14. Characteristics of interventions: mixed populations.
| Review | Intervention | Prevention or treatment | Population (mean age, baseline anaemia status/prevalence, known micronutrient deficiencies) | Dose (mean range) or composition or form of application (including compound, formulation) | Frequency | Start of intervention or duration, or both | Adherence to intervention |
| Supplementation | |||||||
|
Arabi 2020 The effect of vitamin D supplementation on hemoglobin concentration: a systematic review and meta‐analysis |
Oral vitamin D supplements | Prevention and treatment | 14 trials: participants aged 17.5 to 68 years old (including RCTs with healthy adults, anaemic patients, chronic kidney disease patients, heart failure patients, hypertensive patients, critically ill patients and athletes) Baseline anaemia status: not reported Known MN deficiencies: not reported |
Vitamin D fortified food with cholecalciferol (4 trials), oral vitamin D (cholecalciferol) supplements (8 trials), supplemented with ergocalciferol (1 trial), with calcitriol (1 trial). The minimum vitamin D dosage was 20 IU and maximum was 500,000 IU. | Daily | Duration: 3 hours to 36 months | Not reported |
|
Basutkar 2019 Vitamin D supplementation in patients with iron deficiency anaemia: A systematic review and a meta‐analysis |
Vitamin D supplementation | Treatment | Patients with iron deficiency anemia (20 to 45 years) Known MN deficiencies: not reported | Vitamin D and calcium containing snack bar, 10 mcg and 25 mcg of Vitamin D, iron plus vitamin D supplementation | Daily | Duration: 12 (3 months) to 16 weeks | Not reported |
|
Casgrain 2012 Effect of iron intake on iron status: a systematic review and meta‐analysis of randomized controlled trials |
Oral iron, fortified food, or rich natural dietary sources | Prevention | Healthy adults (≥ 18 years) Baseline anaemia status/prevalence: anaemic and non‐anaemic Know micronutrient deficiencies: any baseline iron status (iron deficient in many trials) |
Iron supplementation: 5 mg to 240 mg as iron fumarate, ferrous sulphate (mainly), ferric polymaltose Fortification with iron: 1.42 mg to 27.9 mg (fortified wheat‐based snacks, rice, food bar, fish sauce) |
Daily or weekly | Duration: 3 to 24 weeks | Not reported |
|
Gera 2007a Effect of iron supplementation on haemoglobin response in children: systematic review of randomised controlled trials |
Oral iron, parenteral route or as formula, milk, or cereals fortified with iron | Prevention | Children (0 to 19 years, no age group dominated, i.e. > 60%) Baseline anaemia status/prevalence: anaemic and non‐anaemic (mean baseline Hb < 11 g/dL in 37 analytic components, Hb ≥ 11 in 54 analytic components) Know MN deficiencies: iron deficiency |
Iron: 5 mg to 120 mg/day or 1 mg/kg/day to 4 mg/kg/day (compound not reported) | Daily 2 trials: weekly |
Duration: 1 week to 12 months | Most of the included trials do not provide relevant compliance data. |
|
Gera 2009 Effect of combining multiple micronutrients with iron supplementation on Hb response in children: systematic review of randomized controlled trials |
Oral iron in combination with 2 or more MNs | Prevention | Children (0 to 18 years, no age group dominated, i.e. > 60%) Baseline anaemia status/prevalence: anaemic and non‐anaemic (mean baseline Hb < 11 g/dL in 15 analytic components, Hb ≥ 11 in 18 analytic components) Know MN deficiencies: yes, but not specified |
Iron: 5 mg to 60 mg per day (compound not reported) | Daily to once a week | Duration: 3 weeks to 12 months | Not reported |
|
Silva Neto 2019 Effects of iron supplementation versus dietary iron on the nutritional iron status: Systematic review with meta‐analysis of randomized controlled trials |
Iron supplementation versus dietary intervention (fortification or dietary plan) | 3 trials: prevention, 6 trials: treatment, 3 trials: N/A | 6 trials infants and children (age = 0.25 years to 7.3 years, males and females) 5 trials: adults (mean age = 18.5 to 29 years, females) 1 trial: pregnant women (mean age = 25 years) Baseline anaemia status/prevalence: iron deficiency anaemia (6 trials = yes, 3 trials = no, 3 trials = no information) Known MN deficiencies: iron deficiency |
Dietary plan (4 trials) or fortified food (8 trials): iron dose = 7 mg to 35.4 mg Iron supplementation: 2.5 mg to 105 mg |
Daily (at least 5 times per week) | Not reported | Not reported |
|
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 or folic acid supplementation | Prevention | Older people (60.3 to 80 years) Baseline anaemia status/prevalence: number of individuals with anaemia was small Know MN deficiencies: vitamin B12 deficiency and folate deficiency in some trials |
Vitamin B12 (0.01 mg to 1 mg) or folic acid (0.8 mg to 5 mg) supplementation, including tablet, capsule and intramuscular | 6 trials: daily 1 trial: weekly |
Duration: 4 weeks to 3 years | Not reported |
|
Tay 2015 Systematic review and meta‐analysis: what is the evidence for oral iron supplementation in treating anaemia in elderly people? |
Oral iron | Prevention | Elderly people after hip or knee arthroplasty (mean age range = 70 to 83 years, men and women) Baseline anaemia status/prevalence: participants were anaemic after surgery, but none of the participants were anaemic on admission Known MN deficiencies: not reported |
Ferrous sulphate 200 mg | 2 trials: 3 times daily 1 trial: twice daily |
Duration: 4 weeks to 6 weeks Start of intervention for elderly people: after hip or knee arthroplasty |
1 trial reported poor compliance. |
|
Tolkien 2015 Ferrous sulfate supplementation causes significant gastrointestinal side‐effects in adults: a systematic review and meta‐analysis |
Oral ferrous sulphate | Prevention and treatment | Oral iron versus placebo (20 trials, 3168 participants): adults, including pregnant women (18 to 58.6 years), baseline Hb status in 12 trials = 10.4 g/dL to 15.25 g/dL (not reported for the remaining trials), 19 trials in healthy non‐anaemic individuals, 1 trial in anaemic participants Oral iron versus IV iron (23 trials, 3663 participants): adults, including pregnant women (15 to 66 years), baseline Hb status = 7.6 g/dL to 12.4 g/dL Known MN deficiencies: not reported |
Oral iron versus placebo: oral dose 20 mg/Fe/day to 222 mg/Fe/day Oral iron versus IV iron: oral dose 100 mg/Fe/day to 400 mg/Fe/day (ferrous sulphate) |
Daily | Duration oral iron versus placebo: 1 to 26 weeks Duration oral iron versus IV iron: 4 to 26 weeks |
Not reported |
| Fortification | |||||||
|
Das 2019b Food fortification with multiple micronutrients: impact on health outcomes in general population |
Multiple micronutrient (MMN) fortification (3 or more MNs) by any food vehicle | Prevention | 36 trials: children (29 trials: preschool and school‐aged children, 4 trials: infants, 3 trials: children aged 1 to 3 years) 3 trials: pregnant women 3 trials: adults 1 trial: elderly population over 70 years old mean age: not reported Baseline anaemia status: not reported Known micronutrient deficiencies: not reported |
MMN fortification (3 or more MNs) by any food vehicle: rice and flour (12 trials), dairy products (9 trials), non‐dairy beverages (13 trials), biscuits (6 trials), salt (2 trials) | Daily or weekly | Duration: 8 weeks to 1 year; 29 trials: less than 6 months, 14 trials: between 6 months and 1 year | Not reported |
|
Field 2020 Wheat flour fortification with iron for reducing anaemia and improving iron status in populations |
Fortification of wheat flour with iron alone or in combination with other micronutrients | Prevention | 9 trials: 6 trials included children aged 6 to 11 years, 1 trial included children aged 6 to 12 years, 1 trial included children aged 6 to 13 years, and 2 trials included children aged 6 to 15 years old. Another trial included children aged 9 months to 11 years, primary school children aged 6 to 11 years, and non‐pregnant women. 2 trials included adult women. One trial targeted adolescent girls aged 15.2 ± 2.4 years Baseline anaemia status: varied; low (< 20%) in 2 trials, moderate in 4 trials, high in 2 trials, 1 trial did not specify prevalence Known MN deficiencies: not reported |
Any form of wheat flour iron fortification independent of length of intervention, extraction rate of wheat flour, iron compounds used, preparation of the iron‐flour premix, and fortification levels achieved in the wheat flour or derivative foods Iron compounds: NaFeEDTA ferrous sulphate, elemental iron, ferrous fumarate Amount of elemental iron added to flour: 41 mg iron/kg to 60 mg iron/kg flour (3 trials), < 40 mg iron/kg flour (2 trials), > 60 mg iron/kg flour (2 trials), 80 mg/kg for electrolytic iron and reduced iron and 40 mg/kg for ferrous fumarate (1 trial), unknown (1 trial) |
Daily | 3 to 8 months (8 trials) 24 months (1 trial) |
Adherence was measured in some studies through 24‐hour recalls and in some cases weighing of food remains in the meals. |
|
Finkelstein 2019 Iron biofortification interventions to improve iron status and functional outcomes |
Iron‐biofortified staple crops | Prevention | 1 trial: male and female adolescents aged 12 to 16 years old 2 trials: adults females (18 to 45 years) Baseline anaemia status: 28% to 37% anaemic at baseline Known MN deficiencies: 34% to 86% to iron deficient at baseline |
Crop: rice, pearl millet, beans Iron content: 10 mg/kg to 86 mg/kg dry per crop, iron intake from staple 1.8 mg/d to 17.6 mg/d Percentage of total dietary iron: 18% to 90% |
Daily | Duration: 4 to 9 months | Not reported |
|
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 | Prevention | General population older than 2 years of age without critical illness or severe comorbidities (children = 6 months to 14 years, adolescents = 10 to 19 years, women = 20 to 49 years) Baseline anaemia status/prevalence: < 20% in 3 trials, > 40% in 1 trial and not reported in 1 trial Know MN deficiencies: all trials conducted in settings with a high prevalence of MN deficiencies, especially iron |
3 trials: 2.8 mg to 5.6 mg elemental iron per 100 g maize flour 1 trial: 9.8 mg reduced iron per 100 g flour 1 trial: 42.4 mg ferrous fumarate per 100 g maize flour |
Not specified | Duration: 6 to 10 months | Not reported |
|
Gera 2012 Effect of iron‐fortified foods on hematologic and biological outcomes: systematic review of randomized controlled trials |
Iron food fortification or biofortification | Prevention | Apparently healthy (non‐diseased) individuals, families, or communities Baseline anaemic status/prevalence: Hb concentration ≤ 120 g/L in 49 of 80 (57%) analytic components Known MN deficiencies: iron deficiency (serum ferritin was ≤ 20 μg/L in 22 of 47 (47%)) |
Computed additional iron intake: ≤ 10 mg in 49 trials (63%) and > 10 mg in 29 trials (37%) Cereal‐based fortification (36 trials; 42%): salt (12 trials; 14%), sauces (fish and soy; 9 trials; 11%), and milk (9 trials; 11%) Ferrous sulphate (24 trials; 28%), NaFeEDTA (17 trials; 20%), electrolytic iron (11 trials; 13%), ferric pyrophosphate (7 trials; 8%), hydrogen‐reduced iron (3 trials; 3%), and heme (3 trials; 3%) or ferric orthophosphate (3 trials; 3%), ferrous fumarate (6 trials; 7%), amino acid chelates (2 trials; 2%), iron gluconate (1 trial; 1%), or ammonium citrate (1 trial; 1%) |
Daily in 50 analytic components, intermittent in 35 | Duration: up to 7 months in 44 trials (51%), 7 to 12 months in 30 trials (35%), and 12 months in 11 (13%) trials | Compliance directly observed: 21 analytic components versus 56 others |
|
Hess 2016 Micronutrient fortified condiments and noodles to reduce anemia in children and adults—a literature review and meta‐analysis |
MN (iron, vitamins, zinc, iodine, folate, calcium, phosphorus, magnesium, selenium) fortified condiments or noodles product | Prevention | Children and adults from 5 to 50 years Baseline anaemia status/prevalence: anaemia rate at baseline 46% Known MN deficiencies: not reported |
Salt: 1 mg to 2 mg iron/g salt; masala powder: 25 μg NaFeEDTA/g masala; soy sauce: 0.3 mg to 4 mg NaFeEDTA/mL soy sauce; noodles: 20.6 mg NaFeEDTA/100 g noodles; fish sauce: 1 mg Fe/mL fish sauce | Not specified | Duration: follow‐up mostly under 1 year (range = 2.4 months to 2 years) | Adherence to intervention was not reported in included trials |
|
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 (prevention) | Prevention | Any population in which anaemia is a public health problem (Chinese, aged 3 to 55 years, 3‐ to 6‐year‐old children, 9 trials focusing on teenagers, 3 trials on pregnant women, and 1 trial covered all groups of children > 3 years) Baseline anaemia status/prevalence: anaemic and non‐anaemic Known MN deficiencies: iron deficiency |
Iron in NaFeEDTA ranged from 2.3 to 20 mg/day/person, iron dosages were < 4 mg/day in 8 trials and ≥ 4 mg/day in 7 trials | Daily | Duration: 3 to 18 months | Not reported |
|
Peña‐Rosas 2019 Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition |
Rice fortified with iron alone or in combination with other MNs Rice fortified with vitamin A alone or in combination with other MNs | Treatment or prevention | Population older than 2 years of age, including pregnant women Baseline anaemia status: 5% to 62% in children, 21% in women, and 34% in teenagers Known MN deficiencies: not reported |
Rice fortified with elemental iron, vitamin A, zinc, folic acid, thiamin, riboflavin, niacin, pyridoxine, cobalamin. The amount of elemental iron per 100 g of rice ranged from 0.2 mg to 112.8 mg; vitamin A: 0.15 mg to 2.1 mg; zinc: 2 mg to 18 mg; ferrous sulphate: 18 mg/g | Daily | Duration: 2 weeks to 4 years | Not reported |
|
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 | Prevention | Any participants (subgroup analysis for children aged < 5 years, school‐aged children, non‐pregnant, non‐lactating women of childbearing age, men, pregnant women) Baseline anaemia status/prevalence: not reported Known MN deficiencies: not reported |
Most trials used concentrations of 1 mg to 3 mg elemental Fe/g salt The 3 main iron sources used for salt fortification were ferrous sulphate, ferrous fumarate and ferric pyrophosphate | Not specified | Duration: mostly > 6 months | Not reported |
|
Sadighi 2019 Systematic review and meta‐analysis of the effect of iron‐fortified flour on iron status of populations worldwide |
Fortification of flour (e.g. wheat,maize, or rice), either in a raw form or in a cooking process, with iron or with iron and other MNs | Prevention | 19 trials of infants/toddlers (4 to 36 months), 42 of children (3 to 19 years), 31 of women (15 to 49 years), and 2 of people of all ages Baseline anaemia status/prevalence: not reported Known MN deficiencies: not reported |
Fortification vehicles: 61 trials wheat flour, maize flour in 7 trials, wheat and maize flours in 7 trials, rice flour in 4 trials, wheat and corn flours in 4 trials, maize and soy flours in 2 trials, corn flour in 1 trial, maize, beans, bambara nuts, and groundnuts flours in 1 trial, rice and soybeans flours in 1 trial, rye flour in 1 trial, wheat and soybean flours in 1 trial, and unknown flour in 4 trials; iron alone added to flour: 31 trials, iron with other micronutrients: 63 trials | Not specified | Mean duration: 20.6 months (SD: 25.5, range: 2 to 144) | Not reported |
|
Tablante 2019 Fortification of wheat and maize flour with folic acid for population health outcomes |
Wheat flour fortified with folic acid plus other vitamins and minerals | Prevention | Male and female children (5 to 12 years) (cluster‐RCT reported relevant outcomes: Bangladesh has had more than a 75% decrease in the incidence of malaria cases between 2000 and 2014) | Wheat flour chapattis were fortified with 0.15 mg of folic acid per 100 g of flour (1.5 ppm), along with other MNs (cluster‐RCT reported relevant outcomes) | Daily | Duration: over a six‐month period | Not reported |
|
Yadav 2019 Meta‐analysis of efficacy of iron and iodine fortified salt in improving iron nutrition status |
DFS (iron and iodine) versus iodine only IS | Prevention | Children 1 to 5 years (1 study), school children 5 to 18 years (6 studies), non‐pregnant and non‐lactating females 15 to 45 years (1 study), healthy and nonpregnant females 18 to 55 years (1 study), male and female participants 10 to 65 years (1 study) Baseline anaemia status/prevalence: not reported Known MN deficiencies: not reported |
1 mg/g salt ferrous sulfate (3 trials), 2 mg/g to 3 mg/g salt ferric pyrophosphate (3 trials), 1 mg/g to 2 mg/g salt ferrous fumarate (4 trials) | Not specified | Duration: 6 to 18 months | Not reported |
| 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 |
Consumption or use of food prepared in iron or aluminium pot | Prevention | People in developing countries (minimum age was set at 4 months) Baseline anaemia status/prevalence: high prevalence of anaemia Known MN deficiencies: high prevalence of iron deficiency |
Use of iron or aluminium pots | Daily | Duration: 5 to 12 months | Daily compliance reported in 3 trials Trial 1: initial 10 weeks of iron pot use 80% to 85%, subsequent 10 weeks 68% to 70% Trial 2: 2 of 22 people stopped using iron pots after 4 to 5 months Trial 3: iron pot use 34.7% after 3 weeks, and 31.1% after 20 weeks |
DFS: double‑fortified salt; IDA: iron deficiency anaemia; IS: iodine‐fortified salt; MN: micronutrient; MMNs: multiple micronutrients; NaFeEDTA: sodium iron ethylenediaminetetraacetate; SD: standard deviation.