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European Journal of Clinical Nutrition (1998) 52, 529±535
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The serum selenium concentrations in children and young
adults: a long-term study during the Finnish selenium
fertilization programme
W-C Wang1,5, A-L MaÈkelaÈ2, V NaÈntoÈ1,5, P MaÈkelaÈ3, and H LagstroÈm4,
Departments of 1Clinical Chemistry and 2Pediatrics, 3Department of Nuclear Medicine, Turku University Central Hospital; 4the
Cardiorespiratory Research Unit, University of Turku; and 5the Joint Clinical Biochemistry Laboratory of the University of Turku, Turku
University Central Hospital and Wallac Ltd., FIN-20520 Turku, Finland
Objective: To investigate the effects of the Finnish nationwide selenium (Se) fertilization programme on the Se
status of the population.
Design and subjects: Serum Se concentrations from 1985±1992 from 1568 healthy children and young adults in
southwestern Finland were determined using direct electrothermal atomic absorption spectrometry.
Results: The mean concentration in young adults increased from 1.04 mmol/L in 1985 to 1.59 mmol/L in 1990.
Children younger than 15 y had lower concentrations than adults, with an increase from 0.87 mmol/L in 1985 to
1.31 mmol/L in 1990. The younger the children, the lower the Se concentrations tended to be. At the age of about
seven months no signi®cant difference was noted between breast-fed and formula-fed infants. From 1991, when
the amount of Se added to fertilizers was reduced and less foreign high-Se cereal was imported, the Se
concentrations decreased in all age groups.
Conclusions: The nationwide Se supplementation programme has succeeded in elevating the Se intake and the
serum Se concentrations in the Finnish population.
Sponsorship: Supported by the Juho Vainio Foundation and the Sigrid Juselius Foundation, Finland.
Descriptors: serum selenium; age-dependency; selenium fertilization
Introduction
Subjects
One thousand, ®ve hundred and sixty-eight apparently
healthy people (716 males and 852 females, altogether
2143 serum samples) were investigated during this series
of studies (MaÈkelaÈ et al, 1993, 1995; Wang et al,
1995a,b,c). Of them 1081 are children, with a mean age
of 4.3 y (s.d. 4.0 y, range 0.5 ±14.7 y) and 487 young adults,
with a mean age of 24.3 y (s.d. 3.4 y, range 15 ±30 y). Two
hundred and fourteen were healthy siblings of children
suffering from insulin-dependent diabetes mellitus or
from juvenile rheumatoid arthritis (Wang et al, 1995b,c).
In addition, we were given access to serum specimens,
which had been collected in 1990 ±1992 for determination
of serum lipids in a project on atherosclerosis risk factors in
children at the Cardiorespiratory Research Unit (CRU),
University of Turku (Lapinleimu et al, 1995). Of the
1290 subjects 867 were children under 15 y of age (from
six months to 14.7 y) and 188 were their adult family
members (age range from 19.7±30 y). There was no diet
restriction for the subjects.
Three groups of medical students were included in the
study: 108 students (70 females and 38 males, ages from
18.6 ±29.4 y) from 1985±1990, and 35 students (31 females
and 4 males, ages from 21.3±29.4 y) in 1991 (MaÈkelaÈ et al,
1993). In 1992, 65 students (46 females, 19 males, ages
from 23.1±29.6 y) were investigated. Other adults (91
people) were members of the staff of the clinic.
If more than one sample was taken from same person in
the same year, the mean value of these samples was
calculated and used when calculating the mean values
presented in the tables. The study was approved by the
Commission on Ethics of the University of Turku.
Informed consent was obtained from all adults or all
parents of the children.
Correspondence: Dr W-C Wang, Department of Clinical Chemistry,
University of Turku, FIN-20500 Turku, Finland.
Received 6 February 1998; revised 10 March 1998; accepted 31 March
1998
Methods
The blood samples for the serum Se analysis were collected
into Vacutainer1 tubes (Becton Dickinson, Rutherford, NJ,
Finland is for geochemical reasons a low-Se area and,
consequently, the daily dietary intake of Se in the Finnish
population has been one of the lowest in the world. In 1984
an of®cial decision was made to increase the intake of Se in
the population by adding Se to multimineral agricultural
fertilizers (Ministry of Agriculture and Forestry, 1984).
Fertilizers used for the production of hay and fodder were
supplemented with 6 mg=kg of Se in the form of sodium
selenate, and fertilizers for cereal were supplemented with
16 mg=kg. As a result, Se content increased in agricultural
products, in dairy products and in meat (Varo et al, 1988;
1994; Eurola et al, 1989, 1991; Ekholm et al, 1991). An
increase followed in the Se intake and resulted in higher
serum Se concentration in the whole population. In 1991
the amount of Se added to the fertilizers was reduced to the
level of 6 mg=kg for all fertilizers (Ministry of Agriculture
and Forestry, 1990). We report here observations on the Se
status in healthy children and young adults from the studies
of the effects of the Se fertilization programme in southwestern Finland.
Materials and Methods
Effects of selenium fertilization in Finland
W-C Wang et al
530
USA). After centrifugation, the serum was transferred into
acid-washed polyethylene tubes, which were frozen immediately and stored at 720 C until analysis (Lakomaa et al,
1988). The serum samples from the risk factor project had
been stored frozen at 720 C.
The concentration of Se in serum was determined by
direct electrothermal atomic absorption spectrometry,
according to the method of Alfthan & Kumpulainen
(1982), using a Zeeman=3030 spectrometer (PerkinÈ berlingen, Germany) with an auto sampler (ASElmer, U
60, Perkin-Elmer) and a printer (PR-100, Perkin Elmer).
Internal quality control was carried out with Seronorm
human serum reference controls (Nycomed Pharma AS,
Oslo, Norway). The within-assay relative coef®cient of
variation was 5.4% at a level of 0.82 mmol=L, 4.3% at
1.02 mmol=L, and 5.0% at 1.30 mmol=L. The inter-assay
coef®cient of variation was 5.5% at a level of 0.82 mmol=L,
4.3% at 1.02 mmol=L, and 4.9% at 1.30 mmol=L. The
recovery rates ranged from 102±95.1% at three Se levels
of 0.50 ±2.00 mmol=L. Interlaboratory calibration using
serum samples was carried out with National Public
Health Institute, Helsinki, to con®rm Se analyses.
In the risk factor project group food consumption and Se
intake of children aged 7 and 13 months had been evaluated
using 3-consecutive-day food records. The parents were
carefully taught to record the child's food consumption and
they were also given written instructions of how to ®ll the
food consumption records with exact descriptions and
amounts of all foods and drinks consumed. Amounts
were estimated using household measures (glasses, cups,
tablespoons, slices, deciliters, etc.). The parents or day-care
personnel recorded the type, brand and preparation of all
foods in detail. The records were reviewed, item by item,
by the dietitians for completeness and accuracy during the
follow-up visit. Missing portion sizes, food descriptions,
etc., were added if needed.
Daily energy and Se intakes were calculated as means of
the recorded days for each child. Intake of nutrients from
supplements was not included in these calculations. The
Micro NUTRICA programme (Knuts et al, 1987), developed at the Research Centre of the Social Insurance
Institution, Turku, Finland was used for the calculation.
The programme uses the Food and Nutrient Data Base of
the Social Insurance Institution (Rastas et al, 1993) and it
calculates 63 nutrients of commonly used food stuffs and
dishes in Finland.
statistical signi®cance of the differences among the groups
was tested by analysis of variance using SAS=STAT software (Statistical Analysis Systems, 1985). The Bonferroni
method was used to test the signi®cance of changes within
the groups (Wallenstein et al, 1980). The differences were
considered signi®cant when the P values were less than or
equal to 5%.
Results
Table 1 shows the number of subjects as well as the number
of collected serum samples and the mean serum Se concentrations and ranges for each year. The number of
samples varies from year to year because the samples
were taken from different projects in different years. The
high number of samples in 1990 ±1991 is because a lot of
samples were taken from the large material of the project of
atheriosclerosis risk factors. Serum Se concentrations for
subjects of different ages during the study are shown in
Figures 1 and 2. The most notable changes in Se values
were seen during the initial phase of the Se fertilization
programme, between 1985 and 1986. The increase was
highly signi®cant (P < 0.001). In 1985 the lowest measured
Se value was 0.54 mmol=L, observed in a nine-year old girl,
in the following years such low values were not found any
more.
At the start of the Se supplementation, in 1985, children
younger than 15 y had signi®cantly (P < 0.001) lower mean
serum Se than young adults (Table 2). The full effect of the
supplementation was observed during the following year, in
1986, when the mean value was 1.26 mmol=L in children
and 1.30 mmol=L in young adults. The serum Se concentrations continued to increase, reaching the highest value in
1990 (mean 1.59 mmol=L, range 1.08±2.19 mmol=L) in
adults. Some increase was also documented in children
younger than 15 y until a mean value of 1.31 mmol=L (range
0.82±1.99 mmol=L) was reached in 1990. The increase was
signi®cantly smaller in children than in the older age group
(P < 0.001), and the difference between the two groups
remained. In 1991±1992 a slight decrease in the serum Se
values was documented in both age groups, which
obviously was due to the reduction in the amount of Se
added to fertilizers in 1991.
Another factor which in addition to the supplementation
affected the Se intake was the import of foreign cereal with
a high Se content (Varo et al, 1988). Figure 3 presents the
annual import of foreign cereal together with the serum Se
values in children and adults. In 1988 and 1989 the amount
of foreign cereal was high and may also have contributed to
the increase in the serum Se in the adults up to 1990.
Statistical analyses
The Student's t-test was used for testing the statistical
signi®cance of the differences between two groups. The
Table 1 The number of subjects and serum concentrations (mmol=L, mean and range) in 1985 ±1992
Males
Females
Total
Year
na
nb
na
nb
na
nb
1985
1986
1987
1988
1989
1990
1991
1992
119
56
16
29
39
281
260
46
129
60
20
44
65
284
260
48
179
104
19
46
77
367
250
86
193
115
23
67
116
378
250
91
298
160
35
75
116
648
510
132
322
175
43
111
181
662
510
139
Total
a
Number of subjects.
Number of samples.
b
910
1233
2143
Se
0.97
1.29
1.26
1.34
1.46
1.43
1.32
1.35
(0.54±1.44)
(0.87±1.72)
(1.01±1.60)
(1.04±1.80)
(0.99±2.10)
(0.82±2.19)
(0.72±2.13)
(0.79±1.88)
Effects of selenium fertilization in Finland
W-C Wang et al
531
Figure 1 Serum selenium concentrations of healthy Finnish children and young adults in 1985±1988.
Figure 2 Serum selenium concentrations of healthy Finnish children and young adults in 1989±1992.
Table 2
Serum selenium values (mmol=L, mean and range) in healthy children (<15 y) and young adults (>15 y) in different years
Year
na
nb
1985
1986
1987
1988
1989
1990
1991
1992
119
37
29
41
36
372
473
48
140
52
37
72
72
372
473
48
a
Number of subjects.
Number of samples.
c
Not signi®cant.
b
Children
0.87
1.26
1.26
1.29
1.32
1.31
1.30
1.22
(0.54±1.44)
(0.96±1.57)
(1.01±1.60)
(1.04±1.70)
(1.09±1.75)
(0.82±1.99)
(0.72±1.77)
(0.79±1.52)
na
nb
179
123
6
34
80
276
37
84
182
123
6
39
109
290
37
91
1.04
1.30
1.29
1.40
1.52
1.59
1.57
1.42
Adults
P value
(0.62±1.35)
(0.87±1.72)
(1.16±1.41)
(1.20±1.80)
(0.99±2.10)
(1.08±2.19)
(1.13±2.13)
(1.06±1.88)
<0.001
NSc
NSc
<0.001
<0.001
<0.001
<0.001
<0.001
Effects of selenium fertilization in Finland
W-C Wang et al
532
However, in children serum Se concentrations remained at
the level reached in 1988. In Figure 3 the serum values are
also presented separately in males and females. A more
detailed analysis shows that the differences are only marginal between the two genders even if the results are
presented separately in the groups of adults and of children.
An analysis of serum Se for children in the different age
groups showed that the younger the children, the lower the
serum Se concentrations are for example, in 1990 children
younger than 3 y (n ˆ 259 subjects) had a mean serum Se
value of 1.25 mmol=L (range 0.82±1.76 mmol=L) and children, ages 3±15 y (n ˆ 113 subjects), had a mean serum Se
concentration of 1.46 mmol=L (range 1.11±1.99 mmol=L).
The difference between the groups was highly signi®cant
(P < 0.001). Moreover, the difference has existed during
1985±1992.
In 1990, at the age of about seven months, 66 children
were breast-fed and 83 were formula-fed. Of the formulafed infants 14.3% were given `Piltti' (Van den Bergh,
Lapinlahti, Finland), 5.4% received `Bona' (Chymos-
Figure 3 Serum selenium concentrations in 1985±1992 as compared with the yearly amount of imported Se-rich cereals (information from the Finnish
Grain Board, Helsinki).
Effects of selenium fertilization in Finland
W-C Wang et al
Table 3
533
Estimated selenium intake of infants
Age
Year
(months)
na
1990
1990
1991
1992
7
13
13
13
56
78
422
44
Energy intake (kcal=d)
Mean (s.d., range)
807
952
981
998
(150,
(169,
(172,
(225,
282±1128)
688±1428)
321±1553)
469±1635)
Se intake (mg=d)
Mean (s.d., range)
PRI of Sea
(mg=d)
6.4 (4.9, 0.1±23.8)
16.4 (7.7, 1.2±41.8)
15.8 (8.5, 1.2±46.9)
16.0 (9.3, 2.3±48.8)
8
10
10
10
Serum Se (mmol=L)
Mean (s.d., range)
1.17
1.33
1.29
1.22
(0.15,
(0.14,
(0.15,
(0.15,
0.91±1.49)
1.03±1.63)
0.72±1.77)
0.79±1.52)
a
Number of infants.
PRI ˆ the population reference intake, recommended by the Scienti®c Committee for Food of the European Community.
b
Nestle, Lappeenranta, Finland) and 80.3% were given
`Tutteli' (Valio, Turenki, Finland). In this study no signi®cant difference was found between the serum Se concentrations of breast-fed and formula-fed infants. The mean
serum Se value in the breast-fed infants was 1.18 mmol=L
(s.d. 0.19 mmol=L, range 0.82±1.76 mmol=L) and that in the
formula-fed was 1.16 mmol=L (s.d. 0.14 mmol=L, range
0.89±1.57 mmol=L).
From the formula-fed infants at the age of seven months,
complete food records were available from 56 children
(Table 3). According to food records, the mean calculated
daily intake of Se in this group of children was 6.4 mg (s.d.
4.9 mg). The range extended from 0.1±23.8 mg of Se per day
in individual daily food records, indicating large differences in the intake. Se serum concentrations of these 56
children, however, were on an adequate level, with the
mean value being 1.17 mmol=L (Table 3).
In the age group of 13 months, food records for children
and the calculated average daily Se intake were shown in
Table 3. The range of intake for individual children was
very wide extending from 1.2 mg± 48.8 mg of Se per day. On
the other hand, in these groups of children the Se serum
concentrations were also on adequate levels, the mean
values being in 1990 1.33 mmol=L, in 1991 1.29 mmol=L
and in 1992 1.22 mmol=L (Table 3).
Discussion
Serum Se concentrations between 0.51 and 1.79 mmol=L
have been reported for European populations (for example, Kostakopoulos et al, 1990; Ringstad et al, 1991). In
the 1970s the serum Se concentrations in the Finnish
population ranged from 0.63±0.76 mmol=L (Alfthan,
1988; Knekt et al, 1990) being among the lowest ones
in Europe. In the mid-1970s, the dietary intake of Se in an
average Finnish diet was about 25 mg per 10 MJ (or
2400 kcal) (Mutanen & Koivistoinen, 1983). In the early
1980s, when high-Se grain (200 ±500 mg=kg) was imported
from North America, the daily Se intake was 40 ±50 mg
(Varo et al, 1988). The value was at an adequate level
compared with the average requirement of 40 mg recommended by the Scienti®c Committee for Food of the
European Community (1993).
About two years after the start of the Se-supplemented
fertilization programme, in 1986, the mean daily Se intake of the Finnish population was estimated to be about
80±90 mg=10 MJ (Varo et al, 1988). A level of
110±120 mg=10 MJ was reached in 1987 and remained
constant until 1990 (Varo et al, 1994). The increase in
the serum Se values in the Finnish subjects re¯ected a good
response to the use of Se-enriched agricultural fertilizers,
but as mentioned above, it also re¯ected the increased
amount of imported high-Se grain in 1988±1989 (MaÈkelaÈ
et al, 1993).
In our study, the nutrient composition of the commonly
used baby formulas and commercial infant foods were
added to the database of Micro NUTRICA programme
for use in these analyses. The Se content of Finnish foods
has increased considerably since the addition of Se into the
fertilizers was started in 1985. If the Se content for a certain
food was analysed after the Se supplementation of the
fertilizers, this value has been used in the programme
(Ekholm et al, 1991; Eurola et al, 1989, 1991; Varo et al,
1994). In other cases earlier values are given dating back to
the middle of the 1970s and many of these values, for
example, for ®sh products, mushrooms, wild berries and
imported vegetables and fruits, remain valid today (Varo,
1981).
From 1991 on the amount of Se added to the agricultural
fertilizers was reduced to the level of 6 mg=kg for all
fertilizers (Ministry of Agriculture and Forestry, 1990),
and the import of foreign high-Se grain was considerably
reduced at the same time (MaÈkelaÈ et al, 1993). In 1992 the
Se intake was estimated to be 80±90 mg=10 MJ (Varo et al,
1994). According to the results of our study, in 1991±1992,
the mean serum Se concentrations decreased in all age
groups as a response to the decreased dietary intake of Se.
The results of this study show that the changes in the
serum Se values in the population, as well in adults as in
children of all ages, re¯ect alterations in the mean daily
dietary intake of Se. Children younger than three years had
the lowest concentrations of Se during the whole eight-year
observation period. Lombeck et al, (1977) had earlier
reported that the serum Se concentrations during childhood
were age-dependent. In their study, the healthy children
under the age of 3 y had signi®cantly lower serum Se
concentrations than the children in older age groups.
During the Se fertilization programme no Se has been
added to any infant formulas in Finland. According to the
manufacturers, the Se content of `Piltti' in 1990 ±1991 was
10 mg=L, that of `Bona' 8.8 mg=L in 1990 ±1991 and the Se
content of `Tutteli' in 1991±1992 was 10 ±11 mg=L. The Se
content of breast milk in Finland in 1990 has ranged from
14.6 ±17.2 mg=L (0.18 ± 0.22 mmol=L) as determined from
pooled samples received from breast-milk centers (Kantola
& Vartiainen, 1991). As calculated by food consumption
records, however, the mean dietary daily intake of Se in
infants aged 13 months was higher than the population
reference intake (PRI) recommended by the Scienti®c
Committee for Food of the European Community in those
years, when the Se intake was at the highest level in
general, namely in the years 1990 ±1991. Although the
mean dietary daily intake of Se in infants aged seven
months in 1990 was lower than the PRI, the Se serum
concentrations of these infants were still at an adequate
level.
Effects of selenium fertilization in Finland
W-C Wang et al
534
The mean breast milk concentration of Se (when infants
were at the age of 16 weeks) in Germany (Dorner et al,
1990) was reported to be 17.6 mg=L, being similar compared with that in this study. Robberecht et al (1985)
reported that the Se content of breast milk (two months
post partum) in Belgium was 10.2 mg=L and the estimated
daily intake of Se for Belgian infants of three months of age
was 8.1 mg=L (boys) and 7.1 mg=L (girls). New Zealand is
also recognized as a Se-poor country. Dolamore et al
(1992) reported that a mean Se concentration of breast
milk in New Zealand was 13.4 mg=L and a mean plasma Se
concentration of infants less than 12 months old was
33 mg=L (0.42 mmol=L). Both of the Se concentrations
were lower than those in this study.
Interesting is also, that still in 1990, the Se content of the
breast milk of Finnish women did not reach those values
reported from USA (Litov et al, 1989) or from Japan
(Hatano et al, 1985). The Se content of mature breast
milk in USA from the Se-rich area of Salt Lake City is
reported to be 25 mg=L (USA (Litov et al, 1989). In Japan
the Se content of breast milk is reported to be 20 mg=L
(Hatano et al, 1985). When comparing the Se serum
concentrations of young infants in our study to those
published, for example, from USA (Litov et al, 1989), it
appears, that they do not differ markedly from each other.
In USA the plasma Se concentration of infants at two
months of age is reported to be 1.2 mmol=L (s.d.,
0.15 mmol=L) (Litov et al, 1989).
Conclusions
The nationwide Se supplementation programme has succeeded in elevating the Se intake and the serum Se concentrations in the Finnish population. However, well
planned long-term follow-up studies connected with regular measurements of Se serum concentrations are needed
in order to reveal the possible health effects of increased Se
intake as well as the optimal amount of Se, which should be
added to the fertilizers in Finland to keep the Se intake of
the population at an adequate level.
AcknowledgementsÐThe analyses were carried out at the Joint Clinical
Biochemistry Research Laboratory of the University of Turku, Turku
University Central Hospital and Wallac Ltd., Turku. We thank Dr M
HaÈmaÈlaÈinen, Ph.D., for the technical assistance during this work and Dr
Else-Maj Suolinna, Ph.D., who revised the English language. This study
was supported by the Juho Vainio Foundation and the Sigrid Juselius
Foundation, Finland.
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