Sensitivity of zinc kinetics and nutritional assessment of children submitted to venous zinc tolerance test.

Abstract

The purposes of this study were to investigate the kinetics of zinc in schoolchildren between the ages of 6 and 9 years, of both sexes, and to verify its sensitivity in detecting alterations in body zinc status.
Nutritional assessment was performed by body mass index. Food intake, venous zinc tolerance test, and zinc kinetics were carried out before and after 3-month oral zinc supplementation.
Of the 42 children studied, 76.2% had healthy weight. Only energy, calcium, and fiber intake were suboptimal before and after oral zinc supplementation. Serum zinc and total-body zinc clearance, although at normal levels, increased significantly after zinc supplementation.
We concluded, therefore, that kinetics is a sensitive tool for detecting changes in body zinc status, even in children without a deficiency of this mineral. Furthermore, kinetics showed a positive response to supplementation and may be a sensitive parameter for evaluating the efficacy of this therapy.

Full text

Page 1

Original Research
Sensitivity of Zinc Kinetics and Nutritional Assessment of
Children Submitted to Venous Zinc Tolerance Test
Lu ´cia Dantas Leite, PhD, E´rika Dantas de Medeiros Rocha, MSc, Maria das Grac ¸as Almeida, PhD, Adriana
Augusto Rezende, PhD, Carlos Anto ˆnio Bruno da Silva, MD, PhD, Mardone Cavalcante Franc ¸a, PhD, Ju ´lio Se ´rgio Marchini,
MD, PhD, Jose ´ Branda ˜o-Neto, MD, PhD
Postgraduate Program in Health Sciences (PPGCSA) (L.D.L., E´.D.d.M.R.), Department of Clinical Analyses, UFRN
(M.d.G.A., A.A.R.), Department of Nutrition, UNIFOR (C.A.B.d.S.), Department of Statistics, UFRN (M.C.F.), Division of Clinical
Nutrition, USP-RP (J.S.M.), Department of Internal Medicine, UFRN (J.B.-N.), Universidade Federal do Rio Grande do Norte
(UFRN), Natal-RN, BRAZIL
Key words: zinc kinetics, venous zinc tolerance test, nutrition, children
Objective: The purposes of this study were to investigate the kinetics of zinc in schoolchildren between
the ages of 6 and 9 years, of both sexes, and to verify its sensitivity in detecting alterations in body zinc
status.
Methods: Nutritional assessment was performed by body mass index. Food intake, venous zinc tolerance
test, and zinc kinetics were carried out before and after 3-month oral zinc supplementation.
Results: Of the 42 children studied, 76.2% had healthy weight. Only energy, calcium, and fiber intake were
suboptimal before and after oral zinc supplementation. Serum zinc and total-body zinc clearance, although at
normal levels, increased significantly after zinc supplementation.
Conclusion: We concluded, therefore, that kinetics is a sensitive tool for detecting changes in body zinc
status, even in children without a deficiency of this mineral. Furthermore, kinetics showed a positive response to
supplementation and may be a sensitive parameter for evaluating the efficacy of this therapy.
INTRODUCTION
Interest in zinc in human nutrition has been increasing
steadily over the past few decades. Zinc has several
recognized functions in metalloenzymes, including catalytic,
structural, regulatory, and noncatalytic roles [1]. It partici-
pates in the regulation of genetic expression, in cell division,
and in important biochemical pathways [2]. Zinc acts as a
transcription factor, antioxidant, anti-inflammatory, and
immunomodulator. Zinc fingers have a structural role in
transcription factors and are an essential part of gene
expression and regulation. Besides this activity, they act in
signal transduction, cell proliferation, and apoptosis [3]. As
an antioxidant, zinc protects biological structures from
damage caused by free radicals. It maintains an adequate
level of metallothioneins, is an essential component of
superoxide desmutase, is a protective agent for thiols, and
prevents interaction between chemical groups with iron to
form free radicals [4].
Zinc affects both nonspecific and specific immune function
at a variety of levels. In terms of nonspecific immunity, zinc
affects the integrity of the epithelial barrier, neutrophil
function, natural killer cells, monocytes, and macrophages.
With regard to specific immunity, lymphopenia and declined
lymphocyte function occur, as do alterations in the balance of
T helper cell populations (TH1 and TH2) and cytokine
production. All kinds of immune cells show decreased function
after zinc depletion [2,5].
In addition, zinc plays an important role in growth and
development and in optimizing the sense of smell, taste, and
appetite. Thus, a deficiency of this micronutrient can lead to
serious health problems [6,7].
Zinc deficiency may be caused by low intake or by a diet
low in animal protein or high in phytates, which compromises
Address correspondence to: Jose ´ Branda ˜o-Neto, MD, PhD, Department of Internal Medicine, CCS-UFRN, Av. Gal. Gustavo Cordeiro de Farias, s/n, Petro ´polis, CEP 59
010-180, Natal/RN, BRAZIL 59 012-570, E-mail: jbn@ppgcsa.com.br
Journal of the American College of Nutrition, Vol. 28, No. 4, 405–412 (2009)
Published by the American College of Nutrition
405

Page 2

its bioavailability [8,9]. The presence of preabsorption
antagonists such as iron, calcium, cadmium, and copper also
may compromise its absorption. In addition to these factors,
zinc deficiency may be caused or intensified by clinical
conditions in which there is absorption compromise above
normal losses or increased demands, such as in pregnant and
nursing women, growing children, protein-calorie malnutri-
tion, hypermetabolism, and specific diseases such as sickle cell
anemia and diabetes mellitus [10–12].
Preventive measures and correction of zinc deficiency
consist of food intervention, food fortification, and supple-
mentation. Several studies have shown the benefits of zinc
supplementation in children at risk for zinc deficiency [13–15].
To achieve these benefits, correct planning in terms of type of
supplement and its pharmacologic form, dosage, and admin-
istration frequency is essential, with consideration of the need
or lack of need for an association with other nutrients [2].
Studies that assess the effectiveness of zinc supplementa-
tion in children by comparing daily or weekly frequency, as
well as binomial duration/dose, have been few. The Recom-
mended Dietary Allowance (RDA) of zinc for children aged 4
to 8 years and 9 to 13 years is 5 mg/d and 8 mg/d, respectively
[16]. These values correspond to the recommended daily food
ingestion. The International Zinc Nutrition Consultative Group
(IZiNCG), in turn, suggests supplementation of 10 mg of zinc
per day for children and adolescents between the ages of 4 and
18 years at risk for zinc deficiency [2].
Zinc deficiency and its effects have been studied in a child
population, as has the effect of supplementation as an
intervention measure [17]. Although some symptoms of
insufficient zinc intake are not specific of its deficiency per
se, it is important to investigate this possibility.
Different approaches have been used to assess body zinc
status, such as zinc in plasma, serum, erythrocytes, platelets,
leukocytes, hair, sweat, and urine and in metalloenzyme
activities. However, there is no ‘‘gold standard,’’ because
homeostatic control of the organism makes it impossible to
measure deficiency [18]. Therefore, detecting and diagnosing a
marginal deficiency of this micronutrient is difficult because of
the unreliability of these parameters [19,20].
In this context, kinetic studies have been used as versatile
tools for more accurately assessing body zinc status [21,22].
Kinetic parameters based on compartmental models evaluate
absorption, distribution, and body zinc excretion. They provide
data on sudden changes in zinc status that would not be
detected in other known parameters, mainly if used individ-
ually [2]. Kinetic studies are also important for an understand-
ing of the physiopathologic aspects of zinc metabolism on the
child with marginal deficiency.
The venous zinc tolerance test (VZnTT) was first described
in the study of a number of zinc kinetic parameters in human
beings [23]. This study was used to determine whether it was
more reliable than serum zinc and other biological materials in
estimating the marginal status of zinc nutrition. This test can
be used in any population of children. It is not very invasive
and is easy and quick to apply.
In a study of zinc kinetics in children with type 1 diabetes
mellitus, researchers proposed the assessment of total-body
zinc clearance (CZn) after injection of 0.066 mg Zn/kg body
weight, as an efficient parameter for characterizing marginal or
severe zinc deficiency [24].
Given the role of zinc, the seriousness of its deficiency in
children, and the nonexistence of an ideal method for assessing
its real body status, the purpose of this research was to report
the kinetic results of this micronutrient in children aged 6 to 9
years, before and after oral zinc supplementation.
MATERIALS AND METHODS
Subjects
The sample comprised 42 children, aged 6 to 9 years, of both
sexes, from 3 municipal schools in the city of Natal, Brazil, who
were authorized by their parents or guardians to take part in the
study. Children with acute, chronic, infectious, or inflammatory
disease and those who had undergone surgery or were using
vitamin mineral supplements were excluded. The project was
approved by the Research Ethics Committee of Onofre Lopes
University Hospital (CEP-HUOL) at UFRN, Brazil.
Experimental Design
In this study, all 42 children were submitted to VZnTT and
nutritional assessment before and after 3-month oral zinc
supplementation. The same children were submitted to total-
body zinc clearance during VZnTT. All procedures were
performed between 7:00 and 10:00 AM (Fig. 1).
Nutritional Assessment
Anthropometric Measurement. The assessment of nutri-
tional status was based on body mass index (BMI). BMI is
calculated using the child’s weight and height and then is used
to find the corresponding BMI-for-age percentile for the
child’s age and sex. We collected weight, height, and age data,
as per literature recommendations [25]. Growth curves
published by the Centers for Disease Control and Prevention
(CDC) for individuals from 2 to 20 years of age were used as a
reference [26]. Calculations and classificatory results were
performed and obtained using the online BMI calculator
provided on the CDC website (http://apps.nccd.cdc.gov/
dnpabmi/Calculator.aspx).
BMI-for-age weight status categories and the corresponding
percentiles are as follows: underweight category (less than 5th
percentile); healthy weight category (5th percentile to less than
Sensitivity of Zinc Kinetics
406VOL. 28, NO. 4

Page 3

85th percentile); risk of overweight category (85th percentile
to less than 95th percentile); and overweight category (95th
percentile or greater).
Food Intake Evaluation. Energy, protein, lipid, carbohy-
drate, fiber, calcium, iron, and zinc intake was assessed using
the 3-day prospective food diary. During this period, parents or
guardians recorded all food items consumed by the children. A
composition analysis of the diet then was performed using
NutWin 1.5 software from the Department of Health
Information Technology of the Escola Paulista de Medicina
(UNIFESP/EPM, Brazil).
Venous Zinc Tolerance Test
This test was initiated at 7:00 AM after a 12-hour fast. All
subjects remained in dorsal decubitus throughout the test. An
antecubital vein in each forearm was punctured, and an
infusion device was installed and maintained with physiologic
saline (zinc free). The bladder was emptied, the urine
discarded, and the time recorded. Intravenous administration
of 0.06537 mg/Zn/kg of body weight (1 mmol ZnSO47H2O)
over a period of 1 minute was started at time 0 minutes (8:00
AM). Next, 2.5 mL of blood samples were collected from the
contralateral arm at 230 (before zinc injection), 30, 60, 90,
and 120 minutes [24]. During this period, each child ingested
4 mL of ultra-pure water/kg body weight (Milli-Q Plus,
Millipore, Billerica, MA, USA) to facilitate urine collection
120 minutes after zinc injection (Fig. 2). Urine volume then
was determined in metal-free measuring cylinders.
Kinetic Approach
The procedures, which were performed between 8:00 and
10:00 AM after anthropometric assessment, consisted of bladder
emptying, ingestion of ultra-pure water, and puncture of a
forearm vein without a tourniquet [27]. Additional details are
specified in the venous zinc tolerance test.
Serum zinc level declined exponentially for up to
120 minutes after intravenous injection. Total body zinc
clearance (CZn) was calculated using the following equation:
Czn~Kel|Vd
where Kelis the elimination constant of serum zinc, and Vdis
the distribution volume. DCo, Kel, and Vdwere calculated as
follows:
DCo~Cp{Co
Kel~0:693=T1=2
Vd~dose i:v:=DCo
Fig. 1. Experimental design, aimed at the study of zinc kinetics, of nutritional assessment and the venous zinc tolerance test (VZnTT) in 42 children.
Fig. 2. Schedule of VZnTT used to evaluate the kinetic approach in 43 children from low-income families.
Sensitivity of Zinc Kinetics
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION407

Page 4

Cpis the theoretical serum zinc concentration immediately after
the injection, as calculated from the serum concentration versus
the time profile; Co is the basal serum zinc concentration; DCo
means the difference between Cp and Co; T1/2is the biological
half-life of serum zinc calculated directly from the serum
concentration versus the time profile [24].
Zinc Supplementation
All children were supplemented with 5 mg Zn/d for 3
months (i.e., exactly 90 days). Five drops was added to milk or
juice every morning. Zinc ingestion was controlled every 2
weeks by the same observer. The follow-up visit occurred
throughout the zinc supplementation period.
Drugs, Sample Collection, and Analysis
ZnSO47H2O was purchased from Merck (Darmstadt, Ger-
many). The ampoules were prepared at the InjectCenter–
Manipulac ¸a ˜o de Injeta ´veis, Ribeira ˜o Preto–SP, Brazil. Each
ampoule contained 5 mL 5 40 mmol ZnSO47H2O. The syrups
were prepared at the Pharmacotechnical Laboratory of the
Department of Pharmacy, UFRN. Each drop contained 1 mg of
elemental zinc.
Blood samples were obtained by puncturing a forearm vein
without a tourniquet. Samples showing hemolysis were
discarded because erythrocytes are rich in zinc [28]. All
procedures related to manipulation of zinc samples were
performed according to international standards for prevention
of zinc contamination of the environment [29].
The blood samples were placed in metal-free tubes without
anticoagulants and were kept at 37uC for 120 minutes in the
sterilizer until clot formation. After that, 500 mL of the serum
was collected with metal-free plastic pipettes and was
transferred to metal-free plastic tubes containing 2000 mL of
ultra-pure water to dilute the serum. The samples were kept at
220uC until the time of analysis [30].
Serum zinc was measured by atomic absorption spectro-
photometer (Spech AA-200, Varian, Victoria, Australia)
according to the manufacturer’s instructions. Sensitivity was
0.01 mg/mL, intra-assay coefficient of variation was 2.37%,
and reference values were 70 to 120 mg/dL. No side effects
were reported after intravenous zinc administration.
Other biochemical parameters such as total protein, hemato-
crit, hemoglobin, serum, and urinary creatinine were determined
using standard clinical laboratory methods: hemogram (Micros
60-OT, ABX Diagnostics, Montpellier, France), biochemical
parameters (RA-50, Bayer Diagnostics, Dublin, Ireland), and
urine analysis (RA-50, Bayer Diagnostics, Dublin, Ireland).
Statistical Analysis
We used Student’s t-test for paired samples (before and
after supplementation), using GraphPad Prism 5.0 (GraphPad
Software, Inc, San Diego, CA, USA). A p value of , 0.05 was
accepted as significant.
RESULTS
A total of 42 schoolchildren, aged between 6 and 9 years,
were studied. Forty-eight percent (n 5 20) were boys, and 52%
(n 5 22) were girls. According to BMI, 21.4% (n 5 9) had low
weight, 76.2% (n 5 32) had healthy weight, 2.4% (n 5 1) were
borderline overweight, and none were overweight (Fig. 3).
Food intake, consisting of energy, macronutrients, fibers,
calcium, iron, and zinc, showed no significant difference
before and after zinc supplementation, remaining constant
during the 3-month study. However, we found that energy,
calcium, and fiber consumption was suboptimal, given that it
was below recommended levels (Table 1).
All pharmacokinetic parameters studied (SZn, TK, Kel, Vd,
and CZn) were significantly different before and after zinc
supplementation, except Vd(Figs. 4 and 5, Table 2).
Other serum biochemical parameters, before and after zinc
supplementation, such as total protein and creatinine, were in
the normal range. Hematocrit, hemoglobin, and urinary
creatinine were also normal (data not shown).
DISCUSSION
We found a large percentage of children with healthy
weight (Fig. 3), even children from low-income families, in
this developing country. In recent decades, Brazil has
undergone a nutritional transition process, whereby overweight
and obesity, previously uncommon in low- income popula-
tions, have become increasingly widespread [31]. The
children’s families had a mean monthly income of
US$72.22, below the limit of US$105.55 established by the
United Nations Development Program–Atlas of Human
Development in Brazil, 2000 (UNDP).
However, increasing overweight and decreasing low weight
in low-income social class individuals do not indicate an
Fig. 3. Nutrition status expressed by BMI before oral zinc
supplementation in 42 children.
Sensitivity of Zinc Kinetics
408VOL. 28, NO. 4

Page 5

improved socioeconomic situation, but rather inadequate
nutritional patterns. Their diet may provide the necessary
calories but often is of low nutritional value and generally is
rich in simple carbohydrates and saturated and hydrogenated
fats, in addition to being poor in fibers and micronutrients
[32,33].
Thus, a diagnostic tool based only on proper weight does
not necessarily imply good nutritional status, in that poor
eating habits lead to insufficient intake of some nutrients and
excessive intake of others. Because this is so, food consump-
Table 1. Energy, Nutrient Intake, and Amount of Energy or Nutrient Recommended by Age and Sex before and after Oral Zinc
Supplementation in 42 Children*
Before SupplementationAfter Supplementation Recommendations
Energy, kcal1313 6 313.91378 6 350.1 6–9 years (for boys): 1573–1978 kcal/d1
6–9 years (for girls): 1428–1854 kcal/d1
Protein
%
g
14.615.810%–30%2
4–8 years (both sexes): 19 g/d3
9–13 years (both sexes): 34 g/d3
48.01 6 12.29 54.16 6 13.73
Fat
%
g
26.7 28.8 25%–35%2
ND4
38.90 6 13.6643.90 6 25.32
Carbohydrate
%
g
58.7 55.4 45%–65%2
130 g/d3
4–8 years (both sexes): 25 g/d5
9–13 years (for girls): 26 g/d5
9–13 years (for boys): 31 g/d5
4–8 years (both sexes): 800 mg/d6
9–13 years (both sexes): 1300 mg/d6
4–8 years (both sexes): 10 mg/d7
9–13 years (both sexes): 8 mg/d7
4–8 years (both sexes): 5 mg/d7
9–13 years (both sexes): 8 mg/d7
192.40 6 48.36
11.7 6 2.8
190.50 6 59.48
12.7 6 4.1 Fiber, g
Calcium, mg 515.9 6 209.9563.0 6 230.8
Iron, mg8.8 6 2.39.1 6 2.8
Zinc, mg6.4 6 1.7 6.7 6 1.7
* No significant differences were observed between energy and nutrients intake before and after oral zinc supplementation (p . 0.05).
1Energy requirements during growth [42].
2Acceptable macronutrient distribution ranges [43].
3Recommended Dietary Allowance [43].
4Not determinable (ND) [43].
5Adequate intake [43].
6Adequate intake [44].
7Recommended Dietary Allowance [16].
Fig. 4. Serum zinc levels before and after oral zinc supplementation in
42 children. Significant differences were observed at both moments (p
, 0.0001). Mean 6 SD before (102.4 6 10.5) and after (122.0 6 19.5)
zinc supplementation.
Fig. 5. Total-body zinc clearance before and after oral zinc
supplementation in 42 children. Significant differences were observed
at both moments (p 5 0.0002). Mean 6 SD before (5.50 6 1.20) and
after (6.20 6 1.05) zinc supplementation.
Sensitivity of Zinc Kinetics
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION409

Page 6

tion in children has been the focus of many studies, given the
importance of nutrition in health and in disease prevention
[34,35].
We observed low energy intake (Table 1), despite the
satisfactory percentage distribution of macronutrients. How-
ever, we found a preference for food rich in simple
carbohydrates and poor in unsaturated fat. We also found
low vegetable, grain, and whole food intake and therefore low
fiber ingestion. Among the analyzed micronutrients, we found
low calcium intake, which may have serious long-term health
effects. However, zinc and iron intakes were adequate
(Table 1). A number of studies on food consumption in
children and/or adolescents corroborate our results, in terms of
the nutritional imbalance of the food consumed by this
population [33,36,37].
Although some studies have pointed to the positive effects
of zinc supplementation on the sense of smell and of taste, and
the consequent increase in appetite and food ingestion [17], we
did not observe greater food consumption after 3-month zinc
supplementation (Table 1). Perhaps the economic limitation
for acquiring food items contributed to the unaltered food
consumption. Furthermore, the effect of zinc on taste, appetite,
and food intake seems to be greater in cases of anorexia caused
by zinc deficiency [38].
The lower normality limit of serum zinc suggested for
children younger than 10 years of age is 65 mg/dL, regardless
of whether or not the morning blood sample was collected after
overnight fast [2]. According to this reference, our children did
not have low SZn levels before or after supplementation
(Fig. 4, Table 2). Total protein, hematocrit, and hemoglobin
values were normal (data not shown).
Our results disagree with those of a number of studies
described in the literature. For example, researchers found
plasma zinc values lower than 70 mg/dL in 13% of 126
children between the ages of 2 and 7 years from the city of
Ribeira ˜o Preto, Brazil [39]. Others have reported plasma zinc
levels lower than 72 mg/dL in 38.4% of 159 Venezuelan
children aged 3 months to 8 years and belonging to low-
income families [40].
The normal SZn levels found in our study agreed with the
food pattern analyzed, given that the satisfactory ingestion of
animal protein and of zinc itself and the low phytate
consumption certainly contributed to the better bioavailability
of this mineral. The increase in SZn levels confirmed better
body zinc status as a positive response to supplementation
(Fig. 4, Table 2), because food consumption was constant over
the study period (Table 1).
After supplementation with this micronutrient, an increase
in CZn (Fig. 5) occurred as the result of its better reserves in
the body and the maintaining of organic homeostasis. Marginal
or moderate zinc deficiency may be detected with CZn $
20 mL/kg/h [13]. Nakamura et al. [24], when comparing the
CZn of 17 insulin-dependent diabetic patients and 15 control
subjects with mean age of 11.5 years, observed values of 24.6
6 1.8 and 15.1 6 0.6 mL/kg/h, respectively (p , 0.01). These
data showed marginal zinc deficiency in diabetic patients
despite their having normal SZn values. We were the first to
perform VZnTT after 3 months of oral zinc supplementation.
We believe that this time period is sufficient to reach the
optimum effect, given that changes in enzymatic activities
occur slowly [2].
Corroborating Nakamura et al. data [24], Kaji et al. [41], in
a sample of 30 children with mean age of 10 years, found 9
cases of elevated CZn value ($ 20 mL/kg/h) with normal SZn
concentrations, indicating marginal zinc deficiency. They
concluded that CZn concentrations were more useful than
SZn concentrations in diagnosing marginal zinc deficiency. In
our study, all the children had normal basal SZn levels and
CZn levels lower than 20 mL/kg/h (Table 2). It is likely that
no child had a marginal deficiency of this micronutrient.
However, after 3 months of zinc supplementation, a significant
improvement in SZn levels was observed, even so, within the
normal range. The same occurred with CZn, without exceeding
the value of 20 mL/kg/h. It is the first time that this
experimental model, using zinc supplementation, was used in
humans.
CONCLUSION
Because zinc is an essential trace element in human
nutrition, body zinc status evaluation is needed in some clinical
situations. In light of this, we conclude that the most important
finding reported in this paper, previously not shown in the
literature, was that kinetic sensitivity in detecting changes in
body zinc status was proved, even in children without a
Table 2. Kinetics Parameters of VZnTT before and after Oral Zinc Supplementation in 42 Children1,2
SZn, mg/dL
TK, h
Kel, Kel/h
Vd, L/kgCZn, mL/kg/h
Before supplementation (n 5 42)
After supplementation (n 5 42)
Student’s t-test (p value)
102 6 10.1
122 6 19.5
p , 0.0001*
2.73 6 0.597
2.39 6 0.261
p 5 0.0006*
0.265 6 0.051
0.294 6 0.033
p 5 0.0004*
0.0209 6 0.0028
0.0211 6 0.0022
p 5 0.6432
5.52 6 1.20
6.22 6 1.05
p 5 0.0002*
1p values expressed differences among all the parameters (p , 0.05), except for Vd(p . 0.05).
2Values are means 6 SD.
* Statistical significance (p , 0.05).
Sensitivity of Zinc Kinetics
410VOL. 28, NO. 4

Page 7

deficiency of this micronutrient. Furthermore, kinetics showed
a positive response to supplementation and may be considered
a sensitive parameter for evaluating the efficacy of this
therapy.
ACKNOWLEDGMENTS
This study was supported by CNPq grant no. 304514/03-9
and by CAPES grant no. 200587544. We thank the pharma-
cists Dina Maria de Arau ´jo, Teresa Cristina Paiva da Silva, and
Francisco Paulo Freire Neto for their technical assistance.
REFERENCES
1. Endre L, Beck FWJ, Prasad AS: The role of zinc in human health.
J Trace Elem Exper Med 3:337–375, 1990.
2. Hotz C, Brown KH: Assessment of the risk of zinc deficiency in
populations and options for its control. International Zinc Nutrition
Consultative Group (IZiNCG). Food Nutr Bull 25:S91–S204, 2004.
3. Krishna SS, Mamjumbar I, Grishin NV: Structural classification of
zinc fingers. Nucleic Acids Res 31:532–550, 2003.
4. Stefanidou M, Maravelias C, Dona A, Spiliopoulou C: Zinc: a
multipurpose trace element. Arch Toxicol 80:1–9, 2006.
5. Klaus-Helge I, Lothar R: Zinc-altered immune function. J Nutr
133:1452S–1456S, 2003.
6. Vallee BL, Falchuk KH: The biochemical basis of zinc
physiology. Physiol Rev 73:79–118, 1993.
7. Prasad AS: Zinc in human health. J Trace Elem Exp Med 11:63–
87, 1998.
8. Na ¨vert B, Sandstro ¨m B, Cederblad A: Reduction of the phytate
content of bran by leavening in bread and its effects on absorption
of zinc in man. Br J Nutr 53:47–53, 1985.
9. Sandstro ¨m B, Almgren A, Kivisto ¨ B, Cederblad A˚: Effect of
protein level and protein source on zinc absorption in humans. J
Nutr 199:48–53, 1989.
10. World Health Organization (WHO): ‘‘Trace Elements in Human
Nutrition and Health.’’ Geneva: World Health Organization, 1996.
11. Kawchak DA, Schall JI, Zemel BS, Ohene-Frempong K, Stallings
VA: Adequacy of dietary intake declines with age in children with
sickle cell disease. J Am Diet Assoc 107:843–848, 2007.
12. Branda ˜o-Neto J, Silva CAB, Rezende AA, Almeida MG, Sales
VSP, Marchini JS: Zinc pharmacokinetics in insulin-dependent
diabetes mellitus patients after oral zinc tolerance test. Nutr Res
23:141–150, 2003.
13. Nakamura T, Nishiyama S, Futagoishi-Suginohara Y, Matsuda I,
Higashi A: Mild to moderate zinc deficiency in short children:
effect of zinc supplementation on linear-growth velocity. J Pediatr
123:65–69, 1993.
14. Allen LH: Zinc and micronutrient supplements for children. Am J
Clin Nutr 68:495–498, 1998.
15. Kikafunda JK, Walker AF, Allan EF, Tumwine JK: Effect of zinc
supplementation on growth and body composition of Ugandan
preschool children: a randomized controlled, intervention trial.
Am J Clin Nutr 68:1261–1268, 1998.
16. Food and Nutrition Board, Institute of Medicine: ‘‘Dietary
Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron,
Chromium, Copper, Iodine, Iron, Manganese, Molybdenum,
Nickel, Silicon, Vanadium, and Zinc: A Report of the Panel on
Micronutrients, Standing Committee on the Scientific Evaluation
of Dietary Reference Intakes, Food and Nutrition Board, Institute
of Medicine. National Academy of Sciences, 2003.’’ Washington,
DC: National Academy Press, 2003.
17. Branda ˜o-Neto J, Stefan V, Mendonca BB, Bloise W, Castro AVB:
The essential role of zinc in growth nutrition research. Nutr Res
15:335–358, 1995.
18. Hambidge M: Biomarkers of trace mineral intake status. J Nutr
133:948–955, 2003.
19. Thompson RP: Assessment of zinc status. Proc Nutr Soc 50:19–
28, 1991.
20. Walsh CT, Sandstead HH, Prasad AS, Newberne PM, Fraker PJ:
Zinc: health effects and research priorities for the 1990s. Environ
Health Perspect 102:5–46, 1994.
21. Hotz C, Lowe NM, Araya M, Brown KH: Assessment of the trace
element status of individuals and populations: the example of zinc
and copper. J Nutr 133:1563–1568, 2003.
22. Feillet-Coudray C, Meunier N, Rambeau M, Brandolini-Bunlon
M, Tressol JC, Andriollo M, Mazur A, Cashman KD, Coudray C:
Long-term moderate zinc supplementation increases exchangeable
zinc pool masses in late-middle-aged men: the Zenith Study. Am J
Clin Nutr 82:103–110, 2005.
23. Nakamura T, Higashi A, Takano S, Akagi M, Matsuda I: Zinc
clearance correlates with clinical severity of Crohn’s disease: a
kinetic study. Dig Dis Sci 33:1520–1524, 1988.
24. Nakamura T, Higashi A, Nishiyama S, Fujimoto S, Matsuda I:
Kinetics of zinc status in children with IDDM. Diabetes Care
14:553–557, 1991.
25. World Health Organization: ‘‘WHO Expert Committee on
Physical Status: The Use and Interpretation of Anthropometry
Physical Status,’’ WHO Technical Report Series, Vol. 854.
Geneva: World Health Organization, 1995.
26. Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R,
Grummer-Strawn LM, Curtin LR, Roche AF, Johnson CL:
Centers for Disease Control and Prevention 2000 Growth Charts for
the United States: Improvements to the 1977 National Center for
Health Statistics Version. Pediatrics 109:45–60, 2002.
27. Branda ˜o-Neto J, Silva ACB, Shuhama T, Silva JA, Oba L: Renal
handling of zinc in insulin-dependent diabetes mellitus patients.
BioMetals 14:75–80, 2001.
28. Wood RJ: Assessment of marginal zinc status in humans. J Nutr
130:1350–1354, 2000.
29. Branda ˜o-Neto J, da Silva CAB, Figueiredo NB, Shuhama T,
Holanda MBS, Diniz JMM: Zinc kinetics in insulin-dependent
diabetes mellitus patients. BioMetals 13:141–145, 2000.
30. Branda ˜o-Neto J, da Silva CAB, Figueiredo NB, Shuhama T, da
Cunha NF, Dourado FB, Naves LA: Lack of acute zinc effects in
glucose metabolism in healthy and insulin-dependent diabetes
mellitus patients. BioMetals 12:161–165, 1999.
31. Kac G, Vela ´squez-Mele ´ndez G: A transic ¸a ˜o nutricional e a
epidemiologia da obesidade na Ame ´rica Latina. Cad Saude
Publica 19:4–5, 2003.
32. Escoda MSQ: For a critic to the nutritional transition. Cien Saude
Colet 7:219–226, 2002.
Sensitivity of Zinc Kinetics
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION411

Page 8

33. Maestro V: Padra ˜o alimentar e estado nutricional: caracterizac ¸a ˜o
de escolares de municı ´pio paulista. Dissertac ¸a ˜o de mestrado.
Escola Superior de Agricultura Luiz d Queiroz, 2002.
34. Fleming K, Carlson S, Ohls J, Kennedy ET: The Healthy Eating
Index: design and applications. J Am Diet Assoc 95:1103–1108,
1995.
35. Wolfe WS, Cowell C, Wales KR, Rhoades SJ, Melnik TA: Food
consumption patterns of elementary school children in New York
City. J Am Diet Assoc 98:159–164, 1998.
36. Caroba DCR, Vieira da Silva M: Food consumption of adolescents
registered in the public schools of the city of Piracicaba–SP.
Seguranc ¸a Alimentar e Nutricional 12:55–66, 2005.
37. Rameshwar Sarma KV, Udaykumar P, Balakrishna N, Vijayar-
aghavan K, Sivakumar B: Effect of micronutrient supplementation
on health and nutritional status of schoolchildren: growth and
morbidity. Nutrition 22:8–14, 2006.
38. Shay NF, Mangian HF: Neurobiology of zinc-influenced eating
behavior. J Nutr 130:1493–1499, 2000.
39. Fa ´varo RMD, Vannucchi H: Nı ´veis plasma ´ticos de zinco e
antropometria de crianc ¸as da periferia de centro urbano no Brasil.
Rev Saude Publica 24:5–10, 1990.
40. Amaya D, Urrieta R, Gil NM, Molano NC, Medrano I, Castejo ´n
HV: Valores de zinc plasma ´tico em una poblacio ´n infantil
marginal de Maracaibo, Venezuela. Arch Latinoam Nutr 47:23–
28, 1997.
41. Kaji M, Gotoh M, Takagi Y, Masuda H, Kimura Y, Uenoyama Y:
Studies to determine the usefulness of zinc clearance test to
diagnose marginal zinc deficiency and the effects of oral zinc
suplementation for short children. J Am Coll Nutr 17:388–391,
1998.
42. Human energy requirements: Report of a Joint FAO/WHO/UNU
Expert Consultation. Rome, 17–24 October 2001.
43. Institute of Medicine: ‘‘Dietary Reference Intakes (DRIs) for
Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol,
Protein, and Amino Acids.’’ Washington, DC: National Academy
Press, 2005.
44. Institute of Medicine: ‘‘Dietary Reference Intakes for Calcium,
Phosphorus, Magnesium, Vitamin D, and Fluoride. Standing
Committee on the Scientific Evaluation of Dietary Reference
Intakes. Food and Nutrition Board.’’ Washington, DC: National
Academy Press, 1997.
Received December 20, 2007; Accepted March 25, 2008.
Sensitivity of Zinc Kinetics
412 VOL. 28, NO. 4