Nutritional Anemias, edited by S. J. Fomon and
S. Zlotkin. Nestl6 Nutrition Workshop Series,
Vol. 30, Nestec Ltd.. Vevey/Raven Press, Ltd.,
New York © 1992.
Chairmen's Final Comments
Nutritional anemias may result from deficiency of any number of nutrients. In this
workshop, we have considered anemias associated with deficiencies of iron, folic
acid, vitamin B ) 2 , vitamin E, vitamin A, and copper.
Iron deficiency anemia is by far the most prevalent of the nutritional anemias. Its
prevalence is greatest in infants, preschool children, and premenopausal women and
is substantially higher in non-industrialized than in industrialized countries. In industrialized countries, iron deficiency often occurs as a single nutrient deficiency,
whereas in nonindustrialized countries iron deficiency is commonly complicated by
other nutrient deficiencies and is often aggravated by bacterial and viral infections
and by parasitic infestations. In many of the industrialized countries, iron deficiency
has decreased in recent years, probably as a result of greater consumption of ironfortified foods.
Evidence accumulated over the past 15 years has established an association between iron deficiency anemia of infants and young children and poor performance
on tests of mental and psychomotor development. There is a strong possibility that
the relation is causal. Moreover, as reported in this workshop and elsewhere, even
at 5 or 6 years of age—long after correction of the anemia—the previously anemic
subjects perform less well than do controls in a battery of developmental tests. Thus,
iron deficiency anemia during infancy may be responsible for permanent adverse
effects on central nervous system development.
The prevalence of iron deficiency without anemia greatly exceeds the prevalence
of iron deficiency anemia. Whether iron deficiency without anemia is responsible
for adverse effects on health is unknown. However, because iron deficiency without
anemia is a risk factor for iron deficiency anemia, the condition should be prevented.
The workshop participants agreed that several biochemical and/or erythrocyte
morphologic indices should be used in screening for iron deficiency. However, even
with the use of several indices, interpretation of results is often difficult because
most of the indices are altered in the presence of inflammation. The effect of inflammation on serum ferritin concentration is to increase it into the range of normal
values. Nevertheless, the concentration is generally less than 50 ng/ml in individuals
with iron deficiency anemia, and more than 50 ng/ml in individuals with anemia not
associated with iron deficiency. An additional index of iron deficiency, the serum
concentration of transferrin receptor, is increased in iron deficiency and unaffected
by inflammation. Unfortunately, methods for determining serum concentration of
transferrin receptor are not yet widely available.
An association has been documented between anemias during pregnancy and delivery of low birthweight infants. Whether the association is causal is unknown. We
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cannot exclude the possibility that maternal anemia is merely serving as a marker
for other adverse influences on the fetus.
In industrialized countries, the prevalence of iron deficiency anemia in teenage
girls is relatively high. Low food intakes associated with a sedentary life style and
preference for foods low in iron may be major contributory factors.
Iron absorption early in pregnancy is less than that in the nonpregnant state. Therefore, most of the iron needed for pregnancy must be absorbed during the latter half
of gestation, a time when absorption is substantially increased compared to that of
the nonpregnant state. Despite the high rates of absorption of iron during the latter
months of pregnancy, it is impossible to absorb the required amount of iron (estimated to be 1000 mg) from the normal diet. The threat of iron deficiency in pregnant
women is particularly great in those who begin pregnancy with low iron stores—a
circumstance that is nearly universal with teenage pregnancy. The workshop participants were in general agreement that iron supplements were desirable for pregnant
women. There was, however, no agreement on the recommended dose of iron nor
on the timing of administration of the dose. Suggestions ranged from a daily iron
dose of 30 mg given between meals to more than 100 mg given with meals.
Many of the workshop participants believe that public health efforts aimed at
prevention or correction of iron deficiency have been impeded by concern that iron
administration might increase the risk of infection. Although parenteral administration of iron is associated with increased risk of infection, there is little basis for
concluding that orally administered iron has a similar effect. With the possible exceptions of vigorous iron therapy during initial treatment of severely malnourished
individuals or those with malaria, there was general agreement that neither oral
administration of iron to iron-deficient individuals nor iron fortification of the food
supply increases the risk of infection.
Especially in non-industrialized countries, nutritional anemias often occur with
deficiency of more than a single nutrient. Individuals may develop anemia solely
because of vitamin A deficiency and consequent inability to mobilize iron from storage sites. The anemia will then be corrected by administration of vitamin A. However, vitamin A deficiency and iron deficiency often coexist, and in this circumstance
the anemia will be corrected only when both nutrients are given.
Nutritional copper deficiency in industrialized countries has occurred primarily in
individuals managed with parenteral alimentation without adequate supplements of
copper, and in preterm infants fed formulas low in copper. In non-industrialized
countries, copper deficiency occurs in malnourished infants rehabilitated with feedings that are low in copper.
From the presentations and discussions of anemias of low birth weight infants, it
is evident that there is an urgent need to establish criteria for administration of
transfusions to this group of patients, and to determine whether there are conditions
that will permit successful stimulation of erythropoiesis by administration of erythropoietin, thereby decreasing the need for transfusions.
The hemolytic anemia that was once observed in preterm infants disappeared when
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formulas fed to these infants were modified to provide lesser amounts of polyunsaturated fatty acids and iron and greater amounts of vitamin E. Recently, in some
of the trials of erythropoietin administration, doses of iron of 6 or 9 mg/kg/day have
been given. Careful monitoring of these infants for the occurrence of adverse effects
of iron seems warranted.
In the view of the co-chairmen of the workshop, sufficient information is available
to permit development of strategies for prevention of iron deficiency. Because absorption varies so widely depending on the form of iron in the diet and on the presence
of inhibitors and enhancers of nonheme iron absorption, recommendations should
not be based merely on quantity of iron in the diet, but on meeting the needs for
absorbed iron. Recommendations for prevention of iron deficiency must be specific
for groups based on age, gender, and physiologic state, and will vary from country
to country with types of food available and with dietary customs.
Imaginative educational programs are needed to inform the public about foods and
eating habits that will maximize absorption of dietary iron. Because inhibitors and
enhancers of iron absorption exert their effects only when consumed with iron, meals
that provide the major quantities of iron should, when possible, contain ascorbic
acid and/or meat, fish, and poultry and should avoid inclusion of large quantities of
inhibitors. The inclusion of ascorbic-acid-rich foods and meat, fish, and poultry with
meals that provide the greater portion of dietary iron will enhance iron absorption.
At these meals, consumption of tea and coffee, which are inhibitors of iron absorption, should be quite limited.
Unless great care is taken in developing recommendations for meeting the need
for absorbed iron, such recommendations are likely to be in conflict with other dietary guidelines—for example, guidelines widely publicized in several countries for
preventing atherosclerosis and osteoporosis. Meat, fish, or poultry included in meals
as enhancers of absorption of nonheme iron must be carefully selected to avoid a
major increase in the total fat and saturated fat of the diet. By consuming dairy
products either between meals or with meals that are not relied on as major sources
of iron, the inhibitory effects of calcium and of milk proteins on iron absorption can
be minimized while still permitting generous intakes of calcium. In industrialized
countries, increased intake of dietary fiber has also been recommended. It will not
be easy to avoid the inhibitory effect of phytates on iron absorption while increasing
intakes of dietary fiber. However, products that are high in dietary fiber and quite
low in phytates (e.g., yeast-risen whole-grain baked goods) can be promoted.
Because approaches that are feasible for increasing iron absorption from the foods
currently consumed in many countries will not result in sufficient iron absorption
to prevent iron deficiency, consideration will need to be given in these countries to
judicious fortification of one or more staple foods with iron. For specific subgroups
of the population, iron absorption will be inadequate despite food fortification programs. These subgroups will benefit from regular supplementation of the diet with
medicinal iron preparations. Iron supplements should be consumed either between
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meals (preferably with ascorbic acid) or with meals that include enhancers of iron
absorption and contain few inhibitors.
Much attention has been paid to the need for supplementation of women during
the second half of pregnancy. Less attention has been paid to the need to increase
iron stores of women, especially adolescents, who are not yet pregnant. It seems
likely that the outcome of pregnancy among adolescents would be improved if iron
stores in this group were better at the time of conception.