The Inclusion of Folic Acid in Weekly Iron-Folic Acid Supplements Confers no Additional Benefit on Anemia Reduction in Nonpregnant Women: A Randomized Controlled Trial in Malaysia.
Study Goal
The researchers aimed to determine whether adding folic acid to weekly iron supplements provided any additional benefits for hemoglobin concentration, anemia reduction, or iron status compared to iron alone.
Results Summary
The study found no significant differences in hemoglobin, ferritin, or soluble transferrin receptor levels between groups receiving iron alone or iron with folic acid. However, overall anemia and iron deficiency risks decreased from baseline to 16 weeks.
Population
Nonpregnant Malaysian women aged 18-45 years with low folate status (84% at baseline).
Effective Dosage
60 mg Fe with 0, 0.4, or 2.8 mg folic acid once weekly.
Duration
16 weeks
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
weekly iron-folic acid (IFA) supplements | no change | anemia | nonpregnant Malaysian women | - | did not reduce | #1 |
weekly iron-folic acid (IFA) supplements | no change | iron status | nonpregnant Malaysian women | - | did not improve | #2 |
60 mg Fe with 0 mg folic acid once-weekly | neutral | hemoglobin (Hb) concentration at 16 wk | nonpregnant women (18-45 y old) | 131 (130, 133) g/L | was | #3 |
60 mg Fe with 0.4 mg folic acid once-weekly | neutral | hemoglobin (Hb) concentration at 16 wk | nonpregnant women (18-45 y old) | 131 (129, 132) g/L | was | #4 |
60 mg Fe with 2.8 mg folic acid once-weekly | neutral | hemoglobin (Hb) concentration at 16 wk | nonpregnant women (18-45 y old) | 132 (130, 133) g/L | was | #5 |
60 mg Fe with 0 mg folic acid once-weekly | neutral | ferritin at 16 wk | nonpregnant women (18-45 y old) | 58.2 (53.9, 62.5) μg/L | was | #6 |
60 mg Fe with 0.4 mg folic acid once-weekly | neutral | ferritin at 16 wk | nonpregnant women (18-45 y old) | 56.5 (52.2, 60.9) μg/L | was | #7 |
60 mg Fe with 2.8 mg folic acid once-weekly | neutral | ferritin at 16 wk | nonpregnant women (18-45 y old) | 58.0 (53.7, 62.3) μg/L | was | #8 |
60 mg Fe with 0 mg folic acid once-weekly | neutral | soluble transferrin receptor (sTfR) at 16 wk | nonpregnant women (18-45 y old) | 5.8 (5.5, 6.1) mg/L | was | #9 |
60 mg Fe with 0.4 mg folic acid once-weekly | neutral | soluble transferrin receptor (sTfR) at 16 wk | nonpregnant women (18-45 y old) | 5.8 (5.5, 6.1) mg/L | was | #10 |
60 mg Fe with 2.8 mg folic acid once-weekly | neutral | soluble transferrin receptor (sTfR) at 16 wk | nonpregnant women (18-45 y old) | 5.9 (5.6, 6.2) mg/L | was | #11 |
weekly IFA supplements for 16 wk | decrease | risk of anemia | all women | risk ratio (RR): 0.65; 95% CI: 0.45, 0.96 | were lower | #12 |
weekly IFA supplements for 16 wk | decrease | risk of iron deficiency based on ferritin | all women | risk ratio (RR): 0.30; 95% CI: 0.20, 0.44 | were lower | #13 |
BACKGROUND: Weekly iron-folic acid (IFA) supplements are recommended for all menstruating women in countries where anemia prevalence is ≥20%; however, it is unknown whether the inclusion of folic acid in weekly IFA supplements reduces anemia. OBJECTIVES: We examined whether the inclusion of folic acid in weekly IFA supplements conferred any benefit on hemoglobin (Hb) concentration, anemia reduction, or iron status [ferritin and soluble transferrin receptor (sTfR)], over iron alone. METHODS: In this secondary analysis of a randomized controlled trial in Malaysia, n = 311 nonpregnant women (18-45 y old) received 60 mg Fe with either 0, 0.4, or 2.8 mg folic acid once-weekly for 16 wk. Fasting blood was collected at baseline and 16 wk. A generalized linear model (normal distribution with identity link) was used to assess Hb concentration at 16 wk (primary outcome). RESULTS: At baseline, 84% of women had low folate status (plasma folate < 14 nmol/L). At 16 wk, marginal mean (95% CI) Hb was 131 (130, 133), 131 (129, 132), and 132 (130, 133) g/L; ferritin was 58.2 (53.9, 62.5), 56.5 (52.2, 60.9), and 58.0 (53.7, 62.3) μg/L; and sTfR was 5.8 (5.5, 6.1), 5.8 (5.5, 6.1), and 5.9 (5.6, 6.2) mg/L in the 0, 0.4, and 2.8 mg/wk groups, respectively, with no differences between groups (P > 0.05). Baseline plasma folate concentration did not modify the effect of treatment on Hb concentration at 16 wk. Among all women, the risks of anemia [risk ratio (RR): 0.65; 95% CI: 0.45, 0.96; P = 0.03] and iron deficiency based on ferritin (RR: 0.30; 95% CI: 0.20, 0.44; P < 0.001) were lower at 16 wk than at baseline. CONCLUSIONS: Despite the low folate status among these nonpregnant Malaysian women, the inclusion of folic acid in weekly IFA supplements did not reduce anemia or improve iron status, over iron alone. However, the benefits of folic acid for neural tube defect prevention still warrant its retention in weekly IFA supplements.This trial was registered at www.anzctr.org.au as ACTRN12619000818134.