Minerals and Trace Elements 207provide the energy necessary for all physiological pro-
cesses and movement. The importance of iron as an
element necessary for life derives from its redox reac-
tivity as it exists in two stable, interchangeable forms,
ferrous (Fe^2 +) and ferric (Fe^3 +) iron. This reaction is
an essential part of the electron transport chain,
responsible for the generation of ATP during the oxi-
dation of substances in intermediary metabolism and
for the reductions necessary in the synthesis of larger
molecules from their components.
Defi ciency symptoms
The progression from adequate iron status to iron-
defi ciency anemia develops in three overlapping
stages. The fi rst stage consists of depletion of storage
iron, which is characterized by a decrease in serum
ferritin, which, in turn, refl ects the size of the iron
stores in the liver, bone marrow, and spleen. The
second stage is a decrease in transported iron and is
characterized by a decline in serum iron and an
increase in the total iron-binding capacity, as transfer-
rin has more free binding sites than in normal iron
status. The third stage develops when the supply of
iron is insuffi cient to provide for enough hemoglobin
for new erythrocytes and insuffi cient to fulfi ll other
physiological functions. During the last stage, free
protoporphyrin, destined for hemoglobin, increases
in plasma two- to fi vefold, indicating a lack of tissue
iron. The harmful consequences of iron defi ciency
occur mainly in conjunction with anemia. Iron defi -
ciency anemia is most common in infants, preschool
children, adolescents, and women of child-bearing
age, particularly in developing countries.
The functional effects of iron defi ciency anemia
result from both a reduction in circulating hemoglo-
bin and a reduction in iron-containing enzymes and
myoglobin. Both factors presumably play a role in the
fatigue, restlessness, and impaired work performance
associated with iron defi ciency anemia. Other func-
tional defects include disturbances in normal ther-
moregulation and impairment of certain key steps in
the immune response. For example, there is evidence
that iron defi ciency anemia is associated with lower
T- and B-lymphocyte, macrophage, and neutrophil
function. Although the phagocytic uptake of neutro-
phils is usually normal, the intracellular killing mech-
anism is usually defective. This abnormality is thought
to be owing to a defect in the generation of reactive
oxygen intermediates resulting from a decrease in the
iron-containing enzyme myeloperoxidase. Iron defi -
ciency anemia can also have an adverse effect on psy-
chomotor and mental development in children, and
the mortality and morbidity of mother and infant
during pregnancy.Toxicity
The very effective regulation of iron absorption pre-
vents overload of the tissues by iron from a normal
diet, except in individuals with genetic defects, as in
idiopathic hemochromatosis (see below). Excess iron
via overuse of iron supplements could pose a possible
health risk. The mechanism of cellular and tissue
injury resulting from excess iron is not fully under-
stood. Liabilities may include increased risks for bac-
terial infection, neoplasia, arthropathy, cardiomyopa-
thy, and endocrine dysfunctions. However, there is
still much debate as to the strength of evidence to
support a relationship between dietary iron intake
and cancer or cardiovascular disease.
Gastrointestinal distress does not occur from
consuming a diet containing naturally occurring orTable 9.9 Factors affecting (a) heme and (b) nonheme iron
absorption
Increased absorption Decreased absorption
(a) Heme
Physiological factors
Low iron status High iron status
Dietary factors
Low heme iron intake High heme iron intake
Meat Calcium
(b) Nonheme
Physiological factors
Depleted iron status Replete iron status
Pregnancy Achlorhydria (low gastric
acid)
Disease states (aplastic anemia, hemolytic
anemia, hemochromatosis)
Dietary factors
Ascorbic acid Phytate
Meat, fi sh, seafood Iron-binding phenolic
compounds
Certain organic acids Calcium