with acute gastroenteritis (the trial gave 10 or 20 mg of zinc sulfate a day, depending on age, for 10 days). Among the 141 children analysed, there was no significant difference in the length of diarrhoea, stool frequency on days 1 to 3, vomiting, intravenous fluid use, or the number of children with diarrhoea lasting more than 7 days. The authors concluded that children living in a country where zinc deficiency is rare do not appear to benefit (Patro 2010).

This fits the Cochrane conclusion that the evidence does not support zinc in well-nourished children or where the risk of zinc deficiency is low (Lazzerini 2016). It is one trial of modest size, so it does not settle the question for every high-income setting, but no trial cited here found a benefit in such a setting.

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Vomiting and the Lower-Dose Trial

The side effect that appears in trial after trial is vomiting. The Cochrane review found zinc raised the risk of vomiting by about one and a half times in both age groups (Lazzerini 2016), and the 2008 meta-analysis found a smaller but significant increase (Patro 2008). For a child who is losing fluid, vomiting matters because it can bring up the rehydration solution as well.

That led to a direct test of lower doses. The ZTDT trial, published in the New England Journal of Medicine in 2020, noted in its background that WHO then recommended 20 mg of zinc a day for 10 to 14 days for children with acute diarrhoea, a dose that in earlier trials reduced diarrhoea but increased vomiting. The trial randomly assigned 4,500 children in India and Tanzania, aged 6 to 59 months, to 5 mg, 10 mg or 20 mg of zinc sulfate a day for 14 days (Dhingra 2020).

The differences in diarrhoea lasting more than 5 days and in stool numbers were within the pre-set non-inferiority margins, meaning the lower doses were judged not worse than 20 mg. Vomiting within 30 minutes was significantly less common with 10 mg (relative risk 0.81) and with 5 mg (relative risk 0.71) than with 20 mg, and lower doses were also linked to less vomiting later on. The authors concluded that lower doses had non-inferior efficacy and caused less vomiting than the standard 20 mg dose (Dhingra 2020). The trial had no placebo group, so it compared doses with each other, not zinc with no zinc.

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What WHO's 2024 Guidance States

A 2025 summary of the 2024 WHO guidelines on childhood pneumonia and diarrhoea, published in Indian Pediatrics, reports these points on diarrhoea (Kundu 2025):

• Zinc dose. WHO's guidance states a conditional recommendation of a reduced zinc dose, 5 mg a day for up to 14 days, for children up to 10 years of age with acute watery or persistent diarrhoea. The summary states that the lower dose is intended to lower the risk of vomiting while keeping the treatment effect.
• Antibiotics. Antibiotic use is discouraged for acute watery diarrhoea, except when there is visible blood in the stool, where ciprofloxacin remains the first-line treatment.
• Probiotics. Probiotics are not recommended, because of low-certainty evidence and concerns about feasibility.

A conditional recommendation is a weaker grade than a strong one. Compared with the 20 mg a day for 10 to 14 days that the 2020 trial described as WHO's earlier recommendation (Dhingra 2020), the 2024 guidance lowers the dose to a quarter. The 5 mg dose is the lowest of the three tested in the ZTDT trial, which had found it non-inferior with less vomiting.

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Oral Rehydration Solution Remains the Core Treatment

Zinc is given alongside rehydration, not instead of it. In every major zinc trial described above, the children also received oral rehydration therapy: all 937 children in the New Delhi trial (Sazawal 1995), all children with diarrhoea in the Bangladesh community trial (Baqui 2002), and zinc was tested "given with oral rehydration therapy" in the pooled analysis (Bhutta 2000). The zinc results describe what zinc adds on top of rehydration.

Oral rehydration solution is a measured mix of water, salts and glucose. The glucose helps the gut absorb sodium, and water follows the sodium back into the body. A 2002 Cochrane review states that oral rehydration solution has reduced childhood deaths from diarrhoea in many countries (Hahn 2002). The 2006 Gastroenterology review describes the past 35 years of improved treatment of acute diarrhoea in children as having reduced illness and death substantially, and reviews efforts to improve the solution's recipe (Hoque and Binder 2006).

Low-osmolarity solution. The original WHO solution was later changed to one with less sodium and glucose, called reduced-osmolarity (or low-osmolarity) oral rehydration solution. The 2002 Cochrane review compared the two in children admitted to hospital with diarrhoea. In 8 trials, the reduced-osmolarity solution was linked to fewer unplanned intravenous drips (odds ratio 0.59), less stool output and less vomiting, with no added risk of low blood sodium detected (Hahn 2002).

Severe dehydration is treated in hospital with intravenous fluids; signs of dehydration such as no urine for many hours, a rapid weak pulse and lethargy are described on the cholera oral rehydration and intravenous fluids page. Zinc does not replace fluid.

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Zinc Given to Prevent Diarrhoea

A separate question is whether giving zinc regularly to healthy children prevents diarrhoea in the first place. The 2023 Cochrane review on prevention included 96 randomised trials with 219,584 eligible children aged 6 months to 12 years, in 34 countries, 87 of the trials in low- or middle-income countries. Most children were under 5. Zinc was most often given as zinc sulfate syrup, most commonly at 10 to 15 mg a day, and the median follow-up was 26 weeks (Imdad 2023). The review found:

• Preventive zinc likely reduces how often children get diarrhoea (risk ratio 0.91; 39 studies, 19,468 children; moderate certainty), roughly a 9% reduction.
• It likely makes little or no difference to deaths from diarrhoea (risk ratio 0.95; moderate certainty) and makes little or no difference to deaths from all causes (risk ratio 0.93; high certainty).
• It likely leads to a slight increase in height (moderate certainty).
• It increased the number of children with at least one episode of vomiting (risk ratio 1.29; high certainty).
• Across several outcomes, giving zinc together with iron reduced zinc's beneficial effect.

The authors concluded that the benefits of preventive zinc may outweigh the harms in regions where the risk of zinc deficiency is relatively high (Imdad 2023). Treating a child with zinc during diarrhoea may also have a preventive effect afterwards: in the Bangladesh community trial, children in the zinc clusters had less diarrhoea over the two years (rate ratio 0.85) (Baqui 2002).

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What Is Still Not Known

• Deaths. Whether zinc during acute diarrhoea reduces deaths or hospital admissions remains uncertain; the Cochrane review graded that evidence very low certainty (Lazzerini 2016). The large fall in non-injury deaths in the Bangladesh trial (Baqui 2002) comes from a single cluster trial, and preventive zinc did not change deaths from diarrhoea (Imdad 2023).
• Infants under 6 months. The trials found no benefit in this age group, and vomiting was still more common (Lazzerini 2016).
• Well-nourished children and high-income countries. The evidence does not support a benefit, and the few trials in such settings are small (Patro 2010; Lazzerini 2016).
• Children aged 5 to 10. The 2024 WHO guidance covers children up to 10 years (Kundu 2025), but the Cochrane treatment review only included children up to 5 years (Lazzerini 2016), and the lower-dose trial enrolled children aged 6 to 59 months (Dhingra 2020).
• How it works. The mechanism is still described as poorly understood (Hoque and Binder 2006); the clearest laboratory evidence comes from rat intestine (Hoque, Rajendran and Binder 2005).
• Adults. None of the trials on this page studied adults.

Decisions about treating a child's diarrhoea belong with a clinician or health worker who can judge dehydration.

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Key Research Papers

1. GBD 2016 Diarrhoeal Disease Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Infectious Diseases. 2018;18(11):1211-1228. — PubMed PMID: 30243583
2. Lazzerini M, Wanzira H. Oral zinc for treating diarrhoea in children. Cochrane Database of Systematic Reviews. 2016;12(12):CD005436. — PubMed PMID: 27996088
3. Sazawal S, Black RE, Bhan MK, Bhandari N, Sinha A, Jalla S. Zinc supplementation in young children with acute diarrhea in India. New England Journal of Medicine. 1995;333(13):839-44. — PubMed PMID: 7651474
4. 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(7372):1059. — PubMed PMID: 12424162
5. 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. American Journal of Clinical Nutrition. 2000;72(6):1516-22. — PubMed PMID: 11101480
6. Patro B, Golicki D, Szajewska H. Meta-analysis: zinc supplementation for acute gastroenteritis in children. Alimentary Pharmacology & Therapeutics. 2008;28(6):713-23. — PubMed PMID: 19145727
7. Patro B, Szymański H, Szajewska H. Oral zinc for the treatment of acute gastroenteritis in Polish children: a randomized, double-blind, placebo-controlled trial. Journal of Pediatrics. 2010;157(6):984-988.e1. — PubMed PMID: 20619853
8. Dhingra U, Kisenge R, Sudfeld CR, Dhingra P, Somji S, Dutta A, Bakari M, Deb S, Devi P, Liu E, Chauhan A, Kumar J, Semwal OP, Aboud S, Bahl R, Ashorn P, Simon J, Duggan CP, Sazawal S, Manji K. Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial. New England Journal of Medicine. 2020;383(13):1231-1241. — PubMed PMID: 32966722
9. Kundu S, Das S, Medhagopal RG. An Update on WHO Recommendations on Childhood Pneumonia and Diarrhea (2024). Indian Pediatrics. 2025;62(10):775-778. — PubMed PMID: 40839064
10. Hahn S, Kim S, Garner P. Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children. Cochrane Database of Systematic Reviews. 2002;(1):CD002847. — PubMed PMID: 11869639
11. Hoque KM, Binder HJ. Zinc in the treatment of acute diarrhea: current status and assessment. Gastroenterology. 2006;130(7):2201-5. — PubMed PMID: 16762641
12. Hoque KM, Rajendran VM, Binder HJ. Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2005;288(5):G956-63. — PubMed PMID: 15618279
13. Roy SK, Behrens RH, Haider R, Akramuzzaman SM, Mahalanabis D, Wahed MA, Tomkins AM. Impact of zinc supplementation on intestinal permeability in Bangladeshi children with acute diarrhoea and persistent diarrhoea syndrome. Journal of Pediatric Gastroenterology and Nutrition. 1992;15(3):289-96. — PubMed PMID: 1432467
14. Imdad A, Rogner J, Sherwani RN, Sidhu J, Regan A, Haykal MR, Tsistinas O, Smith A, Chan XHS, Mayo-Wilson E, Bhutta ZA. Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years. Cochrane Database of Systematic Reviews. 2023;3(3):CD009384. — PubMed PMID: 36994923
15. Prasad AS. Impact of the discovery of human zinc deficiency on health. Journal of the American College of Nutrition. 2009;28(3):257-65. — PubMed PMID: 20150599

PubMed Topic Searches

1. PubMed: zinc and acute diarrhoea in children, randomised trials
2. PubMed: zinc and persistent diarrhoea in children
3. PubMed: lower-dose zinc, diarrhoea and vomiting
4. PubMed: preventive zinc and diarrhoea incidence
5. PubMed: oral rehydration solution and zinc

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Connections

• Zinc — Benefits Deep Dive — the hub for the zinc benefit articles
• Zinc — the main topic page
• Zinc for Immune Function — colds, pneumonia and immune cells
• Zinc: History and Discovery — Prasad and acrodermatitis enteropathica
• Zinc Deficiency — signs, causes and recovery
• Rotavirus — the leading cause of diarrhoea deaths in young children
• Cholera: Oral Rehydration Solution and Intravenous Fluids — rehydration in detail
• Cholera in Children and Vulnerable Populations — why young children are at greater risk
• Cryptosporidium — a parasite cause of childhood diarrhoea
• Chronic Diarrhea — diarrhoea that lasts

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