Dietary Factors Influencing Trace Element Homeostasis

Approaches to Improve Iron Bioavailability from Complementary Foods1

Lena Davidsson2
Laboratory for Human Nutrition, Institute of Food Science and Nutrition,
Swiss Federal Institute of Technology, CH-8803 Ruschlikon, Switzerland

ABSTRACT The importance of trace element bioavailability in the etiology of nutritional deficiencies, for example in
the etiology of iron deficiency and iron deficiency anemia, can be expected to be most pronounced in individuals with
high requirements. Of special concern is the situation in poor communities where infants and young children are
consuming monotonous, cereal-based diets. Traditionally, cereal-based gruels are often one of the first semisolid
foods to be introduced into the infant’s diet. These foods can be expected to have low energy and nutrient density as
well as low bioavailability of iron due to the presence of phytic acid. Ascorbic acid is a potent enhancer of non-heme
iron absorption that can overcome the inhibiting effect of phytic acid when present in high enough quantities.
However, home prepared complementary foods based on cereals and legumes contain negligible amounts of
ascorbic acid unless ascorbic acid-rich foods are mixed with the cereal or consumed at the same time. Different
approaches to improve iron bioavailability from plant-based complementary foods, e.g., by enzymatic degradation of
phytic acid and/or by increased consumption of ascorbic acid-rich foods, should be explored and adapted to local
conditions. In addition, there is a need to evaluate efficacy and effectiveness of strategies to increase the dietary
intake of bioavailable iron by dietary diversification and food fortification under realistic conditions. J. Nutr. 133:
1560S–1562S, 2003.

KEY WORDS:  bioavailability  iron  infants

The transition from exclusive breastfeeding to family foods
represents a phase in life when infants are very vulnerable nutri-
tionally. The gradual change to energy and nutrients provided
by semisolid foods, at the expense of human milk, requires
access to appropriate complementary foods with high energy
and nutrient density as well as high nutrient bioavailability.
This review is focused on the importance of adequate iron
bioavailability from the diet during early life and includes a dis-
cussion about different food-based approaches to improve iron
nutrition in infants and young children.
The iron content of human milk is very low and iron
bioavailability (measured as erythrocyte incorporation of iron
1
Published in a supplement to The Journal of Nutrition. Presented as part of the
11th meeting of the international organization, ‘‘Trace Elements in Man and Animals
(TEMA)’’ in Berkeley, California, June 2–6, 2002. This meeting was supported by
grants from the National Institutes of Health and the U.S. Department of Agriculture,
and by donations from Akzo Nobel Chemicals, Singapore; California Dried Plum
Board, California; Cattlemen’s Beef Board and National Cattlemen’s Beef
Association, Colorado; Clinical Nutrition Research Unit, University of California,
Davis; Dairy Council of California, California; GlaxoSmithKline, New Jersey;
International Atomic Energy Agency, Austria; International Copper Association,
New York; International Life Sciences Institute Research Foundation, Washington,
D.C.; International Zinc Association, Belgium; Mead Johnson Nutritionals, Indiana;
Minute Maid Company, Texas; Perrier Vittel Water Institute, France; U.S. Borax Inc.,
California; USDA/ARS Western Human Nutrition Research Center, California;
Wyeth-Ayerst Global Pharmaceuticals, Pennsylvania. Guest editors for the supple-
ment publication were Janet C. King, USDA/ARS WHNRC and the University of
California at Davis; Lindsay H. Allen, University of California at Davis; James R.
Coughlin, Coughlin & Associates, Newport Coast, California; K. Michael Hambidge,
University of Colorado, Denver; Carl L. Keen, University of California at Davis; Bo L.
Lönnerdal, University of California at Davis and Robert B. Rucker, University of
California at Davis.
2
To whom correspondence should be addressed. E-mail: lena.davidsson@
ilw.agrl.ethz.ch.
stable isotopes) has also been demonstrated to be low, with
a geometric mean of 11.8%, and similar to that of low-iron
infant formula (1,2). However, full-term breast-fed infants
generally have adequate iron status during the first 4–6 mo of
life, but after this time, when iron stores have been depleted,
additional dietary iron needs to be supplied for the rapidly
expanding blood volume and replacement of iron losses (3).
The World Health Organization (WHO) recommends intro-
duction of complementary foods, in addition to human milk, at
6 mo of age (4). The recent review ‘‘The optimal duration
of exclusive breast-feeding’’ (5) concludes that, although data
are scarce, exclusive breastfeeding for 6 mo without iron
supplementation may compromise the hematological status of
infants in developing countries. Of special concern is the
situation in low-birth-weight (,2500 g) infants who are born
with very limited storage iron, and double their birth weight
in a shorter time than term infants, and are therefore at higher
risk for development of iron deficiency (3). It is important to
note that the prevalence of low-birth-weight infants is high in
many developing countries (6). The impact of birth weight on
estimated requirements of absorbed iron during the first year of
life is illustrated by Fomon (7): 0.55 mg absorbed iron/d for
infants with a birth weight of 3.5 kg (and an estimated body
weight of 10.5 kg at 1 y) and 0.75 mg absorbed iron/d for infants
with a birth weight of 2.5 kg (estimated body weight 10 kg at
1 y). These values correspond to daily dietary intakes of iron in
the range 5.5–11 mg (for infants with a birth weight of 3.5 kg)
and 7.7–15 mg (for infants with a birth weight of 2.5 kg),
assuming 10% and 5% iron bioavailability, respectively. These
estimates highlight the importance of access to appropriate

0022-3166/03 $3.00 Ó 2003 American Society for Nutritional Sciences.

1560S
 BIOAVAILABILITY OF TRACE ELEMENTS
complementary foods with adequate iron content and of
optimizing iron bioavailability during early life to prevent the
development of iron deficiency and iron deficiency anemia
(IDA). The adverse effects of IDA during infancy on child
development were recently reviewed (8) and will not be
discussed in this paper.
Iron bioavailability: the effect of phytic acid
Traditionally, cereal-based gruels are often one of the first
semisolid foods to be introduced into the infant’s diet. In
resource-poor areas where high extraction-cereal flours are
more readily available, and affordable, than refined cereal flours
and vegetable proteins are added instead of cow milk to im-
prove protein quality, the cereal mixtures often contain rela-
tively high amounts of the strong metal chelator phytic acid
(myo-inositol-hexa-phosphate). Iron bioavailability from cereal
products is typically low due to the presence of phytic acid (9),
however, phytic acid can be degraded by activating native
phytase or by the addition of exogenous phytase. The indus-
trially produced dephytinized infant foods discussed in this re-
view were prepared by the addition of exogenous phytase. In
addition, we have recently demonstrated the usefulness of
whole grain cereals as sources of phytase for production of
complementary foods based on cereals and legumes (10,11).
The strong inhibitory effect of phytic acid on iron bio-
availability in infants was first demonstrated in a study where
soy formulas were evaluated before and after dephytinization.
The geometric mean bioavailability of iron increased from 5.5%
to 6.8% (p , 0.05) after degradation of 83% phytic acid,
whereas a more pronounced effect was shown after 100%
dephytinization; the geometric mean increased from 3.9% to
8.7% (p , 0.001) (12). However, dephytinization of a soy
isolate with relatively low native phytic acid content did not
increase iron bioavailability from infant formula significantly
(13), and no difference in iron bioavailability was observed
between two cereal products based on low extraction-wheat
flour and cow milk before (0.08% phytic acid) and after
dephytinization (0.01% phytic acid) (14). The lack of effect
of dephytinization of infant foods with relatively low native
phytic acid content on iron bioavailability (13,14) can probably
be attributed to the relatively high content of ascorbic acid
in the test meals that counteracted the inhibitory effect of
phytic acid.
Iron bioavailability: the effect of ascorbic acid
Ascorbic acid is a potent enhancer of iron absorption that
can overcome the inhibiting effect of phytic acid when present
in high enough quantities. For example, iron bioavailability
from soy infant formula was enhanced to the same extent by
dephytinization or by increasing the molar ratio of ascorbic acid
(176 g/mol) from 2.1 to 4.2 [relative to iron (56 g/mol)] in the
formula containing native phytic acid (12). Ascorbic acid added
to the wheat- and cow milk-based infant cereal mentioned
earlier (14) at a molar ratio of 2:1 (ascorbic acid:iron) resulted
in relatively high iron bioavailability from both the phytic acid-
containing infant cereal and the dephytinized product. In our
earlier study with infant cereals based on high extraction wheat
flour and soy flour (15), the level of phytic acid was much
higher (0.77% and 0.30%, respectively) and bioavailability of
iron was low even though approximately the same amount of
ascorbic acid was added as in the later study. Thus, the ability of
ascorbic acid to overcome the inhibitory effect of phytic acid
depends both on the level of phytic acid in the food and on the
amount of ascorbic acid present.
1561S
Home prepared complementary foods based on cereals and
legumes consumed by infants in developing countries can be
assumed to contain relatively high amounts of phytic acid and
negligible amounts of ascorbic acid unless ascorbic acid-rich
foods such as fruit, fruit juice or vegetables are mixed with the
cereal or consumed at the same time. The inclusion of ascorbic
acid-rich fruits or vegetables into the diets of infants and young
children depends on availability, affordability, tradition and
other factors. For example, our recent data from Côte d’Ivoire
clearly demonstrated that fruit and fruit juice were rarely
included in the diet of children 6–18 mo old in Abidjan (16).
Strategies to improve iron nutrition
Different approaches to improve iron bioavailability from
plant-based complementary foods, e.g., by enzymatic degrada-
tion of phytic acid and by increased consumption of ascorbic
acid-rich fruits and vegetables, should be explored and adapted
to local conditions. In addition, the possibility of introducing
foods with high iron content/high bioavailability into the diet
should be evaluated. For example, meat, in particular red meat,
is an excellent source of highly bioavailable heme iron. In
addition, the inclusion of beef significantly increased non-heme
iron bioavailability from a vegetable-based meal in infants (17).
Furthermore, novel strategies to increase the dietary intake of
bioavailable iron by food fortification need to be developed. To
establish a food fortification program, several important factors
need to be considered; the choice of the food vehicle and iron
compound, the fortification level and ways to enhance iron
bioavailability from the fortified food. For example, industrially
produced infant formulas are usually fortified with highly bio-
available water-soluble iron compounds, such as ferrous sulfate,
and contain added ascorbic acid. However, cereal products
are difficult to fortify with water-soluble iron compounds due
to unacceptable organoleptic changes (rancidity, flavor/color
changes) during storage and/or during food preparation. Con-
sequently, less soluble, and therefore less bioavailable, iron
compounds such as elemental iron powders and ferric pyro-
phosphate are commonly used to fortify cereal products. Alter-
native compounds, for example ferrous fumarate, which are
poorly soluble in water but soluble in dilute acid such as the
gastric juice, have been shown to cause less unacceptable organo-
leptic changes in the fortified food during storage and have
similar bioavailability as ferrous sulfate in healthy adults (for
a review, please see reference 18). Very limited information is
available on iron bioavailability from compounds that dissolve
slowly or incompletely in the gastric juice, as these compounds
must be intrinsically labeled with stable isotopes of iron before
testing in infants and children. For example, a study in European
infants demonstrated that ferrous fumarate was significantly
more bioavailable than ferric pyrophosphate when added to an
infant cereal (molar ratio of 3:1, ascorbic acid relative to iron);
geometric mean iron bioavailability was 4.1% versus 1.3% (19).
Iron bioavailability from ferrous fumarate has not been compared
directly to ferrous sulfate in Western infants or young children.
However, a recent study reported relative bioavailability of fer-
rous fumarate to be about 30% in 2- to 5-y-old Bangladeshi
children from an infant cereal (molar ratio of 3:1, ascorbic acid
relative to iron) (20). These results indicate that the impact of
iron fortification programs using nonwater soluble iron com-
pounds such as ferrous fumarate should be carefully evaluated in
young children.
CONCLUSION
Effective strategies to combat the most prevalent micro-
nutrient deficiency in the world, iron deficiency, are urgently
1562S SUPPLEMENT
needed, in particular for infants and young children in
developing countries. Efficacy and effectiveness of different
approaches to improve iron content and iron bioavailability
from complementary foods, by food fortification and dietary
diversification, need to be evaluated under realistic conditions.
A large proportion of infants and young children in many
settings do not have access to industrially produced foods, and
traditional food fortification programs are therefore not an
option. Novel approaches need to be explored, for example the
possibility of fortifying complementary foods at the household
level. In addition, the possibilities of degrading phytic acid in
cereal-based complementary foods and increasing consumption
of foods rich in ascorbic acid to counteract the inhibitory effect
of phytic acid should be explored and adapted to local
conditions. The importance of animal products in the diet, in
particular the inclusion of small, realistic amounts of meat into
plant-based diets to improve iron status in infants and children,
needs to be evaluated.
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