Even lower doses of zinc effective in diarrhea in children, claims NEJM study

The findings of the new study have been published in The New England Journal Of Medicine.

The zinc recommendation is based on studies that have shown that the administration of supplemental zinc results in a shorter duration of diarrhea, reduces the number of stools and stool output, reduces the risk of persistent diarrhea, and may reduce the risk of subsequent illness and increase weight gain. The physiological basis for the effects of zinc supplementation on diarrheal diseases is not completely clear. Possible mechanisms include correction of a nutrient deficiency, improvement of immune function, or inhibition of cyclic AMP–mediated chloride secretion.

To date, the recommended zinc dose (20 mg per day for 10 to 14 days) is based on assumptions of increased zinc losses during diarrhea and the need for additional zinc above the recommended dietary allowance for immune and gastrointestinal function. The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but increased vomiting.

The researchers opined that lower zinc doses (5 mg or 10 mg per day), provided they are equally effective, might have the advantage of causing less vomiting than the current recommended dose. With this in mind, Usha Dhingra et al sought to carry out a study to investigate the same.

The team randomly assigned 4500 children in India and Tanzania who were 6 to 59 months of age and had acute diarrhea to receive 5 mg, 10 mg, or 20 mg of zinc sulfate for 14 days.

The three primary outcomes were a diarrhea duration of more than 5 days and the number of stools (assessed in a noninferiority analysis) and the occurrence of vomiting (assessed in a superiority analysis) within 30 minutes after zinc administration.

The results highlighted the following facts.

• The percentage of children with diarrhea for more than 5 days was 6.5% in the 20-mg group, 7.7% in the 10-mg group, and 7.2% in the 5-mg group.
• The difference between the 20-mg and 10-mg groups was 1.2 percentage points (upper boundary of the 98.75% confidence interval [CI], 3.3), and that between the 20-mg and 5-mg groups was 0.7 percentage points (upper boundary of the 98.75% CI, 2.8), both of which were below the noninferiority margin of 4 percentage points.
• The mean number of diarrheal stools was 10.7 in the 20-mg group, 10.9 in the 10-mg group, and 10.8 in the 5-mg group.
• The difference between the 20-mg and 10-mg groups was 0.3 stools (upper boundary of the 98.75% CI, 1.0), and that between the 20-mg and 5-mg groups was 0.1 stools (upper boundary of the 98.75% CI, 0.8), both of which were below the noninferiority margin (2 stools).
• Vomiting within 30 minutes after administration occurred in 19.3%, 15.6%, and 13.7% of the patients in the 20-mg, 10-mg, and 5-mg groups, respectively; the risk was significantly lower in the 10-mg group than in the 20-mg group (relative risk, 0.81; 97.5% CI, 0.67 to 0.96) and in the 5-mg group than in the 20-mg group (relative risk, 0.71; 97.5% CI, 0.59 to 0.86).

Addressing the limited knowledge and clinical trials on this topic, the team wrote "A renewed public health push will be needed to solve these problems and maximize the benefits of this intervention. Our Lower doses were also associated with less vomiting beyond 30 minutes after administration. Our findings may contribute to these programmatic efforts."

For the full article click on the link below: DOI: 10.1056/NEJMoa1915905

Primary source: The New England Journal Of Medicine