Table 1.
Clinical trials that showed a significant impact of vitamin A supplementation/fortification alone or in combination with iron, folic acid, vitamin C and riboflavin on iron status.
| References | Country | Population (Age in Years) | N | Intervention (Groups) | Time (Month) | Impact | Conclusions |
|---|---|---|---|---|---|---|---|
| Children and Adolescents | |||||||
| Mwanri et al. (2000) [6] | Tanzania | Anemic children (9–12) | 135 | 5000 IU VA/3× week; 5000 IU VA + 200 mg Fe/3× week; 200 mg Fe/3× week; Placebo |
3 | ↑Hb = 13.5; ↑Hb = 22.1; ↑Hb = 17.5; ↑Hb = 3.6 |
↑Hb in the Fe + VA group (p < 0.05) |
| Varma et al. (2007) [10] | India | Children (3–5.5) | 516 | Rice and lentils fortified with 500 IU VA + 14 mg Fe + 50 μg folic acid; 6 times/week; Placebo | 6 | ↑Hb = 4.0, ↑serum ferritin = 10.4; ↑Hb = 4.0, ↓serum ferritin = −2.8 |
↑serum ferritin in the VA + Fe + folic acid group (p < 0.001) |
| Zimmermann et al. (2006) [11] | Morocco | Schoolchildren (5–13) | 81 | 200,000 IU VA † at baseline and after 5 months; Placebo | 10 | ↑Hb = 7.0, MCV = 7.0, serum ferritin = −7.0, ↓TfR = −2.3, EPO = 6.9, ZnPP = -4.0; ↑Hb = 1.0, MCV = 0.0, serum ferritin = 1.0, ↓TfR = −0.2, EPO = 3.3, ZnPP = 1.0 |
↑Hb, MCV and EPO in the VA group (p < 0.02) |
| Kapil et al. (2005) [3] | India | Adolescent girls (17–18) | 39 | 200,000 IU VA † + 100 mg Fe + 500 μg folic acid + 60 mg vitamin C/day; 100 mg Fe + 500 μg folic acid + 60 mg vitamin C/day |
3.3 | ↑Hb = 18; ↑Hb = 13 | ↑Hb status in both groups (p < 0.05); higher in the VA group |
| Children and Adolescents | |||||||
| Leenstra et al. (2009) [12] | Kenya | Anemic adolescent girls (12–18) | 249 | 25,000 IU VA + 120 mg Fe/week; 25,000 IU VA + Placebo/week; 120 mg Fe/week + Placebo; Placebo/week |
5 | VA-supplemented group compared to vitamin A placebo group (adjusted for Fe supplementation): ↓Hb = −0.7, ↓serum ferritin = −1.7; Fe-supplemented group compared to Fe placebo group (adjusted for vitamin A supplementation): ↑Hb = 5.2, ↑serum ferritin = 13.3 | ↑Hb and serum ferritin (p < 0.001) only in the Fe supplemented groups |
| Pregnant and Lactating Women | |||||||
| Suharno et al. (1993) [13] | Indonesia | Pregnant women (17–35) | 251 | 8000 IU VA + 60 mg Fe/day; 8000 IU VA + Fe placebo/day; 60 mg Fe/day + vitamin A placebo; Placebo |
2 | ↑Hb = 12.70, Ht = 0.04, ↑ serum ferritin = 1.82, ↑TS = 0.036, ↑serum iron = 1.62, ↓TIBC= −3.00; ↑Hb = 3.68, Ht = 0.01, ↑serum ferritin = 1.34, ↑TS = 0.006, ↑serum iron = 0.22, ↓TIBC = −0.60; ↑Hb = 7.71, Ht = 0.02, ↑serum ferritin = 2.22, ↑TS = 0.017, ↑serum iron = 0.81, ↓TIBC = −1.30; ↑Hb = 2.00, Ht = 0.01, ↑serum ferritin = 1.22, ↑TS = 0.002, ↑serum iron = 0.10, ↓TIBC = −0.10 |
Difference in all parameters between the VA + Fe group and the other groups (p < 0.001) |
| Pregnant and Lactating Women | |||||||
| Muslimatun et al. (2001a, 2001b) [14,15] | Indonesia | Pregnant women (17–35) | 190 | 20,000 IU VA + 120 mg Fe + 500μg folic acid/week; 120 mg Fe + 500 μg folic acid/week; 90–120 mg Fe + 250 μg folic acid ††/day |
5 | ↑Hb = 3.70, ↓serum ferritin = −7.10, ↑TfR = 0.43; ↑Hb = 2.10, ↓serum ferritin = −3.00, ↑TfR = 0.47; ↓Hb = −0.70, ↓ serum ferritin = −5.30, ↑TfR = 0.56 |
Difference in Hb (p < 0.05), serum ferritin, TfR (p < 0.01) between the VA + Fe + folic acid group and the other groups |
| Tanumihardjo (2002) [16] | Indonesia | Pregnant women (18–37) | 27 | 8000 IU VA/day; 60 mg Fe/day; 8000 IU VA + 60 mg Fe/day; Placebo |
2 | ↑Hb = 7.10, ↑Ht = 0.036, ↑serum ferritin = 4.70; ↑Hb = 6.60, ↑Ht = 0.018, ↑serum ferritin = 15.00; ↑Hb = 3.90, ↑Ht = 0.049, ↑serum ferritin = 12.00; ↓Hb = −9.00, ↓Ht = −0.034, ↓serum ferritin = −13.80 |
Positive effect of supplementation with VA + Fe on indicators of iron status (p < 0.05) |
| Suprapto et al. (2002) [17] | Indonesia | Anemic pregnant women (<35) | 84 | 5000 IU VA + 60 mg Fe + 250 μg folic acid + 5 mg riboflavin; 5000 IU VA + 60 mg Fe + 250 μg folic acid; 60 mg Fe + 250 μg folic acid + 5 mg riboflavin; 60 mg Fe + 250 μg folic acid + placebo |
2 | ↑Hb = 4.6; ↑Hb = 1.9; ↑Hb = 8.2; ↑Hb = 4.9 |
Increase in Hb in all groups (p < 0.05), except in the VA + Fe + folic acid group (p > 0.05) |
| Sun et al.
(2010) [18] |
China | Anemic pregnant women (20–30) | 180 | 6000 IU VA+ 60 mg Fe+ 400 μg folic acid/day; 60 mg Fe/day; 60 mg Fe+ 400 μg folic acid/day; Placebo |
2 | ↑Hb = 16.5, ↑serum ferritin = 8.12; ↑Hb = 17.9, ↑serum ferritin = 2.11; ↑Hb = 14.7, ↑serum ferritin = 3.38; ↓Hb = −1.98, ↓serum ferritin = −1.61 |
VA + Fe supplementation was more beneficial to improve iron status and lymphocyte proliferation in pregnancy than Fe alone (p < 0.001) |
N = sample size; VA = vitamin A retinyl acetate; VA † = vitamin A retinyl palmitate (international units—IU); Fe = elementary iron; Hb = hemoglobin (g/L); Serum ferritin (μg/L); Retinol = serum retinol (μmol/L); MCV = mean corpuscular volume (fL); RBP = retinol binding protein (mg/L); Prealbumin (mg/L); EPO = erythropoietin (IU/L); TfR = transferrin receptor (mg/L); ZnPP = zinc protoprphyrin (μmol/mol heme); TS = transferrin saturation; Ht = hematocrit (vol/vol); Serum iron (μmol/L); TIBC = total iron-binding capacity (μmol/L); †† = Free access to iron tablets from the Indonesian Governmental Health Service; RDR = relative dose response (mol/mol).