Minerals and trace elements in commercial infant food.

Adequate nutrition during infancy is essential for lifelong health and wellbeing. Breast-feeding is highly recommended for the first six month of life, but from then on complementary feeding is necessary. Industrially produced food is an important part of the diet for many infants and toddlers in developed countries. We have determined the concentration of major minerals and trace elements in 76 different products of infant formula, porridges, fruit purée and dinners by HR-ICP-MS. The products were collected from three suppliers on the Norwegian market (Nestlé, Tine and Nyco Pharma). A daily menu was also composed and the estimated daily intake was compared with current recommendations. All products were within the upper tolerable limit for the minerals of trace elements analysed and toxic elements were present at very low levels. A diet based solely on industrially prepared food products will provide a sufficient intake of minerals and trace elements.

Trace elements in serum from patients with Parkinson's disease--a prospective case-control study: the Nord-Trøndelag Health Study (HUNT).

To assess whether trace elements are involved in Parkinson's disease (PD) we have conducted a prospective study where 19 trace elements have been determined in serum collected from 33 patients before they were diagnosed with the disease, and 99 controls. As a follow-up, serum from 19 of the same patients collected 4-12 years after they were diagnosed with PD has been analysed. In the prospective part of the study, the only significant difference was a slightly lower content of Hg in the patient group than in the controls. In the follow-up, significantly higher levels of Hg, Ni, and Y, and lower levels of Ca, Fe, Mg, Mn, Rb and Se were found in the serum samples collected after the patients were diagnosed with PD compared with pre-diagnostic levels.

Trace element profiles in single strands of human hair determined by HR-ICP-MS.

Trace element analysis of human hair has the potential to reveal retrospective information about an individual's nutritional status and exposure. As trace elements are incorporated into the hair during the growth process, longitudinal segments of the hair may reflect the body burden during the growth period. We have evaluated the potential of human hair to indicate exposure or nutritional status over time by analysing trace element profiles in single strands of human hair. The hair strands from five healthy and occupationally unexposed subjects were cut into 1-cm long segments starting from the scalp. By using high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), we achieved profiles of 12 elements in single strands of human hair, namely, Ag, As, Au, Cd, Cu, Hg, Fe, Pb, Se, Sr, U and Zn. We have shown that trace element analysis along single strands of human hair can yield information about essential and toxic elements, and for some elements, can be correlated with seasonal changes in diet and exposure. The information obtained from the trace element profiles of human hair in this study substantiates the potential of hair as a biomarker.

Leaching of trace elements from biological tissue by formalin fixation.

In studies of trace elements in biological tissue, it is imperative that sample handling does not substantially change element concentrations. In many cases, fresh tissue is not available for study, but formalin-fixed tissue is. Formalin fixation has the potential to leach elements from the tissue, but few studies have been published in this area. The concentrations of 19 elements were determined by high-resolution inductively coupled plasma mass spectrometry in formalin in which human and rat brain samples had been stored for different time durations ranging from weeks up to several years. Additional analysis was carried out in fixed brain samples. There was substantial leaching of elements from the tissue into the formalin, and the leaching varied considerably between different elements. For example, formalin concentrations of As, Cd, Mg, Rb, and Sb increased more than 100-fold upon long-term (years) storage, while for Ni and Cr, the leaching was negligible. The degree of leaching was strongly time-dependent. In conclusion, formalin fixation and storage of biological tissue has the potential to leach substantial fractions of several trace elements from the tissue. The potential of leaching must be critically considered when using formalin-fixed biological tissue in trace metal analysis.

Trace elements in cerebrospinal fluid and blood from patients with a rare progressive central and peripheral demyelinating disease.

A hereditary neurological disease in a family in Norway has been reported recently. The disease, which we refer to as Skogholt's disease, is a demyelinating disorder of both the central and the peripheral nervous system with adult onset. We investigated whether changes in trace element concentrations could play a role in Skogholt's disease. Using high resolution inductively coupled plasma mass spectrometry, we determined 31 elements in cerebrospinal fluid (CSF), blood plasma and whole blood from these patients, multiple sclerosis patients and a control group. More than threefold increased levels of Cu and Fe, and a twofold increase in Zn were found in the CSF of Skogholt patients compared to controls. Several other significant differences in trace element levels were also found. The increased levels of Cu and Fe in CSF may indicate an active role of these metals in the pathogenesis of Skogholt's disease. Apparently, these metal ions are transferred into the CSF through their protein chelation, as raised protein levels were also seen. We suggest that redistribution of metals from transport proteins into vulnerable sites in the central (and peripheral) nervous system may initiate critical lesions.

Separation of proteins including metallothionein in cerebrospinal fluid by size exclusion HPLC and determination of trace elements by HR-ICP-MS.

A method to study the protein binding patterns of trace elements in human cerebrospinal fluid (CSF) is described. Proteins in CSF samples were separated by size exclusion chromatography combined with high performance liquid chromatography (SEC-HPLC). The column was calibrated to separate proteins in the molecular weight range 6-70 kDa. Fractions were then analyzed off-line for trace elements using high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). We were able to accurately determine more than 10 elements of clinical interest in the CSF fractions. Results are presented for Cd, Mn, Fe, Pb, Cu and Zn. The total concentrations of 16 trace elements in human plasma and CSF are also presented. The method was able to differentiate the relative contribution of metallothionein and other proteins towards metal binding in human CSF.

Iron deficient and manganese supplemented diets alter metals and transporters in the developing rat brain.

Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. Iron (Fe) deficiency is one of the most prevalent nutritional disorders in the world, affecting approximately 2 billion people, especially pregnant and lactating women, infants, toddlers, and adolescents. Fe deficiency can enhance brain Mn accumulation even in the absence of excess Mn in the environment or the diet. To assess the neurochemical interactions of dietary Fe deficiency and excess Mn during development, neonatal rats were exposed to either a control diet, a low-Fe diet (ID), or a low-Fe diet supplemented with Mn (IDMn) via maternal milk during the lactation period (postnatal days [PN] 4-21). In PN21 pups, both the ID and IDMn diets produced changes in blood parameters characteristic of Fe deficiency: decreased hemoglobin (Hb) and plasma Fe, increased plasma transferrin (Tf), and total iron binding capacity (TIBC). Treated ID and IDMn dams also had decreased Hb throughout lactation and ID dams had decreased plasma Fe and increased Tf and TIBC on PN21. Both ID and IDMn pups had decreased Fe and increased copper brain levels; in addition, IDMn pups also had increased brain levels of several other essential metals including Mn, chromium, zinc, cobalt, aluminum, molybdenum, and vanadium. Concurrent with altered concentrations of metals in the brain, transport proteins divalent metal transporter-1 and transferrin receptor were increased. No significant changes were determined for the neurotransmitters gamma aminobutyric acid and glutamate. The results of this study confirm that there is homeostatic relationship among several essential metals in the brain and not simply between Fe and Mn.

A manganese-enhanced diet alters brain metals and transporters in the developing rat.

Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. However, virtually nothing is known regarding excess Mn accumulation during central nervous system development. Developing rats were exposed to a diet high in Mn via maternal milk during lactation (PN4-21). The high Mn diet resulted in changes in hematological parameters similar to those seen with iron (Fe) deficiency in dams (decreased plasma Fe; increased plasma transferrin [Tf]) and pups (decreased hemoglobin [Hb] and plasma Fe; increased plasma Tf and total iron binding capacity). Mn-exposed pups showed an increase in brain Mn, chromium, and zinc concurrent with a decrease in brain Fe. In conjunction with the altered transport and distribution of essential metals within the brain, there was enhanced protein expression of the divalent metal transporter-1 (DMT-1) and transferrin receptor (TfR) overall in the brain; there was a general increase in each region analyzed (cerebellum, cortex, hippocampus, midbrain, and striatum). Neurochemical changes were observed as an increase in gamma-aminobutyric acid (GABA) and the ratio of GABA to glutamate, indicating enhanced inhibitory transmission in the brain. The results of this study demonstrate that developing rats undergo alterations in the transport and distribution of essential metals translating to neurochemical perturbations after maternal exposure to a diet supplemented with excess levels of Mn.

Concentrations of Cd, Co, Cu, Fe, Mn, Rb, V, and Zn in formalin-fixed brain tissue in amyotrophic lateral sclerosis and Parkinsonism-dementia complex of Guam determined by High-resolution ICP-MS.

Amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) are neurodegenerative disorders that occurred with extremely high frequency among the native population on Guam, especially in the 1950s and 1960s, but have substantially declined over the last half-century. The etiology of these diseases is unknown, but the most plausible hypothesis centers on imbalances in essential and toxic metals. We have determined the concentrations of Cd, Co, Cu, Fe, Mn, Rb, V, and Zn in formalin-fixed brain tissue collected during the period 1979-1983 from eight Guamanian patients with ALS, four with PDC, and five control subjects using high-resolution inductively coupled plasma-mass spectrometry. The concentrations of Cd are markedly and significantly elevated both in gray and white matter in ALS, but not in PDC patients. The concentrations of Zn are elevated for both patient groups, in both gray and white matter, but only the difference in gray matter for PDC is significant. For the other metals, no significant differences are found.