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ARTICLE IN PRESS

Journal of Trace Elements in Medicine and Biology 21 (2007) 178183


www.elsevier.de/jtemb

EPIDEMIOLOGY

Molybdenum in human whole blood of adult residents of the


Merida State (Venezuela)
Jose L. Burguera, Marcela Burguera
Department of Chemistry, Faculty of Sciences, University of Los Andes, Merida, Venezuela
Received 31 January 2007; accepted 16 March 2007

Abstract
The concentration of molybdenum was measured in whole blood samples of 418 (244 males and 174 females)
apparently normal donors ranging in age from 18 to 27-years old and living in nine different locations in the Merida
State (Venezuela). The geometric mean concentration of molybdenum of 418 subjects was of 2.6670.66 mg L1 (range:
1.204.80 mg L1). The levels of molybdenum in whole blood samples found in this work were of 2.5770.52 and
2.5470.51 (range: 1.204.80 and 1.404.20) mg L1 for males and females, respectively. The data of the content
molybdenum in whole blood had no statistical correlation with age, sex or height above the sea level of the sampling
sites. However, there was a tendency to decrease the levels of the element in those sampling sites located in highlands
(X1900 m above the sea level). This variability may be due to the source of molybdenum from the soil to the food
chain that has affected its levels in donors from these areas under study. The results of this study are compared with
values previously reported for subjects studied in other populations.
r 2007 Elsevier GmbH. All rights reserved.
Keywords: Molybdenum; Blood; Trace elements; Biomonitoring

Introduction
The transition element molybdenum exists in ve
oxidation states (IIVI), the predominant states are
Mo(IV) and Mo(VI). Within this risk assessment, the
word molybdenum refers to ionic molybdenum except
where the specic compound is stated. Molybdenum
does not exist naturally in the metallic state, but occurs
in association with other elements. The predominant
form of molybdenum occurring in soil and natural
waters is the molybdate anion, MoO2
4 .

Corresponding author.

E-mail address: burguera@ula.ve (J.L. Burguera).


0946-672X/$ - see front matter r 2007 Elsevier GmbH. All rights reserved.
doi:10.1016/j.jtemb.2007.03.005

Molybdenum is an essential element [1,2], but also


potentially toxic [3,4] to humans. Molybdenum is
considered an essential element for man because it is
bound to and required for the function of several
molybdoenzymes. In these molybdoenzymes, Mo is
inserted as part of a prosthetic group, known as the
molybdenum cofactor. Two of these molybdoenzymes,
xanthine oxidase and aldehyde oxidase are important to
man and one, sulte oxidase, is indispensable [2]. A rare
inborn error of metabolism, molybdenum cofactor
deciency, is characterized by a combined deciency of
the three above enzymes. Molybdenum has been
claimed to reduce the incidence and severity of dental
caries. Also, it has been reported to be benecial to
various groups of individuals, including those with
sulte sensitivity, asthmatics with elevated urinary ratios

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J.L. Burguera, M. Burguera / Journal of Trace Elements in Medicine and Biology 21 (2007) 178183

of sultes to sulfates, and those intolerant to intravenous sulfur containing amino acids. Molybdenum
poisoning is virtually unknown [1,2]. Excessive dietary
intake of grains, seeds, and legumes rich in molybdenum
can cause deposits in soft tissues and joints, and trigger
arthritic symptoms. Other symptoms include gout,
severe diarrhea, growth depression, and anemia (typical
symptoms of copper deciency) [1,2]. Also, molybdenum is important for uric acid metabolism [5].
Absorption of molybdenum varies over a wide range
(2593%). Reports suggest that soluble molybdenum
compounds are readily absorbed [6], whilst insoluble
compounds are not. It is recognized that molybdenum
interacts with copper and sulfates in living organisms,
but the mechanism of this interaction has not been
elucidated. The presence of dietary copper and sulfate
affects the amount of molybdenum absorbed and
retained by the body. In addition, molybdenum is
present in the diet and body in small quantities and has
been difcult to measure. The basis of the importance of
molybdenum is in its role. Molybdenum is readily and
rapidly absorbed from most diets and inorganic forms
of the element [7]. Molybdenum is available in food
supplements at levels up to 0.33 mg and licensed
medicines. The latter are used (maximum daily dose
0.25 mg) to treat patients with malabsorption states
and conditions leading to hypoproteinaemia and in
perioperative nutritional support [1]. Most natural
waters contain low levels of molybdenum. The WHO
recommends a maximum level of molybdenum in
drinking water of 0.07 mg L1 and notes that concentrations of molybdenum in drinking water are typically
less than 0.01 mg L1 [8]. However, in areas near
mining sites, molybdenum concentrations up to
0.2 mg L1 have been reported. The minimum dietary
requirements for molybdenum compatible with satisfactory growth and health cannot be given in even
approximate terms for any animal species, including
man, nor has Mo deciency been observed under
natural conditions with any species. The exact human
Mo requirements are unknown and the results of shortterm balance studies with this element are not very
informative because of the widely varying amounts of
Mo involved. The WHO [8] estimated a daily requirement for molybdenum of between 0.1 and 0.3 mg/day
for adults.
Molybdenum deciency has not been identied in
free-living human or animal species. It has, however,
been identied in a single subject receiving total
parenteral nutrition and can be achieved in animal
studies. In goats, a molybdenum decient diet was
associated with reduced fertility and increased mortality
in both the mothers and the offspring. In a rare inherited
metabolic disorder, molybdenum deciency is associated
with genetic deciency of the molybdenum pterin
cofactors. Neurological disorders, abnormal urinary

179

metabolites, dislocated ocular lenses and failure to


thrive are observed. The disorder is fatal by the age of
23 years.
There are insufcient data from human or animal
studies to establish a Safe Upper Level for molybdenum.
Also, there are few reliable data on the oral toxicity of
molybdenum. A limited human study [9] suggests that
molybdenum intake of 115 mg/person/day could be
associated with an increase in gout-like symptoms,
e.g., joint pains and increased serum uric acid levels.
The form of molybdenum to which the population
was exposed is unclear, but as exposure is via water
and locally grown/produced food, it is most likely
to be the more toxic hexavalent molybdate ion.
However, this epidemiological evidence is not robust,
as there is no means of unbiased assessment, no control
group and the exposure to molybdenum cannot
accurately be determined. Lack of evidence makes it
impossible to determine whether higher intakes would
be problematic.
Little research has been done on molybdenum
requirements of humans, partly because deciency
symptoms have not been observed in healthy humans.
Molybdenum can be measured in various tissues.
Molybdenum occurs in low concentrations in all the
uids and tissues of the body. The greatest amounts are
found in the kidney, liver, small intestine and adrenals.
It is found largely as molybdoenzymes. In plasma,
molybdenum is bound specically to 2-macroglobulin.
Blood serum, plasma and whole blood Mo concentration is associated with intake of this trace element [10].
Thus, the Mo content in these matrixes is considered to
serve as an index in the evaluation of its nutritional
status. Although, few studies have provided reliable
information on the Mo content in blood serum and
plasma [47,1115], lesser numbers of studies on whole
blood have been reported [9,1618].
Concerning Venezuelan people, there has not been
report on whole blood molybdenum. We thus determined the whole blood in 418 Venezuelan adults,
residents from different places of the Merida State, in
an attempt to establish a reference range of whole blood
molybdenum concentration of healthy Venezuelan
adults.

Materials and methods


Subjects, samples and analysis of Mo
The study followed the Declaration of Helsinki.
A total of 418 healthy subjects (244 males, 174 females)
donors, ranging in age from 18 to 27 years and residing
in the area were selected in this study (see below). None
had any supplementation of diets with trace elements or
showed any abnormality on physical examination and

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J.L. Burguera, M. Burguera / Journal of Trace Elements in Medicine and Biology 21 (2007) 178183

their body weight and height were within the normal


range. The specimens were obtained between 8:00
and 10:00 a.m. and were drawn from an antecubital
vein using vacutainer tubes. The sample preparation
for analysis was performed as previously indicated
in a work of our research team [19]. The on-line owinjection microwave-assisted mineralization with
a precipitation/dissolution system was used for the
determination of molybdenum in whole blood [20].
Gender, age, location of sampling places at different
heights above the sea level were used as grouping
variables.

Table 1. Molybdenum content in whole blood of healthy


Venezuelan adults
Sexa

Parameter

Value

M+F

n
Mean Mo concentration /mg L1
SD
CV
Minimum value/mg L1
Maximum value/mg L1

418
2.66
0.66
24.80
1.20
4.80

n
Mean Mo concentration /mg L1
SD
CV
Minimum value/mg L1
Maximum value/mg L1

244
2.57
0.52
15.32
1.20
4.80

n
Mean Mo concentration /mg L1
SD
CV
Minimum value/mg L1
Maximum value/mg L1

174
2.54
0.51
17.12
1.40
4.20

Statistical analysis
Summary statistic (n, mean, standard deviation (SD),
minimum and maximum values of variables, correlation
analysis based on Pearson correlation coefcient,
correlation coefcients were calculated. The changes to
determine the signicance difference between groups
were analyzed using Students t-test [21]. Because the
distribution of data in some population groups was
slightly skewed, analyses using these variables were
also done after logarithmic transformation, but the
results were essentially unchanged. The relationship
between variables (age, sex and height above the sea
level of each place) was assessed by using backward
stepwise-multiple-regression
analyses.
Statistical
analysis was performed with STATISTIX 7.0 for
Windows. To adequately interpret the differences
within the dened groups, the statistical signicance
was accepted for a condence level of 95% of pp0.05
[21].

Results and discussion


Mean concentrations and concentration rages of
molybdenum in whole blood samples of the 418 human
subjects are given in Table 1. The geometric mean
concentration of molybdenum of the 418 subjects
(males+females) was of 2.6670.66 mg L1 (range:
1.204.80 mg L1). These values are consistently considered normal with those for most individuals (from 0.6
to 13.1 mg L1) [11]. Also, our range values overlapped
most information available in the literature, such as the
results reported by Heitland and Koster (range:
0.064.00 mg L1) [18] and Iyengar (range: 0.83.3 mg L1)
[22,23]. The concentration reported in this study for
molybdenum is lower than those reported by some other
authors: 18 mg L1 by Pandey et al. [14]; 14.7 mg L1 by
Bala and Lifshits [24]; 5 mg L1 by Allaway et al. [17].
However, difculties for comparison purposes arise by
the disparate values of molybdenum content in human
whole blood obtained by different workers.

M males and F females.

A wide range of plasma molybdenum concentrations


have been reported, with average values from 5.6 to
257 mg L1 prior to 1973 [1113]. Certain environmental
and individual differences may of course exist, but such
large discrepancies are more likely to be caused by the
use of analytical techniques of insufcient accuracy as
well as by contamination factors. However, the normal
molybdenum content in blood plasma and serum
appears to be about 0.5 mg L1 [1113,2530] with
concentration within the range from 0.5 to 18 mg L1
[3,11,14,15]. The values of molybdenum in whole blood
are slightly higher than those reported for blood plasma
and blood serum. The previous differences could be
likely due to the fact that molybdenum is rmly
bound only to the erythrocyte and plasma proteins
[1,24,31], which may cause an increase of the
element in the red cells of whole blood with no change
in serum and plasma. The more probable values for Mo
in whole blood seem to be in range 0.610.2 mg L1
[11,1618].
The levels of molybdenum in whole blood found in
this work were of 2.5770.52 and 2.5470.51 (range:
1.204.80 and 1.404.20) mg L1 for males and females,
respectively (Table 1). There was no signicant difference in the molybdenum content between the two
genders (Fig. 1). An analysis of variance between the
sex groups revealed that in all cases the groups were
homogeneous (CVo30%).
There was not a statistically signicant difference in
the molybdenum content with respect to the age of

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J.L. Burguera, M. Burguera / Journal of Trace Elements in Medicine and Biology 21 (2007) 178183

3.5

[Mo] / gL

-1

3.0

2.5

2.0

1.5

1.0
F

Fig. 1. Box plots showing the content of molybdenum in


whole blood samples of males and females from the Merida
State, Venezuela (M males and F females).

Table 2.

181

subjects. An analysis of variance between the different


samples with age revealed a homogeneous distribution
of values.
The means and standard deviations of the molybdenum levels obtained for the subjects from the places
located above 1900 m tended to be lower than those
obtained from other populations (Table 2 and Fig. 2).
However, there may be therefore a source of molybdenum from the soil of those highland zones to the
food chain that affects the levels of molybdenum in
whole blood due to the effect of some local factors
upon the human molybdenum intake [6,7]. This
effect could be likely be explained by the fact that
pronounced differences in the kind of crops are found,
which are highly related to the height of the area under
study. However, a study of environmental sources of
molybdenum in the areas under study would be
worthwhile.

Molybdenum content in whole blood of healthy Venezuelan adults

Place

Height above the sea level/m

Sexa

Mucuchies

2983

M
F
M+F

Bailadores

1900

Timotes

nb

Mean7SD

Range

17
9
26

1.8470.34
1.9370.31
1.8870.33

1.422.40
1.502.40
1.422.40

M
F
M+F

20
10
30

1.5770.22
1.6670.18
1.6070.21

1.202.01
1.412.00
1.202.01

1994

M
F
M+F

18
16
34

2.4270.71
2.3670.57
2.3970.63

1.503.31
1.503.20
1.503.31

952

M
F
M+F

16
15
31

2.8070.45
2.7170.44
2.7670.44

1.923.40
1.833.24
1.833.40

1603

M
F
M+F

77
37
114

2.9070.67
2.9570.68
2.8470.50

2.114.80
2.204.21
2.114.80

150

M
F
M+F

27
21
48

2.8370.57
2.7870.45
2.8170.52

1.944.10
1.933.71
1.934.10

1100

M
F
M+F

21
21
42

2.6870.33
2.6470.33
2.6670.33

2.133.14
2.023.20
2.023.20

Zea

910

M
F
M+F

20
19
39

3.1770.65
2.9470.57
3.0670.62

2.424.20
2.324.00
2.324.20

Santa Cruz

622

M
F
M+F

28
26
54

2.9670.60
2.9470.51
2.8770.56

2.244.00
2.134.10
2.134.10

Tovar

Merida city

El Vigia

Lagunillas

M males and F females.


n number of subjects.

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J.L. Burguera, M. Burguera / Journal of Trace Elements in Medicine and Biology 21 (2007) 178183

F
3.0

[Mo] / gL-1

2.5
2.0
1.5
1.0
0.5
0.0
0

500

1000
1500
2000
Height above the sea level / m

2500

3.0

3000

[Mo] / gL-1

2.5
2.0
1.5
1.0
0.5
0.0
0

500

1000
1500
2000
Height above the sea level / m

2500

3000

Fig. 2. Mean concentration of molybdenum of subjects from places located at different height above the sea level (M males and
F females).

Acknowledgments
This research was supported by FONACIT (Fondo
Nacional de Ciencia, Tecnolog a e Innovacion), Venezuela. Proyect S1-2000000449.

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