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Division of Human Nutrition, Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 77555-1109
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUMMARYREFERENCES |
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KEY WORDS: • iron • zinc • cognition • brain • diet • humans
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUMMARYREFERENCES |
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),
and Zn deficiency is also common (Gibson 1994
,
Sandstead 1995
). Because Fe and Zn are most bioavailable
from many of the same foods and their absorption is inhibited by many
of the same dietary substances, Fe and Zn deficiencies may occur
simultaneously (Sandstead and Smith 1996
).
The National Health and Nutrition Examination Survey (NHANES)-III found
that 16% of black and 20% of Mexican-American women, aged 20–49
y in the United States were Fe deficient (Looker et al. 1997
). Women who were poor (~17%), less educated (<12 y;
~15%), and high gravida (
4; ~21%), girls ages 12–19 y
(9–11%) and toddlers (~9%) were especially affected. Thus, in the
U.S., ~7.8 million women and 700,000 toddlers are Fe deficient and
~3.3 million women and 240,000 toddlers have Fe deficiency anemia
Consumption data (Alaimo et al. 1994
) and factorial
estimates of requirements (Sandstead and Smith 1996
)
suggest that mild Zn deficiency is also common in the U.S.
NHANES-III found median Zn intakes less than the RDA in almost all
groups. For example, Zn intakes of females, aged 12–79 y, were
53–78% of the 1989 RDA (NRC 1989
).
With the exception of some fortified foods, beef is the richest common
dietary source of both Fe and Zn. The 1989–1991 USDA Continuing Survey
of Food Intakes of Individuals (U.S. Department of Agriculture 1995
) found that ready-to-eat cereals and yeast bread
were the major sources of Fe (18.6 and 13.6%, respectively) and that
beef was the major source of Zn (25.7%) for U.S. adults (Subar et al. 1998a
and 1998b
).
Food Fe occurs in two forms, heme-Fe and nonheme-Fe. Nearly
50% of the Fe in meat is heme-Fe (Fe-protoporphyrin); it is
15–35% bioavailable (Monsen 1988
). With the exception
of calcium (Ca), dietary inhibitors that impair nonheme-Fe
absorption do not impair heme-Fe absorption (Hallberg et al. 1991
). Most Fe in the diet is nonheme-Fe. Its absorption
ranges from 2 to 20% (Monsen 1988
), depending on the
person’s Fe status and the presence in the diet of facilitators and
inhibitors of absorption. Facilitators of nonheme-Fe include meat
(Hulten et al. 1995
) and ascorbic acid (Hallberg et al. 1989
). Zn absorption is facilitated by meat (Hunt et al. 1995
). Ascorbic acid has no beneficial effect on Zn
retention (Sandstrom and Cederblad 1987
).
Phytates (5 and 6 phosphate inositol) in cereal products, legumes and
nuts inhibit Fe and Zn absorption. Humans are unable to compensate for
the inhibitory effects of phytate (Brune et al. 1989
).
High phytate:Zn and phytate x Ca:Zn molar ratios increase the
risk of Zn deficiency (Gibson et al. 1991
, Gibson and Huddle 1998
). The phytate content of foods is not currently
listed in publicly available USDA databases (Food Nutrition Information Service 1998
).
Other nondigestible ligands that inhibit absorption of nonheme-Fe
and Zn include some dietary fibers (Brune et al. 1992
,
Knudsen et al. 1996
), lignins (Fernandez and Phillips 1982
) and products of nonenzymatic Maillard browning
(Lykken et al. 1986
, Rehner and Walter 1991
). Phenolic polymers inhibit nonheme-Fe absorption
(Tuntawiroon et al. 1991
) but have little effect on Zn
(Ganji and Kies 1994
).
Ca (dietary or supplemental) impairs absorption of heme- and
nonheme-Fe in a dose-dependent manner and independently of
other dietary factors (Gleerup et al. 1995
). Ca
supplements may (Wood and Zheng 1997
) or may not
(Dawson-Hughes et al. 1986
) inhibit Zn absorption.
Impaired neuropsychologic function is one of the adverse effects of
severe Fe and Zn deficiencies (Henkin et al. 1975
,
Pollitt 1993
). Less severe deficiencies also impair
performance (Pollitt 1993
, Sandstead et al. 1998
).
Fe is highly localized in dopaminergic-peptidergic regions, such as
the globus pallidus, substantia nigra, red nucleus, thalamus, caudate
nucleus and nucleus accumbens (Youdim and Ben-Shachar 1987
). Nonheme-Fe concentrations in brain and the number of
dopamine D2 receptors are decreased by Fe deficiency in experimental
animals, and learning is decreased. The neuropsychologic effects of Fe
deficiency with or without anemia have been studied in infants and
children (Pollitt 1993
). Some studies found Fe repletion
improved function, whereas others did not. Some studies found that Fe
deficiency during brain development resulted in residual abnormalities
(Roncagliolo et al. 1998
). The role of simultaneous
deficiencies of other nutrients such as Zn in these phenomena is
unclear (Hallberg 1989
).
Research on the effects of Fe nutriture on cognition of adolescents and
adults has been limited. In college students (n = 68), serum ferritin concentrations were related directly to
characteristics of the electroencephalogram (EEG) and cognitive
performance (Tucker et al. 1984
). A study of nonanemic
Fe-deficient high school girls found improved verbal learning and
memory after Fe repletion (Bruner et al. 1996
). A
cross-sectional study in the elderly (n = 28)
found that Fe status was associated with characteristics of the EEG
(Tucker et al. 1990
).
Concentrations of Zn in brain are highest in telencephalon and gray
matter of cerebral cortex (Hu and Friede 1968
). Severe
Zn deficiency caused increases in brain norepinephrine concentrations
in rats (Wallwork et al. 1982
), but had no effect on Zn
concentrations in hippocampus or cortex (Wallwork et al. 1983
). In contrast, mild Zn deficiency had no effect on
whole-brain catecholamines (Halas et al. 1982
). A
special class of glutaminergic neurons has Zn-containing vesicles
in its axon terminals (Frederickson and Moncrieff 1994
).
Vesicle Zn released during neurotransmission modulates postsynaptic
N-methyl-D-aspartate receptors for glutamate
(Westbrook and Mayer 1987
), including
calcium-channels (Browning and O’Dell 1995
). In
vitro findings indicate that oxidation of metallothionein by oxidized
glutathione or analogous selenium compounds releases Zn to specific
ligands. Glutathione and ATP facilitate this process (Jacob et al. 1998
, Jiang et al. 1998
). Zn-ATP is
necessary for synthesis of pyridoxal-5-phosphate (Churchich et al. 1989
) and flavin adenosine
dinucleotide(Yamada et al. 1990
), coenzymes
essential for biogenic-amine synthesis (Dakshinamurti et al. 1990
) and monamine oxidase metabolism (Hsu et al. 1988
).
Acute Zn deficiency impairs electrophysiology and behavior of rats
(Hesse 1979
, Hesse et al. 1979
). Zn
deficiency during early brain development causes malformations
(Hurley and Swenerton 1966
). Zn deficiency during later
brain development impairs neuronal growth and synaptogenesis
(Dvergsten 1984
), and causes behavioral sequellae
(Golub et al. 1995
, Halas and Eberhardt 1987
, Strobel and Sandstead 1984
).
Relationships between Zn-nutriture and brain function of humans
have been reported. In Egyptian women, consumption of foods derived
from animals rich in Zn during pregnancy was associated with their
infants having higher attention scores on the Brazelton Neonatal
Development Assessment Scale (Kirksey et al. 1991
). At 6
mo of age, motor performance on the Bayley Scales of Infant Development
was inversely related to maternal intakes of low bioavailable Zn from
plants, phytate and fiber (Kirksey et al. 1994
). Low
hair Zn concentration, an indicator of low Zn status, was associated
with poor reading performance and decreased EEG coherence in the
frontal lobe (Thatcher et al. 1984
). Two 10-wk
double-blind, randomized controlled trials found improved
neuropsychologic function in 740 Chinese (Sandstead et al. 1998
) and 240 Mexican-American 6- to 9-y-old children
(Penland et al. 1999
) who were repleted simultaneously
with 20 mg Zn/d and other potentially limiting micronutrients. A
postmortem study of 12 elderly women found a negative association
between plasma Zn 1 y before death and the number of senile and
diffuse plaques in their brains (Tully et al. 1995
).
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SUMMARY |
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TOPABSTRACTINTRODUCTIONSUMMARYREFERENCES |
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FOOTNOTES |
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REFERENCES |
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TOPABSTRACTINTRODUCTIONSUMMARYREFERENCES |
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