216 Introduction to Human Nutrition
About 10% of motor neuron disease cases are
familial and 20% of these are owing to autosomal
dominant inheritance of mutations in the Cu/Zn-
SOD (SODI) gene. It is unclear how changes in
activity of this copper enzyme might be involved
in the progressive muscle weakness and atrophy
of motor neuron disease or in Down’s syndrome,
where additional Cu/Zn-SOD activity results
from the SODI gene being present in the extra chro-
mosome 21.
Assessing status
It is possible to diagnose severe copper defi ciency in
infants from plasma or serum copper, ceruloplasmin
protein, and neutrophils. These measures, however,
cannot be used to detect suboptimal copper status in
individuals, as such measures are insensitive to small
changes in copper status and there are intractable
problems in interpretation. Ceruloplasmin, the major
copper protein in plasma or serum, is an acute-phase
reactant and is raised by cigarette smoking, oral
contraceptives, estrogens, pregnancy, infections,
infl ammation, hematological diseases, hypertension,
diabetes, cardiovascular diseases, cancer, and cirrho-
sis, and after surgery and exercise.
Currently, there is no adequate measure of subop-
timal (or supraoptimal) copper status and this is a
major barrier to determining precise dietary require-
ments for copper and the possible role of suboptimal
or supraoptimal copper status in the etiology of
chronic disease. Table 9.16 gives some of the func-
tional indices (classifi ed as molecular, biochemical,
and physiological) that might be used to defi ne sub-
optimal or supraoptimal status in humans. A valid
functional index of copper status in humans must
respond sensitively, specifi cally, and predictably to
changes in the concentration and supply of dietary
copper or copper stores, be accessible for measure-
ment and measurable, and impact directly on health.
As such, indices in Table 9.16 have not been validated
and many lack sensitivity and specifi city. Perhaps, the
best way forward is to use a combination of measures.
Among the more promising are erythrocyte
super-oxide dismutase activity, platelet cytochrome c
oxidase, plasma diamine oxidase, plasma peptidyl
glycine α-amidating mono-oxygenase, urinary pyri-
dinium cross-links of collagen (may indicate lowered
activity of the cuproenzyme, lysyl oxidase), and
various immunological measures.
Requirements and dietary sources
Although copper is the third most abundant trace
element, after iron and zinc, in the body, precise
dietary requirements for copper are still subject to
conjecture because of the diffi culty in assessing copper
status. Current estimates suggest that the require-
ments for copper for the great majority of adults are
below about 1.5 mg copper/day, while most people
can tolerate 3 mg copper/day or more over the long
term and 8–10 mg copper/day or more in the shorter
term (over several months). Using similar data from
copper supplementation trials where there was an
absence of any adverse effects on liver function, UL
for copper was derived to be 10 mg/day in the US and
5 mg/day in the EU; the difference owing to the use
of different uncertainty factors in the derivation.
Estimates of average intakes of copper are about 1.5
and 1.2 mg copper/day for men and women, respec-
tively, on mixed diets, with higher intakes for those
on vegetarian diets or those consuming water withTable 9.16 Putative functional indices of copper statusMolecular indices
Changes in activity/concentration of Cu-metalloproteins
Ceruloplasmin oxidase
Ceruloplasmin protein
Superoxide dismutase
Cytochrome c oxidase
Lysyl oxidase
Diamine oxidase
Dopamine β-monooxgenase
Peptidylgycine α-amidating monooxgenase
Tyrosinase
Factor V
Factor VIII
Transcuprein
Biochemical indices
Pyridinium cross-links of collagen
Various measures of oxidative stress (TBARS)
Catecholamines
Encephalins
Polyamines
Physiological indices
Immune function
Hemostasis
Cholesterol metabolism
Glucose tolerance
Blood pressure
Arterial compliance
Arterial plaque
DNA damage and repair
Bone density