Chemistry Reference
In-Depth Information
3.3.3 Subclinical Biomarkers of Defi ciency
with or without Clinical Signifi cance
anemia, suggesting effects on tissue level unrelated to
oxygen-transport capacity (Zhu and Haas, 1997).
Another example is a decrease in ceruloplasmin lev-
els in low copper intakes and decreased erythrocyte
superoxide dismutase (ESOD) when copper intakes
are low (WHO/IPCS, 1998). Although these changes
are considered useful indicators of decreased biologi-
cal copper activity, their clinical signifi cance has not
been well defi ned.
When iron intakes are low, serum ferritin levels
decrease, and transferring saturation and increased
erythrocyte protoporphyrin are decreased. Although
these indicators are excellent indicators of low body
iron stores, slight decreases in iron stores are of
debatable clinical signifi cance.
A number of markers related to decrease in enzyme
levels have been shown to occur in persons with low
intakes of some essential metals. In some cases, such
an infl uence on enzyme levels is believed to be of func-
tional signifi cance and may even be a precursor of
clinical disease. In other cases, a slight decrease in an
enzyme level may be tolerated without any functional
signifi cance, namely, if there is a great surplus of this
enzyme in the medium in which it is measured.
An example of such a subclinical marker of defi -
ciency is the saturation of glutathione peroxidase
(GSHPx) in plasma, erythrocytes, and platelets that is
impaired when selenium intakes are low. Incomplete
GSHPx saturation in plasma does not occur until Se
intakes fall below approximately 40
3.3.4 Lethal Toxic Effects
g/day (Yang
et al.
, 1989a,b). For saturation of GSHPx in erythrocytes
higher intakes are required, and for saturation in plate-
lets more than 100
µ
Excessive doses of soluble salts of iron or copper by
the oral route that may be ingested by accident or with
suicidal intent give rise to extensive and severe gas-
trointestinal manifestations, systemic toxicity, shock,
and death (Borch-Johnsen and Petersson-Grawé, 1995;
WHO, 1998).
g/day is required (Whanger
et al.
,
1988). The clinical or health importance of such incom-
plete GSHPx saturation is debated, particularly in the
most sensitive compartment (i.e., platelets).
For some essential metals (e.g., zinc) specifi c and
sensitive biochemical indicators of defi ciency are lack-
ing. In absence of such indicators, the estimates of
requirements have to be evaluated by a factorial tech-
nique (i.e., by adding together the requirements for
tissue growth, metabolism, and endogenous losses).
It is notable that the activity of zinc-dependent proc-
esses and plasma and tissue zinc concentrations can be
maintained over long periods of time at low intakes
by substantial reductions in endogenous losses of zinc.
This adaptive ability was taken into account by WHO
(1996) for estimates of the physiological requirement
of absorbed zinc using data from long-term balance
studies at very low intakes (Baer and King, 1984; Hess
et al.
, 1977). At the basal requirement level, the abil-
ity to increase the effi ciency of zinc retention has been
fully exploited. Observations made during the early
phase of the same studies of zinc depletion were used
to estimate the normative physiological requirement.
For adult males, an uptake of 1.4 mg/day was judged
to maintain zinc equilibrium without the need of adap-
tive changes in endogenous losses. With 30% fractional
uptake from the diet, this corresponds to a daily nor-
mative dietary requirement of 4.7 mg/day. Lacking
corresponding long-term studies in other age groups,
endogenous losses in relation to basal metabolic rates
were used as the basis for extrapolation.
A reduction of maximal oxygen consumption has been
demonstrated in physical performance tests in young
women with low serum-ferritin concentrations without
µ
3.3.5 Toxic Effects with Clinical Signifi cance
Clinical disease (without fatal outcome) may occur
as a result of ingestion of high doses of soluble sele-
nium salts. Such poisoning cases display nausea, vom-
iting, and subsequently hair and nail changes and skin
lesions (Alexander, 1993; Chapter 38). Persons ingest-
ing large doses of copper may develop hematuria and
jaundice in addition to vomiting, nausea, and diarrhea
(WHO/IPCS, 1998; Chapter 26). Also ingestion of solu-
ble iron salts may give rise to gastrointestinal manifes-
tations with vomiting and diarrhea often with bloody
stools, and later cirrhosis may occur (Borch-Johnsen
and Peterson-Grawé, 1995; Chapter 30).
3.3.6 Subclinical Toxic Effects with or without
Functional Signifi cance—Biomarkers of
Critical Effect
Like the situation with biochemical markers of
defi ciency, subclinical markers of toxicity have been
identifi ed in the form of changes in enzyme levels.
To use such a biomarker as a critical effect, it is of
great importance to be able to determine the extent to
which increased levels of such biomarkers in media
easily accessible for analysis (blood, urine, hair) sig-
nals a subclinical stage of a disease or abnormality in
organ function. Unfortunately, for several potentially
useful markers, there is a lack of such information,
and further defi nition of the clinical and functional
