Klinisk Biokemi i Norden · 3 2019
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mical function of selenoproteins. Several of these
proteins have functions that include antioxidative
oxidoreductases, such as the five glutathione pero-
xidases (GPx), which protect the organism against
oxidative damage by reducing lipoperoxides and
hydrogen peroxide. The three thioredoxin reducta-
ses (TrxR) control redox status of thioredoxins that
are key proteins involved in redox regulation of cel-
lular processes. Methionine-R-sulfoxide reductase 1
(MSRB1) reduces oxidized methionine residues in
proteins. Another important selenoprotein family
controls activation and inactivation of thyroid hor-
mones, i.e. the three deiodinases (DIO1, DIO2 and
DIO3). SELENOP is a glycoprotein and the major
selenoprotein in plasma transporting selenium from
the liver to peripheral tissues. It can also act as an
extracellular antioxidant and appears to be coupled
to carbohydrate metabolism in the liver and insulin
secretion (13). SELENOP synthesis is suppressed
by the acute phase reaction in the liver (10). Other
selenoproteins reside in the endoplasmatic reticu-
lum and have putative functions in protein folding,
endoplasmatic stress, regulation of calcium and mus-
cle function, and there are also selenoproteins with
unknown function (1).
Health effects related to suboptimal or deficient
selenium status
In several European countries, the intake of selenium
is below the European (5) and the Nordic nutrition
recommendations (14), and substantially lower than
the intakes of populations in the USA where the soil
is rich in selenium (Figure 1). Here we will discuss
the possible role of suboptimal intake of selenium for
prevalent diseases in the Nordic populations, namely
cardiovascular diseases and cancer.
Cardiovascular disease (CVD)
Two large studies have indicated that a low selenium
status is an independent risk factor for myocardial
infarction, with increased risk at plasma values below
about 1.0 μmol/L (about 80 µg/L). Salonen and co-
workers (15) observed a two-to-three-fold increase in
cardiovascular morbidity and mortality for subjects
with serum selenium levels less than 0.60 μmol/L
(45 μg/L), compared with those with higher selenium
levels at the start of the study. In a large prospective
study in Denmark (16), an increased risk of ischaemic
heart disease (relative risk 1.55) was observed among
subjects with serum selenium below 1.0 μmol/L
(80 μg/L). This is consistent with observations that
lower serum selenium 0.76 vs 0.91 μmol/L (61 vs.
71.5 μg/L ) was associated with higher cardiovascu-
lar mortality (17) and a recent study from Sweden
(7).The latter investigators reported significantly
increased cardiovascular mortality in the quartile
with lowest selenium levels, below 0.72 μmol/L (57
μg/L). Kardinaal and co-workers (18) found a signi-
ficant inverse association between toenail selenium
levels and risk of myocardial infarction only for the
included European center with the lowest selenium
levels (Germany) in their EURAMIC study from
1997. A lack of effect on CVD mortality was seen in
the French SU.VI.MAX study that supplemented a
population, with a mean baseline plasma selenium
above this threshold (1.1 µmol/L) (19). No association
between the risk of CVD and serum selenium could
be detected in a study on US physicians in which very
few had plasma levels below 1.0 μmol/L (80 μg/L)
(20). In 2013 Rees and co-workers (21) published a
Cochrane report indicating no effect of selenium sup-
plementation on cardiovascular mortality. However,
95% of their included participants were from studies
in selenium replete US populations. In a more recent
meta-analysis of 16 observational studies, Zhang and
co-workers (22) found a reduced cardiovascular risk.
RR: 0.87 (CI 0.76-0.99) for those in the high selenium
group (median 101.5 μg/L) versus those in the low
selenium group (median 53.7 μg/L). The signifi-
cantly reduced CVDmortality obtained in the recent
Swedish KiSel study that supplemented a population
with mean baseline plasma selenium of 0.85 µmol
Se/L with 200 μg Se/d for 4 years is consistent with
the results in the latter meta-analysis (7). Of particu-
lar interest is observation in the Swedish KiSel study
that a significant protective effect of selenium sup-
plementation was only observed among participants
with baseline selenium below 1.08 µmol/L (85 µg/L).
Taken together, the results from the studies on car-
diovascular effects is consistent with an apparent risk
threshold of around 1.1 µmol Se/L in plasma, above
which further selenium supplementation appears to
have little effect.
Cancer
A recent meta-analysis concluded that selenium at
recommended daily intakes above 55
μ
g/day decrea-
sed the risk of cancer (23). In this study an inverse
