Judith R. Turnlund

Human whole-body copper metabolism.

Whole-body copper metabolism is difficult to study in human subjects. However, the use of isotopic tracers and kinetics modeling has added a dimension beyond what can be learned in humans by direct measurement. Mechanisms regulating total body copper seem to be strong, given the relatively small and constant body pool, but they are not yet well understood. The efficiency of copper absorption varies greatly, depending on dietary intake. Changes in efficiency of absorption help to regulate the amount of copper retained by the body. In addition, endogenous excretion of copper into the gastrointestinal tract depends heavily on the amount of copper absorbed. When dietary copper is high and more is absorbed, endogenous excretion increases, protecting against excess accumulation of copper in the body. When intake is low, little endogenous copper is excreted, protecting against copper depletion. Regulation is not sufficient with very low amounts of dietary copper (0.38 mg/d) and appears to be delayed when copper intake is high. The use of isotopic tracers and kinetic modeling should aid in elucidating the regulatory mechanisms.

Effect of Barley β-Glucan in Durum Wheat Pasta on Human Glycemic Response

ABSTRACT High-fiber, high-carbohydrate diets, including foods with low glycemic index, have been associated with prevention and treatment of diseases such as coronary heart disease and diabetes. β-glucan, a soluble, viscous polymer found in oat and barley endosperm cell wall, was incorporated into pasta test meals. Five fasted adult subjects were fed test meals of a barley and durum wheat blend pasta containing 100 g of available carbohydrate, 30 g of total dietary fiber (TDF) and 12 g of β-glucan, or an all durum wheat pasta containing the same amount of available carbohydrate, 5 g of TDF, and negligible β-glucan. The β-glucan and durum wheat pasta resulted in a lower glycemic response as measured by average total area and maximum increment of the blood glucose curves. Lower insulin response to the β-glucan and durum wheat pasta was also indicated by lower average area and increment characteristics of the insulin curves. Barley β-glucans may be an economical and palatable ingredient for processed food pr...

Zinc and copper in Asian pregnancies–is there evidence for a nutritional deficiency?

Summary. In 92 Hindu Asians, 59% of them vegetarian, and 51 Europeans longitudinal measurements were made during pregnancy of the zinc and copper concentrations in plasma and hair together with urinary zinc excretion, as indices of their zinc and copper status. Maternal diets were assessed once at booking. Zinc intakes ranged from 3·1 to 16·9 mg/day, with average intakes least in vegetarian Hindus and most in Europeans. Average copper intakes ranged between 1·48 and 1·80 mg/day and were similar in the three patient groups. Both ethnic groups showed the pregnancy‐associated fall in the plasma concentration of zinc and rise in that of copper but throughout the study Hindus had statistically significant lower levels of zinc and higher levels of copper than Europeans. Urinary zinc excretion was not only significantly lower throughout the study in Hindus than in Europeans but the increase in excretion which occurred after 20 weeks gestation was smaller. There were no ethnic differences in the zinc content of hair. Urinary zinc excretion correlated with both plasma zinc levels and dietary zinc. Mean birth‐weight in the Hindus was 2912 g and 34% of infants were below the 10th centile, using the Aberdeen standards, compared with 6% of the European babies (mean birthweight 3349 g). No association was found between crude or adjusted birthweight and any of the measures of zinc or copper status in either ethnic group. The Hindus had an apparently lower average zinc status than the Europeans, but there was no evidence that this had acted as a nutritional constraint and was the cause of their slower rate of intrauterine growth.

Human Zinc Requirements

The dietary requirement for zinc is literally the amount required in the diet to maintain optimally the various metabolic and physiological functions of life (Smith et al. 1983). The dietary zinc requirement for a population is not a single value. Instead it varies over a wide range depending on the age and physiological state of the individuals and on composition of the diet, particularly with respect to the amount and proportion of organic and inorganic components of the diet which influence zinc absorption and utilization (Hambidge et al. 1986).

Compartmental model of copper metabolism in adult men

Abstract A compartmental model of copper metabolism in adult men was developed from stable isotope data obtained in a 90-day study during which three levels of dietary copper (1.68, 0.785, 7.52 mg/d) were fed. The tracer 65 Cu was administered intravenously (i.v.) three times and orally four times during the study period. The model contains five compartments, two delay components, and two excretion pathways interpreted as two plasma compartments, two liver compartments, an other-tissue compartment, and fecal and urinary excretion routes. Dietary copper level influences the flow from the second liver compartment to the second plasma compartment and from the second plasma compartment to the other-tissues compartment. The model suggests that the tissue uptake of oral and i.v. copper is different, with flow from plasma to the first liver compartment varying with route of isotopic administration. The model-predicted masses of copper within the compartments and delay components follow a pattern of expected masses within the body. The major storage sites predicted are the second liver compartment, the delay after the other-tissue compartment, and the delay in the fecal excretion pathway. The model predicts that 65% of plasma copper is bound to ceruloplasmin, compared with 56 to 68% calculated from the data. Approximately 4.1 ± 0.8% of total body copper was predicted to be in plasma compared with 2 to 6% expected.

Zinc Protoporphyrin Past, Present, and Future

The course of zinc protoporphyrin research has progressed at an increasingly rapid pace on several fronts. A variety of biochemical and clinical evidence viewed in toto now suggests that ferrochelatase catalyzes zinc protoporphyrin formation in states of relative iron-deficient erythropoiesis and in lead-inhibited iron metabolism. Furthermore, a redefinition of the relationship of zinc protoporphyrin to certain other parameters of iron status has been made based upon changes during the earliest states of iron depletion. These clinical studies show that the zinc protoporphyrin level and the ferritin level vary in concert but that changes in the percent transferrin saturation and in the hematocrit results are less consistent. Thus zinc protoporphyrin and ferritin are closely linked metabolically such that iron-deficient erythropoiesis becomes an initial manifestation of iron depletion. The measurement and expression of results as mumoles zinc protoporphyrin/mole heme have improved the quality of results, partly by the elimination of the assumed hematocrit designed into existing instruments. Other refinements in hematofluorometry technology have permitted exploration of the potentially extensive applications of zinc protoporphyrin measurements for lead surveillance and diagnosis, blood banking, pediatrics, obstetrics, sports medicine, and other clinical situations where a very sensitive, cost-effective indication of iron status is required.

In Vitro Copper Stimulation of Plasma Peptidylglycine|[alpha]|-Amidating Monooxygenase in Menkes Disease Variant with Occipital Horns

We determined the concentrations of copper, the activities of ceruloplasmin and peptidylglycine α-amidating monooxygenase (PAM), and the stimulation index of PAM by the in vitro addition of copper in plasma samples obtained from three male patients with occipital horns and a milder Menkes disease phenotype, having severe copper deficiency due to the defect in copper transport. We found a decreased plasma ceruloplasmin activity and an increased copper stimulation index of plasma PAM in these patients compared with healthy control subjects. The combination of these two determinations may provide a means for the assessment of copper nutriture in humans using blood samples obtained in a single microhematocrit tube. Further investigation is warranted to evaluate whether these noninvasive measurements can be used for the diagnosis of mild copper deficiency in humans with sufficient specificity and sensitivity.

Determination of molybdenum and enriched Mo stable isotope concentrations in human blood plasma by isotope dilution ICP-MS

An isotope dilution method was developed to measure total molybdenum and molybdenum stable isotope concentrations in 0.5 mL of human blood plasma by ICP-MS. To minimize contamination, a microwave digestion method was developed without molybdenum separation. Plasma aliquots were weighed into PTFE beakers placed on supporting PTFE beakers inside PFA liners, adding 1.4 mL HNO3 to the plasma and 8 mL HNO3 to the liner base. The samples were digested in five 10-min steps under pressure control from 20 to 100 psi. Repeated microwave digestions of the liners and beakers reduced processing blanks from 6.6 to 0.03 ng Mo. The samples were analyzed by ICP-MS. Analysis of a reference human serum produced an average molybdenum concentration of 1.02 ± 0.12 µg L−1versus the informational value of 1.07 ± 0.04 µg L−1. Total Mo and 97Mo were measured in plasma collected from a human subject following intravenous adminstration of 33 µg 97Mo, with concentration RSDs <2% for ten replicates. This ICP-MS isotope dilution method with microwave digestion can be used to determine the total molybdenum and molybdenum stable isotope concentrations in as little as 0.5 mL of human blood plasma, allowing the measurement of the appearance of molybdenum stable isotope tracers in the blood.

Use of enriched stable isotopes to determine bioavailability of trace elements in humans

Use of stable isotopes with analysis by thermal ionization mass spectrometry can determine trace element availability from dietary sources safely and with a high degree of accuracy. Stable isotopes of zinc (70Zn), copper (65Cu) and iron (58Fe) were fed with semipurified diets to humans. Excretion of isotopes was determined by isotope dilution in fecal composites collected for 15 days following the feedings. A thermal ionization, magnetic sector mass spectrometer was used to measure isotopic ratios. Total mineral content of fecal composites was determined by atomic absorption spectrophotometry. Mean absorption of zinc, iron and copper in six elderly men was 17.3, 8.7 and 26.0% respectively. Results agreed closely with absorption determined simultaneously in the same subjects using radioisotopes.

Isotope ratios of calcium determined in calcium-46 enriched samples from infants by automated multiple-collector thermal ionization mass spectrometry

A high-precision method was developed for automated multiple-collector determination of 46Ca enrichment using magnetic sector, thermal ionization mass spectrometry (TIMS). Calcium was separated from biological samples by precipitation as calcium oxalate. The calcium oxalate was washed, then dissolved in nitric acid, and isotope ratios were determined in 10 µg samples. The 44Ca, 46Ca and 48Ca isotopes were collected simultaneously. The 46Ca:48Ca ratios were measured and corrected for fractionation by iterative normalization, using the 44Ca:48Ca ratio, in order to achieve the required precision. Blocks of ten ratios were measured with an internal or within-run precision of 0.14% relative standard deviation (RSD) in urine samples and 0.10% RSD in faecal samples. The external or between-run precision for nine replicates was 0.07% RSD for urine and 0.09% RSD for faecal samples. Enrichment of samples collected following the feeding of 46Ca to pre-term infants ranged from 8 to 179 Δ% excess in faecal samples and from 19 to 91 Δ% excess in urine samples. If another isotope in addition to 46Ca is to be enriched, the identical analytical method can be applied by collecting 42Ca, 43Ca, 44Ca and 46Ca simultaneously, using the two unenriched isotopes to correct for fractionation.