27.9: Other indices of copper status (24b.8)
- Page ID
- 117279
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)• Hair copper concentrations
Concentrations of copper in hair appear to correlate with levels in the liver (Jacob et al., 1978), heart, and kidney (Klevay, 1981). of rats. However, the validity of hair copper concentrations as a biomarker of copper status in humans is less certain. In a detailed human study of therosclerosis patients, hair copper concentrations did not correlate with the copper content of heart, muscle, liver, kidney, aorta, or rib (Aalbers and Houtman, 1985).
Many studies have confirmed that gender (in adults), pregnancy, lactation, prematurity, hair color, race, and age all affect hair copper concentrations (Petering et al., 1971; Creason et al., 1975; Gibson and DeWolfe, 1980; Taylor, 1986). The marked rise in hair (and serum) copper concentrations during early infancy is presumably associated with the redistribution of tissue copper which occurs at this time, and not with changes in dietary copper intake (Gibson and DeWolfe, 1980) (Figure 24b.6).
Figure 24b.6: Changes in hair copper concentrations during infancy. Redrawn from Gibson RS, (1982). The trace metal status of some Canadian full-term and low-birth-weight infants at one year of age. Journal of Radioanalytical Chemistry 70: 175–189,
Normal hair copper levels are found in two conditions in which copper accumulates in the liver — primary biliary cirrhosis (Epstein et al., 1980) and Wilson's disease (Rice and Goldstein, 1961; Gibbs and Walshe, 1965). Additionally, infants with copper deficiency, characterized clinically by neutropenia and biochemically by concentrations of serum copper and ceruloplasmin below the detection limit, did not have lower hair copper levels than age and sex-matched controls (Bradfield et al., 1980). Similarly, the copper content of the hair of children with Menkes kinky hair syndrome is normal (Danks, 1980). It appears, therefore, that hair copper cannot be used as a biomarker of copper status in humans.
• Urinary copper concentrations
Urinary copper is seldom used as an index of copper status; levels are very low in healthy subjects(10–60µg/d) because copper is efficiently reabsorbed by the renal tubules. The main excretory route for copper is the biliary system. Urinary copper concentrations do decrease in persons receiving TPN copper-deficient solutions (Solomons, 1979), conserving body copper. However, in a 13wk experimental depletion-repletion study in which men were fed three levels of dietary copper, urinary copper levels were unaffected by dietary copper levels (Turnlund et al., 1990).
• Other indices
Very limited data are available on copper concentrations in erythrocytes (Vitoux et al., 1999), and fingernails (Martin, 1964). Elevated values for erythrocyte copper have been reported in patients with the two inherited metabolic disorders associated with defects in copper metabolism (Wilson's disease and Menkes syndrome), as well as in children with Down's syndrome and cystic fibrosis. Further studies are needed to ascertain the validity of these measures of copper status.
Changes in some biochemical markers of bone metabolism have been noted during experimental copper depletion-repletion (Baker et al. 1999). and also in some supplementation trials (Baker et al., 1999; Cashman et al., 2001). Results suggest that changes in both urinary pyridinoline and deoxypyridinoline (biomarkers of bone resorption) may serve as additional functional markers of copper status in populations that consume diets low in copper; details of these biomarkers of bone resorption are given in Section 23.1.5.
Peptidylglycine α-amidating monooxygenase (PAM) is a cuproenzyme required for neuropeptide synthesis. Prohaska and colleagues have suggested its enzyme activity, but not protein levels, may be modulated by mild copper deficiency (Bousquet-Moore et al. 2010; Prohaska et al. 1995). .
• Multiple indices
Serum copper is frequently used to assess copper status in both clinical and community studies, but it is not very sensitive or specific (Harvey and McArdle 2008). Increasingly, because of its higher sensitivity and specificity, the activity of Cu,Zn-SOD in erythrocytes is used in combination with serum copper. In the future, the activity of cytochrome c oxidase in platelets or diamine oxidase in serum may be used in combination with serum copper, instead of erythrocyte Cu,Zn-SOD, if their validity as biomarkers of copper status in a community setting is confirmed.