Iron Absorption from the Whole Diet:
Comparison of the Effect of Two Different Distributions of Daily Calcium Intake
Hypothesis - If a woman distributes her daily intake of calcium by having less of it in
her lunch and dinner meals and more in her breakfast and evening meals, then this would
reduce the inhibitory effects calcium has on heme iron and nonheme iron absorption.
Background Information - This experiment is one of many that addresses calcium's
inhibitory affects on iron absorption. In 1994, the Consensus Development Panel in
Optimal Calcium Intake suggested an increase of the current Recommended Dietary
Allowances of calcium(Whiting, p.77). This goal of this increase was to aid in the
prevention of osteoporosis and other bone diseases. Unfortunately, this attempt at
prevention could have an adverse affect on the human body's ability to absorb iron.
Recent studies have shown that eating a normal daily allowance of calcium cuts iron
absorption by as much as 50-60%(Hallberg et al. p.118). Other studies examine the affect
of iron bioavailability on menstruating, pre-menopausal, and post-menopausal
women(Rossander-Hulten et al and Gleerup et al). One of the fears of an increased amount
of calcium intake is the increased possibility of anemia in women who are already
susceptible to this condition. The iron inhibition by calcium is a classical example of
how the correction of one nutritional problem can be the cause of another.
The physiological mechanism of this calcium-iron relationship remains a mystery, however
there are two feasible theories. One states that calcium competes for an iron binding
site on intestinal epithelial cells. It is believed calcium binds to the protein
mobilferrin on the epithelial cells, which is the iron transport protein(Whiting, p.78).
Another group of scientists theorizes that iron is able to be transported into the
epithelial cells without problem, however the iron then has trouble getting into the
blood stream. The presence of calcium inhibits iron's ability to leave the epithelial
layer.
Another very interesting theory is not on the microscopic level but in the evolutionary
plane. Eaton et al. state that one possibility for this phenomenon could lie in the Homo
sapiens genetic ancestry. As little as 200 years ago humans had almost double the amount
of calcium intake as they do in the present, because humans evolved in a high-calcium
nutritional environment. With the decrease in calcium, there has also been a large
decrease in physical activity(Eaton et al.). The inhibitory effect of calcium on iron
absorption could be related to the low intakes of iron and calcium in conjunction with
the present low-energy lifestyle(Glerrup et al. p. 103).
Terms -
Extrinsic radioisotopic iron tracer - Radioisotopes of iron (59Fe and 55Fe) which can be
traced from outside the body.
Heme - The heme molecule is a heterocyclic ring system of porphyrin derivation which has
a molecule of iron in the center of the ring structure. Myoglobin and each of the four
subunits of hemoglobin noncovalently bind to a single heme group. Heme is also the site
at which each globin monomer binds one molecule of O2 (Voet et al, p. 216).
Heme iron - Iron which is located in the heme molecule.
Nonheme iron - Iron found in human tissue that is not a part of the heme molecule.
Oral reference dose - An oral dose of radio-labeled iron given to the subjects in order
to examine their uninhibited iron absorption. This process was used as a control rate
for each subject.
Experiment - The absorption of nonheme was measured from all meals during four 5-d
periods (A1, A2, B1, and B2). Each day four meals were served to the subjects:
breakfast, lunch, dinner, and an evening meal. The menu of the two B weeks were
identical to the two A weeks, except for the distribution of dairy products. All meals,
except for the evening meal, were served under supervision in the lab. A precise measyre
of the iron content of each meal was required to enable the homogeneous labeling of the
nonheme iron with radioisotopic iron. One wheat-rye roll served as the carrier of the
radioisotope, and this was eaten throughout the course of the meal.
Before starting the 4-wk absorption study, a blood sample was drawn to determine
hemoglobin and serum ferritin concentrations. Three weeks after the last serving, the
total retention of 59Fe and 55Fe was measured by a whole-body counter to determine their
ratio. An oral reference dose of 59Fe was also given to the subjects to determine the
retention of absorbed iron. During the study, measurements were made of the blood
menstrual losses in 19 of the subjects. One subject had no menustrationfor 4 years and
the other had an irregular cycle.
The subject sample consisted of 21 healthy female volunteers in a fertile age period.
Most of these subjects were senior students or staff members of the institute, and were
all highly motivated to participate in the experiment.
All meals were prepared in the laboratory kitchen. All the amounts of food were weighed
and prepared for the subjects. Subjects with higher energy requirements than provided by
the meal served were allowed to eat more of the special unlabeled wheat roll. Each
whole-grain roll was labeled from the radioisotopic iron standard solutionjust before
serving I amounts that gave exactly the same specific activity of nonheme iron in all
meals.
Fresh samples of raw and boiled vegetables and potatoes were analyzed for ascorbic acid
on the same day that they were served. Weighed amounts from the meat dishes were
analyzed for total iron and analysis of nonheme iron content of the meat. The mineral
analyses of calcium, phosphorous, and magnesium were made after completion of the wet-ash
method in sulfuric acid and hydrogen peroxide.
The measurement of nonheme iron absorption was done by using a liquid-scintillation
spectrometer. The following equation wasused to determine heme iron absorption: heme
iron absorption% = reference dose absorption % X 0.322 +15.71.
Results - The nonheme iron absorption of high calcium intake was 12.1 +- 2.20% (range,
1.8%-32.3%) and low calcium intake was 15.9 +- 2.50% (range, 1.6% - 40.6%). When log
serum ferritin concentration was used as a measure of iron status, the r-squared values
were 0.68 and 0.51, respectively.
The mean difference of the individual total iron-absorption figures from the two 10-d
periods was 0.52 mg. In 16 of the 20 women , total iron absorption was higher when the
calcium intake with the two main meals was low. No obvious explanation was found for the
four subjects who responded differently to the higher calcium intake.
Conclusion - The absorption of heme and nonheme iron are both influenced by calcium to
some extent. A main result of this study was that 30-50% more iron was absorbed when the
intake of calcium was low at lunch and dinner compared with when the intake of calcium
was high at these meals. This difference in iron absorption corresponds to 0.44
mgFe/day. In 5 of the original 21 women in our study, iron absorption was unexpectedly
lower when milk was not served with the lunch and dinner meals. In 4 of the 5 subjects
the difference was small and no obvious explanation could be found. In 11 of the 42
periods studied, nonheme iron absorption exceeded 20% and in four periods, 30%.
An important condition for this kind of long-term and rather complex absorption study
is access to highly motivated and knowledgeable subjects who follow experimental
instructions carefully.
Misgivings - The one facet of this experiment I felt was very lacking was the diversity
of the sample. The entire sample had a very similar background and all came from the
same place, the university. I was also disappointed in the size of the sample. It seems
this sample could have been bigger, or they could have had another trial.
Personal Response - Overall, I really enjoyed reading this article. The questions about
our diet that it poses in the conclusion were extremely interesting. I also thought it
was written well. The terms and ideas were easy enough for the layman to understand,
while it was also able to discuss complicated ideas.
Works Cited
Eaton SB, and Nelson DA. "Calcium in evolutionary perspective." American Journal of
Clinical Nutrition 1991;54:281S-287S.
Gleerup A, Rossander-Hulthen L, Gramatkovski E, and Hallberg L. "Iron absorption fom the
whole diet: comparison of the effect of two different distributions of daily calcium
intake." American Journal of Clinical Nutrition 1995;61:97-104.
Hallberg L, Brune M, Erlandsson M, Sandberg A, and Rossander-Hulthen. "Calcium: effect
of different amounts on nonheme- and heme-iron absorption in humans." American Journal of
Clinical Nutrition 1991;53:112-119.
Rossander-Hulten L, and Hallberg L. "Iron requirements in menstruating women." American
Journal of Clinical Nutrition 1991;54:1047-1058.
Voet D, and Voet JG. "Hemoglobin Function." Biochemistry. New York, NY. 1995.
Whiting S. "The Inhibitory Effect of Dietary Calcium on Iron Bioavailability: A Cause
for Concern?" Nutrition Reviews, Vol. 53, No. 3, pp. 77-80.
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