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. 2020 Oct 31;12(3):904–941. doi: 10.1093/advances/nmaa136

TABLE 2.

Studies using the RDRs to monitor VA status changes due to an intervention1

First author, year (reference) Country Group Age EAR, μg RAE/d Treatment Time point Treatment, average μg RAE/d n Test used Dose-response test value2 VAD, %
Mobarhan, 1981 (99) USA Males 46–69 y 625 Daily VA supplements Baseline 8 RDR 21 ± 9% 503
4 wk 10,000 8 RDR 5 ± 2%†† 133
Flores, 1984; Campos, 1987 (25, 136) Brazil Children 1.5–7 y 210–275 200,000-IU VA supplement Baseline 57 RDR 19 ± 23% 37
30 d 2000 42 RDR — 0
120 d 500 31 RDR — 0
180 d 333 29 RDR 7 ± 10% 10
210–275 200,000-IU VA supplement, chickenpox at day 120 Baseline 36 RDR 20 ± 26% 38
30 d 2000 30 RDR — 0
120 d 500 31 RDR — 10
180 d 333 31 RDR 38 ± 22% 74***
Amedee-Manesme, 1987 (22) France One child 15 mo 210 33-mg VA supplement Baseline 1 RDR Positive —
2 mo 550 1 RDR Negative —
Amatayakul, 1989 (137) Thailand Women 18–35 y 500 38-mg VA supplement Baseline 39 RDR Range: −25–29% 2.5
30 d 1267 39 RDR Range: −29–17% 0
Tanumihardjo, 1990 (26) USA Children 3.7–6.2 y 210–275 52.4-μmol VA supplement Baseline 3 MRDR 0.018, 0.031, 0.014 0
14 d 1070 3 MRDR 0.011, 0.019, 0.008 0
Stoltzfus, 1993 (4) Indonesia Mothers <50 y 885–900 Placebo Baseline 71 RDR — 9.2
2.5 mo 0 69 RDR — 10
5.5 mo 0 72 RDR — 3.0
104-μmol VA supplement Baseline 69 RDR — 4.3
2.5 mo 425 70 RDR — 9.0
5.5 mo 193 67 RDR — 1.5
Infants 7–21 d 4004 Mothers receiving placebo 5.5 mo 0 64 RDR — 23
4004 Mothers receiving a VA supplement 5.5 mo —5 67 RDR — 10*
Humphrey, 1994 (28) Indonesia Children 12–59 mo 210–275 105-μmol VA supplement Baseline 174 RDR — 19.5
3 mo 335 123 RDR — 8.9
6 mo 168 137 RDR — 9.5
210–275 210-μmol VA supplement Baseline 170 RDR — 21
3 mo 670 126 RDR — 8.7
6 mo 335 134 RDR — 3.1*
Tanumihardjo, 1994 (29) Indonesia Children 0.7–6.5 y 275–5004 157–315 μmol VA in 1 or 2 supplements Baseline 8 RDR 18 ± 11% 63
Baseline 8 MRDR 0.08 ± 0.05 75
2 wk 3207–6435 8 MRDR 0.04 ± 0.02† 13
Azaïs-Braesco, 1995 (73) France Elderly adults 83 ± 6.1 y 500–625 20,000 IU VA/d Baseline 5 RDR 15.7, 18.8, 20.3, 28.7, 31.0% 60
3 wk 6000 5 RDR 2.8, 16.1, 21.6, 2.6, 15.6% 20
de Pee, 1995, 1997 (62, 138) Indonesia Lactating women 900 Daily placebo wafer Baseline 49 MRDR 0.096 [0.04–0.13] 687
12 wk 68 49 MRDR Change: +0.029 (0.01–0.4) —
Daily 100–150 g vegetables Baseline 47 MRDR 0.096 [0.05–0.15] 687
12 wk 2088 47 MRDR Change: −0.019 (−0.03–0)* —
Daily βC-enriched wafer Baseline 52 MRDR 0.076 [0.04–0.11] 687
12 wk 2208 52 MRDR Change: −0.039 (−0.05 to −0.01)††† —
Manorama, 1996, 1997 (30, 139) India Children 7.6 ± 1.0 y 275–445 Daily red palm oil Baseline 12 MRDR 0.07 ± 0.08 25
2 mo 2008 12 0.02 ± 0.01† 0
Daily VA supplement Baseline 11 0.09 ± 0.08 44
2 mo 600 10 0.02 ± 0.01† 0
Rahman, 1996 (5) Bangladesh Infants ∼73 ± ∼23 d 4004 Placebo 12 wk 0 28 RDR — 82
Three 15-mg VA doses over 12 wk 12 wk 536 33 RDR — 61‡
Tanumihardjo, 1996 (63) Indonesia Lactating women 24.7 ± 6.3 y 900 Daily VA supplement Baseline 23 MRDR 0.100 ± 0.054 74
35 d 2402 23 MRDR 0.040 ± 0.021††† 13
Tanumihardjo, 1996 (31) Indonesia Children ∼3.3 ± ∼1.3 y 210–275 Placebo, not dewormed Baseline 50 MRDR 0.056 ± 0.032 36
4 wk 0 50 MRDR 0.050 ± 0.031 22
210–275 Placebo, dewormed before the study Baseline 51 MRDR 0.059 ± 0.045 35
3 wk 0 51 MRDR 0.057 ± 0.037 33
210–275 Placebo, dewormed during study Baseline 52 MRDR 0.065 ± 0.059 40
4 wk 0 52 MRDR 0.057 ± 0.054 35
210–275 210-μmol VA supplement, not dewormed Baseline 49 MRDR 0.060 ± 0.062 37
4 wk 2145 49 MRDR 0.033 ± 0.014 2
210–275 210-μmol VA supplement, dewormed before the study Baseline 54 MRDR 0.056 ± 0.018 33
3 wk 2860 54 MRDR 0.036 ± 0.018 13
210–275 210-μmol VA supplement, dewormed during the study Baseline 52 MRDR 0.054 ± 0.038 31
4 wk 2145 52 MRDR 0.029 ± 0.018 VA main effect*** 6
Raghuramulu, 1998 (32) India Children 1–5 y 210–275 200,000 IU VA divided into 1–4 doses Baseline 11 RDR — 263
4–10 d 6000–15,000 11 RDR — 293
Ribaya-Mercado, 1999 (74) Guatemala Elderly adults 60–81 y 500–625 Daily VA supplement Baseline 9 7-h RDR −16.9 ± 10.1% —
32 d 800 9 7-h RDR −6.2 ± 2.6% —
Rice, 1999; Filteau, 1999, (6, 140) Bangladesh Lactating women ∼20–∼30 y 885–900 Placebo Baseline 35 RDR 3.2%9 (2.6–3.8%) 14
2.5 mo 0 35 RDR 5.4%9 (4.3–6.9%) 54
5.5 mo 0 36 RDR 4.5%9 (3.7–5.5%) 33
8.5 mo 0 31 RDR 5.2%9 (3.9–6.9%) 42
885–900 7.8-mg βC supplement Baseline 35 RDR 4.0%9 (3.0–5.3%) 31
2.5 mo 39008 36 RDR 5.1%9 (4.1–6.4%) 42
5.5 mo 39008 32 RDR 3.1%9 (2.4–3.8%) 19*
8.5 mo 39008 35 RDR 3.9%9 (3.2–4.8%) 26
885–900 200,000-IU VA supplement Baseline 36 RDR 3.2%9 (2.5–3.9%) 19
2.5 mo 2857 34 RDR 3.8%9 (3.1–4.7%)* 18**
5.5 mo 1299 35 RDR 3.9%9 (3.1–4.9%) 31
8.5 mo 840 32 RDR 4.4%9 (3.7–5.2%) 28
Infants 7–21 d 4004 Mothers receiving placebo 6 mo —5 70 RDR 11.8%9 (10.6–13.2%) 93
4004 Mothers receiving βC 6 mo —5 69 RDR 10.2%9 (9.0–11.4%) 58‡
4004 Mothers receiving VA 6 mo —5 69 RDR 9.2%9 (8.1–10.5%)** 60
Tyson, 1999 (7) USA Neonates GA 26.8 ± 1.8 wk 4004 Daily ∼1000 IU VA/kg BW 28 d ∼200 155 3-h i.m.-RDR 7.3%10 [−6.2–49%] 45
Daily ∼4000 IU VA/kg BW 28 d ∼800 145 3-h i.m.-RDR 2.9%10 [−10–18%]*** 2211,***
Solon, 2000 (33) Philippines Children 9.5 ± 2.0 y 275–445 Daily placebo bun 30 wk 0 77 MRDR 0.057,12 [0.04–0.07] 29
Daily VA-fortified bun 30 wk 97 72 MRDR 0.047,11 [0.03–0.06] 16‡
Ncube, 2001 (64) Zimbabwe Lactating women ∼27 ± ∼7 y 900 Placebo Baseline 0 11 RDR 49 ± 18% 91
60 d 0 11 RDR 42 ± 21% 73
Daily 6-mg βC supplement Baseline 9 RDR 44 ± 22% 78
60 d 30008 9 RDR 21 ± 21%† 33
Daily papaya supplement Baseline 12 RDR 35 ± 19% 58
60 d 5008 12 RDR 15 ± 33%† 33
Daily carrot supplement Baseline 11 RDR 36 ± 30% 82
60 d 5008 11 RDR 25 ± 20% 64
Bahl, 2002 (8) Ghana Infants 4004 Placebo Baseline 103 MRDR — 76
4.5 mo 0 93 MRDR — 54
7.5 mo 0 61 MRDR — 49
Maternal 60 mg VA, infant 3 × 7.5 mg VA supplements over 3.5 mo Baseline 99 MRDR — 76
4.5 mo >1795 94 MRDR — 44
7.5 mo >1075 79 MRDR — 46
India Infants 6 wk 4004 Placebo Baseline 95 MRDR — 91
4.5 mo 0 98 MRDR — 77
7.5 mo 0 94 MRDR — 60
Maternal 60 mg VA, infant 3 × 7.5 mg VA supplements over 3.5 mo Baseline 95 MRDR — 87
4.5 mo >1795 97 MRDR — 62.9*
7.5 mo >1075 93 MRDR — 55
Peru Infants 6 wk 4004 Placebo Baseline — 91 MRDR — 69
4.5 mo 0 117 MRDR — 33
7.5 mo 0 111 MRDR — 15
Maternal 60 mg VA, infant 3 × 7.5 mg VA supplements over 3.5 mo Baseline 97 MRDR — 83
4.5 mo >1795 117 MRDR — 29
7.5 mo >1075 106 MRDR — 15 Overall 4.5 mo,* 7.5 mo NS
Stephensen, 2002 (34) Peru Children 12–50 mo 210–5004 Placebo 2–5 d 0 41 RDR — 34
150,000–300,000 IU VA over 2 d 2–5 d 9000–30,000 45 RDR — 16‡
Tanumihardjo, 2002 (70) Indonesia Pregnant women 18–37 y 885–900 Placebo Baseline 7 MRDR 0.032 ± 0.008 —
8 wk 0 7 MRDR 0.031 ± 0.011 —
Daily VA supplement Baseline 7 MRDR 0.043 ± 0.034 —
8 wk 2402 7 MRDR 0.043 ± 0.044 —
Daily iron supplement Baseline 5 MRDR 0.032 + 0.009 —
8 wk 0 5 MRDR 0.037 ± 0.007 —
Daily VA and iron supplements Baseline 8 MRDR 0.042 ± 0.013 —
8 wk 2402 8 MRDR 0.021 ± 0.015* —
Ambalavanan, 2003 (9) USA Neonates GA 25 ± 2 wk 4004 500–1500 IU/kg BW daily plus 5000 IU 3 d/wk 28 d ∼750–950 28 2-h i.m.-RDR 17 ± 33% 2711
500–1500 IU/kg BW daily plus 10,000 IU 3 d/wk 28 d ∼1400–1600 27 2-h i.m.-RDR 14 ± 16% 4811
500–1500 IU/kg BW daily plus 15,000 IU 1 d/wk 28 d ∼750–950 30 2-h i.m.-RDR 27 ± 34% 5211,‡
Davidsson, 2003 (35) Cote d'Ivoire Children 6–12 y 275–445 Single 210-μmol VA supplement Baseline 13 MRDR 0.156 ± 0.065 100
39 d 1540 13 MRDR 0.125 ± 0.052 92
Wieringa, 2003 (10) Indonesia Infants 4.2 ± 0.5 mo 4004–5004 Placebo 6 mo 0 43 MRDR — 81
Iron supplements 5 d/wk 6 mo 0 49 MRDR — 51***
Iron and zinc supplements 5 d/wk 6 mo 0 39 MRDR — 49***
Zinc supplements 5 d/wk 6 mo 0 48 MRDR — 82
Zinc and 2.4 mg βC 5 d/wk 6 mo 8578 39 MRDR — 94
2.4 mg βC 5 d/wk 6 mo 8578 38 MRDR — 83
Tanumihardjo, 2004 (36) Indonesia Children 3.9 ± 1.3 y 210–275 Ascariasis with or without Trichuriasis, single 210-μmol VA supplement and deworming Baseline 51 MRDR 0.054 ± 0.038 31
1 mo 2145 51 MRDR 0.030 ± 0.018††† 5.9
Trichuriasis only, single 210-μmol VA supplement and deworming Baseline 29 MRDR 0.049 ± 0.040 24
1 mo 2145 29 MRDR 0.031 ± 0.015† 6.9
Children 3.4 ± 1.1 y 210–275 Single 210-μmol VA supplement, dewormed prior to baseline Baseline 21 MRDR 0.023 ± 0.014 0
1 mo 2145 21 MRDR 0.025 ± 0.013 0
Single 210-μmol VA supplement prior to baseline, dewormed during trial Baseline 19 MRDR 0.019 ± 0.019 0
1 mo 0 19 MRDR 0.024 ± 0.024 0
Single 210-μmol VA supplement prior to baseline, not dewormed Baseline 11 MRDR 0.021 ± 0.010 0
1 mo 0 11 MRDR 0.023 ± 0.015 0
van Jaarsveld, 2005 (37) South Africa Children ∼7.3 ± 1.2 y 275–445 White sweet potato Baseline 0 89 MRDR 0.038 ± 0.024 14
10.6 wk 0 89 MRDR 0.042 ± 0.025 18
Orange sweet potato Baseline 89 MRDR 0.040 ± 0.028 22
10.6 wk 7368 89 MRDR 0.036 ± 0.019* 13
Tchum, 2006 (141) Ghana Mothers postpartum ∼29 ± 6.9 y 900 Single 200,000-IU VA supplement postpartum Baseline 82 MRDR 0.048 ± 0.0377 177
1 mo 2143 21 MRDR 0.026 ± 0.0157,††† 57
3 mo 719 27 MRDR 0.031 ± 0.0207,††† 117
5 mo 429 28 MRDR 0.023 ± 0.0127,††† 07
Two 200,000-IU VA supplements postpartum Baseline 85 MRDR Treatment group differences NS; values pooled
1 mo 4286 30 MRDR
3 mo 1429 25 MRDR
5 mo 857 25 MRDR
van den Broek, 2006 (71) Malawi Pregnant women 14–28 y 530–550 Placebo Baseline 0 232 MRDR — 2.2
36–38 wk 0 176 MRDR — 7.5
Daily 5000 IU VA supplement Baseline 234 MRDR — 3.5
36–38 wk 1500 174 MRDR — 4.8
Daily 10,000 IU VA supplement Baseline 234 MRDR — 3.0
36–38 wk 3000 180 MRDR — 4.2
Ayah, 2007 (11) Kenya Infants At birth 4004 Maternal placebo; infant placebo 26 wk 0 139 MRDR 0.0919 (0.082–0.100) 76
Maternal 400,000 IU VA; infant placebo 26 wk —5 140 MRDR 0.0829 (0.075–0.088) 80
Maternal placebo; infant 100,000 IU VA 26 wk 357 143 MRDR 0.0739 (0.067–0.079) 69
400,000 IU maternal VA; infant 100,000 IU VA 26 wk >3575 142 MRDR 0.0769 (0.069–0.082) infant VA,*** maternal VA NS 70
Idindili, 2007 (12) Tanzania Infants 1.41 ± 0.96 mo 4004 Maternal 200,000 IU VA; infant 3 x 25,000 IU VA, then 100,000 IU VA at 9 mo Baseline 390 3-h MRDR — 84
6 mo >1345 282 3-h RDR — 47
9 mo >2085 269 3-h MRDR — 40
Two maternal 200,000 IU VA; infant 3 x 50,000 IU VA, then 100,000 IU VA at 9 mo Baseline 390 3-h MRDR — 82
6 mo >2685 293 3-h MRDR — 43
9 mo >2985 278 3-h MRDR — 41, Dose size NS
Permaesih, 2009; Rosmalina, 2009 (65, 125) Indonesia Lactating women — 900 Placebo and placebo cooking oil Baseline 34 MRDR 0.084 ± 0.041 —
100 d ∼500 34 MRDR 0.11 ± 0.063 —
Placebo and VA-fortified cooking oil Baseline 30 MRDR 0.087 ± 0.045 —
100 d ∼600 30 MRDR 0.085 ± 0.043* —
Two 200,000 IU VA supplements and placebo cooking oil Baseline 32 MRDR 0.080 ± 0.077 —
100 d ∼800 32 MRDR 0.083 ± 0.052* —
Two 200,000 IU VA supplements and VA-fortified cooking oil Baseline 35 MRDR 0.071 ± 0.051 —
100 d ∼1000 35 MRDR 0.064 ± 0.028* —
Agne-Djigo, 2012 (13) Senegal Infants ∼6.2 ± 0.4 mo 4004 Maternal placebo Baseline 347 MRDR 0.064 ± 0.0197 747
14 d 389 ± 15113 19 MRDR 0.073 ± 0.017 95
Two maternal 200,000 IU VA supplements; Baseline 347 MRDR 0.064 ± 0.0197 74
14 d 365 ± 21513 13 MRDR 0.055 ± 0.017* 54*
Ambrosio, 2012 (38) Brazil Children 1–6 y 4004 6 g dehydrated pumpkin flakes 5 d/wk Baseline 97 RDR — 16
90 d 2148 97 RDR — 0
Dougherty, 2012 (39) USA Children ∼7.6 ± ∼2.9 y 275–445 Placebo Baseline 18 RDR 4.4 ± 5.8% —
1 y 0 18 RDR 3.7 ± 7.2% —
Daily RDA of VA supplement Baseline 23 RDR 1.1 ± 10.1% —
1 y 300–600 18 RDR 2.3 ± 5.6% —
Daily RDA of VA and 10–20 mg zinc supplement Baseline 15 RDR 2.9 ± 6.6% —
1 y 300–600 12 RDR 1.9 ± 6.4% —
Mactier, 2012 (15) Scotland Preterm infants GA 24–33 wk 4004 Placebo 6 wk 0 32 3-h RDR 14%14 [−22–55%] 28
6–12 × 10,000 IU VA i.m 6 wk 2143–4286 31 3-h RDR 12%14 [−21–36%] 26
Bresnahan, 2014 (142) Zambia Children 4.5 ± 0.9 y 210–275 White maize 6 d/wk Baseline 94 MRDR 0.030 ± 0.023 15
70 d 0 86 MRDR 0.050 ± 0.025††† 17
Orange maize 6 d/wk Baseline 99 MRDR 0.032 ± 0.021 6
70 d 688 95 MRDR 0.049 ± 0.021††† 21
Ahmad, 2020 (108) Bangladesh Infants <48 h 4004 Placebo 15 wk 0 24 MRDR 0.035 ± 0.020 12.5
Single 50,000 IU VA supplement 15 wk 143 21 MRDR 0.029 ± 0.017 9.5
1

VAD was defined as ≥20% RDR or ≥0.060 MRDR unless otherwise noted. BW, body weight; GA, gestational age; MRDR, modified relative dose-response; RDR, relative dose-response; VA, vitamin A; VAD, vitamin A deficiency; βC, β-carotene; —, missing data.

2

Values are reported as mean ± SD (unless noted otherwise), as available. Significant differences between intervention and placebo denoted by *P <0.05; **P < 0.01; ***P < 0.001. Significant differences from baseline denoted by †P < 0.05; ††P < 0.01; †††P < 0.001. Results trending towards significant differences between intervention and placebo denoted by ‡P < 0.1. Note that these were determined by their respective authors and, in many cases, statistical tests were not performed.

3

RDR cutoff for deficiency was >14% in this study.

4

Estimated Average Requirements in infants <12 mo old are unknown so Adequate Intakes (AIs) are listed.

5

Milk-derived VA intake not measured.

6

Reported as median [IQR].

7

Value was reported for entire study population and not separately for each group.

8

Includes provitamin A carotenoids according to the Institute of Medicine conversion factors of 2:1 (supplemental βC), 12:1 (dietary βC) and 24:1 (dietary α-carotene and β-cryptoxanthin) (103).

9

Reported as mean (95% CI).

10

Reported as median [5th percentile–95th percentile].

11

RDR cutoff for deficiency was >10% in this study.

12

Estimated from figure in source.

13

Milk VA intake estimated by deuterium transfer (dose-to-mother approach) (143).

14

Reported as median [range].