Zinc, the most abundant metal in the human body after iron, plays a fundamental role in protein synthesis, cell growth, and differentiation. Inadequate zinc intake is associated with diarrhea and respiratory illnesses, especially in children younger than 5 years of age, and its supplementation can reduce the duration of diarrhea and pneumonia [
1].
Acute gastroenteritis (AGE) in children, often caused by acute infectious diarrhea, is the second leading cause of mortality and morbidity, especially in low-income countries. The global mortality rate due to infectious diarrhea has declined owing to rotavirus vaccination, refined diarrhea management, and improved nutrition in infants and children; however, it is often associated with adverse outcomes that require prolonged medical support or hospitalization. Dehydration, the major consequence of diarrhea, vomiting, and fever, is the main cause of AGE-related morbidity in children. Dehydration reflects disease severity; thus, its prevention or management is the main goal of the treatment of infectious diarrhea in infants and children.
Replacing fluid loss with oral rehydration solutions (ORS) is the first-line treatment for AGE in children. Since the World Health Organization adopted ORS as its primary tool for treating dehydration, various ORS have become available worldwide. Probiotics and zinc are effective adjuvant therapies for reducing diarrhea duration and intensity. Specific strains, including Lacticaseibacillus rhamnosus GG and Saccharomyces boulardii may be recommended for managing AGE in children due to evidence of its ability to reduce the duration of diarrhea or prevent antibiotic-associated diarrhea [
2]. Zinc supplementation in acute infectious diarrhea reportedly reduced intestinal permeability and the mean duration of diarrhea by 19.7%, especially among malnourished children aged 6 months or older [
3]. However, oral zinc carries an increased risk of vomiting, and its use in infants younger than 6 months of age or well-nourished children with a low risk of zinc deficiency was reportedly ineffective [
4]. Although zinc supplementation in children with AGE showed no consistent benefit, several studies reported its benefit when administered to malnourished children with AGE [
1,
3,
5].
A recent randomized controlled trial (RCT) of the effectiveness of probiotics and zinc in managing acute infectious diarrhea in children was reported in Iraq [
6]. Although previous studies reported conflicting results about the effectiveness of zinc supplementation in treating children with AGE [
3-
5], it can reportedly shorten disease duration as an adjunct to oral rehydration therapy in malnourished children older than 6 months [
1,
3,
7]. In this RCT, zinc supplementation with probiotics shortened the duration of diarrhea by 1.34 days compared to supplementation with probiotics alone (2 days;
P<0.001). However, no significant intergroup differences were noted in the reduction of disease severity or relief of symptoms including vomiting and fever [
6].
Several issues were encountered when interpreting the results of that study. First, it included children of various ages and rotavirus vaccination statuses as well as a high proportion of participants with mild dehydration. Second, no information was provided on the pre-illness weight or nutritional status of children with AGE. Dehydration was assessed using the Clinical Dehydration Scale, which can be useful for evaluating the degree of dehydration in non-malnourished children with AGE [
8]. Third, no placebo group was included. The participants in the two randomly assigned groups were supplemented with the same probiotics, which may have mitigated the effect of the zinc supplementation. However, the results of this study can be strengthened by a well-designed RCT.
Although the rotavirus vaccine has been widely available, rotavirus enteritis remains the major cause of AGE worldwide, including in South Korea [
9,
10]. Therefore, a standard prevention and treatment protocol for childhood infectious diarrhea based on a well-designed RCT remains necessary.