A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: interactions between iron and zinc.

Community-based randomized controlled trial in healthy singleton infants in Central Java, Indonesia, enrolled at about 6 months of age and followed to 12 months. The population was at risk of iron and zinc deficiency and lived in a setting with a plant-based diet, little animal protein, and high phytate intake.

Children received daily oral syrup from 6 to 12 months of age. Active regimens were iron alone (10 mg as ferrous sulfate), zinc alone (10 mg as zinc sulfate), or iron plus zinc (10 mg of each) given once daily for 180 days; the matched syrup also contained 30 mg ascorbic acid, sugar, and water. A placebo syrup was used for comparison.

Daily supplementation improved micronutrient status, but the combined iron-plus-zinc regimen was less effective than single-nutrient supplementation. At 12 months, hemoglobin differed across groups (Fe 119.4 ± 15.3 g/L; Zn 115.7 ± 15.2; Fe+Zn 115.3 ± 13.9; placebo 113.5 ± 16.0; P=0.012), ferritin was highest with iron alone (46.5 ± 2.0 g/L; P<0.001), and serum zinc was highest with zinc alone (11.58 ± 1.41 mol/L; P<0.001). Two-factor ANOVA showed significant iron-zinc interaction for hemoglobin (P=0.021) and serum ferritin (P=0.032), consistent with iron reducing zinc effectiveness in the combined regimen. Endpoint anemia prevalence was 25% with iron, 36% with zinc, 38% with iron+zinc, and 44% with placebo; low ferritin was 5%, 35%, 10%, and 37%, respectively.

Arm sizes were modest and follow-up lasted only 6 months, limiting precision and long-term inference. Findings come from healthy Indonesian infants in a specific high-phytate, low-animal-protein diet context, which may limit generalizability. The study relied mainly on biochemical outcomes and included multiple comparisons and dose-response analyses, increasing the risk of multiplicity-related findings.