Klinisk Biokemi i Norden · 3 2019
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tective mechanisms. In the nutrient mode, selenium
plays a role in the catalytic center of antioxidant
selenoproteins. Other modes include formation of low
molecular weight “cytostatic” selenium metabolites,
α-keto acid metabolites of selenium that may effec-
tively inhibit histone deacetylases (a target used for
anti-cancer pharmaceuticals) and epigenetic mecha-
nisms, e.g. DNA methylation (12,29,30).
Lower and upper levels of tolerance – the medi-
cal biochemistry of selenium
Symptoms of toxicity has been reported, i.a. in Chi-
nese populations with high selenium intakes, and
include neurotoxicity, brittle hair and loss of hair,
dermatitis and pathological nail changes and hepa-
totoxicity. The apparent toxicity threshold was 850
μg/day for biochemical liver toxicity (2). Based on
this and other studies a tolerable upper level of 300
μg/day was established by the EU Scientific Com-
mittee on Food (5) using a factor of 3 to allow for
uncertainties in different studies. The corresponding
plasma level of selenium to an intake level of 300 μg/
day depends on the species of selenium provided.
Whereas a high selenomethionine intake from food
or supplements will further increase plasma levels, a
high intake of most other selenium species will lead
to plateau around 1.4 μmol/L (110 μg/L,. Based on
results from the literature, we estimate that an upper
tolerable intake level of 300 μg/day from food would
correspond to a selenium concentration in plasma of
around 3.0 μmol/L.
A clinical state of selenium deficiency in humans
is at present not possible to define and use as a basis
for determination of nutritional requirements for
optimal health. Instead, decreased function of seleno-
proteins as a result of selenium deficiency has been
considered an appropriate basis for assessing adequate
requirements (5). It is reasonable to assume that when
selenoprotein P in plasma levels off, the body pool
of selenium is saturated and adequate physiological
functions of selenium are attained. Based on supple-
mentation studies in the literature, selenoproteins P
1
2
/
3
4
selen/
in plasma is optimized at plasma selenium concen-
trations between 1.14-1.77 µmol/L (90-140 µg/L) (5).
From available data we may conclude that a plasma
selenium for optimization of plasma selenoprotein P
and also of platelet and plasma GPx. concentration
≥1.2 µmol/L (≥100 µg/L) is likely to be sufficient.
This approach is essentially in line with recent
assessments of nutritional requirements of selenium,
e.g. by EFSA (5) and the Nordic Nutrition Recom-
mendations (14). The question as to whether defici-
ency signs or symptoms may occur at levels below
plasma concentrations that are consistent with an
optimal expression selenoprotein P is still unresolved,
however, population studies indicate that increased
risk of health hazards occurs in low selenium areas.
Reference ranges of plasma selenium versus an
adequate nutritional status
In Norway, national reference intervals for medical
laboratories are 0.8-1.6 µmol/L (63-126 µg/L)
1
, and
corresponding value for Sweden
2
is 0.7-1.2 µmol/L
(55-95 µg/L) and for Denmark
3
0.89-1.65 µmol/L (70-
130 µg/L). The lower ends of these reference ranges
are all well below values required for a saturation of
selenoprotein P and thus represent an inadequate
intake of selenium from both a nutritional and medi-
cal point of view. A medical laboratory in Germany
(Labor Lademanbogen, Hamburg 2017) also provides
advice on adequate values: 1.27-1.77 µmol/L (100-140
µg/L)
4
, when reporting individual results from their
selenium analyses. Intakes below the present recom-
mended window characterise several segments of the
European population, in particular populations in the
Nordic countries. Although our understanding of the
essentiality of selenium has increased substantially
in recent years, there remains an urgent need for
continued studies on the role of selenium and seleno-
proteins in health and pathophysiological conditions.
Conflicts of interest
The authors have no conflicts of interest to declare.
