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1
*
Centro de Medicina Experimental, Laboratorio de Fisiopatología, Instituto Venezolano de Investigaciones Científicas (IVIC);
Universidad Central de Venezuela; and
**
Unidad de Investigaciones en Nutrición Eleazar Lara Pantin, Universidad de Carabobo, Caracas, Venezuela
1To whom correspondence should be addressed.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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KEY WORDS: • iron fortification • polyphenol • phytates • humans • and iron bis-glycine chelate.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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, Hurrell 1997
, International Nutritional Anemia Consultive Group 1977).
The majority of the iron compounds selected for fortification
have a low availability as a result of phytates present in the food
vehicle (most of the time a cereal), which reduce iron absorption. The
iron compound that is affected only slightly by the inhibitory effect
of phytate on iron absorption is iron-EDTA (Layrisse et al.1977
, Martínez-Torres et al. 1979
)
A new iron compound, iron bis-glycine chelate (Ferrochel,
Albion Laboratories, Salt Lake City, Utah) has been used recently as a
therapeutic agent to treat iron deficiency anemia (Coplin et al. 1991
, Pineda et al. 1994
) and to fortify food
vehicles (Allen 1998, Lost et al. 1998
,
Souza-Queiroz and Almeida-Torres 1995
). The
objective of this study was determine the bioavailability of this
compound as a fortificant compared with those of ferrous sulfate and
iron-EDTA and to examine whether there is an inhibitory effect of
phytate and polyphenols on iron absorption when this compound is used.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Iron absorption studies
Five absorption studies were performed and two basal breakfasts were prepared. The first breakfast contained 100 g of precooked corn flour + 50 g cheese + 10 g margarine. The iron content of the basal breakfast was 1.5 mg. The second breakfast contained 100 g white wheat flour, 50 g cheese and 10 g of margarine. The iron content of this basal breakfast was 1.6 mg.
Studies 1 and 2. Iron absorption from ferrous sulfate, ferrochel
and Fe-EDTA.
In study 1, breakfast was prepared from precooked corn flour and
in study 2 from white wheat flour. Four meals were administered to the
same subjects on four different occasions. Meal A was given alone (no
extrinsic iron addition, except for 26 kBq 59Fe) and was
administered in the morning after an overnight fast. Meal B, enriched
with 3 mg Fe as ferrous sulfate (labeled with 37 kBq 55Fe)
was given in the afternoon of the same day. Blood was drawn 15 d
later to determine the hematologic profile (Crosby et al. 1954
, Flowers et al. 1986
, International Committee for Standardization in Hematology 1978a
and 1978b
) of
each subject and to measure radioactivity of blood samples. The
subjects were fed again in the morning and afternoon of d 15 with meals
C and D enriched with 3 mg Fe as ferrochel + 59Fe and 3 mg
Fe as Fe-EDTA (Sigma Chemical, St. Louis MO) + 55Fe,
respectively. Blood was drawn once more on d 30 to measure
radioactivity and ferritin concentration. Each subject was allowed to
participate in only one study (3 or 4 meals). Subjects for each study
were selected randomly.
The protocol for the administration of radioactive food in the morning
and in the afternoon of the same day was based on experiments published
previously (Taylor et al. 1995
). Intervals of 4 h
between meals are sufficient for iron absorption studies.
Duplicate 10-mL blood samples together with triplicate samples of
radioactive food were prepared for scintillation counting using the
technique of Dern and Hart 1961a
and 1961b
). Iron
absorption from food was calculated from the radioactivity in the
subject’s blood using estimated blood volume based on sex, weight and
height (Nadler et al.1962
).
Study 3. Iron absorption from ferrous sulfate and ferrochel given in the same meal and in different meals. The basal breakfast prepared from wheat flour was administered in three different meals. Meal A was enriched with 3 mg Fe as ferrous sulfate labeled with 26 kBq 59Fe as ferric chloride + 3 mg ferrochel labeled with 37 kBq 55Fe as intrinsically labeled ferrochel (prepared following guidelines from Albion Laboratories). Blood was drawn on d 15 to measure radioactivity and hematologic profile. Meal B was enriched with ferrous sulfate labeled with 26 kBq 59Fe as ferric chloride, and Meal C contained 3 mg Fe ferrochel 37 kBq 55Fe as intrinsically labeled ferrochel. On d 30, blood was drawn again to measure absorption and to compare the effects of both iron compounds administered in the same meal and in different meals.
Study 4. Effect of polyphenols on iron absorption from ferrochel. In this study, four meals were administered containing corn bread enriched with 3 mg Fe as ferrochel. In meal A, breakfast was given alone. Meals B and C contained 2 and 4 g coffee, respectively, as a beverage, and meal D was served with a tea infusion containing 1.6 g of tea leaves. Meals were labeled as indicated in studies 1 and 2.
Study 5. Effect of phytates on iron absorption. This study was designed to determine whether iron absorption from Ferrochel is affected by the phytate content of corn flour as occurs with absorption from ferrous sulfate. In meals A and C, bread was enriched with 3 mg Fe as ferrous sulfate (labeled with 59Fe and 55Fe, respectively). Meal C additionally contained 304 U phytase (Sigma Chemical). Meals B and D were enriched with 3 mg Fe as ferrochel, and in meal D, 304 U phytase was added.
Chemical analysis
The total iron concentration in foods was determined by the
digestion method (Bothwell et al. 1979
). The mean
phytate concentration was 168 and 257 mg/100 g in precooked corn flours
and white wheat flour, respectively, according to the method of
Haug and Lantzsch 1983
. The tannin concentration
determined by the method of Price and Butler 1977
in
coffee powder and in tea was 2500 and 14,736 mg/100 g, respectively.
Because hard water is used in several regions to prepare corn and wheat bread, this water was analyzed for its mineral content by atomic emission spectrometry (ICP) and used in the laboratory to evaluate the organoleptic changes when bread was prepared with this hard water.
Statistical analysis
ANOVA with Bonferroni as a post-test was used to compare absorption data. Geometric values and standard errors were calculated for all absorption data and serum ferritin concentrations. Differences were considered significant when P < 0.05.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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. Iron absorption was significantly higher (P < 0.05)
when ferrochel or Fe-EDTA was added, compared with the breakfast
given alone or with ferrous sulfate. Of the 13 subjects tested in this
experiment (study 1), only four subjects were iron deficient; the mean
iron absorption of these subjects was 6% in the test with ferrous
sulfate,13% in the test with ferrochel and 14.4% in the test with
iron-EDTA. Differences were significant between ferrous sulfate and
ferrochel or Fe-EDTA (P < 0.05).
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. Ferrochel and Fe-EDTA produced significantly higher absorption
than ferrous sulfate or the breakfast alone. Only four subjects were
iron deficient, and their mean iron absorption increased significantly
to 7% with ferrous sulfate, to 12% with ferrochel and to 15% with
iron-EDTA.
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).
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). The same breakfast administered with espresso coffee, which contains
twice the coffee concentration of American coffee, resulted in a
significant 50% reduction in iron absorption compared with the
breakfast alone. The same finding was observed when breakfast was
administered with a tea infusion containing 1.6 g tea leaves.
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).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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, Foke et al. 1998
,
García-Casal et al. 1998
, Jeppsen and Borzellca 1999
, Pineda 1998
,
Souza-Queiroz and Almeida-Torres 1995
). As stated earlier, in a program of iron fortification of a food vehicle, it is essential that the iron compound not change the organoleptic properties of food and that it have a high bioavailability. In experiments performed using corn flour enriched with ferrochel and hard water obtained from certain regions of Venezuela, we found no changes in organoleptic properties.
Iron absorption from basal breakfasts, containing either corn or wheat flours enriched with ferrochel, showed that its bioavailability was twice that of ferrous sulfate in both food vehicles, and close to that of NaFe- EDTA.
The use of ferrochel and ferrous sulfate given in the same meal or
separately showed that iron absorption from ferrochel was significantly
higher than that from ferrous sulfate, administered together or
separately in the same subjects. These results are not in agreement
with previous results in which iron absorption from these compounds was
not significantly different (De Oliveira et al. 1996
).
The concentration of polyphenols in the infusion of American-type
coffee as a possible inhibitory effect was not sufficient to modify
iron absorption significantly, but espresso coffee and tea reduced iron
absorption by 50%. When phytase was added to the basal breakfast
prepared from corn, the increase in iron absorption was proportionally
the same with ferrous sulfate or ferrochel, compared with the basal
breakfast without phytase. Iron absorption from ferrochel was higher
than that from ferrous sulfate, but phytase addition resulted in a
doubling of absorption for both compounds. These results show also that
ferrochel partially prevents the inhibitory effect of phytates. It
appears that the increase in absorption from ferrochel was due to the
chemical structure of this compound, which partially prevents
iron-phytate interactions. Similar findings were reported when
vitamin A or ß-carotene was incorporated into the same basal
breakfast (García-Casal et al. 1998
,
Layrisse et al. 1997
).
Ferrochel was used in the treatment of iron deficiency anemia in
infants, preschool children and adolescents over a 4-wk period for the
correction of anemia and supplementation of iron stores (Foke et al. 1998
, Pineda et al. 1994
, Pineda 1998
). This iron compound has also been used to fortify milk at
a level of 3 mg/L in infants 12–23 mo of age. Results showed that 67%
of the infants recovered from anemia during this period (Souza-Queiroz and Almeida-Torres 1995
, Torres et al. 1996). Lost et al. (1998)
found similar results from milk fortified with
ferrochel. On the other hand, (Olivares et al. 1997
)
demonstrated that milk inhibits and ascorbic acid enhances iron
absorption from ferrochel. They found that bioavailability from
ferrochel in water is high, and recommended that the compound be used
to fortify drinking water (De Oliveira et al. 1996
).
In a recent study, whole corn was fortified with ferrous sulfate in one test and with ferrochel in the other test. Iron absorption in the test with ferrous sulfate was only 1.5%, whereas it increased to 6.9% with ferrochel, indicating a high phytate content (Allen 1998, Bovell-Benjamin et al. 1999).
The properties of ferrochel, including its promotion of iron absorption, its solubility in aqueous solutions even at pH 6, its low toxicity, its lack of effect on the organoleptic properties of the food vehicle and its low cost relative to Fe-EDTA, support its role in the treatment of iron deficiency anemia and as a fortificant of food vehicles.
Manuscript received November 2, 1999. Initial review completed January 25, 2000. Revision accepted April 11, 2000.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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