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OCR for page 299
1 r
Trace Elements
With the exceptions of iron and iodine, the trace elements are the
nutrients most recently identified as essential for humans. The roles of
some have not been clearly defined, despite substantial progress over
the past 30 years. Periodic reevaluation is needed as the boundaries of
knowledge expand. The trace elements included in this chapter are those
for which Recommended Dietary Allowances (RDAs) or safe and adequate
daily dietary intakes have been established by the Food and Nutrition Board
(NRC, 1989), with the exception of iron (see Chapter 14~.
Progressive physiologic changes during gestation contribute to the
difficulty of interpreting laboratory data. Although mild deficiency of one
or more trace elements may be one etiologic factor in a multifactorial
problem such as premature delivery or intrauterine growth retardation, a
causal role would be difficult to detect. Suboptimal status, or marginal
deficiency, of trace elements has been documented in human and animal
models, but it is typically difficult to identify. The selection of appropriate
subjects, the large number of subjects required, and the difficulties of
implementing intervention studies in free-living populations are among the
factors that hamper definitive research to determine whether and when
increased intakes of specific trace elements may be of any value to the
course of pregnancy and to the developing fetus.
With respect to potential toxicity, the trace elements in general have
an intermediate position between the fat-soluble vitamins and the water-
soluble vitamins (see Chapters 17 and 18~. Of greater concern than overt
299
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300
DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
toxicity is the potential for interactions between trace elements. For ex-
ample, relatively large doses of iron may interfere with the absorption of
zinc in pregnant women. Zinc supplementation may compensate for this
interaction but may, in turn, affect the metabolism of copper and other
micronutrients. The full extent of nutrient-nutrient interactions is not yet
completely known.
ZINC
Cell Replication and Differentiation
At the molecular level, zinc is involved extensively in nucleic acid
and protein metabolism and, hence, in the fundamental processes of cell
differentiation and replication (see the review by Hambidge et al., 1986~.
Zinc and zinc-dependent enzymes, for example, are involved in the synthesis
of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and ribosomes.
Zinc deficiency reduces the activity of these enzymes, but disturbances of
cell replication and differentiation appear to be attributable primarily to
the adverse effects of zinc deficiency on gene expression (Cheaters, 1978;
Crossley et al., 1982~. For example, zinc fingers (Klug and Rhodes, 1987)
play a critical role in the attachment of the transcription proteins to DNA.
These fingers are projections, the shape of which is dependent on a zinc
atom at the base. This essential step in the initiation of the transcription
process is but one example of the numerous ways in which zinc is involved
in all stages of the cell cycle.
Reproduction in Animals
In view of the multiple physiologic roles of zinc in cell replication
and differentiation, it is not surprising that an adequate supply of this
micronutrient is necessary for reproduction. Animal studies have shown
that all phases of reproduction in the female, from estrus to parturition
and lactation, are affected adversely by zinc deficiency (Hambidge et al.,
1986~. Severe zinc deficiency in rodents disrupts the estrous cycle and
causes infertility (Swenerton and Hurley, 1980~. Zinc is necessary for the
normal development of the preembryonic conceptus. In the immediate
postfertilization period, zinc deficiency can result in abnormal development
of Reimplantation eggs (Hurley and Schrader, 1975~.
In the rat, maternal dietary zinc restriction during embryogenesis has
profound teratogenic effects involving many organ systems, especially the
skeletal and central nervous systems (Dreosti, 1982; Hurley, 1981~. The
pattern of malformations depends on the precise period of zinc depriva-
tion and the embryonic events that are occurring at that stage of gestation
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TRACE ELEMENTS
301
(Record et al., 1985~. Zinc restriction can result in fetal growth retar-
dation in male fetuses of monkeys and fetuses of both sexes of rats and
sheep (Hurley et al., 1985~. Zinc deficiency in the postembryonic period
has been associated with behavioral abnormalities in the offspring of rats
and monkeys (Strobe! et al., 1979) and with abnormalities in the ontogeny
and postnatal function of the immune system (Haynes et al., 1985~. Ma-
ternal zinc deficiency also has species-dependent effects on the course of
pregnancy and delivery. In rats, zinc deficiency in late pregnancy causes
prolonged labor with atonic bleeding (Apgar, 1968~. Such effects appear to
result from a failure of normal hormonal changes at delivery. Premature
delivery may be the most likely complication of maternal zinc deficiency in
the ewe and guinea pig (Apgar, 1987~.
Reproduction in Humans
There have been a few reported cases of severe human zinc deficiency
during pregnancy that resulted from inadequately treated acrodermatitis
enteropathica a hereditary condition in which zinc absorption is impaired.
Among these cases, there was a high incidence of major obstetric com-
plications and congenital malformations in the offspring (Hambidge et al.,
1975~. The prevalence and consequences of milder zinc deficiency during
human pregnancy remain poorly defined. In several studies, associations
were found between low zinc levels in plasma or tissue and complications of
pregnancy and delivery, such as pregnancy-induced hypertension; prolonged
labor; intrapartum hemorrhage; and impaired fetal development such as
congenital malformations, intrauterine growth retardation (Adeniyi, 1987;
Crosby et al., 1977; Fehily et al., 1986), and prematurity (Cherry et al.,
1987~. Campbell-Brown et al. (1985) reported unusually low dietary zinc
levels among Hindu vegetarian women in London, England, whose off-
spring had low birth weights. However, there was no correlation between
the maternal serum zinc level and birth weight. In general, there has been
a lack of consistency in the findings of different studies (see reviews by
Hambidge, 1989, and Swanson and King, 1987~.
In randomized controlled trials of groups believed to be at relatively
high risk of zinc deficiency, zinc supplements have had limited and incon-
sistent effects. For example, in a study of low-income women of Mex-
ican descent, Hunt et al. (1984) found a significantly lower incidence of
pregnancy-induced hypertension in the zinc-supplemented group than in the
placebo-treated group. They speculated that zinc may reduce the incidence
of pregnancy-induced hypertension by affecting prostaglandin metabolism.
In a subsequent study of teenage pregnancies in the same population, this
effect was not observed (Hunt et al., 1985~. Nor was a zinc supplement
found to have a beneficial effect on pregnancy-induced hypertension in
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302
DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
black adolescent teenagers in New Orleans (Cherry et al., 1987), despite an
association between low plasma zinc concentrations and pregnancy-induced
hypertension in an earlier study of that population (Cherry et al., 1981~.
Zinc supplementation was, however, associated with a lower incidence of
premature births in that study.
Sample sizes have been inadequate to assess definitively the effect of
zinc supplements on intrauterine growth. Nevertheless, the results of one
recent study (Mahomed et al., 1989) indicated that an effect on fetal growth
is unlikely in an unselected population of pregnant women.
Estimated Zinc Requirements During Pregnancy
Swanson and King (1987) estimate that 100 mg of zinc is retained
in maternal and fetal tissues during pregnancy and that 0.7 mg/day is
accumulated during the last trimester. At most, 1 mg/day is retained during
the third trimester, allowing for intra- and interindividual variation. If
fractional absorption is 25% during the third trimester, a maximum of
an additional 4 mg of zinc per day is needed. Corresponding increments
in dietary requirements during the first and second trimesters would be
approximately 0.5 and 1.5 mg of zinc per day, respectively. It is not yet
known whether fractional zinc absorption increases during late gestation in
humans as it does in rats (Davies and Williams, 1977~.
Studies of nonpregnant adults provide information about zinc absorp-
tion, utilization, and excretion that is potentially relevant to human preg-
nanc~y. Wada et al. (1985) report that nonpregnant adults adapt to a wide
range of zinc intakes. Because of this, results of traditional balance studies
cannot be used to establish dietary requirements for this micronutrient.
The effects of mild zinc deficiency are subtle and nonspecific. Thus, it is
extremely difficult to determine the point at which adaptation gives way to
accommodation, i.e., when the earliest adverse effects occur. Reliable esti-
mates of dietary zinc requirements for nonpregnant adults therefore remain
elusive. Gibson and Scythes (1982), Holden et al. (1979), and Patterson et
al. (1984) have reported that zinc intakes by apparently healthy adults in
North America average 8 to 10 mg daily. When these data are considered
along with those of Swanson and King (1987), it appears likely that 12 to
14 mg of zinc per day is ample in the third trimester of pregnancy. Indeed,
the requirement may be substantially lower than this figure, especially if
there are adaptive mechanisms specifically related to pregnancy.
Usual Zinc Intakes
Usual daily dietary zinc intakes during pregnancy range from 8.8 ~
3.5 to 14.4 ~ 1.5 (standard deviation) mg/day (Campbell, 1988~. Among
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TRACE ELEMENTS
303
vegetarians, usual zinc intakes may be even lower. For example, Campbell-
Brown et al. (1985) reported a mean intake by Hindu vegetarian women of
only 7.5 mgtday.
Dosage Range and Toxicity
The level of zinc supplementation that is safe for pregnant women has
not been clearly established. Doses used in zinc supplementation studies in
pregnant women have ranged from 15 to 45 mg/day, but one unconfirmed
report suggests an association between zinc supplements of 45 mg/day
during pregnancy and premature delivery (Kumar, 1976~. A daily zinc
intake of 50 mg is sufficient to impair copper and iron metabolism (Yadrick
et al., 1989~. One report, based on the metabolic balance technique and a
diet low in copper, indicates that copper absorption is slightly impaired at
a dietary zinc intake of only 18.5 mg/day (Festa et al., 1985~.
Criteria for Status Assessment
There are no pathognomonic clinical features of zinc deficiency in hu-
mans, except in cases of very severe zinc deficiency. The potential adverse
effects of maternal zinc deficiency on obstetric course (e.g., pregnancy-
induced hypertension) and fetal development (e.g., fetal growth retarda-
tion) are also nonspecific and are not helpful in diagnosing zinc deficiency.
No reliable and sensitive functional indices of zinc status have been found,
including the activity of the metalloenzymes. Indicators of T-cell function
have been suggested but are nonspecific. In the second trimester, mater-
nal leukocyte zinc concentrations have been associated with fetal growth
retardation (Meadows et al., 1981~; however, this is a complex technique
that is not applicable outside the research laboratory. Moreover, there are
valid reasons to doubt that zinc deficiency is resected in lower leukocyte
zinc concentrations (Milne et al., 1985~.
The most widely used laboratory assays for assessment of zinc status
include measurements of plasma or serum zinc. Plasma measurements are
potentially more accurate but technically more difficult to perform. ~
make valid comparisons among samples, it is necessary to collect them at
a predetermined time relative to meals. Prebreakfast samples are least
subject to day-to-day variation (Hambidge et al., 1989~.
There is a well-established physiologic decline in plasma zinc through-
out gestation, starting early in the first trimester (Hambidge et al., 1983~.
The cause of this decline is probably multifactorial, including hormonal
factors and, later in gestation, increased plasma volume. Because of this
decline, normal ranges are needed for each stage of gestation; some guide-
lines for this have been published (Hambidge et al., 1983~. Another putative
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DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
concern about the use of plasma or serum zinc is the lack of adequate sen-
sitivity in identifying women with zinc deficiency. Other tissue zinc assays,
such as hair analysis (Hambidge, 1982), have not been demonstrated to be
reliable indicators of zinc status in humans.
Because of the limitations of laboratory assays and functional indices,
their use in assessing zinc status is not recommended as a routine part
of prenatal care. Studies of response to zinc supplementation offer the
most definitive approach to confirming zinc deficiency in groups, but not in
individuals.
Prevalence of Zinc Deficiency
Without large-scale zinc supplementation studies, the prevalence of
maternal zinc deficiency during pregnancy remains speculative.
Effects of Other Supplements and of Nonnutritive Substances
Alcohol consumption increases losses of zinc in the urine and depresses
plasma zinc concentrations (Flynn et al., 1981~. Infants with fetal alcohol
syndrome have been reported to have low plasma zinc levels and increased
urine zinc losses (Anonymous, 1986b). It has been hypothesized, but
not confirmed, that the lack of zinc plays a role in the abnormal facial
appearance that is typical of fetal alcohol syndrome. Placental transport of
zinc was disturbed by chronic alcohol ingestion and did not improve with
maternal zinc supplementation in an animal model (Ghishan and Greene,
19834.
In pregnant smokers, whose placental cadmium levels are high, the
placental zinc-to-cadmium ratio is positively related to infant birth weight
(Kuhnert et al., 1988~. In an animal model, administration of cadmium was
teratogenic only when marginal zinc deficiency was present as well (Sato
et al., 1985~; low zinc-to-cadmium ratios in the kidney were suggested
as a cause of hypertension. Because of these potential interrelationships
between zinc and cadmium, it may be especially important to ensure an
adequate zinc intake by pregnant smokers.
Interactions between iron and zinc during gastrointestinal absorption
have been well documented (Hamilton et al., 1978; Solomons, 1986), but
not consistently in pregnant women. However, prenatal iron supplements,
especially if administered in doses >60 mg of elemental iron per day, can
lower maternal plasma zinc concentrations (Dawson et al., 1989; Hambidge
et al., 1987~. Administration of iron and zinc in the same multimineral
supplement also impairs zinc absorption (Sandstrom et al., 1985~. Milne
et al. (1984) observed that modest folate supplements may impair zinc
absorption, whereas Fuller et al. (1988) reported no effect. If folate has
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TRACE ELEMENTS
305
any effect on zinc absorption, it is evidently not of sufficient magnitude to
be of much practical importance (Krebs et al., 1988~.
Recommendations for Supplementation
There is insufficient evidence on which to base a recommendation for
routine zinc supplementation during pregnancy. Iron in large doses (>60
mg/day) and possibly in lower doses (Dawson et al., 1989) does appear to
depress plasma zinc in pregnant women and should, therefore, be avoided.
Zinc supplementation is recommended when >30 mg of supplemental iron
is administered per day.
COPPER
Importance in Pregnancy
Copper-containing enzymes such as cytochrome oxidase play key roles
in many oxidative processes and, hence, in the production of most of
the energy required for metabolism. Certain cuproenzymes are important
in the body's defense against free radicals (e.g., superoxide dismutase
in cytosol and mitochondria), in the synthesis of connective tissue (e.g.,
lysyl oxidase), in the transport and utilization of iron (e.g., ferroxidases,
including ceruloplasmin), in the synthesis of norepinephrine (dopamine
p-hydroxylase), and in other metabolic pathways (Solomons, 1985~.
In animal models, maternal copper deficiency can cause infertility,
abortion, and stillbirth (Davis and Mertz, 1987~. However, low-copper
diets have been shown to be teratogenic only when fed in combination with
chelators that bind copper and further compromise copper status (Keen et
al., 1982~. When pregnant ewes graze on severely copper~eficient pastures,
enzootic neonatal ataxia (swayback) occurs in their lambs (Davis and Mertz,
1987~. This necrologic disorder results from the decreased activity of
cytochrome oxidase in the central nervous system. Feeding of a marginally
copper-deficient diet to rats beginning 4 months prior to breeding and
continuing through gestation and lactation and to the weaned offspring
causes no overt problems but does result in ultrastructural abnormalities
in arterial elastin that are similar to the early changes of atherosclerosis
(Hunsaker et al., 1984~.
Copper deficiency has not been documented in humans during preg-
nancy. It is quite possible that the demonstrated teratogenic effects of the
drug penicillamine, which is a copper chelator, may be mediated through
copper deficiency, but copper status has not been investigated in the re-
ported cases (MjOlner0d et al., 1971~. Serum copper has been reported to
be lower in women who deliver prematurely (Kiiholma et al., 1984), and
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DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
weak correlations have been observed between levels of copper in maternal
serum and hair and indices of fetal growth (dir et al., 1981~.
Pregnancy has a major effect on maternal copper metabolism. There
are marked increases in serum ceruloplasmin and in plasma copper (Ham-
bidge and Mauer, 1978~. Deviations from normal pregnancy-related changes
in serum copper are likely to result from an abnormal obstetric course, e.g.,
placental insufficiency or intrauterine death, rather than from inadequate
copper intake.
Estimated Requirements During Pregnancy
During pregnancy, total copper retention is approximately 30 ma, in-
cluding 17 mg accumulated by the fetus. Most of this copper is accumulated
in late gestation, when copper retention has been calculated to average 0.28
mg/day (Campbell, 1988~. At 40% fractional absorption (~rnlund et al.,
1983), these figures indicate an increased dietary copper requirement of 0.7
mg/day. Most studies of copper requirements in humans have been con-
ducted in males. Requirements for nonpregnant adult females are expected
to be slightly lower. Klevay et al. (1980) concluded that a copper intake
of 1.3 mg/day is necessary for males to avoid negative balance. However,
rnlund et al. (1989) clearly demonstrated that adults can adapt to a wide
range of copper intakes with changes in copper absorption. They showed
that a positive copper balance can be achieved by young men on a diet
that provides only 0.8 mg of copper per day. Depending on which figures
are accepted, estimated copper requirements during pregnancy would be
either 1.5 or 2.0 mg/day.
Usual Intakes
Average copper intake by nonpregnant adults is approximately 1
mg/day (Holder et al., 1979; Pennington et al., 1989) and by pregnant
women, 1.4 to 1.8 mg/day (see Table 13-2; Campbell, 1988~. Additional
careful estimates of copper intake during pregnancy are needed.
Dosage Range and Toxicity
No studies of copper supplementation of pregnant women have been
reported. Several prenatal multivitamin-mineral preparations currently
marketed provide 2 mg of copper per tablet. Spitalny et al. (1984) reported
chronic copper toxicity in adults who drank' water containing approximately
8 mg of copper per liter.
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307
Criteria for Status Assessment
Copper and ceruloplasmin concentrations are low in copper-deficient,
nonpregnant adults. Pregnancy is accompanied by a progressive increase in
circulating ceruloplasmin and, hence, in serum copper up to approximately
twice the values in nonpregnant individuals (Hambidge and Mauer, 1978~.
It is not known if and to what extent these pregnancy-related changes are
affected by copper deficiency. An unusually low serum ceruloplasmin or
copper concentration occurs during pregnancy if there is a failure of normal
placental development, regardless of copper intake. Erythrocyte superoxide
dismutase activity is a potentially valuable index of copper status (Uauy et
al., 1985), but its use in pregnancy has not yet been established.
Prevalence of Deficiency
Nutritional copper deficiency during human pregnancy has not been
documented.
Effects of Other Supplements
Even a moderately excessive zinc intake (e.g., 50 mg of elemental zinc
per day, which is approximately three times the 1989 RDA) can interfere
with copper absorption and metabolism (Yadrick et al., 1989~. A negative
change in copper balance may occur if an individual takes supplements
providing enough zinc to achieve a total intake of 20 to 25 midday (Festa
et al., 1985~. There is a need for further substantiation of this effect, which
has been reported only with very low copper intakes.
Recommendations for Supplementation
Although the estimated mean intake of copper is lower than the
estimated copper requirements during the last trimester of pregnancy, there
is no evidence that any pregnant woman is deficient in copper to the extent
that normal fetal growth and development are jeopardized. Therefore, no
recommendation is made for prenatal copper supplementation. If a zinc
supplement is administered, however, the subcommittee recommends that
a 2-mg copper supplement also be given. This relatively high dose should
be at least sufficient to compensate for the relatively poor absorption that
occurs when copper is administered with zinc.
IODINE
Iodine is an essential component of the thyroid hormones thyroxine
and triiodothyronine. Maternal iodine deficiency during pregnancy is the
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DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
cause of a wide spectrum of iodine deficiency disorders in the fetus and
in the offspring (Anonymous, 1983; Hetzel, 1983; Matovinovic, 1983), in-
cluding stillbirth, abortions, and congenital anomalies; endemic cretinism,
characterized by mental deficiency; profound deafness; spastic dysplegia;
or less commonly, the myxedematous type of cretinism. Milder disorders
include necrologic impairment manifested by suboptimal intellectual per-
formance and motor skill development and hearing loss in children born in
geographic areas where there is an endemic deficiency of iodine (Yan-You
and Shu-Hua, 1985~. To avoid damage to the fetus, iodine deficiency needs
to be corrected prior to conception (Hetzel and Hay, 1979~.
A 50- to 70-,ug intake of iodine per day is sufficient to avoid the
risk of hypothyroidism in adult women. The RDA of 150 fig for adult
women is sufficient to offset the adverse effects of dietary goitrogens, and
an additional 25 fig of iodine per day is recommended during pregnancy
(NRC, 1989~.
In the Food and Drug Administration's Total Diet Study, the mean
iodine intake by women aged 25 to 30 in the United States during 1986
was 170 ,ug/day approximately half the typical intake in 1982 but still high
relative to requirements (Pennington et al., 1989~. There is no evidence
of residual iodine deficiency in the United States, and no iodine supple-
ments are recommended. Although excess dietary iodine intake has been
associated with both goiters (Mu et al., 1987) and thyrotoxicosis (Connolly,
1973), this is not a contraindication to the moderate use of iodized salt
during pregnancy. In certain countries in Africa, Asia, South America, and
Europe, iodine deficiency disorders continue to be a major public health
problem. Strenuous international efforts are under way to eradicate this
disorder by promoting the use of iodized oil or salt (Anonymous, 1986a).
SELENIUM
Selenium is an essential component of the enzyme glutathione peroxi-
dase, which catalyzes the conversion of hydrogen peroxide to water. Thus,
selenium is an important component of the body's defenses against free
radical damage (Hoekstra, 1975~. In animal models, the effects of selenium
deficiency are more apparent if there is a concurrent deficiency of other
antioxidants, especially vitamin E.
Selenium deficiency has been identified in humans living in a large area
of the People's Republic of China where there is a severe geochemical de-
ficiency of this micronutrient. The deficiency is manifested by a frequently
fatal cardiomyopathy (Keshan disease) that occurs in young children and
women of childbearing age. Although the etiology of this disease is prob-
ably multifactorial, a severe dietary deficiency of selenium is the major
etiologic factor (Keshan Disease Research Group, 1979a,b). There have
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TRACE ELEMENTS
309
been scattered case reports of similar cardiomyopathies (Johnson et al.,
1981) and of skeletal myopathies (van Rij et al., 1979) in selenium-deficient
patients maintained on prolonged total parenteral nutrition without sele-
nium supplements (Johnson et al., 1981~. Milder selenium deficiency in
parenterally fed children has been associated with macrocytosis and hair
pigment changes (Vinton et al., 1987~.
Keshan disease occurs in areas where the average selenium intake
by adult males is 8 ~g/day (Yang et al., 1987~. Where Keshan disease
was not evident, the average selenium intake by Chinese men was 19
~g/day. Maximal plasma glutathione peroxidase activity in Chinese men
was achieved with 40 ,ug of selenium per day (Yang et al., 1988~. The
average weight of a Chinese man is 60 kg, which is similar to that of
women in the United States.
Selenium retentions of 10 and 22 ,ug/day between weeks 10 to 20
and 30 to 40 of gestation, respectively, have been reported (Swanson
et al., 1983) in women with a high selenium intake. However, since
selenium homeostasis changes over a wide range of selenium intakes, the
metabolic balance technique is not helpful in determining human selenium
requirements (Levander and Burk, 1986~. On a factorial basis, estimates of
selenium retention in the fetus have varied from as little as 1 ~g/day to an
average of 14 ~g/day during the last trimester (NRC, 1989~. If fractional
absorption from the mother's gastrointestinal tract is 80% (Levander, 1983),
an additional 18 fig of dietary selenium would be required daily during late
gestation. Thus, the estimated selenium requirement during late gestation
would be approximately 60 ,ug/day. The estimated average dietary selenium
intake by women aged 25 to 30 during 1985 and 1986 was about 70 ~g/day
in the United States (Pennington et al., 1989~.
Several cases of selenium toxicity in nonpregnant adults resulted from
large intakes of selenium supplements that provided about 30 mg per
tablet approximately 200 times more selenium than that advertised on
the label (Helzlsouer et al., 1985~. Symptoms of selenium toxicity included
nausea, vomiting, nail changes, hair loss, fatigue, and irritability.
Whole blood or erythrocyte selenium levels and glutathione peroxidase
activity are used to assess selenium status in nonpregnant adults (Levander,
1986~. Plasma selenium is also used, although it is subject to short-term
changes. However, the value of these indices is limited by the wide range of
values found in apparently healthy subjects. In the United States, plasma
selenium concentrations in nonpregnant adults usually range from 100 to
200 ng/ml. Adults with evidence of mild and severe selenium deficiency
have plasma levels of less than 40 and 10 ng/ml, respectively. Selenium
concentrations in plasma, but not in erythrocytes, decline during gestation.
There is no indication of a need to conduct laboratory tests to assess
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DIETARY INTAKE AND NUTRIENT SUPPT FMENTS
selenium status during pregnancy or to advise pregnant women to take
supplemental selenium.
MANGANESE
Manganese is a component of two enzymes-mitochondrial superoxide
dismutase, an important antioxidant, and pyruvate carboxylase. Manganese-
activated enzymes include the glycosyltransferases, which are necessary for
the synthesis of polysaccharides and glycoproteins.
When rat dams are raised from the time of weaning on a manganese-
deficient diet, the pups experience poor survival and ataxia. These abnor-
malities can be prevented by correcting the manganese deficiency as late
as day 14 of gestation (Hurley, 1981~. Offspring of manganese-deficient
dams also have low blood glucose concentrations, which are associated with
decreased activity of phosphoenolpyruvate carboxykinase a manganese en-
zyme involved in gluconeogenesis (Baly et al., 1984~. Deficiency impairs
mucopolysaccharide synthesis in the developing otoliths of the pig's inner
ear, resulting in a lack of coordination (Hurley, 1981~.
There are no adequate data on manganese accumulation in the human
conceptus. Usual intake by nonpregnant women aged 25 to 30 is approx-
imately 2 mg/day (Pennington et al., 1989~. Both positive and negative
manganese balances were observed during late pregnancy in women whose
daily manganese intake averaged 2 to 7 mg (Armstrong, 1985~.
Manganese deficiency has not been observed in human adults, includ-
ing pregnant women. The intestine (through absorption) and liver (through
biliary excretion) provide strong homeostatic controls of body manganese.
Thus, manganese supplements are not indicated during pregnancy. Some
data indicate that supplemental iron can interfere with manganese absorp-
tion (Davidsson et al., 1988~. This merits further research. Manganese
administered orally to nonpregnant adults appears to be nontoxic in quan-
tities considerably in excess of requirements (NRC, 1989~.
CHROMIUM
Chromium is believed to play a physiologic role as a cofactor for in-
sulin, facilitating the initial attachment of the hormone to its peripheral
receptors (Mertz, 1969~. However, chromium has not been found in the
insulin receptor (Kahn, 1985~. There have been numerous, but uncon-
firmed, reports of chromium deficiency in humans, primarily in patients
maintained on prolonged parenteral nutrition (Jeejeebhoy et al., 1977~.
Glucose intolerance has been the most consistently observed effect of very
low chromium intake.
Some reports of chromium concentrations in plasma and tissues suggest
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TRACE ELEMENTS
311
that pregnancy may be associated with chromium depletion (Davidson and
Burt, 1973; Hambidge and Rodgerson, 1969~. It is difficult to substantiate
these results, however, because accurate analysis of chromium in human
tissues is exacting and there is a lack of established laboratory indices of
human chromium status. Thus, the extent to which chromium is important
in human nutrition remains uncertain, and there are no data suggesting
that chromium supplementation is advisable during pregnancy.
MOLYBDENUM
In humans, molybdenum is a component of two enzymes xanthine
oxidase, which is involved in the degradation of adenosine monophosphate,
and sulfite oxidase. Molybdenum deficiency has been described only in one
patient who was on prolonged total parenteral nutrition. Excess molyb-
denum intake interferes with copper metabolism (Mills and Davis, 1987~.
Molybdenum supplementation during pregnancy is contraindicated.
FLUORIDE
Administration of fluoride is the most effective means to prevent dental
caries. Public health measures, including fluoridation of the community or
school water supplies or oral supplementation, have been directed primarily
toward infants and children younger than age 16. Adults may also derive
some benefit from a fluoridated water supply or a 1-mg fluoride supplement
per day (American Dental Association Council on Dental Therapeutics,
1984~.
The precise mechanism by which fluoride exerts its cariostatic (decay-
retarding) effects is uncertain. Most fluoride accumulates in the external
enamel layer. Both topical and systemic fluoride appear to provide protec-
tion against dental caries most effectively in the tooth's first two posteruptive
years (Stookey, 1981~. During the preeruptive phase, systemic fluoride may
have some beneficial effect, but there is no unanimity of opinion on this
subject (American Dental Association Council on Dental Therapeutics,
1984~.
- Maternal fluoride supplementation during pregnancy has been re-
ported to decrease the incidence of caries in the offspring, even when
administered in an area with a fluoridated water supply (Glenn and Glenn,
1987~. The designs of the studies on which this claim is partially based
have been challenged (Driscoll, 1981~. Fluoride supplementation during
pregnancy has not been endorsed by the American Dental Association and
has not been generally accepted as a validated procedure.
Dental fluorosis, or mottled enamel, has been observed in developing
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312
DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
teeth in areas where water supplies contain more than twice the opti-
mal fluoride concentration of 1 mg/liter. Excessive fluoride intake should
therefore be avoided.
The subcommittee concluded that there is insufficient evidence to
warrant recommending fluoride supplementation during pregnancy as a
means of benefiting the teeth of the offspring.
SUMMARY
Although dietary intake of zinc and copper may be considerably lower
than the RDA, there is no convincing evidence that this has adverse effects
on pregnancy outcome. There is also no persuasive evidence that routine
antenatal supplements of any trace element other than iron are potentially
beneficial for pregnant women in the United States.
CLINICAL IMPLICATIONS
· Laboratory tests to determine trace element status are not suffl-
ciently sensitive or predictive to justify their expense in routine prenatal
care.
· The best means of ensuring an optimal intake of trace elements
appears to be consumption of a well-balanced and adequate diet rather
than use of mineral supplements.
· Although vegetarian diets can provide reasonable quantities of trace
elements, flesh foods frequently contribute larger amounts that are more
readily absorbed and are thus potentially advantageous during pregnancy.
· There is no persuasive evidence that it is potentially beneficial to
routinely supplement pregnant women with any trace element other than
iron in the United States.
· Although zinc nutrition during pregnancy has attracted recent pro-
fessional and public interest, there is insufficient evidence to support a
recommendation for routine prenatal zinc supplementation.
· Although the subcommittee concluded that the iodine content of
the food supply in the United States is sufficiently high to make iodine
supplementation unnecessary, use of iodized salt is not contraindicated.
· The intake of fluoride provided by fluoridated water supplies is
encouraged, but fluoride supplements that result in intake above approxi-
mately 1 mg/day are not recommended.
OCR for page 313
TRACE ELEMENTS
313
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Representative terms from entire chapter:
trace elements
