The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among nonpregnant Cambodian women of reproductive age: A 2 × 2 factorial, double-blind, randomized controlled supplementation trial

Crystal D. Karakochuk, Mikaela K. Barker, Kyly C. Whitfield, Susan I. Barr, Suzanne M. Vercauteren, Angela M. Devlin, Jennifer A. Hutcheon, Lisa A. Houghton, Sophonneary Prak, Kroeun Hou, Tze Lin Chai, Ame Stormer, Sokhoing Ly, Robyn Devenish, Christian Oberkanins, Helene Pühringer, Kimberly B. Harding, Luz M. De-Regil, Klaus Kraemer, Tim Green

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Background: Despite a high prevalence of anemia among nonpregnant Cambodian women, current reports suggest that iron deficiency (ID) prevalence is low. If true, iron supplementation will not be an effective anemia reduction strategy. Objective: We measured the effect of daily oral iron with or without multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant Cambodian women screened as anemic. Design: In this 2 × 2 factorial, double-blind, randomized trial, nonpregnant women (aged 18-45 y) with hemoglobin concentrations ≤117 g/L (capillary blood) were recruited from 26 villages in Kampong Chhnang province and randomly assigned to receive 12 wk of iron (60 mg; Fe group), MMNs (14 other micronutrients; MMN group), iron plus MMNs (Fe+MMN group), or placebo capsules. A 2 × 2 factorial intention-to-treat analysis with the use of a generalized mixed-effects model was used to assess the effects of iron and MMNs and the interaction between these factors. Results: In July 2015, 809 women were recruited and 760 (94%) completed the trial. Baseline anemia prevalence was 58% (venous blood). Mean (95% CI) hemoglobin concentrations at 12 wk in the Fe, MMN, Fe+MMN, and placebo groups were 121 (120, 121), 116 (116, 117), 123 (122, 123), and 116 (116, 117) g/L, with no iron × MMN interaction (P = 0.66). Mean (95% CI) increases in hemoglobin were 5.6 g/L (3.8, 7.4 g/L) (P <0.001) among women who received iron (n = 407) and 1.2 g/L (20.6, 3.0 g/L) (P = 0.18) among women who received MMNs (n = 407). The predicted proportions (95% CIs) of women with a hemoglobin response ($10 g/L at 12 wk) were 19% (14%, 24%), 9% (5%, 12%), 30% (24%, 35%), and 5% (2%, 9%) in the Fe, MMN, Fe+MMN, and placebo groups, respectively. Conclusions: Daily iron supplementation for 12 wk increased hemoglobin in nonpregnant Cambodian women; however, MMNs did not confer additional significant benefit. Overall, ∼24% of women who received iron responded after 12 wk; even fewer would be likely to respond in the wider population. This trial was registered at as NCT02481375. Am J Clin Nutr 2017;106:233-44.

Original languageEnglish
Pages (from-to)233-244
Number of pages12
JournalAmerican Journal of Clinical Nutrition
Issue number1
Publication statusPublished - 1 Jul 2017


  • Anemia
  • Cambodia
  • Hemoglobin
  • Iron
  • Micronutrient
  • Supplementation
  • Women

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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