Zinc supplementation increases cellular immune response in children – Nestle-funded study

The study also involved the supplementation of vitamin A.

While the supplementation of vitamin A alone did not show significant improvements to the immune response, both zinc and vitamin A supplementation in young children was able to bring out the benefits of vitamin A supplementation.

Findings of the study was published in the Asia Pacific Journal of Clinical Nutrition. ​It was conducted by researchers from the Diponegoro University in Indonesia, University of Queensland, and Griffith University.

The study was also supported by a Nestle foundation research grant.

The study took place in Semarang, Indonesia, where over 1,000 children aged two to five were recruited.

At recruitment, the children were generally underweight and short, but not thin, had low serum retinol and mild zinc deficiency.

Moderate and severely malnourished children were excluded.

The children were randomly assigned to take daily zinc supplement (10mg) or placebo for four months.

After the first two months of the study, both the zinc intervention and placebo groups took a single dose of 200,000 IU vitamin A capsule, as part of a routine national vitamin A supplementation program.

Just before the vitamin A supplementation commenced, a sub-sample of 81 children from each group (with zinc and without zinc supplementation) was randomly selected. Blood samples from both groups were collected.

Four months after the study, another subgroup sample of 81 children were taken. This time round, the children took either 1) zinc and vitamin A or 2) only vitamin A.

Eventually, there were four groups for comparison: 1) took zinc and no vitamin A 2) did not take zinc and vitamin A 3) took vitamin A and no zinc 4) took zinc and vitamin A.

Data from the four subgroups and the entire group, including measurements from hair, blood, saliva samples, were included in the final analysis.

Effects of zinc supplementation ​

Zinc supplementation was shown to increase IFN-gamma production, one of the indicators of cell mediated immune response.

The effect was larger in boys than girls, where there was a higher ex-vivo IFN-gamma production.

For instance, boys with zinc supplementation alone had a mean of 7.4 ± 0.8 pg/mL ex-vivo IFN-gamma production using the ANOVA analysis model, a statistically significant increase from baseline. When girls are taken into consideration, the mean ex-vivo IFN-gamma production dropped to 6.5 ± 0.5 pg/mL.  

“This result is in line with other studies showing that zinc supplementation increases cell mediated immunity and that zinc supplementation benefits boys more,”​ the researchers said.

Children younger than 3.5 years old also benefitted more. Among children with low-base retinol (a form of vitamin A), both vitamin A and zinc supplementation showed significant effects on ex-vivo IFN-gamma production.

For instance, their mean ex-vivo IFN-gamma production after supplementation of zinc and vitamin A was 7.1 ± 0.8 pg/mL using the ANOVA analysis model. When older children are also considered, mean ex-vivo IFN-gamma production had dropped to 7.0 ± 0.5 pg/mL.

“Younger children have immature immune systems, including cell mediated immunity, which develops throughout the childhood. ​

“This possibly explains why the younger children benefitted more from zinc supplementation,”​ the researchers said.

Effects of zinc and vitamin A supplementation ​

The researchers also measured the impact of zinc and vitamin A supplementation on serum IgG and IgA levels – another two biomarkers related to the immune system.

They found that in general, vitamin A and zinc supplementation did not lead to increase in serum IgG and salivary IgA levels – both play a role in the immune system by affecting the Th2 response.

This is except for young children who took both zinc and vitamin A supplementation, where there was an increase in serum IgG. 

Vitamin A deficiency is linked to the immune system by reducing Th2 response – which is linked to serum IgG levels and salivary IgA levels.

Where there is an elevated Th2 response, the Th2 cell produces cytokine IL-4 and delivers it to B cells, activating the B cells to produce antibodies.

“The study provides evidence that zinc supplementation increases cellular immune responses (ex-vivo IFN-gamma) and modifies the effect of vitamin A supplementation on immune responses in at least some sub-groups for humoral (serum IgG and salivary IgA) and local mucosal (salivary secretory IgA) immunity,”​ the researchers concluded.

Source: Asia Pacific Journal of Clinical Nutrition​

DOI: 10.6133/APJCN.202012_29(4).0008

Effect of zinc and vitamin A supplementation on immune responses in Indonesian pre-schoolers​

Authors: Martha Irene Kartasurya and et al