REVIEW

Impact of Double-Fortified Salt with Iron and

Iodine on Hemoglobin, Anemia, and Iron
Deficiency Anemia: A Systematic Review and
Meta-Analysis
María J Ramírez-Luzuriaga,1 Leila M Larson,1 Venkatesh Mannar,3 and Reynaldo Martorell1,2
1 Emory University, Nutrition and Health Science Program, Laney Graduate School, and 2 Hubert Department of Global Health, Rollins School of Public Health,

Emory University, Atlanta, GA; and 3 Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Canada

ABSTRACT
Double-fortified salt (DFS) containing iron and iodine has been proposed as a feasible and cost-effective alternative for iron fortification in low- and
middle-income countries (LMICs). We conducted a systematic review and meta-analysis from randomized and quasi-randomized controlled trials
to 1) assess the effect of DFS on biomarkers of iron status and the risk of anemia and iron deficiency anemia (IDA) and 2) evaluate differential effects
of DFS by study type (efficacy or effectiveness), population subgroups, iron formulation (ferrous sulfate, ferrous fumarate, and ferric pyrophosphate),
iron concentration, duration of intervention, and study quality. A systematic search with the use of MEDLINE, EMBASE, Cochrane, Web of Science,
and other sources identified 221 articles. Twelve efficacy and 2 effectiveness studies met prespecified inclusion criteria. All studies were conducted in
LMICs: 10 in India, 2 in Morocco, and 1 each in Côte d’Ivoire and Ghana. In efficacy studies, DFS increased hemoglobin concentrations [standardized
mean difference (SMD): 0.28; 95% CI: 0.11, 0.44; P < 0.001] and reduced the risk of anemia (RR: 0.59; 95% CI: 0.46, 0.77; P < 0.001) and IDA (RR 0.37; 95%
CI: 0.25, 0.54; P < 0.001). In effectiveness studies, the effect size for hemoglobin was smaller but significant (SMD: 0.03; 95% CI: 0.01, 0.05; P < 0.01).
Stratified analyses of efficacy studies by population subgroups indicated positive effects of DFS among women and school-age children. For the
latter, DFS increased hemoglobin concentrations (SMD: 0.32; 95% CI: 0.03, 0.60; P < 0.05) and reduced the risk of anemia (SMD: 0.48; 95% CI: 0.34, 0.67;
P < 0.001) and IDA (SMD: 0.37; 95% CI: 0.25, 0.54; P < 0.001). Hemoglobin concentrations, anemia prevalence and deworming at baseline, sample
size, and study duration were not associated with effect sizes. The results indicate that DFS is efficacious in increasing hemoglobin concentrations
and reducing the risk of anemia and IDA in LMIC populations. More effectiveness studies are needed. Adv Nutr 2018;9:207–218.

Keywords: hemoglobin, double-fortified salt, fortification, anemia, iron, IDA

Introduction function among children and maternal mortality and low

Anemia remains an important public health problem world-
wide, primarily among women, infants, and children from
low- and middle-income countries (LMICs), where tradi-
tional diets provide little bioavailable iron and where in-
fections, especially malaria and hookworm, exacerbate the
problem by increasing iron losses (1–3). Iron deficiency (ID),
defined as the decrease in the total content of iron in the body,
has been identified as a major cause of anemia for decades
(4), and it has been linked to poor cognitive and neurologic
MJR-L and LML received PhD funding from the Laney Graduate School, Emory University.
Author disclosures: MJR-L, LML, VM, and RM, no conflicts of interest.
Supplemental Tables 1–3 and Supplemental Figures 1–4 are available from the
“Supplementary data” link in the online posting of the article and from the same link in the
online table of contents at https://academic.oup.com/advances/.
Address correspondence to MJR-L (e-mail: mrami24@emory.edu).
Abbreviations used: DFS, double-fortified salt; ID, iron deficiency; IDA, iron deficiency anemia;
LMIC, low- and middle-income country; SMD, standardized mean difference.
productivity in adults, with long-term health and economic
consequences (5, 6). Iron deficiency anemia (IDA) occurs
when ID is sufficiently severe to reduce erythropoiesis. Be-
cause ID is an important cause of anemia, efforts to reduce
its burden have been directed mostly toward increasing iron
intakes through food fortification, supplementation, and di-
etary diversification (7).
Salt is an ideal vehicle for providing micronutrients; al-
most everyone consumes it and it is relatively inexpensive
to fortify. The iodization of salt worldwide has been an out-
standing public health success story, leading to remarkable
reductions in iodine deficiency disorders (8). Several reviews
and meta-analyses have examined the effects of iodine fortifi-
cation on various outcomes (i.e., mental development, goiter,
cretinism, iodine deficiency) (9–11) and therefore this will
not be reviewed here.

© 2018 American Society for Nutrition. All rights reserved. Adv Nutr 2018;9:207–218; doi: https://doi.org/10.1093/advances/nmy008. 207
 One suggested way to simultaneously combat both iron
and iodine deficiency disorders is through the fortification
of salt with both iron and iodine, referred as double-fortified
salt (DFS). DFS was first conceived of in 1969, but it took
decades to develop a stable form due to technical difficulties
of combining the 2 micronutrients (12). Iron microen-
capsulation and chelation technologies were developed
to minimize iron-iodine interactions. Different types of
DFS have been produced, which vary by iron and iodine
compound, encapsulation of the iron or iodine, addition
of additives (colorizing agents, binders, or stabilizers), and
sophistication of the production method (12).
The stability, acceptability, and bioavailability of different
types of DFS have been analyzed (13–24). Overall, all types of
DFS have been found to be acceptable to consumers, and lab-
oratory studies conducted have indicated good stability and
bioavailability of both iron and iodine.
Several studies in various populations and contexts have
examined the effects of DFS on iron and anemia; yet, to our
knowledge, no formal meta-analysis of the impact of DFS
on iron status has been published. We are aware of only one
systematic review, which focused on cost-benefit analyses of
DFS compared with other iron interventions and did not re-
view effects on iron status (25).
The primary objective of this meta-analysis was to as-
sess the impact of DFS on biomarkers of iron status, and the
risk of anemia and IDA. The secondary objective was to as-
sess differential effects of DFS on selected outcomes by study
type (efficacy or effectiveness), population subgroups, iron
formulation (ferrous sulfate, ferrous fumarate, and ferric py-
rophosphate), iron concentration, duration of intervention,
and study quality.
Methods
Literature search strategy
An electronic literature search was performed in MED-
LINE (https://www.ncbi.nlm.nih.gov/pubmed/), EMBASE
(https://www.embase.com/login), Cochrane (http://www.
cochranelibrary.com), and Web of Science databases (http://
apps.webofknowledge.com) to identify relevant studies that
investigated the effects of DFS on iron status. The following
search strategy was used for each database: (“double fortified
salt” OR “dual fortified salt” OR “dual salt” OR “double salt”
OR “iodine and iron”) AND (“anemia” OR “iron” OR “fer-
ritin” OR “hemoglobin” OR “iron deficiency anemia”) AND
(“trial” OR “intervention” OR “RCT” OR “Program”). The
search was restricted to human studies, and no language or
date restrictions were applied. The above search strategy was
supplemented by a review of citations included in relevant
studies and reviews. The PRISMA (Preferred Reporting
Items for Systematic Reviews and Meta-Analyses) guidelines
were followed (26).
Inclusion and exclusion criteria
The following inclusion criteria were used: 1) the study
was a randomized or quasi-randomized controlled trial; 2)
hemoglobin, ferritin, transferrin receptor, anemia and/or
208 Ramírez-Luzuriaga et al.
IDA were measured and reported postintervention. Studies
were excluded from the meta-analysis if published reports
presented insufficient information for estimating effects sizes
and variances and if these could not be obtained through per-
sonal communication with the authors. Other exclusion cri-
teria included studies analyzing the effect of salt fortified with
multiple micronutrients or with iron alone and secondary
analyses of original studies.
Study selection and data extraction
Two independent reviewers scanned titles and abstracts of
retrieved articles and excluded irrelevant studies. Full texts
of the remaining articles were reviewed to identify studies
that met the inclusion criteria. If data in the original publi-
cation lacked sufficient details, the corresponding author of
the study was contacted by e-mail for additional information.
Reference lists of articles included and relevant literature re-
views were checked for additional articles.
Retrieved studies that reported biomarkers of iron status
(i.e., ferritin and transferrin receptor) presented values in a
variety of ways: medians, means, and geometric means for
measures of central tendency, and IQRs, SDs, and ±1 SD
for measures of dispersion. Given the complexity of combin-
ing these estimates, a decision was made to focus only on
hemoglobin, anemia, and IDA.
Key descriptive data, including sample size, study design,
study type, duration of intervention, salt consumption, iron
formulation and concentration, deworming status before the
intervention, mean hemoglobin, anemia, IDA at baseline and
end line in treatment and control groups, quality assessment,
DFS stability, and sensory testing, were extracted into a stan-
dardized form. The reported sample size refers to the number
of participants who completed the intervention. All data were
entered twice and inconsistencies resolved.
Quality assessment
The Effective Public Health Practice Project (EPHPP)
quality-assessment tool was used to assign a global rating to
each study (27). The EPHPP assesses 8 dimensions: selec-
tion bias, study design, confounders, blinding, data collection
methods, withdrawals and dropouts, intervention integrity,
and robustness of the analysis. Each dimension is rated on a
3-point scale as strong, moderate, or weak, all of which con-
tribute to the calculation of the global rating. Studies received
a global rating of strong when all of the dimensions were clas-
sified as strong. Moderate and weak global scores were as-
signed to studies with 1 or >1 weak components, respectively.
The effect of pooling results from studies of different quality
was examined in subgroup analyses when possible.
Statistical analysis
The outcomes of interest were hemoglobin concentration
and prevalence of anemia and IDA. Because hemoglobin
was measured in a variety of ways across trials (i.e., venous
blood, capillary blood, arterial blood), we used the standard-
ized mean difference (SMD) to express the effect size (28).
However, to provide the reader with a notion of mean change
of hemoglobin in interpretable units (grams per liter), mean
differences were also calculated for the overall pooled esti-
mate. For anemia and IDA, we present summary effects as
RRs with 95% CIs.
Postintervention hemoglobin values (means ± SDs) were
used instead of changes from baseline to end line because
most studies did not report the SD of the change (28).
The SMD was calculated by dividing the difference in
mean hemoglobin between intervention and control groups
at end line by the pooled SD. Mean differences were estimated
by calculating the difference in mean hemoglobin between
the intervention and control groups at end line. RRs for ane-
mia and IDA were calculated by dividing the risk of an event
in the intervention group by the risk of an event in the con-
trol group at end line. The risk of an event is estimated as the
number of events divided by the total sample size.
In studies with multiple intervention groups and a single
control group, the sample size of the control group was di-
vided equally by the number of intervention groups to avoid
double-counting of participants (29).
Pooled estimates for the overall effect and subgroup anal-
yses were conducted when data were available from >1 study
by using both fixed-effects and random-effects model as-
sumptions. The random-effects model was preferred if there
was evidence of significant heterogeneity. We assessed het-
erogeneity of effect sizes with the use of the chi-square test of
homogeneity; P < 0.05 for Cochran’s Q test was considered
as evidence of heterogeneity. I-square values were also exam-
ined and values >50% were deemed as exhibiting substan-
tial statistical heterogeneity (28). We visually evaluated the
presence of publication bias with the use of funnel plots (30).
Sensitivity and subgroup analyses were conducted to explore
predictors of positive response.
Because of the differences in coverage and compliance
between efficacy and effectiveness studies, we stratified the
results by study type. The specified variables for subgroup
analyses included the following: 1) adult, child, and sex sub-
groups; 2) iron formulation; 3) iron concentration; 4) study
duration; and 5) study quality. All of the statistical tests were
2-sided, with P < 0.05 reported as significant. Review Man-
ager version 5.3 (Cochrane Collaboration) was used for the
analysis of pooled estimates and preparation of forest plots
and funnel plots. Effects sizes were compared informally be-
tween subgroups without performing a statistical test (28).
Random-effects meta-regression analyses were performed
with the “metareg” command (STATA version 12.0; Stata-
Corp) to explore the influence of potential effect modifiers on
hemoglobin concentrations and risk of anemia. Explanatory
variables included in the models were baseline hemoglobin
and anemia prevalence, deworming status at baseline, sam-
ple size, and study duration.
Results
Study selection
The literature search from electronic databases and records
identified through other sources yielded 221 references
(Figure 1), of which 41 were duplicates and were excluded.
An additional 166 studies were excluded after the title and
abstract review. A total of 14 articles were assessed for eli-
gibility, and all were included in the systematic review and
meta-analysis.
Study characteristics and risk of bias
Twelve efficacy and 2 effectiveness studies were included. All
were conducted in LMICs: 10 in India (22, 31–41), 2 in Mo-
rocco (42, 43), and 1 each in Côte D’Ivoire and Ghana (44,
45) (Supplemental Table 1). Efficacy trials provided data on
3234 intervention and 3335 control participants and effec-
tiveness studies on 20,024 intervention and 19,402 control
participants. With the use of the EPHPP quality-assessment
tool test (27), 3 studies were classified as being of strong qual-
ity, 3 were of moderate quality, and 8 were of weak quality.
Pooled effects of DFS
Efficacy studies. Twelve trials reported data on the effect
of DFS on hemoglobin concentrations compared with a
control group, which in all studies received iodine-fortified
salt. The pooled SMD for hemoglobin concentrations by
random-effects model was 0.28 SD (95% CI: 0.11, 0.44;
P < 0.001) (Table 1). The SMD ranged from −0.32 SD
in a trial in India (22) to 1.36 SD in a study in Morocco
(43) (Figure 2A). The pooled mean difference for postin-
tervention hemoglobin concentrations by random-effects
model was 3.74 g/L (95% CI: 1.42, 6.06 g/L; P = 0.002).
Eight studies reported data on the prevalence of ane-
mia and 4 studies reported on the prevalence of IDA.
Pooled analysis showed significant effects of DFS on re-
ducing the RRs of anemia (RR: 0.59; 95% CI: 0.46, 0.77;
P < 0.001) and IDA (RR: 0.37; 95% CI: 0.25, 0.54; P < 0.001)
(Table 1). The funnel plots were symmetrical for hemoglobin
(Figure 3) and IDA (Supplemental Figure 1), which sug-
gests an absence of publication bias in the trials included.
Funnel plots for the SMD of hemoglobin of pooled efficacy
and effectiveness studies were symmetrical (Supplemental
Figure 2). The funnel plots were asymmetrical for anemia
(Supplemental Figure 3).
Effectiveness studies. Data on hemoglobin and anemia were
available from 2 effectiveness trials. The pooled SMD for
hemoglobin by fixed-effects model was 0.03 SD (95% CI:
0.01, 0.05; P = 0.007). Pooled effect sizes for anemia were
not significant (Table 2). The 2 effectiveness studies used fer-
rous sulfate for salt fortification with concentrations of 1 mg
Fe/g salt, lasted >6 mo, and differed in quality (Supplemental
Table 1).
Efficacy and effectiveness studies. The pooled effect size for
hemoglobin concentrations (SMD) when effectiveness stud-
ies were included in the estimation was 0.21 SD (95% CI: 0.12,
0.29; P < 0.001). The pooled mean difference was 3.01 g/L
(95% CI: 1.79, 4.24 g/L; P < 0.001) (Table 3). With regard
to anemia, pooled effects of efficacy and effectiveness studies
showed a significant 16% reduction in the RR of anemia for
participants receiving DFS (Supplemental Figure 4). Effect
Impact of double-fortified salt on biomarkers of iron status 209
FIGURE 1 Flowchart showing the selection of trials for inclusion in the systematic review and meta-analysis.
sizes were not computed for IDA because effectiveness stud-
ies did not report the prevalence of IDA.
Population subgroups
The SMD of hemoglobin concentration by random-effects
model for school-age children was 0.32 SD (95% CI: 0.03,
0.60; P = 0.03) (n = 7 efficacy studies) (Table 1). The effect
size (SMD) was 0.26 SD (95% CI: 0.08, 0.44; P = 0.005) when
the 2 effectiveness studies were included into the pooled es-
timate (Table 3). Among women, significant effects of DFS
on hemoglobin concentrations were observed for pregnant
women (SMD: 0.69; 95% CI: 0.36, 1.01; P < 0.001), although
only 2 efficacy studies provided data (Table 1). No significant
effect of DFS on hemoglobin concentration was observed
210 Ramírez-Luzuriaga et al.
among preschool-age children (SMD −0.04; 95% CI: −0.18,
0.10; P = 0.58) (n = 2 efficacy studies).
Concerning anemia and IDA, pooled results of efficacy
studies showed significant effects of DFS among school-age
children, with 52% and 63% reductions in the RRs of anemia
and IDA, respectively (Table 1). When effectiveness studies
were included in the pooled estimate, there still was a signifi-
cant reduction in the RR of anemia (49%) among school-age
children who received DFS (Table 3).
Iron sources used for DFS formulation
The 3 main iron sources used for salt fortification were fer-
rous sulfate, ferrous fumarate, and ferric pyrophosphate. Sig-
nificant and similar effects were observed on hemoglobin
TABLE 1 Pooled and stratified estimates of efficacy studies assessing the effect of DFS in hemoglobin concentrations and risk of anemia
and IDA1
Sample size, n Test for heterogeneity3
Stratification variable Trials, n I C Combined effect2 (95% CI) P I2 , % Q P
Pooled effect
Hemoglobin (SMD) 12 3199 3134 0.28 (0.11, 0.44) <0.001 89 191.09 <0.001
Hemoglobin (MD), g/L 12 3199 3134 3.74 (1.42, 6.06) 0.002 91 226.86 <0.001
Anemia (RR) 8 1469 1208 0.59 (0.46, 0.77) <0.001 91 129.22 <0.001
IDA (RR) 4 398 433 0.37 (0.25, 0.54) <0.001 18 4.86 0.30
Population group
Hemoglobin (SMD)
Children aged <5 y 2 382 422 −0.04 (−0.18, 0.10) 0.58 41 1.69 0.19
School-age children 7 1710 1580 0.32 (0.03, 0.60) 0.03 93 137.45 <0.001
WCA 4 414 436 0.15 (0.01, 0.28) 0.03 0 2.33 0.51
Men 2 173 166 0.10 (−0.12, 0.31) 0.37 12 1.14 0.29
Pregnant women 2 92 68 0.69 (0.36, 1.01) <0.001 44 1.78 0.18
Anemia (RR)
School-age children 5 1214 929 0.48 (0.34, 0.67) <0.001 95 131.21 <0.001
WCA 2 165 166 0.86 (0.70, 1.06) 0.16 31 1.44 0.23
IDA (RR)
School-age children 4 398 433 0.37 (0.25, 0.54) <0.001 18 4.86 0.30
Iron formulation
Hemoglobin (SMD)
Ferrous sulfate 6 2222 2233 0.24 (0.01, 0.46) 0.04 92 147.47 <0.001
Ferrous fumarate 3 327 281 0.22 (0.05, 0.38) 0.01 0 1.26 0.74
Ferric pyrophosphate 3 265 212 0.64 (−0.05, 1.34) 0.07 92 25.97 <0.001
Anemia (RR)
Ferrous sulfate 3 892 722 0.69 (0.50, 0.96) 0.03 94 61.60 <0.001
Ferrous fumarate 3 328 301 0.60 (0.34, 1.06) 0.08 82 17.05 <0.001
Ferric pyrophosphate 3 249 185 0.40 (0.17, 0.94) 0.03 83 11.67 0.003
IDA (RR)
Ferric pyrophosphate 3 202 222 0.47 (0.29, 0.75) 0.001 0 1.97 0.37
Iron concentration, mg/g salt
Hemoglobin (SMD)
≤1.1 9 2794 2856 0.21 (0.04, 0.38) 0.02 89 151.45 <0.001
>1.1 3 405 278 0.56 (0.07, 1.06) 0.03 89 28.32 <0.001
Anemia (RR)
≤1.1 5 1080 947 0.74 (0.58, 0.94) 0.02 90 67.49 <0.001
>1.1 3 389 261 0.32 (0.14, 0.74) 0.007 85 20.09 0.0002
IDA (RR)
>1.1 3 334 367 0.40 (0.26, 0.61) <0.001 21 3.78 0.29
Study duration, mo
Hemoglobin (SMD)
≤6 2 127 117 0.57 (0.12, 1.03) 0.01 68 3.12 0.08
>6 10 3072 3017 0.25 (0.08, 0.42) 0.005 90 182.42 <0.001
Anemia (RR)
≤6 2 127 117 1.31 (0.31, 5.58) 0.72 73 3.75 0.05
>6 6 1342 1091 0.54 (0.41, 0.72) <0.001 93 129.28 <0.001
IDA (RR)
>6 3 352 384 0.30 (0.19, 0.48) <0.001 0 1.79 0.62
Study quality4
Hemoglobin (SMD)
Strong 3 362 375 0.81 (0.18, 1.43) 0.01 94 31.48 <0.001
Moderate 2 330 195 0.30 (0.12, 0.48) <0.001 0 0.29 0.87
Weak 7 2507 2564 0.16 (−0.01, 0.33) 0.06 86 110.59 <0.001
Anemia (RR)
Strong 2 149 154 0.50 (0.17, 1.53) 0.22 83 5.94 0.01
Moderate 2 344 215 0.34 (0.12, 0.94) 0.04 89 17.84 <0.001
Weak 4 976 839 0.72 (0.55, 0.96) 0.02 91 64.63 <0.001
IDA (RR)
Strong 2 87 94 0.23 (0.10, 0.53) <0.001 0 0.22 0.64
Moderate 2 311 339 0.43 (0.28, 0.66) 0.0001 22 2.57 0.28
1
C, control; DFS, double-fortified salt; I, intervention; IDA, iron deficiency anemia; MD, mean difference; SMD, standardized mean difference; WCA, nonpregnant, nonlactating
women of childbearing age.
2
Values are SMDs, MDs, or RRs of pooled estimates, as indicated. Pooled estimates for the overall effect and subgroup analyses were conducted when data were available from
>1 study.
3
Random-effects models were conducted if there was evidence of significant heterogeneity; otherwise, fixed models were conducted. The inverse variance method was used
for SMDs and MDs and Mantel-Haenszel was used for RRs.
4
Studies received a global rating of “strong” when all dimensions of the Effective Public Health Practice Project quality-assessment tool (selection bias, study design, confounders,
blinding, data collection methods, withdrawals and dropouts, intervention integrity, and robustness of the analysis) were classified as strong. Moderate and weak global scores
were assigned to studies with 1 or >1 weak components, respectively.

Impact of double-fortified salt on biomarkers of iron status 211

FIGURE 2 Pooled estimates of efficacy studies assessing the effect of DFS vs. control (iodized-salt) for hemoglobin concentrations (A),
anemia (B), and iron deficiency anemia (C). DFS, double-fortified salt; IV, inverse variance; M-H, Mantel-Haenszel; Std., standardized.

concentration in studies that used ferrous sulfate (SMD:
0.24; 95% CI: 0.01, 0.46; P = 0.04) (n = 6 efficacy stud-
ies) or ferrous fumarate (SMD: 0.22; 95% CI: 0.05, 0.38;
P < 0.05) (n = 3 efficacy studies) (Table 1). The effect size
on hemoglobin for ferric pyrophosphate was larger relative
to ferrous sulfate and ferrous fumarate but had a wider CI
(SMD: 0.64; 95% CI: −0.05, 1.34: P = 0.07) (n = 3 efficacy
studies).
Reductions in the RR of anemia were greater for stud-
ies that used ferric pyrophosphate (RR: 0.40; 95% CI: 0.17,
0.94; P = 0.03) (n = 3 efficacy studies) relative to ferrous
sulfate (RR: 0.69; 95% CI: 0.50, 0.96; P = 0.03) (n = 3

212 Ramírez-Luzuriaga et al.

FIGURE 3 Funnel plot of efficacy studies for the SMD of hemoglobin (after intervention) of double-fortified salt compared with iodized
salt. Values are effect sizes (SMDs) and SEs of the effect size. SMD, standardized mean difference.

efficacy studies) and ferrous fumarate (RR: 0.60; 95% CI: 0.34,
1.06; P = 0.08) (n = 3 efficacy studies) (Table 1). Effect sizes
on IDA were available for efficacy studies that used ferric py-
rophosphate, showing important and significant reductions
in the risk of IDA (RR: 0.47; 95% CI: 0.29, 0.75; P = 0.01)
(n = 3 studies).
The 2 effectiveness studies used ferrous sulfate for salt
fortification. Pooled analysis of efficacy and effectiveness
studies resulted in smaller but significant effect sizes for
hemoglobin concentrations (SMD: 0.16; 95% CI: 0.07, 0.25;
P < 0.01) and anemia (RR: 0.92; 95% CI: 0.86, 1.00;
P = 0.04) relative to pooled estimates of efficacy studies alone
(Table 3).
Iron concentration of DFS
Most studies used concentrations of 1–1.1 mg elemental Fe/g
salt. Only 3 efficacy studies reported DFS formulations with
greater concentrations of iron. Zimmermann et al. (43) and
Andersson et al. (34) reported the use of 2 mg Fe/g salt and
Wegmüller et al. (45) reported the use of 3 mg Fe/g salt (Sup-
plemental Table 1).
A significant improvement in hemoglobin concentration
was observed in the stratified analysis that used DFS concen-
trations of >1.1 mg Fe/g salt (SMD: 0.56; 95% CI: 0.07, 1.06;
P = 0.03) (n = 3 efficacy studies). Studies that used DFS iron
concentrations of <1.1 mg/g salt showed a smaller but still
significant effect of DFS on hemoglobin concentration (SMD:
0.21; 95% CI: 0.04, 0.38; P = 0.02) (n = 9 efficacy studies)
(Table 1).
The 2 effectiveness studies used iron concentrations of
≤1.1 mg/g salt. Pooled estimates combining efficacy and ef-
fectiveness studies that used ≤1.1 mg Fe/g salt showed signif-
icant effects on hemoglobin concentration (SMD: 0.15; 95%
CI: 0.07, 0.24; P = 0.0002) (n = 11 studies) and significant
reductions in the risk of anemia (RR: 0.91; 95% CI:0.85, 0.98;
P = 0.01) (n = 7 studies) (Table 3).

TABLE 2 Summary of pooled estimates of effectiveness studies assessing the effect of DFS on hemoglobin concentrations and prevalence
of anemia1
Sample size, n Test for heterogeneity3
Pooled effect Trials, n I C Combined effect2 (95% CI) P I2 , % Q P
Hemoglobin
SMD 2 20,024 19,402 0.03 (0.01, 0.05) 0.007 37 4.79 0.19
MD, g/L 2 20,024 19,402 0.40 (0.09, 0.70) 0.01 46 5.57 0.13
Anemia (RR) 2 20,024 19,402 0.97 (0.93, 1.01) 0.16 67 9.03 0.03
1
All of the effectiveness studies used ferrous sulfate with concentrations of 1 mg Fe/g salt and lasted >6 mo. C, control; DFS, double-fortified salt; I, intervention; MD, mean
difference; SMD, standardized mean difference.
2
Values are SMDs, MDs, or RRs of pooled estimates as indicated. Pooled estimates for the overall effect and subgroup analyses were conducted when data were available from
>1 study.
3
Random-effects models were conducted if there was evidence of significant heterogeneity; otherwise, fixed models were conducted. The inverse variance method was used
for SMDs and MDs and Mantel-Haenszel was used for RRs.

Impact of double-fortified salt on biomarkers of iron status 213

TABLE 3 Summary of pooled and stratified estimates of efficacy and effectiveness studies assessing the effect of DFS on hemoglobin
concentrations and prevalence of anemia1
Sample size, n Test for heterogeneity3
Stratification variable Trials, n I C Combined effect2 (95% CI) P I2 , % Q P
Pooled effect
Hemoglobin (SMD) 14 23,223 22,536 0.21 (0.12, 0.29) <0.001 91 296.27 <0.001
Hemoglobin (MD), g/L 14 23,223 22,536 3.01 (1.79, 4.24) <0.001 91 294.00 <0.001
Anemia (RR) 10 21,493 20,610 0.84 (0.78, 0.92) <0.001 87 111.3 <0.001
Population group
Hemoglobin (SMD)
Children aged <5 y 2 382 422 −0.04 (−0.18, 0.10) 0.58 41 1.69 0.19
School-age children 8 2436 2260 0.28 (0.04, 0.53) 0.02 94 161.58 <0.001
WCA 5 6691 6564 0.01 (−0.02, 0.04) 0.59 39 6.56 0.16
Men 3 5421 5315 0.04 (0.00, 0.08) 0.04 0 1.43 0.49
Pregnant women 2 92 68 0.69 (0.36, 1.01) <0.001 44 1.78 0.18
Anemia (RR)
School-age children 6 1940 1609 0.51 (0.37, 0.70) <0.001 94 130.41 <0.001
WCA 3 6442 6294 1.00 (0.98, 1.03) 0.83 54 4.37 0.11
Iron formulation by outcome
Hemoglobin (SMD)
Ferrous sulfate 8 22,246 21,635 0.16 (0.07, 0.25) <0.001 92 204.18 <0.001
Ferrous fumarate 3 327 281 0.22 (0.05, 0.38) 0.01 0 1.26 0.74
Ferric pyrophosphate 3 265 212 0.64 (−0.05, 1.34) 0.07 92 25.97 <0.001
Anemia (RR)
Ferrous sulfate 5 20,916 20,124 0.92 (0.86, 1.00) 0.04 87 61.62 <0.001
Ferrous fumarate 3 328 301 0.60 (0.34, 1.06) 0.08 82 17.05 <0.001
Ferric pyrophosphate 3 249 185 0.40 (0.17, 0.94) 0.03 83 11.67 0.003
Iron concentration, mg/g salt
Hemoglobin (SMD)
≤1.1 11 22,818 22,258 0.15 (0.07, 0.24) 0.0002 90 208.03 <0.001
>1.1 3 405 258 0.56 (0.07, 1.06) 0.03 89 28.32 <0.001
Anemia (RR)
≤1.1 7 21,104 20,349 0.91 (0.85, 0.98) 0.01 84 67.88 <0.001
>1.1 3 389 261 0.32 (0.14, 0.74) 0.007 85 20.09 0.0002
Study duration, mo
Hemoglobin (SMD)
≤6 2 127 117 0.57 (0.12, 1.03) 0.01 68 3.12 0.08
>6 12 23,096 22,419 0.18 (0.10, 0.27) <0.001 91 251.11 <0.001
Anemia (RR)
≤6 2 127 117 1.31 (0.31, 5.58) 0.72 73 3.75 0.05
>6 8 21,366 20,493 0.85 (0.78, 0.92) <0.001 88 106.7 <0.001
Study quality4
Hemoglobin (SMD)
Strong 3 362 375 0.81 (0.18, 1.43) 0.01 94 31.48 <0.001
Moderate 3 1056 875 0.19 (−0.03, 0.41) 0.09 68 9.26 0.03
Weak 8 21,805 21,286 0.12 (0.04, 0.20) 0.002 87 143.51 <0.001
Anemia (RR)
Strong 2 149 154 0.50 (0.17, 1.53) 0.22 83 5.94 0.01
Moderate 3 1070 895 0.44 (0.23, 0.84) 0.01 84 18.97 <0.001
Weak 5 20,274 19,561 0.92 (0.86, 1.00) 0.04 86 63.61 <0.001
1
C, control; DFS, double-fortified salt; I, intervention; MD, mean difference; SMD, standardized mean difference; WCA, nonpregnant, nonlactating women of childbearing age.
2
Values are SMDs, MDs, or RRs of pooled estimates, as indicated. Pooled estimates for the overall effect and subgroup analyses were conducted when data were available from
>1 study.
3
Random-effects models were conducted if there was evidence of significant heterogeneity; otherwise, fixed models were conducted. The inverse variance method was used
for SMDs and MDs and Mantel-Haenszel was used for RRs.
4
Studies received a global rating of “strong” when all dimensions of the Effective Public Health Practice Project quality-assessment tool (selection bias, study design, confounders,
blinding, data collection methods, withdrawals and dropouts, intervention integrity, and robustness of the analysis) were classified as strong. Moderate and weak global scores
were assigned to studies with 1 or >1 weak components, respectively.

All studies that reported data on IDA were efficacy studies Study duration
that used concentrations of iron >1.1 mg/g salt and showed Most efficacy and all effectiveness studies lasted >6 mo (Sup-
a 60% reduction in the RR of IDA (RR: 0.40; 95% CI: 0.26, plemental Table 1). The effect size for hemoglobin concen-
0.61; P < 0.001) (Table 1). trations (SMD) of efficacy studies that lasted >6 mo was

214 Ramírez-Luzuriaga et al.

0.25 SD (95% CI: 0.08, 0.42; P = 0.005) and the RR for anemia
was 0.54 (95% CI: 0.41, 0.72; P < 0.001) (Table 1).
The pooled estimate combining efficacy and effectiveness
studies of >6 mo duration for hemoglobin concentration
(SMD) was 0.18 (95% CI: 0.10, 0.27; P < 0.001) and for
anemia the RR was 0.85 (95% CI: 0.78, 0.92: P < 0.001)
(Table 3).
For studies that lasted ≤6 mo, effect sizes for hemoglobin
were larger relative to studies of longer duration but had a
wider CI (SMD: 0.57; 95% CI: 0.12, 1.03; P = 0.01) (n = 2
efficacy studies) (Table 1).
Study quality
For efficacy studies of strong and moderate quality, the SMDs
for hemoglobin were 0.81 (95% CI: 0.18, 1.43; P = 0.01) and
0.30 (95% CI: 0.12, 0.48; P < 0.001), respectively. Efficacy
studies of weak quality showed a significant effect size for
anemia (RR: 0.72; 95% CI: 0.55, 0.96; P = 0.02) but had a
wider CI for hemoglobin (SMD: 0.16; 95% CI: −0.01, 0.33;
P = 0.06) (Table 1).
Effect modification from population baseline and study
characteristics
With the use of multiple variable meta-regression analyses,
we found that baseline anemia and hemoglobin values, de-
worming status before the intervention, sample size, and
study duration were not significant predictors of the risk
of anemia and hemoglobin concentration response to DFS
(Supplemental Tables 2 and 3).
Stability of DFS
Seven efficacy studies presented some data on the stability of
iodine, iron, and color change in DFS (Supplemental Table 1).
Overall, no significant color changes were observed in DFS
and control salts during transport and storage conditions,
with the exception of 2 studies conducted in Morocco and
Ghana (42, 44). Zimmermann et al. (42) reported that, during
the dry season, when moisture content was <1%, no signifi-
cant color differences between the salts were observed. How-
ever, during the damp season, when moisture content reaches
∼3%, DFS developed a mild yellow color. In the study con-
ducted by Asibey-Berko et al. (44) in Ghana, the DFS turned
a slightly darker color than the control salt.
Discussion
To our knowledge, this is the first systematic review and
meta-analysis of the effects of DFS on hemoglobin status and
risk of anemia and IDA. In this review of 12 efficacy and 2 ef-
fectiveness studies, we found that, among efficacy trials, DFS
significantly increased hemoglobin concentrations by a mean
of 3.74 g/L and reduced the RRs of anemia and IDA by 41%
and 63%, respectively. Pooled estimates including the 2 effec-
tiveness studies in addition to the efficacy trials resulted in
lower but still significant effect sizes on hemoglobin but no
effects on anemia.
Pooled estimates of DFS trials showed significant ef-
fects for hemoglobin concentrations, anemia, and IDA in
school-age children. No effect of DFS was observed in
preschool-age children in the 2 studies available. Preschool-
age children have a higher potential to benefit from DFS
given their increased iron demands. However, intakes of salt
among preschool-age children in developing countries could
be quite low because their diets usually differ from that of the
rest of the family. Their food may be cooked separately and
include less DFS, and consumption is highly dependent on
caregiver feeding practices, which are often poor in the set-
tings examined here (46). More studies on the effects of DFS
are needed in preschool-age children.
Among women of childbearing age, pooled estimates of
efficacy studies for hemoglobin concentrations were signifi-
cant. Effect sizes in pregnant women were larger relative to
nonpregnant women of childbearing age, but only 2 stud-
ies were available. These findings might be explained by the
higher iron demands that occur in this physiologic state in
which more iron is needed to support the growing fetus and
placenta and to increase the maternal RBC mass (47, 48). Fur-
thermore, there is a higher intestinal absorption of dietary
iron during the second and third trimesters of gestation to
accommodate for the expansion of RBC mass (49).
In terms of DFS formulations, pooled estimates of ef-
ficacy studies showed that ferrous sulfate and ferrous fu-
marate resulted in significant effects, with similar SMDs for
hemoglobin concentrations. Estimates that included efficacy
and effectiveness studies yielded similar effect sizes for fer-
rous fumarate and ferrous sulfate on hemoglobin concen-
tration and the RR of anemia. Although the evidence from
studies that used ferric pyrophosphate as the source of forti-
fication (n = 3 efficacy studies) did not show a significant ef-
fect on hemoglobin concentrations, the SMD was larger than
for ferrous sulfate and ferrous fumarate, and borderline sig-
nificant (P = 0.07). Furthermore, the RR of IDA was reduced
by 53% in studies that used ferric pyrophosphate (P = 0.001).
Some limitations should be mentioned. First, we were un-
able to pool results on biomarkers of iron status due to the
lack of comparable statistics. Second, the unknown preva-
lence of infection or inflammation in the studied popula-
tions limits our ability to rely on serum ferritin and other
iron biomarkers to clearly detect changes in iron status (50).
Third, effect sizes were calculated on the basis of end-line val-
ues. However, all studies were randomized trials and baseline
characteristics were comparable across intervention groups
in most studies. Furthermore, the meta-regression showed
no evidence of baseline hemoglobin concentrations and ane-
mia prevalence predicting the risk of anemia and hemoglobin
concentration response to DFS. However, the sample size was
low (n = 14 studies) and the statistical power also was con-
sequently low.
Efficacy and effectiveness of DFS
Pooling the effects of efficacy and effectiveness trials may
not be the best approach for analyzing the body of epidemi-
ologic evidence, given differences in coverage and compli-
ance between these 2 types of studies. Efficacy trials deter-
mine whether an intervention produces the expected results
Impact of double-fortified salt on biomarkers of iron status 215
under ideal circumstances, whereas effectiveness trials mea-
sure the effect under “real world” conditions. For this reason,
in this meta-analysis, we present pooled estimates differen-
tiating between efficacy and effectiveness studies in addition
to combining them.
To our knowledge, only 2 effectiveness studies of DFS have
been conducted (38, 39). Krämer et al. (39) undertook an
evaluation of the Indian school feeding program in rural Bi-
har and found that DFS reduced the prevalence of anemia by
20%. Banerjee et al. (38) conducted a feasibility study of DFS
purchase among households in rural Bihar. Their study ex-
amined the effectiveness of DFS sold through the local mar-
ket, or distributed for free, compared with control communi-
ties and found improvements in hemoglobin concentration
and a reduction in anemia prevalence among adolescents.
No impact was observed for other subgroups on any of the
indicators measured (anemia, cognition, mental health, and
physical fitness). However, coverage was low among partic-
ipants who had the option of purchasing DFS; only 14.5%
of respondents were using DFS at the time of the end-line
survey.
Implications for policies and programs
The direction and magnitude of the effect size for
hemoglobin concentration observed in the current meta-
analysis are similar to that of Gera et al. (51), who reviewed
60 trials of food fortification with iron. The study re-
ported an overall significant improvement in hemoglobin
concentrations of 4.2 g/dL (95% CI: 2.8, 5.6 g/dL). A sep-
arate review of micronutrient fortification of foods by Das
et al. (52) found that iron fortification of foods resulted in a
combined SMD of 0.55 (95% CI: 0.34, 0.76) for hemoglobin
concentrations and an RR of 0.55 (95% CI: 0.42, 0.72) for
anemia in children. In women, effects were similar for
hemoglobin concentrations (0.62 SD; 95% CI: 0.36, 0.89)
and for anemia (RR: 0.68; 95% CI: 0.49, 0.93). These effect
sizes were larger than those reported in this meta-analysis
of DFS and could be explained by a higher consumption of
iron when using a combination of food vehicles such as pro-
cessed foods, cereals, sauces, salt, condiments, and milk, as
opposed to salt alone. However, although iron fortification of
cereals is considered a low-cost intervention, it is difficult to
implement on a large scale in contexts in which flour milling
occurs at the village level (25). Despite these challenges, an
experimental community-level iron-fortification program in
Udaipur district, Rajasthan, has reported a successful local
milling initiative (53). The sustainability and generalizability
of such an initiative remain to be seen.
Stability and sensory testing of different DFS
formulations
The stability of DFS depends on the chemical form of iron
and iodine compounds, salt quality, storage conditions, and
packaging material. Stability-specific studies have generally
tested several DFS formulations to identify those combina-
tions that are most stable. Currently, most DFS formulations
retain >80% of their iodine content after 1 y and are well
216 Ramírez-Luzuriaga et al.
accepted by consumers (12). Stability could be further af-
fected by the in-country salt quality and humidity (12).
Changes in DFS stability have significant policy implications
because of repercussions on uptake and acceptability among
beneficiaries, particularly for countries with humid climates.
In addition, in settings in which food is cooked for extended
periods, degradation and oxidation of the iron from specific
formulations could make the food unappealing.
Conclusions
Overall, these findings have important and timely implica-
tions for policies and programs that are looking to scale up
DFS, as is the case for Sri Lanka, which is initiating the use
of DFS in a school feeding program, as well as several Indian
states that are interested in distributing DFS through the In-
dian food security system (i.e., ration shops). The results of
this meta-analysis point to a significant potential for impact
from DFS on hemoglobin concentration and a reduced risk
of anemia and IDA, particularly among school-age children
and women of childbearing age, including pregnant women,
and begin to create the foundation to move toward more ef-
fectiveness studies.
Acknowledgments
The authors’ responsibilities were as follows—MJR-L, LML,
and RM: designed the study; MJR-L and LML: conducted
the search and extracted the data; MJR-L: performed the
quality assessment and statistical analyses and drafted the
manuscript; VM: contributed to the study design; RM, LML,
and VM: contributed to drafting the manuscript; and all au-
thors: read and approved the final manuscript.
References
1. Oppenheimer SJ. Iron and its relation to immunity and infectious
disease. J Nutr 2001;131:616S–33S; discussion 33S–5S.
2. Brabin BJ, Hakimi M, Pelletier D. An analysis of anemia and pregnancy-
related maternal mortality. J Nutr 2001;131:604S–14S; discussion 14S–
5S.
3. Brabin BJ, Premji Z, Verhoeff F. An analysis of anemia and child
mortality. J Nutr 2001;131:636S–45S; discussion 46S–8S.
4. WHO. Nutritional anaemias. Report of a WHO scientific group. World
Health Organ Tech Rep Ser 1968;405:5–37.
5. Balarajan Y, Ramakrishnan U, Ozaltin E, Shankar AH, Subramanian
SV. Anaemia in low-income and middle-income countries. Lancet
2011;378:2123–35.
6. Hunt JM. Reversing productivity losses from iron deficiency: the
economic case. J Nutr 2002;132:794S–801S.
7. Trowbridge F, Martorell R. Summary and Recommendations. J Nutr
2002;132:875S–879S.
8. Pretell EA, Pearce EN, Moreno SA, Dary O, Kupka R, Gizak M, Gorstein
J, Grajeda R, Zimmermann MB. Elimination of iodine deficiency
disorders from the Americas: a public health triumph. Lancet Diabetes
Endocrinol 2017;5:412–4.
9. Bougma K, Aboud FE, Harding KB, Marquis GS. Iodine and mental
development of children 5 years old and under: a systematic review and
meta-analysis. Nutrients 2013;5:1384–416.
10. Aburto NJ, Abudou M, Candeias V, Wu T. Effect and safety of salt
iodization to prevent iodine deficiency disorders: a systematic review
with meta-analyses. WHO eLibrary of Evidence for Nutrition Actions
(eLENA). Geneva (Switzerland); WHO; 2014.
11. Qian M, Wang D, Watkins WE, Gebski V, Yan YQ, Li M, Chen
ZP. The effects of iodine on intelligence in children: a meta-analysis
of studies conducted in China. Asia Paci J Clin Nutr 2005;14:
32–42.
12. Baxter J, Zlotkin S. Compendium of evidence on double fortified
salt. Micronutrient Initiative Centre for Global Child Health. Toronto,
Ontario, Canada; 2014.
13. Diosady LL, Alberti JO, Ramcharan K, Mannar MG. Iodine stability in
salt double-fortified with iron and iodine. Food Nutr Bull 2002;23:196–
207.
14. Yadava D, Olive Li Y, Diosady LL, Wesley AS. Optimisation of
polymer coating process for microencapsulating ferrous fumarate for
salt double fortification with iodine and iron. J Microencapsul 2012;29:
729–38.
15. Li YO, Yadava D, Lo KL, Diosady LL, Wesley AS. Feasibility
and optimization study of using cold-forming extrusion process for
agglomerating and microencapsulating ferrous fumarate for salt double
fortification with iodine and iron. J Microencapsul 2011;28:639–49.
16. Oshinowo T, Diosady LL, Yusufali R, Wesley AS. Production of iron
premix for the fortification of table salt. Int J Food Eng 2012;8:1556–
3758.
17. Diosady L, Yusufali R, Oshinowo T, Laleye L. A study of storage and
distribution of double fortified salts in Kenya. J Food Eng 2006;76:547–
56.
18. Oshinowo T, Diosady L, Yusufali R, Laleye L. Stability of salt
double-fortified with ferrous fumarate and potassium iodate or iodide
under storage and distribution conditions in Kenya. Food Nutr Bull
2004;25:264–70.
19. Li YO, Diosady LL, Wesley AS. Iron in vitro bioavailability and iodine
storage stability in double-fortified salt. Food Nutr Bull 2009;30:327–35.
20. Ranganathan S, Karmarkar MG, Krupadanam M, Brahmam GNV,
Vishnuvardhana Rao M, Vijayaraghavan K, Sivakumar B. Stability
of iodine in salt fortified with iodine and iron. Food Nutr Bull
2007;28:109–15.
21. Ranganathan S, Sesikeran B. Development of the double-fortified salt
from the national institute of nutrition. Compr Rev Food Sci Food Saf
2008;7:390–6.
22. Sivakumar B, Brahmam GN, Madhavan Nair K, Ranganathan S,
Vishnuvardhan Rao M, Vijayaraghavan K, Krishnaswamy K. Prospects
of fortification of salt with iron and iodine. Br J Nutr 2001;
85:S167–73.
23. Sattarzadeh M, Zlotkin SH. Iron is well absorbed by healthy adults
after ingestion of double-fortified (iron and dextran-coated iodine)
table salt and urinary iodine excretion is unaffected. J Nutr 1999;129:
117–21.
24. Wegmuller R, Zimmermann MB, Moretti D, Arnold M, Langhans
W, Hurrell RF. Particle size reduction and encapsulation affect the
bioavailability of ferric pyrophosphate in rats. J Nutr 2004;134:3301–4.
25. Horton S, Wesley A, Mannar MGV. Double-fortified salt reduces
anemia, benefit:cost ratio is modestly favorable. Food Policy
2011;36:581–7.
26. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred
reporting items for systematic reviews and meta-analyses: the PRISMA
statement. J Clin Epidemiol 2009;62:1006–12.
27. Jackson N, Waters E; Guidelines for Systematic Reviews in Health
Promotion and Public Health Taskforce. Criteria for the systematic
review of health promotion and public health interventions. Health
Promot Int 2005;20:367–74.
28. Deeks JJ, Higgins JPT, Altman DG, editors. Chapter 9: Analysing
data and undertaking meta-analyses. In: Higgins JPT Green S. (eds).
Cochrane Handbook for Systematic Reviews of Interventions Version
5.1.0 (updated March 2011). The Cochrane Collaboration; 2011.
Available from: www.handbook.cochrane.org.
29. Higgins JPT, Deeks JJ, Altman DG, editors. Chapter 16: Special topics
in statistics. In: Higgins JPT Green S. (eds). Cochrane Handbook
for Systematic Reviews of Interventions Version 5.1.0 (updated
March 2011). The Cochrane Collaboration; 2011. Available from:
www.handbook.cochrane.org.
30. Sterne JA, Egger M, Smith GD. Systematic reviews in health care:
Investigating and dealing with publication and other biases in meta-
analysis. BMJ 2001;323:101–5.
31. Rajagopalan S, Vinodkumar M. Effects of salt fortified with iron and
iodine on the haemoglobin levels and productivity of tea pickers. Food
Nutr Bull 2000;21:323–9.
32. Brahmam GNV, Nair KM, Laxmaiah A, Reddy CG, Ranganathan
S, Rao MV, Naidu AN, Vijayaraghavan K, Sivakumar B,
Krishnaswamy K et al. Community trials with iron and iodine
fortified salt (double fortified salt). 2000;955–60. http://www.
worldsaltsymposium.org/download/community-trials-with-iron-and-
iodine-fortified-salt-double-fortified-salt/.
33. Vinodkumar M, Rajagopalan S, Bhagwat I, Singh S, Parmar B,
Mishra O, Upadhyay S, Bhalia N, Deshpande S. A multicenter
community study on the efficacy of double-fortified salt.
Food Nutr Bull [Internet]. 2007;28:100–8. Available from:
http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/591/CN-
00611591/frame.html. (accessed February 8, 2017).
34. Andersson M, Thankachan P, Muthayya S, Goud RB, Kurpad AV,
Hurrell RF, Zimmermann MB. Dual fortification of salt with iodine and
iron: a randomized, double-blind, controlled trial of micronized ferric
pyrophosphate and encapsulated ferrous fumarate in southern India.
Am J Clin Nutr 2008;88:1378–87.
35. Haas JD, Rahn M, Venkatramanan S, Marquis GS, Wenger MJ, Murray-
Kolb LE, Wesley AS, Reinhart GA. Double-fortified salt is efficacious in
improving indicators of iron deficiency in female Indian tea pickers. J
Nutr 2014;144:957–64.
36. Reddy KJ, Nair S. Double fortified salt: an effective measure to control
micronutrient deficiencies in Indian pregnant women. Int J Community
Med Public Health 2016;3:679–86.
37. Reddy KJ, Nair S. Double fortified salt and deworming—game
changers in the battle against iodine and iron malnutrition in
Indian school children. Indian J Community Health 2014;26:175–
82.
38. Banerjee A, Barnhardt S, Duflo E. Can iron-fortified salt control
anemia? Evidence from two experiments in rural Bihar. National Bureau
of Economic Research. Cambridge (MA); 2016.
39. Kraemer M, Kumar S, Vollmer S. Impact of delivering iron-fortified
salt through a school feeding program on child health, cognition and
education: Evidence from a randomized controlled trial in rural India.
GlobalFood Discussion Papers. Goettingen: University of Goettingen;
(in press).
40. Nadiger H, Krishnamachari K, Naidu AN, Rao BN, Srikantia S. The
use of common salt (sodium chloride) fortified with iron to control
anaemia: results of a preliminary study. British Journal of Nutrition
1980;43:45–51.
41. Sivakumar B, Nair KM. Double fortified salt at crossroads. Indian J
Pediatr 2002;69:617–23.
42. Zimmermann MB, Zeder C, Chaouki N, Saad A, Torresani T, Hurrell
RF. Dual fortification of salt with iodine and microencapsulated iron: a
randomized, double-blind, controlled trial in Moroccan schoolchildren.
Am J Clin Nutr 2003;77:425–32.
43. Zimmermann MB, Wegmueller R, Zeder C, Chaouki N, Rohner F,
Saissi M, Torresani T, Hurrell RF. Dual fortification of salt with iodine
and micronized ferric pyrophosphate: a randomized, double-blind,
controlled trial. Am J Clin Nutr 2004;80:952–9.
44. Asibey-Berko E, Zlotkin S, Yeung G, Nti-Nimako W, Ahunu B, Kyei-
Faried S, Johnston J, Tondeur M, Mannar V. Dual fortification
of salt with iron and iodine in women and children in rural
Ghana. East Afr Med J [Internet]. 2007;84:473–80. Available from:
http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/393/CN-
00622393/frame.html. (accessed January 14, 2017).
45. Wegmüller R, Camara F, Zimmermann M, Adou P, Hurrell R.
Salt dual-fortified with iodine and micronized ground ferric
pyrophosphate affects iron status but not hemoglobin in children
in Cote d’Ivoire. J Nutr [Internet]. 2006;136:1814–20. Available fron:
http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/962/CN-
00556962/frame.html. (accessed January 14, 2017).
Impact of double-fortified salt on biomarkers of iron status 217
46. Dewey KG, Brown KH. Update on technical issues concerning
complementary feeding of young children in developing countries and
implications for intervention programs. Food Nutr Bull 2003;24:5–28.
47. Allen LH. Anemia and iron deficiency: effects on pregnancy outcome.
Am J Clin Nutr 2000;71:1280S–4S.
48. Suitor CW. Perspectives on nutrition during pregnancy: Part I,
weight gain; Part II, nutrient supplements. J Am Diet Assoc 1991;91:
96–8.
49. Cao C, O’Brien KO. Pregnancy and iron homeostasis: an update. Nutr
Rev 2013;71:35–51.
50. Suchdev PS, Namaste SM, Aaron GJ, Raiten DJ, Brown KH, Flores-Ayala
R, BRINDA Working Group. Overview of the Biomarkers Reflecting
218 Ramírez-Luzuriaga et al.
Inflammation and Nutritional Determinants of Anemia (BRINDA)
Project. Adv Nutr 2016;7:349–56.
51. Gera T, Sachdev HS, Boy E. Effect of iron-fortified foods on hematologic
and biological outcomes: systematic review of randomized controlled
trials. Am J Clin Nutr 2012;96:309–24.
52. Das JK, Salam RA, Kumar R, Bhutta ZA. Micronutrient fortification of
food and its impact on woman and child health: a systematic review.
Syst Rev 2013;2:67.
53. Banerjee A, Duflo E, Glennerster R. Is decentralized iron fortification a
feasible option to fight anemia among the poorest? In: Wise DA. (ed).
Explorations in the economics of aging. Chicago (IL): University of
Chicago Press; 2011. p. 317–44.