26. Results of included systematic reviews: mixed populations.
| Review | Comparison | Outcome | Number of studies; number of participants | Results | GRADE assessment |
| Supplementation | |||||
|
Arabi 2020 The effect of vitamin D supplementation on hemoglobin concentration: a systematic review and meta‐analysis |
Vitamin D supplements versus control | Hb (g/L) | 1 trial, 205 healthy adults; 2 trials, 466 anaemic patients |
SMD 0.13, 95% CI ‐0.16 to 0.42 (P = 0.38), vitamin D supplementation leads to a non‐significant reduction in haemoglobin levels; SMD 0.02, 95% CI −0.20 to 0.24 (P = 0.84), vitamin D supplementation leads to a non‐significant reduction in haemoglobin levels |
Not assessed |
| Ferritin | 3 trials, 303 healthy adults; 2 trials, 466 anaemic patients |
SMD −0.17, 95% CI −0.72 to 0.39 (P = 0.56) SMD −0.18, 95% CI −0.36 to 0.01 (P = 0.06) |
Not assessed | ||
|
Basutkar 2019 Vitamin D supplementation in patients with iron deficiency anaemia: A systematic review and a meta‐analysis |
Vitamin D supplementation versus control groups administered placebo | Hb (g/L) | 4 trials, 407 participants | MD −0.05, 95% CI −0.39 to 0.28 (P < 0.18), vitamin D supplementation had no statistically significant impact on the outcomes of haemoglobin | High |
| Ferritin | 3 trials, 396 participants | MD 1.70, 95% CI −9.12 to 12.53 (P < 0.21), Vitamin D supplementation had no statistically significant impact on the outcomes of serum ferritin | High | ||
| Casgrain 2012 Effect of iron intake on iron status: a systematic review and meta‐analysis of randomized controlled trials |
Iron supplementation versus placebo or control | Hb (g/L) | 37 trials, 49 arms; 3577 participants | MD 5.10, 95% CI 3.70 to 6.50 (P < 0.001), significant increase in Hb concentration for participants receiving iron supplementation | Not assessed |
| Gera 2007 Effect of iron supplementation on haemoglobin response in children: systematic review of randomised controlled trials |
Iron supplementation versus placebo | Hb (g/L) | 55 trials; 12,198 participants | WMD 7.40, 95% CI 6.10 to 8.70 (P < 0.001), significant increase in Hb concentration for children receiving iron supplementation | Not assessed |
| Gera 2009 Effect of combining multiple micronutrients with iron supplementation on Hb response in children: systematic review of randomized controlled trials |
Iron and multiple micronutrient supplementation versus placebo or no treatment | Hb (g/L) | 23 trials; 4981 participants | WMD 6.50, 95% CI 5.00 to 8.00 (P < 0.001), significant increase in Hb concentration for children receiving iron and multiple micronutrients versus placebo or no treatment | Not assessed |
| Iron and multiple‐micronutrient supplementation versus iron supplementation | Hb (g/L) | 13 trials; 1483 participants | WMD 1.40, 95% CI 0.00 to 2.80 (P = 0.044), significant increase in Hb concentration for children receiving iron and multiple micronutrients versu2`s iron alone | Not assessed | |
| Silva 2018 Effects of iron supplementation versus dietary iron on the nutritional iron status: systematic review with meta‐analysis of randomized controlled trials |
Children: dietary intervention versus iron supplementation | Hb (g/L) | Iron status: anaemia or deficient = 3 trials; 425 children |
MD 3.19, 95% CI 1.31 to 5.07 (P < 0.001), significant increase in Hb concentration for children with anaemia or iron deficiency anaemia receiving supplementation | Not assessed |
| Iron status: non‐anaemia or sufficient = 3 trials; 305 children | MD −6.58, 95% CI −11.52 to −1.64 (P = 0.009), significant reduction in Hb concentration for non‐anaemic children receiving dietary intervention | Not assessed | |||
| Final prevalence of anaemia | 3 trials; number of participants: not reported | 3 trials reported final anaemia prevalence after supplementation versus fortification: 4.3% versus 9.7%, 42.5% versus 54.9%, and 6.6% versus 9.7% | Not assessed | ||
| Adolescents and adults: dietary plan versus iron supplement only | Hb (g/L) | 5 trials; 165 participants | MD 0.04, 95% CI −2.50 to 2.58, no evidence of a difference | Not assessed | |
| Pregnant women: dietary plan versus iron supplement only | Hb (g/L) | 1 trial; number of participants: not reported | 113.3 (± 8.8) for supplementation versus 112.1 (± 8.4) for fortified food, significant increase in Hb for pregnant women receiving supplementation | Not assessed | |
|
Smelt 2018 The effect of vitamin B12 and folic acid supplementation on routine haematological parameters in older people: an individual participant data meta‐analysis |
Vitamin B12 supplementation versus placebo | Hb (g/L) | 4 trials; 343 participants | MD 0.00, 95% CI −0.19 to 0.18, no evidence of a difference | Not assessed |
| Folic acid supplementation versus placebo | Hb (g/L) | 3 trials; 929 participants | MD −0.09, 95% CI −0.19 to 0.01, no evidence of a difference | Not assessed | |
|
Tay 2015 Systematic review and meta‐analysis: what is the evidence for oral iron supplementation in treating anaemia in elderly people? |
Oral iron supplementation versus no oral supplementation or placebo | Hb (g/L) | 3 trials; 438 elderly people | MD 3.50, 95 % CI 1.20 to 5.90 (P = 0.003), significant increase in Hb concentration for elderly people taking oral iron | Not assessed |
| Adverse effects | 3 trials; 440 participants | 36 participants with oral iron supplementation reported adverse events (constipation, diarrhoea, abdominal pain, indigestion, nausea and vomiting) | Not assessed | ||
|
Tolkien 2015 Ferrous sulfate supplementation causes significant gastrointestinal side‐effects in adults: a systematic review and meta‐analysis |
Adults, including pregnant women: oral iron supplementation versus placebo | Incidence of GI side effects | 20 trials; 3168 participants | OR 2.32, 95% CI 1.74 to 3.08 (P < 0.0001), significant increase in the incidence of GI side effects for participants receiving oral iron versus placebo | Not assessed |
| Adults, including pregnant women: oral iron supplementation versus IV iron | Hb | 20 trials; number of participants: not reported | Increase in Hb for oral iron supplementation was lower than for IV iron | Not assessed | |
| Incidence of GI side effects | 23 trials; number of participants: not reported | OR 3.05, 95% CI 2.07 to 4.48 (P < 0.0001), significant increase in the incidence of GI side effects for participants receiving oral iron versus IV iron | Not assessed | ||
| Adults, including pregnant women: oral iron supplementation versus placebo or IV iron | Constipation | 27 trials; number of participants: not reported | Incidence in the oral iron group was 12%, 95% CI 10% to 15% | Not assessed | |
| Nausea | 30 trials; number of participants: not reported | Incidence in the oral iron group was 11%, 95% CI 8% to 14% | Not assessed | ||
| Diarrhoea | 25 trials; number of participants: not reported | Incidence in the oral iron group was 8%, 95% CI 6% to 11% | Not assessed | ||
| Pregnant women only: oral iron supplementation versus placebo or IV iron | Incidence of GI side effects | 5 trials; 561 pregnant women | OR 9.44, 95% CI 2.23 to 39.93 (P = 0.002), increase in the incidence of GI side effects for participants receiving oral iron versus IV iron | Not assessed | |
| Fortification | |||||
|
Das 2019b Food fortification with multiple micronutrients: impact on health outcomes in general population |
MMN fortification versus placebo/no intervention | Serum Hb level (g/L) | 20 trials; 6985 participants | MD 3.01 g/L, 95% CI 2.14 to 3.87 (P < 0.001), significant increase in Hb concentration for participants receiving MMN fortification | Low |
| Anaemia (Hb < 11 g/dL) | 11 trials; 3746 participants | RR 0.68, 95% CI 0.56 to 0.84 (P < 0.001), significant decrease in anaemia for participants receiving MMN fortification | Low | ||
| IDA (Hb < 11 g/dL with serum ferritin < 15 μg/L) | 6 trials; 2189 participants | RR 0.28, 95% CI 0.19 to 0.39 (P < 0.001), significant decrease in IDA for participants receiving MMN fortification | Low | ||
| ID (serum ferritin < 5 μg/L) | 11 trials; 3289 participants | RR 0.44, 95% CI 0.32 to 0.60 (P < 0.001), significant decrease in ID for participants receiving MMN fortification | Low | ||
|
Field 2020 Wheat flour fortification with iron for reducing anaemia and improving iron status in populations |
Wheat flour fortified with iron alone versus unfortified wheat flour | Hb (g/L) | 7 trials; 2355 participants | MD 3.30 g/L, 95% CI 0.86 to 5.74 (P = 0.008), significant increase in Hb concentration for participants receiving fortified flour | Very low |
| Anaemia | 5 trials; 2200 participants | RR 0.81, 95% CI 0.61 to 1.07, no evidence of a difference | Low | ||
| ID | 3 trials; 633 participants | RR 0.43, 95% CI 0.17 to 1.07, no evidence of a difference | Moderate | ||
| Wheat flour fortified with iron in combination with other micronutrients versus unfortified wheat | Hb (g/L) | 3 trials; 384 participants | MD 3.29 g/L, 95% CI ‐0.78 to 7.36, no evidence of a difference | Low | |
| Anaemia | 2 trials; 322 participants | RR 0.95, 95% CI 0.69 to 1.31, no evidence of a difference | Low | ||
| ID | 3 trials; 387 participants | RR 0.74, 95% CI 0.54 to 1.00, no evidence of a difference | Moderate | ||
| Wheat flour fortified with iron in combination with other micronutrients versus fortified wheat flour with same micronutrients (but not iron) | Hb (g/L) | 2 trials; 488 participants | MD 0.81 g/L, 95% CI ‐1.28 to 2.89, no evidence of a difference | Low | |
| Anaemia | 1 trial; 127 participants | RR 0.24, 95% CI 0.08 to 0.71 (P = 0.009), significant decrease in anaemia for participants receiving fortified flour | Very low | ||
| ID | 1 trial; 127 participants | RR 0.42, 95% CI 0.18 to 0.97 (P = 0.04), significant decrease in ID for participants receiving fortified flour | Very low | ||
|
Finkelstein 2019 Iron biofortification interventions to improve iron status and functional outcomes |
Iron‐biofortified staple crops versus conventional crops | Anaemia (Hb < 120 g/L) | 3 trials; 597 participants | OR 0.83, 95% CI 0.58 to 1.19, no evidence of a difference | Not assessed |
| ID (serum ferrin < 15.0 μg/L) | 3 trials; 603 participants | OR 0.86, 95% CI 0.61 to 1.23, no evidence of a difference | Not assessed | ||
|
Garcia‐Casal 2018 Fortification of maize flour with iron for controlling anaemia and iron deficiency in populations |
Maize flour or maize flour products fortified with iron plus other vitamins and minerals versus unfortified maize flours or maize flour products (not containing iron nor any other vitamin and minerals) | Hb (g/L) | 3 trials; 1144 participants | MD 1.25, 95% CI −2.36 to 4.86, no evidence of a difference | Very low |
| Anaemia | 2 trials; 1027 participants | RR 0.90, 95% CI 0.58 to 1.40, no evidence of a difference | Very low | ||
| IDA | 1 trial; 515 participants | RR 1.04, 95% CI 0.58 to 1.88, no evidence of a difference | Not assessed | ||
| ID | 2 trials; 1102 participants | RR 0.75, 95% CI 0.49 to 1.15, no evidence of a difference | Very low | ||
| Gera 2012 Effect of iron‐fortified foods on hematologic and biological outcomes: systematic review of randomized controlled trials |
Fortification with iron versus control | Hb (g/L) | 54 trials (77 analytic components); 19,161 participants | WMD 4.20, 95% CI 2.80 to 5.60 (P < 0.001), significant increase in Hb concentration for participants receiving fortification | Not assessed |
| Anaemia at end of fortification | 33 trials; 13,331 participants | RR 0.59, 95% CI 0.48 to 0.71 (P < 0.001), significant reduction in anaemia for participants receiving fortification | Not assessed | ||
| ID | 21 trials; 5765 participants | RR 0.48, 95% CI 0.38 to 0.62 (P < 0.001), significant reduction in ID for participants receiving fortification | Not assessed | ||
| Hess 2016 Micronutrient fortified condiments and noodles to reduce anemia in children and adults—a literature review and meta‐analysis |
Fortified condiments and noodles versus non‐fortified condiments or noodles | Hb (g/L) | 13 trials (14 comparisons); 8845 participants | WMD 6.80, 95% CI 5.10 to 8.50, significant increase in Hb concentration for participants receiving fortified food | Not assessed |
| Anaemia prevalence | 10 trials (11 comparisons); 5498 participants | RR 0.59, 95% CI 0.44 to 0.80, significant reduction in anaemia for participants receiving fortified food | Not assessed | ||
| Huo 2015 Effect of NaFeEDTA‐fortified soy sauce on anemia prevalence in China: a systematic review and meta‐analysis of randomized controlled trials |
NaFeEDTA‐fortified soy sauce versus non‐fortified soy sauce | Hb (g/L) | 12 trials; 8071 participants | MD 8.81 g/L, 95% CI 5.96 to 11.67 (P < 0.001), significant increase in Hb concentration for participants receiving fortified soy sauce | Not assessed |
| Anaemia rates | 16 trials; 16,819 participants | OR 0.25, 95% CI 0.19 to 0.35 (P < 0.001), significant reduction in anaemia for participants receiving fortified soy sauce | Not assessed | ||
|
Peña‐Rosas 2019 Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition |
Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice or no intervention | Hb (g/L) | 11 trials, 2163 participants | MD 1.83 g/L, 95% CI 0.66 to 3.00, significant increase in Hb concentration for participants consuming rice fortified with iron or in combination with other micronutrients | Low |
| Anaemia (WHO cut‐off) | 7 trials, 1634 children | RR 0.72, 95% CI 0.54 to 0.97, significant reduction in anaemia for children consuming rice fortified with iron or in combination with other micronutrients | Low | ||
| ID | 8 trials, 1733 participants | RR 0.66, 95% CI 0.51 to 0.84, significant reduction in ID for participants consuming rice fortified with iron or in combination with other micronutrients | Low | ||
| Diarrhoea | 1 trial, 258 children | RR 0.3.52, 95% CI 0.18 to 67.39, no significant reduction in diarrhoea for children consuming rice fortified with iron or in combination with other micronutrients | Very low | ||
| Adverse effect (hookworm infection risk) | 1 trial, 785 participants | RR 1.78, 95% CI 1.18 to 2.70, significant increase the hookworm infection risk for participants consuming rice fortified with iron or in combination with other micronutrients | Low | ||
| Adverse effect (abdominal pain more than three days) | 1 trial, 234 children | RR 0.77, 95% CI 0.42 to 1.42, no significant increase the risk of abdominal pain more than three days for children given rice fortified with iron or in combination with other micronutrients | Not reported | ||
| Rice fortified with vitamin A alone or in combination with other micronutrients versus unfortified rice or no intervention | Hb (g/L) | 1 trial, 74 participants | MD 10.00 g/L, 95% CI 8.79 to 11.21, significant increase in Hb concentration for participants receiving rice fortified with vitamin A alone or in combination with other micronutrients | Low | |
|
Ramírez‐Luzuriaga 2018 Impact of double‐fortified salt with iron and iodine on hemoglobin, anemia, and iron deficiency anemia: a systematic review and meta‐analysis |
DFS versus control salt | Hb (g/L) | 14 trials; 45,759 participants | MD 3.01, 95% CI 1.79 to 4.24 (P < 0.001), SMD 0.21, 95% CI 0.12 to 0.29 (P < 0.001), significant increase in Hb concentration for participants receiving DFS | Not assessed |
| Anaemia | 10 trials; 42,103 participants | RR 0.84, 95% CI 0.78 to 0.92 (P < 0.001), significant reduction in anaemia for participants receiving DFS | Not assessed | ||
| IDA | 4 trials; 831 participants | RR 0.37, 95% CI 0.25 to 0.54 (P < 0.001), significant reduction in IDA for participants receiving DFS | Not assessed | ||
|
Sadighi 2019 Systematic review and meta‐analysis of the effect of iron‐fortified flour on iron status of populations worldwide |
Iron‐fortified flour versus control | Hb (g/L) | 46 trials (10,353 infants/toddlers, children, women) | MD 2.63 g/L, 95% CI 1.31 to 3.95 (P < 0.001), significant increase in Hb concentration for participants receiving iron‐fortified flour | Not assessed |
| Prevalence of anaemia | 27 trials (6950 infants/toddlers, children, women) | MD −0.08 (−8.1 %), 95% CI −0.117 to −0.044 (P < 0.001), significant reduction in anaemia prevalence for participants receiving iron‐fortified flour | Not assessed | ||
| Prevalence of IDA | 15 trials (4260 infants/toddlers, children, women) | MD −0.209 (−20.9%), 95% CI −0.384 to −0.034 (P = 0.019), significant reduction in IDA prevalence for participants receiving iron‐fortified flour | Not assessed | ||
| Prevalence of ID | 23 trials (5371 infants/toddlers, children, women) | MD −0.120 (−12%), 95% CI −0.189 to −0.051 (P = 0.001), significant reduction in ID prevalence for participants receiving iron‐fortified flour | Not assessed | ||
|
Tablante 2019 Fortification of wheat and maize flour with folic acid for population health outcomes |
Wheat flour fortified with folic acid and other micronutrients versus unfortified wheat flour | Hb g/L | 1 trial, 334 children | MD 0.00 g/L (2.08 lower to 2.08 higher), there were no significant effects of fortified wheat flour flatbread, compared to unfortified wheat flour flatbread, on haemoglobin concentrations | Low |
| Anaemia | 1 trial, 334 children | RR 1.07, 95% CI 0.74 to 1.55 (P = 0.72), there were no significant effects of fortified wheat flour flatbread, compared to unfortified wheat flour flatbread, on anaemia | Low | ||
|
Yadav 2019 Meta‐analysis of efficacy of iron and iodine fortified salt in improving iron nutrition status |
Double‑fortified salt (iron and iodine) (DFS) versus iodine only fortified salt (IS) | Hb g/L | 10 trials | MD 4.40, 95% CI 1.60 to 7.10 (P < 0.01), significant increase in Hb levels for participants consuming DFS | Not assessed |
| Anaemia | 7 trials (1526 participants) | Risk difference (RD) −0.16, 95% CI −0.26 to −0.06 (P < 0.001), significant risk reduction in anaemia for participants consuming DFS | Not assessed | ||
| IDA | Not reported | RD −0.08, 95% CI −0.28 to 0.11, no evidence of a difference | Not assessed | ||
| ID | 5 trials (1306 participants) | RD −0.20, 95% CI: −0.32 to −0.08 (P < 0.001), significant risk reduction in iron deficiency for participants consuming DFS | Not assessed | ||
| Improving dietary diversity and quality | |||||
| Geerligs 2003 Food prepared in iron cooking pots as an intervention for reducing iron deficiency anaemia in developing countries: a systematic review |
Food prepared in cast iron pots versus food prepared in non‐cast iron pots | Change in Hb concentration | 3 trials (784 participants) | 2 of the 3 trials found a difference in haemoglobin at the end of the trial, with children eating food prepared in iron pots having a significantly higher haemoglobin. trial 1: Hb 13 g/L higher in iron pot group after 12 months (P < 0.001), Malaria endemicity very low trial 2: Hb 13 g/L higher in iron pot group after 8 months (P = 0.02), Malaria endemicity none trial 3: Hb 0.2 g/L higher in iron pot group after 5 months for those aged 1‐11 years (parasite rate 45.3%), Hb 3 g/L higher in iron pot group after 5 months for those > 12 years of age (parasite rate 17.5%), not significant |
Not assessed |
CI: confidence interval; DFS: double‐fortified salt; GI: gastrointestinal, Hb: haemoglobin; IS: iodine‐fortified salt; IV: intravenous; MD: mean difference; MMN: multiple micronutrient; OR: odds ratio; RR: risk ratio; SMD: standardised mean difference; WMD: weighted mean difference.