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A SUSTAIN Task Force Report:

ENHANCING THE ABSORPTION OF FORTIFICATION IRON

Richard Hurrell
1
, Sean Lynch
2
, Thomas Bothwell
3
, Hctor Cori
4
, Ray Glahn
5
, Eva
Hertrampf
6
, Zdenek Kratky
7
, Dennis Miller
8
, Mario Rodenstein
9
, Hugo Streekstra
10
, Birgit
Teucher
11
, Elizabeth Turner
12
, C. K. Yeung
8
, Michael Zimmermann
1

1
Institute of Food Science and Nutrition, Swiss Federal Institute of Technology Zurich,
Switzerland
2
Eastern Virginia Medical School, Norfolk, Virginia, USA
3
Department of Medicine, University of Witwatersrand, J ohannesburg, South Africa
4
DSM Nutritional Products, Santiago, Chile
5
USDA-ARS Plant Soil and Nutrition Laboratory, Ithaca, New York, USA
6
Institute of Nutrition and Food Technology, Santiago, Chile
7
Nestl, New Milford, Connecticut, USA
8
Department of Food Science, Cornell University, Ithaca, New York, USA
9
Unilever, Englewood Cliffs, New J ersey, USA
10
DSM Food Specialties, Delft, Netherlands
11
Institute of Food Research, Norwich Laboratory, Norwich, UK
12
SUSTAIN, Washington, DC, USA

The Authors wish to acknowledge the exceptional efforts of the following SUSTAIN team
members for their editorial and technical support in the preparation of this publication, and
for their assistance with the organization of the Workshop: Betty Bugusu, Fred Grant,
Martha Lassiter, Wayne Moore and Sue Wunder. Additionally, we wish to thank and
acknowledge the following individuals who contributed expertise during the workshop and
in the subsequent review of this manuscript: Erick Boy, Helene Carlson, Ram Chaudhari,
Michael DiNovi, Alison Edwards, Chuck Gagel, Brent Hagen, Leif Hallberg, J anet Hunt,
A. Patrick MacPhail, Haile Mehansho, Manuel Olivares, Paul Richardson, Steve Schorn,
Geoff Smith, Wolfgang Vogl, Carel Wreesmann

Correspondence to: Richard Hurrell
Swiss Federal Institute of Technology Zurich (ETH)
Laboratory of Human Nutrition
PO Box 747
CH-8803 Rschlikon
Switzerland
Fax: ++41-1-704 57 10
email: [email protected]

Running title:

Key words: iron fortification, ascorbic acid, EDTA, amino acid chelates,
phytate degradation, encapsulation

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ABSTRACT

Iron deficiency remains a major global health problem affecting an estimated 2 billion
people [1]. The World Health Organization ranked it as the 7
th
most important preventable
risk for disease, disability and death in 2002 [2]. Since an important factor in its causation
is the poor bioavailability of iron in the cereal based diets of many developing countries,
SUSTAIN set up a Task Force, consisting of nutritional, medical, industry and government
experts, to consider strategies for enhancing the absorption of fortification iron. This paper
summarizes the findings of this Task Force. Detailed reviews of each strategy follow this
overview.

Highly soluble compounds of iron like ferrous sulfate are desirable food fortificants but
cannot be used in many food vehicles because of sensory issues. Thus, potentially less
well-absorbed forms of iron commonly are used in food fortification. The bioavailability
of iron fortificants can, however, be enhanced with innovative ingredient technologies.
Ascorbic acid, NaFeEDTA, ferrous bisglycinate, and dephytinization all enhance the
absorption of fortification iron, but add to the overall costs of fortification. While all
strategies cannot be recommended for all food fortification vehicles, individual strategies
can be recommended for specific foods. For example, the addition of ascorbic acid is
appropriate for dry blended foods such as infant foods and other dry products made for
reconstitution that are packaged, stored and prepared in a way that maximizes retention of
this vitamin. NaFeEDTA can be recommended for fortification of fish sauce and soy
sauce, whereas amino acid chelates may be more useful in milk products and beverages.
With further development, dephytinization may be possible for low cost cereal-based
complementary foods in developing countries. Encapsulation of iron salts in lipid
coatings, while not an iron absorption-enhancing strategy per se, can prevent soluble forms
of iron from interacting undesirably with some food vehicles and hence broaden the
application of some fortificants.

Research relevant to each of these strategies for enhancing the bioavailability or utility of
iron food fortificants is reviewed. Individual strategies are evaluated in terms of enhancing
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effect and stability, organoleptic, cost and regulatory issues of interest to the nutrition
community, industry and consumers. Recommendations are made on potential usages and
further research needs.

Effective fortification depends on the selection of technically feasible and efficacious
strategies. Once suitable strategies have been identified cost becomes very important in
selecting the best approach to implement. However it is essential to calculate cost in
relation to the amount of bioavailable iron delivered. An approach to the calculation of cost
using conservative estimate of the enhancing effects of the innovative technologies
discussed in the supplement is given in the final section.
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IRON DEFICIENCY A GLOBAL PROBLEM

Deleterious Effects of Iron Deficiency

Many infants, children and women of childbearing age, particularly in the poorer countries
of the developing world, are iron deficient. About half of these iron deficient individuals
develop iron deficiency anemia (IDA), the most advanced form of the disease, which has
several major negative impacts on health, and contributes substantially to the risk of early
death and disability [2].

There are five major negative health consequences of IDA. Firstly in the pregnant woman,
IDA leads to sub-optimal pregnancy outcome, including lower birth weight, increased
morbidity in mothers and neonates, increased infant mortality, and a greater risk of the
infant developing iron deficiency after 4 months of age [3, 4]. Secondly, during infancy,
IDA leads to delayed mental and motor development with effects on behavior and
cognitive performance when the child reaches school age. The effects of early IDA on
brain development may not be reversible by subsequent treatment, and failure to reach
educational goals may affect earning capacity later in life [5, 6]. In children, IDA can also
lead to increased frequency and duration of upper respiratory infections [7] and to
increased risk for goiter due to diminished utilization of iodine for thyroid hormone
production [8]. Finally, physical work capacity is impaired for all individuals as IDA
negatively affects aerobic capacity related to intense physical activity, and reduces
endurance capacity, voluntary activity and work productivity. This results in a lower
income for the individual, the family and the country [9, 10].

Iron deficiency is therefore a major health problem in the developing world and recently
WHO [2] ranked it as 7th out of the 10 major global preventable risks for disease,
disability and death, that together account for 40% of the 56 million deaths that occur
world-wide each year and for one third of the global loss of healthy life years. In
developing countries, underweight has been reported to be the greatest risk factor and
accounts for 9.5% of the global DALY`s (disability-adjusted life years, one DALY is equal
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to the loss of one year of healthy life). Iron deficiency is the next highest nutritional risk
factor and accounts for 2.4% of global DALY`s, preceded only by sexually transmitted
diseases, diseases related to unsafe water, poor sanitation and hygiene, alcohol abuse, and
indoor smoke from solid fuels. It has been estimated that if iron deficiency were eliminated
worldwide, more than 35 million people would have one additional year of healthy life.

Prevention of Iron Deficiency

The elimination of iron deficiency however has not proved easy. Dietary diversification
(promoting the consumption of iron-rich foods) is hindered by the difficulty in achieving
behavioral change as well as by the predominance in developing countries of plant-based
diets deficient in the more bioavailable heme form of iron. Iron supplementation has been
mainly targeted at high-risk groups such as pregnant women and young children.
Supplementation interventions however have often been compromised as the side effects
of the high doses impact compliance. There are often supply or distribution problems in
developing countries as well [11].

Food fortification offers a more cost-effective approach to providing additional iron to
most segments of the population by mass fortification of staples such as wheat and maize
flour, or condiments such as salt, fish sauce or soy sauce. Infants and young children can in
addition be specifically targeted through iron fortified infant formulas and cereal-based
complementary foods. However because iron is such a difficult mineral to add to foods in
a sufficiently bioavailable form without adverse sensory changes, not all fortified foods
have provided enough absorbable iron to improve iron status. While infant formulas, infant
cereals, soy sauce and fish sauce are generally regarded as effective vehicles for food
fortification, some doubt remains as to the usefulness of iron fortified cereal flours and salt
because of continuing technical barriers [12].

The first technical barrier that still remains, particularly for cereal flours and salt, is finding
an iron compound that is sufficiently bioavailable but which causes no adverse sensory
changes to the food vehicle. In an attempt to partially address this barrier, an earlier
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SUSTAIN task force [13] evaluated the usefulness of elemental iron powders for cereal
flour fortification. The task force concluded that of the five elemental iron powders sold
for food fortification, only electrolytic iron had been demonstrated to be a useful iron
fortificant. Because this powder was judged to be only half as well absorbed as ferrous
sulfate, they recommended that it should be added to foods at twice the level of ferrous
sulfate. The second technical barrier to successful food fortification is overcoming the
inhibitory effect of dietary components, such as phytate, phenolic compounds and calcium,
which are often present in the food vehicle itself or in the accompanying diet. For example,
iron absorption may be unacceptably low from high-phytate whole cereal flours even when
fortified with highly absorbable iron compounds such as ferrous sulfate [14].

SUSTAIN TASK FORCE REVIEW

The present Task Force was set up to assess the different strategies that are available for
increasing the bioavailability of fortification iron from diets containing significant amounts
of inhibitors of iron absorption, while, at the same time, not causing adverse sensory
changes in the chosen vehicles. The 5 approaches that were considered included the
following:

Addition of ascorbic acid and other organic acids
Addition of NaFeEDTA or other EDTA compounds
Addition of amino acid chelates
Degradation of phytate
Encapsulation of highly bioavailable compounds, such as ferrous sulfate

This overview paper briefly reviews the successful iron fortification programs or trials, and
then summarizes the key issues in relation to each of the enhancers of iron absorption.
Relevance to finished food staples and widely consumed condiments is emphasized. These
short review sections are followed by a consensus statement framed by a SUSTAIN task
force consisting of academic and industry experts on the strategies to enhance the
absorption of fortification iron. The task force based its consensus points in part on
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industry and scientific review papers presented at SUSTAINs Workshop on Innovative
Ingredient Technologies to Enhance Iron Absorption (Washington, DC, March 2003).
Workshop discussions of these materials among participants from industry, the science
community and government also helped shape the consensus as did new information
obtained in consultations with experts from these sectors subsequent to the Workshop.
Five invited review papers, one on each iron enhancing technology, are published in full
after this overview.

Successful Iron Fortification Programs and Field Trials

The ultimate proof that an iron-fortified food is efficacious is the demonstration that it
improves or maintains iron status in a target population. The iron-fortified food must
provide an adequate amount of absorbable iron to the consumer so as to counter the deficit
between normal intake of absorbable iron and the iron needs. The amount of absorbable
iron provided thus depends on the amount of iron added to the fortified food and the
bioavailability of that iron when the fortified food is consumed as part of a mixed diet.
Because such efficacy studies are technically difficult, expensive, and usually take 6
months to one year to complete, few have been published. It is noteworthy however that
most of the successful efficacy studies have added ascorbic acid as an enhancer of iron
absorption together with the iron compound or employed an iron compound which is
protected from absorption inhibitors. Some successful efficacy studies are described
below.

Ascorbic Acid: Although ascorbic acid enhances the iron absorption of all iron
fortification compounds [15], there is little direct evidence of its influence on iron status
when added to iron fortified foods. The best evidence comes from two separate efficacy
studies on iron fortified powdered milk fed to infants and young children in Chile [16].
The studies were made with a similar protocol but 2 years apart (1972 and 1974). In the
first study, 3 month old infants who had spontaneously discontinued breastfeeding, were
fed a reconstituted milk powder that had been fortified or not
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with ferrous sulfate (15 mg Fe per liter). At 15 months, the prevalence of anemia was 35%
in the group receiving the non-fortified milk compared to 13% in the infants consuming
the fortified milk. In the second trial, ascorbic acid was added to the milk at a 2:1 molar
ratio relative to iron and, at 15 months, the prevalence of anemia was again high in the
group receiving the non-fortified milk (28%) but had fallen to less than 2% in the group
receiving the fortified milk. In addition, the satisfactory iron status of most American
infants is thought to be due in part to the widespread use over the last few decades of
commercial infant formulas (fortified with ferrous sulfate and ascorbic acid) and
complementary foods (fortified with various iron compounds). Anemia surveys of
American infants in the 1980s to 1990s showed significantly lower prevalences compared
to the 1970s, a trend corresponding to the decline in exclusive cow milk use and
simultaneous increase in fortified formula use beyond 6 months of age [17]. In some
countries, infant formulas are also commonly added to reconstituted infant cereals. This
practice could partially explain the efficacy of an electrolytic iron fortified infant cereal in
improving the iron status of infants in Chile when fed regularly over a one year period
[18]. However, the high iron content and the relatively high intake of the cereal (which
provided an extra 14-17mg per day) undoubtedly played a role.

Chelated Iron Compounds: Iron status in target populations was significantly improved
when NaFeEDTA was used to fortify fish sauce in Thailand and Vietnam [19, 20], soy
sauce in China [21], sugar in Guatemala [22], and curry powder in South Africa [23].
Similarly when ferrous bisglycinate was added to flavored milk in Saudi Arabia [24] and a
whey drink in Brazil [25], anemia prevalence was drastically reduced in children and
adolescents after 3 months and 12 months respectively of regular daily consumption. Iron
is strongly chelated in both NaFeEDTA and ferrous bisglycinate and is thus protected from
reacting with dietary components that inhibit iron absorption.

Encapsulated Ferrous Sulfate: One recent study [26], reported a substantial improvement
in iron status of school children in Morocco consuming iron fortified salt. The prevalence
of IDA decreased from 35% at baseline to 8% at 40 weeks. The salt was fortified with
ferrous sulfate encapsulated with partially hydrogenated soybean oil (1 mg Fe/g) but
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contained no enhancer of iron absorption. The lipid capsule helped prevent unwanted color
changes and iodine losses often associated with highly soluble ferrous sulfate. The salt was
provided to the family at the household level and was added primarily to bread, olives and
family meals. The children consumed 7-12 g per day providing 7-12 mg of iron. While it
has been suggested that encapsulation may in some way protect iron from reacting with
absorption inhibitors, no research has been conducted on this issue.

These successful efficacy studies demonstrate that iron fortification of foods can be a
useful strategy to combat iron deficiency. They indicate as well that protecting the
fortification iron from absorption inhibitors such as phytate is a useful way to ensure
adequate iron absorption and to improve iron status. However the addition of an absorption
enhancer or protected iron compound may not be necessary if the amount of added iron
is sufficiently high. The various strategies that can be used to enhance iron absorption are
now considered separately.

Potential Strategies for Enhancing Absorption of Fortification Iron

Ascorbic Acid and other Organic Acids

Commercial Usage: Ascorbic acid is the most commonly added compound for the
enhancement of iron absorption from iron-fortified foods. It is routinely added to infant
formulas and infant cereals to improve iron absorption, and is also added to iron fortified
chocolate drink powders and other dietetic beverages.

When adding ascorbic acid to a finished product, its sensitivity to heat (prolonged boiling,
baking and frying temperatures), water and oxygen must be taken into consideration. In
the dry state, ascorbic acid is reasonably stable in air, but in solution and interfacing with
other components, it oxidizes rapidly. Cooking typically degrades ascorbic acid by
accelerating the oxidation reaction. In order to keep ascorbic acid stable, heat, oxygen and
humidity should be avoided. Storage at high ambient temperatures in oxygen and
humidity-permeable packaging will lead to losses. Proper packaging and encapsulation
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can mitigate some of these losses, but will also add cost. Ascorbic acid is relatively stable
in dry blended foods such as infant formulas, precooked cereal-legume infant foods,
powdered milk and other dry products made for reconstitution.It is less stable in liquid
beverages and liquid milk, and not stable in cereal products that are baked.

Biochemical Effects: The enhancing effect of ascorbic acid has been attributed to its
reducing and chelating properties during digestion of the food [27]. In the pH range 2 to 6,
ferric iron in the food is reduced to ferrous iron thus preventing the formation of the more
insoluble, and non-absorbable, ferric hydroxide as the pH rises in the duodenum. Above
pH 5, a ferric ascorbate chelate can be formed keeping iron in a soluble, absorbable form
[28]. The same reducing and chelating properties presumably also explain the reported
ability of ascorbic acid to overcome the negative effects of all major inhibitors of iron
absorption including phytate, polyphenols [29], calcium, and casein from milk products
[30]. Ferrous iron binds less strongly to the inhibitory compounds than ferric iron. Because
of these unique properties, ascorbic acid can increase by several fold the absorption of
most iron fortification compounds as well as non-heme food iron.

Isotopic Absorption Studies: In single meal isotopic studies, there appears to be a linear
dose response at lower amounts of ascorbic acid addition, which eventually levels off into
a plateau. When feeding an iron-fortified liquid formula meal, Cook and Monsen [31]
reported a linear increase in iron absorption with additions of ascorbic acid up to a 7.5
molar ratio of ascorbic acid to iron. At this level of ascorbic acid, iron absorption was
increased 3 fold. The magnitude of the increase in iron absorption however depends not
only on the molar ratio of ascorbic acid to iron but also on the presence of other enhancers
and inhibitors in the fortified food or in the meal. An ascorbic acid to iron molar ratio of
2:1 has been reported to increase iron absorption from fortification iron by 2-12 fold in
adult women fed infant formula or cereal porridges [32], by 3 fold in J amaican children fed
a chocolate drink [33], and by about 2 fold in infants fed an infant formula [30]. On the
other hand, in foods containing high levels of phytate such as soy infant formulas, a
minimum 4:1 molar ratio was necessary to increase iron absorption about 3 fold [34].
Hurrell [15] has recommended that a molar ratio of 2:1 should be used to enhance the
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absorption of soluble iron compounds from milk products and low-phytate foods but at
least 4:1 should be used for foods high in phytate or phenolics. There are not enough
studies to ascertain whether ascorbic acid enhances the absorption of the more insoluble
iron compounds in a similar way to the soluble compounds although from the results of
Forbes et al [35] any differences would not appear to be substantial.

Questions have been raised as to whether the enhancing effect of ascorbic acid on
fortification iron absorption observed in single meal studies can be translated into a better
efficacy of the fortification iron in improving or maintaining iron status when the fortified
food is fed over a period of time. Some doubt has been cast on the ability of ascorbic acid
to improve iron status by the suggestion that single meal studies over-emphasize iron
absorption from a complete diet [36]. More recently, Cook and Reddy [37] were unable to
demonstrate an influence of high ascorbic acid intake on iron absorption from typical
meals in the United States fed over 5 days. In addition, high dose supplementation with 1 g
of ascorbic acid with meals for 20 months by 5 iron replete healthy adults did not increase
their iron stores [38]. It should, however, be emphasized that the body has a strong control
over intestinal iron absorption and, although ascorbic acid renders iron available for
absorption, the body will not absorb iron if it does not need it. Ascorbic acid may
therefore have no measurable beneficial effect on dietary iron absorption in iron replete
individuals. It has however been shown to increase iron status in iron depleted people in
both developing [16] and industrialized countries [39].

Other Organic Acids: Other organic acids, such as citric, lactic, malic and tartaric, also
complex iron [40] but have no reducing activity. Although they have been demonstrated to
enhance iron absorption in human studies, they have not been considered as an enhancer of
fortification iron because the amount of compound needed to enhance iron absorption
would likely change the taste of the food. Levels of organic acids are often considerably
higher than the level of ascorbic acid in many fruits and vegetables [41], and their presence
might help explain the beneficial effect of fruit juices [42] and some fruits and vegetables
on iron absorption [42, 43]. The amounts required however are high and 1 g or more of
citric acid, malic acid or tartaric acid was necessary to increase 2-3 fold the absorption of 3
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mg iron as ferrous sulfate from a rice meal [44]. A more practical utilization of far lower
levels of organic acids may be needed to stabilize iron compounds in liquid products. For
example, small amounts of citric acid have been found to stabilize ferrous sulfate and
prevent peptide precipitation in ferrous sulfate fortified fish sauce [45].

NaFeEDTA and other EDTA Compounds

J ECFA Guidance and Regulatory Status of NaFeEDTA.

Evidence suggests that sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) is a
highly effective iron fortificant, being 2-3 times better absorbed from inhibitory meals than
ferrous sulfate (46-48), and causing fewer organoleptic problems in many foods than freely
water soluble compounds. However, it has not yet been widely introduced as a fortificant.

In 1993 the J oint FAO/WHO Expert Committee on Food Additives (J ECFA) evaluated
NaFeEDTA for use in supervised food fortification programs in populations in which iron
deficiency anemia is endemic [49] and provisionally concluded it was suitable for such an
application. At the time, however, J ECFA requested further animal toxicology data. When
J ECFA reviewed additional data on the compound in 1999, it removed the provisional
qualification from its previous decision and concluded that NaFeEDTA could be
considered safe when used in supervised fortification programs [50]. J ECFA is not,
however, a regulatory body. In the USA or elsewhere, petitions for the use of NaFeEDTA
as a direct food additive have not been submitted to regulatory authorities nor has anyone
submitted a Generally Recognized As Safe (GRAS) notice to the FDA in the United States
regarding NaFeEDTA. Further constraining the use of NaFeEDTA are the lack of a
consolidated body of evidence on its stability during processing, storage and cooking, as
well as questions relating to its possible interactions with other dietary minerals and trace
elements.

Though NaFeEDTA is not currently recognized by FDA in the United States for use as a
direct food additive, two other salts of EDTA, disodium EDTA (Na
2
EDTA) and calcium
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disodium EDTA (CaNa
2
EDTA) have long been used by the food industry as preservatives,
processing aids and color stabilizers in a variety of foods [51]. In 1974, based on animal
toxicology studies, J ECFA evaluated CaNa
2
EDTA and Na
2
EDTA as food additives and
allocated an acceptable daily intake (ADI) of 2.5 mg EDTA/kg body weight/day.

FDA has evaluated Na
2
EDTA and CaNa
2
EDTA specifically for use as sequestrants in
various foods, with intended use and limitations on use levels stated in the respective
regulations for these additives. At present, Na
2
EDTA and CaNa
2
EDTA have not been
evaluated by FDA for use in the enhancement of mineral absorption (as when combined
with an iron fortificant). It should be noted, however, that infant formula is not listed by
the FDA among the approved uses of either Na
2
EDTA

or

CaNa
2
EDTA. Similarly the
fortification of milk and cereal formulas with NaFeEDTA does not seem appropriate, since
the amounts of NaFeEDTA required to deliver sufficient fortification iron would approach
the ADI of 2.5 mg EDTA/kg body weight/day.

The use of iron enhancers is of more relevance to countries where the prevalence of iron
deficiency is high. Interest exists in the use of NaFeEDTA as an iron source in some such
settings, in part because NaFeEDTA is beneficial for enhancing iron absorption in highly
inhibitory meals, such as the cereal-based diets typically consumed in developing
countries. Vietnam is at present planning a national fortification program with NaFeEDTA
fortified fish sauce. China has announced its plans to use NaFeEDTA for the mass
fortification of soy sauce and wheat flour in two different provinces.

Use as a Fortificant: Although EDTA can complex with virtually every metal in the
periodic table, it binds most strongly to ferric iron at the pH of the gastric juice and then
exchanges the ferric iron for other metals as the pH rises in the duodenum. EDTA acts as a
shuttle, protecting iron in the stomach from binding to phytate and polyphenols, and then
releasing iron for absorption in the duodenum [52]. Such properties make the addition of
NaFeEDTA a potentially useful fortification strategy for phytate containing food vehicles
such as cereal flours, or for addition to condiments such as salt, fish sauce and soy sauce
which are commonly consumed with phytate containing meals. NaFeEDTA is most stable
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and bioavailable in slightly acidic conditions of pH less than 7 [53]. It could be especially
useful as an iron fortificant for whole grain cereal products. Iron absorption by iron replete
adults from wheat bread rolls made from high extraction wheat flour was only 1% when
fortified with ferrous sulfate compared to 4% when fortified with NaFeEDTA. The
corresponding iron absorption values from rolls made with low extraction wheat flour were
6% and 12% [54]. On the other hand, iron absorption from ferrous sulfate and NaFeEDTA
is similar from meals containing no phytate [52] or a low level of phytate such as
contained in a meal of white rice and vegetables consumed with fish sauce [54].

Other EDTA complexes: Na
2
EDTA or CaNa
2
EDTA, added together with the fortification
iron compound is a possible alternative to the addition of NaFeEDTA. Na
2
EDTA has been
demonstrated to increase absorption of iron from ferrous sulfate added to a rice meal [56]
and ferrous sulfate fortified wheat-soy complementary foods [54], even at EDTA to iron
molar ratios below 1. There are, however, no efficacy studies showing that this approach
works. Unfortunately, EDTA appears to enhance only the absorption of soluble iron
compounds and not the more insoluble compounds, which dissolve only slowly in the
gastric contents. Na
2
EDTA at a 1:1 molar ratio did not increase iron absorption by
adolescent girls consuming ferrous fumarate fortified tortillas [57], or by adults consuming
either a ferric pyrophosphate fortified cereal porridge [54] or an elemental iron fortified
breakfast cereal [58].

Organoleptic Effects: Systematic sensory studies have been made with soy sauce and fish
sauce but not with cereal flours. In relation to cereal flours, NaFeEDTA added to wheat
flour has been reported not to cause fat oxidation during a 6 month storage at 37C, in
contrast to the rancidity which occurred on addition of ferrous sulfate with Na
2
EDTA [59].
There are however reports of color development in cereal-based foods [22] and questions
have been raised about a possible inhibitory effect of EDTA on yeast action and thus a
negative effect on bread volume [60].

Unlike ferrous sulfate and other soluble iron compounds, NaFeEDTA does not precipitate
peptides during storage of fish sauce and soy sauce. The taste and color of NaFeEDTA
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fortified sauces is also satisfactory. NaFeEDTA in liquid products however can be
degraded by UV rays from sunlight. While this does not appear to be a problem with soy
sauce, presumably due to its dark brown color, up to 35% losses of EDTA have been
reported in the lighter colored fish sauce which had been filled into clear glass bottles and
left for 2-6 weeks in the open air under daily sunlight [61]. Storage in amber bottles, or
storage of clear bottles indoors under artificial light resulted in little or no degradation of
EDTA. As EDTA enhances iron absorption at molar ratios below 1, this level of
degradation should not affect the nutritional efficacy of the fish sauce. The degradation
products, ethylenediamine triacetic acid, - diacetic acid and monoacetic acid can further
degrade into a range of compounds which include formaldehyde. However, the amounts of
formaldehyde that could theoretically be formed are within the limits considered safe [62].

Interactions with other dietary minerals: The influence of EDTA on the absorption of
other minerals and trace elements was discussed by INACG [52]. Considering the relative
amounts of dietary minerals and the amount of NaFeEDTA in fortified foods, they
concluded that EDTA would not be expected to influence the metabolism of dietary
calcium and magnesium but could theoretically influence the metabolism of zinc and
copper, and of the potentially toxic metals, lead, cadmium, aluminium and mercury
[52].There are few studies to confirm this although there is some evidence from rat and
human studies that EDTA can increase zinc and copper absorption from meals containing
phytate but does not effect calcium metabolism [63-64].

Data on how EDTA might influence the metabolism of potentially toxic minerals is limited
but available evidence suggests that EDTA does not increase their absorption and may
even reduce their retention. Studies in mice showed no influence of EDTA on lead
absorption [65], while the results of two human studies indicated that the absorption of
203
Pb was markedly reduced by EDTA [66]. In a third unpublished study, mineral balances
were carried out on women fed NaFeEDTA fortified bread. Stool and urine samples were
subsequently analyzed for heavy metals. There was no difference between ferrous sulfate
and NaFeEDTA with respect to the fecal excretion of lead, cadmium, aluminium or
mercury, or with respect to the urinary excretion of cadmium, aluminium or mercury.
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Urinary lead excretion was however increased [67]. In two other studies acute cadmium
toxicity in mice was reduced from 90% to zero by the concomitant administration of
EDTA [68], while manganese absorption and excretion were unaffected in women fed an
infant cereal containing NaFeEDTA [69]. Notably, while Na
2
EDTA and CaNa
2
EDTA
have been present in the U.S. diet for 30 years, there has been no evidence of heavy metal
toxicity.

The most appealing reason to use EDTA for food fortification is that NaFeEDTA fortified
foods have been consistently shown to improve iron status of targeted human populations.
These foods include fish sauce in Thailand [19] and Vietnam [20], sugar in Guatemala [22]
curry powder in South Africa [23], and soy sauce in China [21]. To date however there are
no demonstrations of efficacy in wheat or maize flours.

Amino Acid Chelates

Ferrous bisglycinate (ferrous bisglycine chelate) is the major amino acid chelate produced
commercially, although ferric trisglycinate and ferric glycinate are also available. A newly
developed product, ferrous bisglycinate hydrochloride, has undergone in vitro
bioavailability testing. A new fortified juice powder based on ferrous bisglycinate
hydrochloride is ready for commercial release [70]. A patented ferrous bisglycinate
compound manufactured by Albion Laboratories, Clearfield, Utah, USA, has been used in
most of the published studies. This chelate is reported to be formed by 2 glycine molecules
combining with ferrous iron in a double heteracyclic ring structure [71]. Evidence would
suggest that the iron is protected from absorption inhibitors by the chelate, since in most
studies iron absorption from ferrous bisglycinate has been 2-3 times higher than from
ferrous sulfate when added to cereal and milk products containing absorption inhibitors
such as phytate or calcium [72-74].

GRAS Status and Organoleptic Effects: The main advantage of ferrous bisglycinate over
NaFeEDTA is that it has GRAS status and can be considered a natural compound with no
potential anti-physiological effects. However, it readily promotes fat oxidation in cereal
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foods [75] unless an antioxidant is added [76], and undesirable color reactions occur in
some foods [77]. Data available in the literature on the organoleptic functionality of iron
glycinate chelates are very scarce. However, several fortified commercial products seem
to have good consumer acceptance. Ferrous bisglycinate is suitable for the fortification of
commercial food products such as liquid milk as well as other dairy products and flavored
beverages that are reconstituted from dry products, all of which vehicles allow the delivery
of significant amounts of bioavailable iron. Further research is needed to establish the
compatibility of iron amino acid chelates with different food matrices during processing
storage and food preparation.

Efficacy Studies: Four efficacy studies with ferrous bisglycinate fortified foods all reported
a marked decrease in the prevalence of anemia or iron deficiency anemia in children or
adolescents. Unfortunately none of these studies had a control group receiving no iron, so
there is no certainty that the improvement in iron status was due to the iron fortified food.
Three studies were made in Brazil. These studies investigated the influence of a ferrous
glycinate fortified liquid milk [78], sweetened bread roll [79] and whey based beverage
[25] on iron status of children. A further study made in Saudi Arabia investigated an iron
fortified flavored milk drink [24].

Phytate Degradation

Cereal grains and legume seeds are rich in phytate (myo-inositol-6-phosphate), a food
component which strongly inhibits the absorption of iron and of other essential minerals
[80]. In the digestive tract, phytate is thought to bind iron in insoluble complexes from
which the iron is unavailable for absorption. While the formation of such complexes can be
retarded by the addition of ascorbic acid, EDTA or iron as ferrous bisglycinate, an
alternative approach for the enhancement of iron absorption would be the removal of
phytate from cereal flours by milling; or the degradation of phytate in cereal or legume
foods with native (endogenous) or added (exogenous) phytases during the manufacturing
process and/or food preparation [49]. Another approach would be to add an active phytase
to cereal foods or condiments after processing. The active phytase would then degrade
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phytate in the gastrointestinal tract so preventing the formation of iron-phytate complexes
[81]. Phytases are widely used in this manner in animal husbandry to increase the
liberation of phosphate from the food to enhance the bioavailability of added minerals and
the conversion of feed proteins. They have not been applied as a means of improving the
absorption of fortification iron from human foods.

Inhibitory Effect of Phytate on Iron Absorption: Phytate is a potent inhibitor of iron
absorption even at relatively low levels and partial degradation (ca. 50%) of phytate in
whole grain products would not be expected to markedly improve iron absorption [82-84].
In order to achieve the maximum increase in the absorption of fortification iron from cereal
and legume based foods, phytate degradation should be virtually complete. Hurrell [12, 15]
has recommended complete phytate degradation as the goal but, as this is not always
possible, it has been recommended that the molar ratio of phytate to iron should be
decreased to <1:1 and ideally to <0.4:1. The nutritional benefit of these low phytate levels
in cereal foods is exemplified by the reports that decreasing the phytate in whole wheat by
90% during milling might be expected to double iron absorption [82] Complete
dephytinization has been reported to increase iron absorption by as much as 12 fold in a
single meal study (.99% to 11.54%) [49].

Methods for Reducing Dietary Phytate: Phytate can be degraded through the enzymatic
action of phytase in cereal foods during the manufacturing processes with native or added
phytases yielding a phytate-degraded food. Cereal and legume based complementary foods
or soy-based infant formula are good candidates for dephytinization, as infants over 6
months often depend on these foods as the main sources of dietary iron. Breakfast cereals
and breads can also be considered. Phytase enzymes are required to degrade phytate to the
recommended low levels. These enzymes may be exogenous phytases (purified from
bacterial, fungi or plants) which are added during the manufacture of foods [85] or native
phytases (intrinsic to the cereal) which are activated during the manufacturing process
[86]. Iron absorption in babies was doubled when fed phytatefree soy formula which had
been manufactured using a phytase from Aspergillus niger [85]. Similarly, using the same
enzyme to manufacture phytate-free complementary foods based on rice, maize, oat or
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wheat increased iron absorption in single meal studies in adults [from .33-1.80% to 2.79-
11.54%] [49]. Low phytate or phytate-free complementary foods can also be manufactured
using traditional food processes such as soaking, germination and fermentation [87-88].
Traditional lactic acid fermentation of cereal flours in India can reduce phytate by up to
80% [89-90], and yeast fermentation during bread manufacture, depending on the
fermentation time, can decrease phytate by up to 50% in whole grain flours and almost
completely in low extraction flours [91]. Iron absorption from a wheat bread roll made
from low extraction flour was twice as high as iron absorption from a chapatti made from
the same flour [92].The bread roll preparation included a yeast fermentation step, while the
chapatti preparation did not. A slightly different approach commonly employed in the
animal feed industry makes use of the addition of active phytases to finished products. In
the type of application, the degradation occurs in the intestinal tract. This approach has
also been demonstrated to increase iron absorption in humans [81].

Manufacturing Issues: The main concern of including a phytate degradation step in the
manufacture of cereal-based complementary foods is that the cereal mixture should be held
for 1-2 hours in an aqueous medium at 55C and with a slightly acid pH so that the added
or native phytase remains active and degrades most or all of the phytate. Complementary
foods manufactured in pilot studies have been dephytinized in an aqueous slurry with an
exogenous enzyme [49] or by activating the native phytases in a small amount of added
whole wheat or whole rye [86]. Dephytinization has been followed by a steam injection
step to precook the cereal and then by roller drying. Such precooked cereals can be fed
mixed with hot water or milk (although milk itself is an inhibitor without the addition of
ascorbic acid). While such dephytinized cereals should benefit the iron status of all
weaning infants, infants in developing countries would be expected to benefit most. A
potential problem in developing countries however is that many low-cost complementary
foods, including most of those provided in food aid programs do not include the aqueous
phase necessary for dephytinization in their manufacturing process. Dry cereal and legume
flours are often mixed with other ingredients and extruded and thus have to be cooked
prior to consumption. Other technical issues, including technologies to prevent the growth
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of undesirable microorganisms during holding of the aqueous slurry at 55C may also need
to be addressed Dephytinization of these low cost extruded cereals would be a challenge.

Practical Applications: No studies have been made to compare the effect of high phytate
complementary foods (phytate to iron molar ratio >2) with phytate free complementary
foods (molar ratio <0.5) (in the absence of ascorbic acid) on iron status of infants during
the weaning period. A recent study by Lind et al [93] however has cast some doubt on the
usefulness of dephytinization of Swedish baby foods. These authors compared a cereal
porridge and cereal milk drink (phytate to iron molar ratios 0.9-2.6 and 1.4 respectively)
with identical products after dephytinization (phytate to iron molar ratios 0.4-0.9 and 0.5
respectively). These products were fed to infants from 6-12 months of age as part of a diet
including either breast milk or iron fortified formula. Dephytinization caused no
improvement in iron status. These results can perhaps be explained by the relatively low
phytate levels together with the relatively high levels of ascorbic acid in the cereal porridge
and cereal milk drink (ascorbic acid:iron molar ratio around 5:1).

High phytate is not such a concern in complementary foods or soy-based infant formulas
sold in industrialized countries as these foods can be fortified with ascorbic acid to
overcome the inhibitory effect of phytate and thus provide an adequate amount of
absorbable iron [85, 94]. In developing countries however, ascorbic acid is often not stable
due to the inferior packaging used for low cost complementary foods and phytate
degradation would be a better option.

Microencapsulated Ferrous Sulfate and Ferrous Fumarate

Microencapsulation is a process whereby the iron compound is encapsulated with a
continuous layer or layers of coating material, which separate the iron compound from the
food matrix. Its main advantage is that it should allow the addition of iron compounds of
high relative bioavailability to difficult food vehicles, such as cereal flours and low-grade
salt, without causing the customary color and flavor changes. There is no evidence that
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microencapsulation will enhance the absorption of fortification iron. Bioavailability
however potentially can be decreased by encapsulates. This should be strictly controlled.

Encapsulated ferrous sulfate and encapsulated ferrous fumarate, now used mainly to fortify
infant formulas and cereals, have potential to be used in wheat and maize flours as well,
provided that manufacturing and cooking practices do not result in unacceptable
organoleptic changes to foods if the capsule material melts. Encapsulated iron compounds
are suitable for most dry products, such as infant foods, dry beverage mixes, and other
minimally processed foods. Other promising vehicles are condiment sachets for noodle
flavorings and sprinkle sachets for mixing with complementary foods.

Choice of Coating Materials: Several different coating materials and processes are used to
manufacture microencapsulated ingredients and variations can occur in the thickness and
tightness of the coating as well as in the amount of compound still exposed on the surface
of agglomerates. Microencapsulated ferrous sulfate and ferrous fumarate are usually
manufactured using fluidized bed or spray chilling technology. Commonly the coatings are
hydrogenated palm oil or soybean oil, although maltodextrin and celluloses have also been
used. The hydrogenated oils protect against moisture but melt during heat treatments above
52-70C, whereas maltodextrin and celluloses are usually water-soluble and do not provide
adequate protection against iron oxidation in moist environments. When the ratio of
coating material to iron compound is close to 1:1, there is no change in the bioavailability
of ferrous sulfate in rat assays [95] and the efficacy of the encapsulated ferrous sulfate to
improve iron status in school children is high [26]. Greater amounts of coating material or
the inclusion of other compounds, such as waxes, into the coating however may decrease
bioavailability.

Organoleptic Issues: Ferrous sulfate encapsulated with hydrogenated soybean oil
prevented fat oxidation in stored infant cereals [95]. When, however, the dried cereals were
reconstituted with hot water or hot milk, unacceptable colors developed. Similarly a series
of different encapsulated ferrous sulfate and ferrous fumarate compounds failed to prevent
color changes and iodine losses in moist, low grade salt during storage in Morocco or the
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Ivory Coast [96]. Presumably sufficient iron was still on the surface of the capsule or, due
to the moist conditions, leaked from within the capsule and reacted with impurities in the
salt. Thus, although salt is a good potential vehicle for encapsulated iron, sensory issues
still need to be resolved, particularly for low-grade salt. Further sensory testing of flours
with encapsulated iron is also needed.

Future Potential of Microencapsulation: The potential of microencapsulation technology
to allow use of iron compounds of high bioavailability without problematic sensory
changes has not been fully evaluated. Current commercial compounds are used in infant
foods and would be expected to prevent fat oxidation in stored cereal flours, although this
and efficacy questions remain to be investigated. Ferrous sulfate and ferrous fumarate
encapsulated with hydrogenated oils were recently recommended by PAHO [97] as useful
compounds for the fortification of wheat and maize flours. Further improvements in
encapsulation technology are necessary to produce microencapsulated iron compounds for
the addition to low-grade salt, or alternatively the quality of the salt needs improvement.
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CONSENSUS STATEMENT FROM SUSTAIN TASK FORCE

This consensus statement on appropriate uses of iron enhancing technologies was reached
after expert review of an extensive body of information. Presentations by science and
industry as well as background review papers were rigorously discussed at a SUSTAIN
Workshop in Washington, DC (March 9-12, 2003), resulting in a draft consensus
statement. Subsequently, nutrition, science, medical and industry experts collaborated to
evaluate relevant literature and industry experience to address information gaps and areas
needing further clarification. The implications of processing, storage and (where
applicable) cooking were evaluated for the enhancers in various food vehicles with a focus
on the end product consumed rather than on intermediate products (e.g., flours) alone. In
some cases regulatory issues were also addressed.

Ascorbic Acid

1. Ascorbic acid enhances the absorption of both intrinsic food iron and major iron
fortificants in a dose dependant fashion
1
. The enhancement is attributed to its reducing
and chelating properties.

2. Numerous scientific studies report 2 to 3 fold increases in iron absorption associated
with ascorbic acid use.

3. The addition of ascorbic acid to improve iron absorption is recommended for iron-
fortified dry food preparations, such as pre-cooked complementary infant foods (e.g.
cereal and legume-based blends), powdered milk and other dry beverage products
made for reconstitution.

4. A 2:1 molar ratio is recommended for powdered milk and low phytate products; the
ratio should be 4:1 for high phytate.

1
Combinations of certain enhancers are not additive. For example ascorbic acid is not an effective enhancer
of iron absorption from NaFeEDTA.
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5. The use of ascorbic acid as an enhancing agent is limited by its instability in aqueous
solutions (due to exposure to oxygen) and during prolonged heat processing methods.
Proper packaging to exclude oxygen can be used to mitigate oxidation, but this
approach will increase cost. Nearly all ascorbic acid is destroyed during prolonged
cooking and high heat.

6. Ascorbic acid is not recommended for liquid foods, unless stability can be maximized
by adequate packaging, or for foods that require baking and prolonged cooking (e.g.
breads and gruels).

Other Organic Acids

1. Organic acids, such as citric, lactic, malic and tartaric acid, are commonly used as food
additives and preservatives. There is limited evidence indicating that they have an
enhancing effect on iron absorption.

2. Available data suggests that organic acids may only be effective at high molar ratios (in
excess of 100:1, organic acid:iron).

3. The necessary quantities will cause unacceptable flavor changes in most food vehicles,
although applications in fruit drinks merit further consideration.

Chelates

Iron EDTA Chelates

1. NaFeEDTAs promoting effect on iron absorption from inhibitory meals has been
shown in a number of radioisotopic studies and has been confirmed in five efficacy
trials, using condiments as the vehicle. The iron in NaFeEDTA is 2-3 times better
absorbed than is the iron in ferrous sulfate when present in high phytate meals. The
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absorption of the native food iron is also enhanced to a similar extent by the EDTA.
Iron absorption from NaFeEDTA and ferrous sulfate is similar in low-phytate meals.

2. NaFeEDTA is recommended for use in soy and fish sauces, and potentially with high
phytate flours and other condiments. Fish sauce should be packaged in amber bottles to
prevent UV degradation of EDTA. Research is needed on its sensory effects on flour-
based food staples.

3. NaFeEDTA is not recommended for complementary foods consumed by children
under the age of three years because the amounts required to supply sufficient iron for
effective fortification would approach the acceptable daily intake for EDTA (2.5 mg/kg
body weight/day).

4. NaFeEDTA does not adversely affect the metabolism of nutritionally important metals
such as zinc, copper and calcium.

5. The available data indicates that EDTA does not increase the absorption of lead or
cadmium in human beings or experimental animal models and may even reduce
retention. In this context, the intravenous injection of EDTA has been a therapy for
lead poisoning for many years. Current evidence is, however, limited and further
research is desirable.

6. NaFeEDTAs widespread introduction as an iron enhancer is currently hampered by its
ambiguous regulatory status.

7. There is little published evidence on the stability and organoleptic effects of
NaFeEDTA during processing, storage, and cooking. Although it has been
successfully used in several extended fortification trials, and maize and soy sauce have
been commercially fortified, additional research, using a wider range of vehicles,
including flour-based food staples, is recommended.

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Amino Acid Chelates

1. In most studies iron absorption from ferrous bisglycinate has been 2 to 3 times higher
than from ferrous sulfate when added to bread rolls and milk products containing
absorption inhibitors such as phytate or calcium. Ferrous bisglycinate is more
bioavailable than ferric trisglycinate. Ferrous bisglycinate HCL is another amino acid
chelate that appears to merit further consideration and may offer favourable cost
attributes. However its bioavailability needs to be established in human studies.

2. Amino acid chelates are recommended for milk and beverage products. The iron in
ferrous bisglycinate, a patented product, appears to be well absorbed from milk, milk
products, beverages and high-phytate cereal products.

3. There is very little published evidence on stability and organoleptic effects of amino
acid chelates during processing, storage and cooking. The data available indicates that
they may promote sensory changes in some food vehicles and may promote fat
oxidation in cereals in the absence of an antioxidant. Additional research is needed.

4. Further research is needed for amino acid chelates in vehicles other than milk and
beverage products.

Phytate Degradation

1. Phytate is a potent inhibitor of absorption for native and fortification iron in cereals and
legume-based foods. Effective enhancement of iron absorption requires near-complete
degradation or removal of phytate. Under controlled experimental conditions, native
and exogenous phytases effectively degrade phytate. This requires prolonged wet
processing, within a narrow pH range at controlled temperatures. A phytate:iron
molar ratio of <1:1 is recommended for effective enhancement of iron absorption, with
<0.4:1 being optimal.

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2. Complete dephytinization has been reported to increase percentage iron absorption
between 2 and 12 fold in single-meal studies. However, if dephytinization is not
complete (or not at least achieving a phytate:iron molar ratio of <1:1), then the
increases in iron absorption are substantially lower or non-existent.

3. Low cost cereal and legume-based complementary foods reconstituted with potable
water may be the most appropriate vehicles for dephytinization in the developing
world. Milk, however, without the addition of ascorbic acid, is an inhibitor of iron
absorption.

4. While commercial phytase products are commonly used in feed for monogastric
animals to free phosphates, and to increase mineral availability and protein conversion,
their use in food products for humans has been limited.

5. Questions about technical feasibility and cost need to be resolved for food uses.

Encapsulation

1. Encapsulation has been shown to effectively overcome many of the limiting sensory
and stability problems associated with adding soluble iron forms to finished food
products. It may improve the potential shelf life of fortified products by preventing iron
mediated fat oxidation. It also appears to provide protection from oxidation of the
soluble ferrous to the less soluble ferric form.

2. The main advantage of microencapsulation is that it should allow the addition of iron
compounds of high relative bioavailability into difficult food vehicles. There is no
evidence that microencapsulation will enhance the absorption of fortification iron. The
effect of encapsulation on bioavailability depends on the capsule material and the
capsule to substrate ratio. Research indicates that encapsulation of ferrous sulfate and
ferrous fumarate with coatings composed of hydrogenated palm and soy oils, mono-
and diglycerides, and maltodextrin does not compromise bioavailability, provided that
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the capsule to iron compound ratio does not exceed 1:1 and provided that the coating
does not contain other additives.

3. Industry produces a large variety of encapsulated compounds. The technical properties
of the capsules vary considerably. The bioavailability of encapsulated iron compounds
needs to be demonstrated in animal or human studies before they are used for large-
scale fortification. Standards for appropriate encapsulation of iron compounds to
ensure optimal bioavailability are needed.

4. Preferred systems for including encapsulated iron are those that are low in moisture
and stored at low temperatures. Encapsulated iron compounds are suitable for most dry
products, such as infant foods, dry beverage mixes, and other minimally processed
foods. Other promising vehicles are condiment sachets for noodle flavorings and
sprinkle sachets for mixing with complementary foods.

5. However, food preparation that involves heat may cause melting of the capsule, which
in turn, may lead to undesirable organoleptic changes. Encapsulation may be a useful
strategy for preventing iron-catalyzed sensory changes in cereal based staples, provided
that manufacturing and cooking practices do not result in unacceptable organoleptic
changes if the capsule material melts. Encapsulation is not recommended for stored
liquids because elevated moisture leads to leaching of the iron fortificant from the
capsule, with accompanying sensory problems.

Other Strategies

Vitamin A has not been consistently demonstrated to improve the absorption of
fortification iron. It is, however, necessary for normal iron metabolism in the body. Since
vitamin A and iron deficiency are commonly found together, dual fortification with iron
and vitamin A is frequently appropriate.
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CONCLUSION

The success of iron fortification as a strategy for alleviating iron deficiency can potentially
be improved by ingredients/technologies that enhance iron absorption and/or mitigate
undesirable interactions between fortificant iron and food vehicles. Less soluble forms of
iron are commonly used in food fortification because of shelf life and sensory concerns
associated with more soluble iron salts such as ferrous sulfate in many food vehicles.
Enhancing the bioavailability of widely used iron fortificants and/or preventing
undesirable interactions between more soluble iron fortificants and food vehicles could
benefit iron deficient populations.

Different ingredients/technologies will be more (or less) appropriate for different classes of
staple foods and widely consumed condiments. The practical applications of individual
ingredient technologies are limited with respect to some food vehicles by issues of
ingredient stability, cost and consumer acceptance. A SUSTAIN Task Force has evaluated
the limitations of each technology and recommended appropriate applications of the
technologies, based on reviews of the scientific literature, as well as extensive input from
and dialogue among industrial, nutrition, medical and government experts.

Effective fortification depends primarily on the selection of technically feasible and
biologically efficacious strategies. However, once suitable strategies have been identified
cost becomes very important in selecting the best approach to implement. Manufacturers
catering to the target population in developing countries can absorb only minimal increases
in production costs of fortified products and governmental subsidies are usually not
sustainable. It is essential to calculate cost with reference to the delivery of bioavailable
iron. Smaller quantities of highly bioavailable iron are equivalent to larger amount of a less
bioavailable product. Price per unit cost alone may therefore be misleading. Section
provides an illustration of the appropriate approach to cost analysis using conservative
estimates of the potential enhancing effects of the innovative strategies described in the
other sections.
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