Anemia among adolescent girls remains a major public health problem in Indonesia despite nationwide iron supplementation programs. Poor adherence to iron tablets and limited iron bioavailability reduces treatment effectiveness. Centella asiatica nanoparticles may enhance iron absorption and erythropoiesis by improving the bioavailability of bioactive compounds. This study aimed to evaluate whether nanoparticle-based Centella asiatica enhances the hematologic response to iron supplementation. A randomized pretest–posttest control group study was conducted from October to November 2025 at the Department of Midwifery, Poltekkes Kemenkes Semarang, Central Java, Indonesia. Forty anemic adolescent girls aged 16–19 years were recruited using purposive sampling and randomly assigned to intervention or control groups. The intervention group received oral Centella asiatica nanoparticles (500mg/day; particle size<200 nm) together with iron tablets (60mg/day), while the control group received iron alone for 14 days. Hemoglobin levels were measured before and after the intervention. Statistical analyses included paired and independent t-tests, and effect size was calculated using Cohen's d. Ethical approval was obtained from the institutional ethics committee. Hemoglobin levels increased significantly in both groups after the intervention (both p<0.001). The intervention group demonstrated a greater increase in hemoglobin concentration (11.19 ± 0.29 to 13.25 ± 0.52 g/dL) than the control group (11.39 ± 0.32 to 13.04 ± 0.46 g/dL), with a large effect size (Cohen's d=1.53). Between-group analysis indicated that the combined intervention produced significantly greater hemoglobin improvement than iron supplementation alone (p<0.05). Centella asiatica nanoparticles may serve as a promising adjunct to iron supplementation for improving hemoglobin levels in anemic adolescent girls. Larger and longer-term studies are needed to confirm their effectiveness and support integration into adolescent anemia prevention programs.
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