Review: Bioavailability of trace elements in farm animals: definition and practical considerations for improved assessment of efficacy and safety.

Currently, the authorisation procedure of trace elements as feed additives in the European Union according to Regulation (EC) No. 1831/2003 does not consider the bioavailability of trace element sources. This manuscript provides framework conditions for in vivo experiments that aim to estimate differences in the relative bioavailability between supplements of essential trace elements. Framework conditions encompass necessary technical information on the test substance, the experimental design and diet composition as well as the suitability of status parameters that allow for relative comparisons of regression variables. This manuscript evolves recommendations for researchers to conduct solid and reliable experiments on the matter as well as decision makers to interpret the value of studies submitted with authorisation applications regarding a certain trace element supplement.

The Reference Values of Hair Content of Trace Elements in Dairy Cows of Holstein Breed.

The objective of this study was to assess trace element content in hair of Holstein dairy cows bred in the Leningrad Region of Russia and to calculate the site-specific reference intervals. Hair content of arsenic, boron, cadmium, cobalt, chromium, copper, iron, mercury, iodine, lithium, manganese, lead, selenium, silicon, tin, strontium, vanadium, and zinc in 148 cows during first (n = 50), second (n = 48), and third (n = 50) lactation periods of life was determined using inductively coupled plasma mass spectrometry. Dietary intake of trace elements corresponded to the adequate values according to national and international recommendations. Comparative analysis did not reveal any significant differences in hair content of main essential elements on the animals depending on the number of lactation. At the same time, the first-lactation cows had significantly (P < 0.05) lower concentration of lead in hair as compared to the third-lactation cows and a higher level of mercury as compared to the second-lactation cows. The reference intervals and 90% confidence intervals for the lower and upper limits were calculated in agreement with the American Society for Veterinary Clinical Pathology Quality Assurance and Laboratory Standard Guidelines.

Analysis of whole human blood for Pb, Cd, Hg, Se, and Mn by ICP-DRC-MS for biomonitoring and acute exposures.

We improved our inductively coupled plasma mass spectrometry (ICP-MS) whole blood method [1] for determination of lead (Pb), cadmium (Cd), and mercury (Hg) by including manganese (Mn) and selenium (Se), and expanding the calibration range of all analytes. The method is validated on a PerkinElmer (PE) ELAN® DRC II ICP-MS (ICP-DRC-MS) and uses the Dynamic Reaction Cell (DRC) technology to attenuate interfering background ion signals via ion-molecule reactions. Methane gas (CH4) eliminates background signal from 40Ar2+ to permit determination of 80Se+, and oxygen gas (O2) eliminates several polyatomic interferences (e.g. 40Ar15N+, 54Fe1H+) on 55Mn+. Hg sensitivity in DRC mode is a factor of two higher than vented mode when measured under the same DRC conditions as Mn due to collisional focusing of the ion beam. To compensate for the expanded method's longer analysis time (due to DRC mode pause delays), we implemented an SC4-FAST autosampler (ESI Scientific, Omaha, NE), which vacuum loads the sample onto a loop, to keep the sample-to-sample measurement time to less than 5min, allowing for preparation and analysis of 60 samples in an 8-h work shift. The longer analysis time also resulted in faster breakdown of the hydrocarbon oil in the interface roughing pump. The replacement of the standard roughing pump with a pump using a fluorinated lubricant, Fomblin®, extended the time between pump maintenance. We optimized the diluent and rinse solution components to reduce carryover from high concentration samples and prevent the formation of precipitates. We performed a robust calculation to determine the following limits of detection (LOD) in whole blood: 0.07µgdL-1 for Pb, 0.10µgL-1 for Cd, 0.28µgL-1 for Hg, 0.99µgL-1 for Mn, and 24.5µgL-1 for Se.

Stability of Vitamin A, Iron and Zinc in Fortified Rice during Storage and Its Impact on Future National Standards and Programs--Case Study in Cambodia.

Fortified rice holds great potential for bringing essential micronutrients to a large part of the world population. The present study quantified the losses of three different micronutrients (vitamin A, iron, zinc) in fortified rice that were produced using three different techniques (hot extrusion, cold extrusion, and coating) and stored at two different environments (25 ± 5 °C at a humidity of 60% and 40 ± 5 °C at a humidity of 75%) for up to one year. Fortified rice premix from the different techniques was mixed with normal rice in a 1:100 ratio. Each sample was analyzed in triplicate. The study confirmed the high stability of iron and zinc during storage while the retention of vitamin A was significantly affected by storage and the type of techniques used to make rice premix. Losses for iron and zinc were typically <10% for any type of rice premix. After 12 months at mild conditions (25 °C and humidity of 60%), losses for vitamin A ranged from 20% for cold extrusion, 30% for hot extruded rice 77% for coated rice premix. At higher temperatures and humidity, losses of vitamin A were 40%-50% for extruded premix and 93% for coated premix after 6 months. We conclude that storage does lead to a major loss of vitamin A and question whether rice is a suitable food vehicle to fortify with vitamin A. For Cambodia, fortification of rice with iron and zinc could be an effective strategy to improve the micronutrient status of the population if no other food vehicles are available.

A Call to Action to Bring Safer Parenteral Micronutrient Products to the U.S. Market.

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) started an intensive review of commercially available parenteral vitamin and trace element (TE) products in 2009. The chief findings were that adult multi-TE products currently available in the United States (U.S.) provide potentially toxic amounts of manganese, copper, and chromium, and neonatal/pediatric multi-TE products provide potentially toxic amounts of manganese and chromium. The multivitamin products appeared safe and effective; however, a separate parenteral vitamin D product is needed for those patients on standard therapy who continue to be vitamin D depleted and are unresponsive to oral supplements. The review process also extended to parenteral choline and carnitine. Although choline and carnitine are not technically vitamins or trace elements, choline is an essential nutrient in all age groups, and carnitine is an essential nutrient in infants, according to the Food and Nutrition Board of the Institute of Medicine. A parenteral choline product needs to be developed and available. Efforts are currently under way to engage the U.S. Food and Drug Administration (FDA) and the parenteral nutrient industry so A.S.P.E.N.'s recommendations can become a commercial reality.

Review of trace mineral requirements for preterm infants: what are the current recommendations for clinical practice?

Inadequate nutrient stores at birth are an inevitable consequence of being born prematurely. Preterm infants also have high nutrient requirements, which increase with earlier gestational ages. As a result, early nutrition intervention is required to prevent further deficits that, if not corrected, can affect growth and long-term outcomes. Preterm infants often require several weeks of parenteral nutrition (PN) support, which includes trace mineral supplementation. Trace minerals are considered essential nutrients, unable to be synthesized in the human body. Deficiencies of trace minerals have been reported, yet evidence-based guidelines for assessment and supplementation have not been clearly defined. Food and Drug Administration-approved parenteral trace mineral intake guidelines are more than 30 years old. In an effort to more clearly define trace mineral supplementation and monitoring guidelines for preterm infants, a review of literature was performed with the purpose to (1) summarize trace mineral roles in preterm infants, (2) describe clinical signs of deficiency and toxicity, and (3) present intake recommendations and considerations for preterm infants based on current available literature. Review of literature was completed using PubMed and Cochrane databases to find relevant studies specific to trace mineral requirements for preterm infants, trace mineral supplementation of PN, human milk fortifiers, and preterm infant formulas. Review of literature supports that trace mineral depletion can lead to clinical compromise in preterm infants; therefore, suggesting that every effort be made to ensure adequate provision of trace minerals is given to preterm infants. Practical considerations for the clinical nutrition management of preterm infants were also identified in this review.

Multivitamins/multiminerals in Switzerland: not as good as it seems.

BACKGROUND: Multivitamin/multimineral (MVM) supplements are commonly consumed by the general population, but little is known regarding their composition and compliance with local regulations. We assessed the composition and compliance with regulations [no indication in the label of vitamin/minerals amounting <15% of the acceptable daily intake (ADI)] of MVM available in Switzerland. METHODS: The composition of vitamin/minerals supplements was obtained from the Swiss drug compendium, the Internet, pharmacies, parapharmacies and supermarkets. MVM was defined as the presence of at least 5 vitamins and/or minerals. RESULTS: Of the 254 vitamin/mineral supplements collected, 95 (37%) were considered as MVM. The most frequent vitamins were B6 (73.7%), C (71.6%), B2 (69.5%) and B1 (67.4%); the least frequent were K (17.9%), biotin (51.6%), pantothene (55.8%) and E (56.8%). Approximately half of MVMs provided >150% of the ADI for vitamins. The most frequent minerals were zinc (66.3%), calcium (55.8%), magnesium (54.7%) and copper (48.4%), and the least frequent were fluoride (3.2%), phosphorous (17.9%), chrome (22.1%) and iodine (25%). More than two thirds of MVMs provided between 50 and 150% of the ADI for minerals, and few MVMs provided >150% of the ADI. While few MVMs provided <15% of the ADI for vitamins, a considerable fraction did so for minerals (32.7% for magnesium, 26.1% for copper and 22.6% for calcium). CONCLUSION: There is a great variability regarding the composition of MVMs available in Switzerland. Several MVM do not comply with Swiss regulations, which calls for monitoring and corrective measures.

Baseline element composition of foliose and fruticose lichens along the steep climatic gradient of SW Patagonia (Aisén Region, Chile).

Samples of foliose (Nephroma antarcticum) and fruticose (Usnea sp.) lichens were collected across a steep climatic and vegetation gradient in a remote, almost pristine region of SW Chilean Patagonia. Concentrations of major and trace elements in lichens from the rainforest were among the lowest ever reported worldwide for foliose and fruticose lichens and can be considered background levels for the region. The two lichen growth forms showed different elemental compositions mainly due to the greater capacity of foliose thalli to intercept elements from windborne and canopy-leached particles. The patterns of spatial variation in the chemical composition of lichens were effectively explained by statistical methods and reflected the different availability of wet and dry deposition along the steep climatic gradient. Baseline values established for N. antarcticum samples growing in temperate Nothofagus forests were therefore distinct from those of samples growing in more open, drier habitats. The fruticose Usnea sp. showed a higher affinity for atmophile Hg, low concentrations of lithophilic elements, and the same baseline composition whether from temperate forests or from dry, barren environments. The provided background and baseline values against which variations can be measured will be useful in the early detection of local or regional climatic and environmental change, especially in view of the planned construction of hydropower dams under the recently approved HidroAysén Project.

Defining reference values of trace elements in the tear film: diagnostic methods and possible applications.

The study has been performed on tears of apparently healthy subjects who live and work in urban and rural areas, respectively. After the collection the following elements were investigated: chromium (Cr); arsenic (As); copper (Cu); zinc (Zn); selenium (Se); rubidium (Rb); barium (Ba); lead (Pb) and cobalt (Co). Significantly higher values of As were found in subjects living and working in rural areas as compared to those found in urban area residents (0.290 vs. 0.025; p<0.001). Conversely, Ba and Pb were significantly lower in rural area residents (1.10 vs. 2.50, p=0.027 and 1.70 vs. 1.10, p=0.057, respectively). Our data show that trace elements analysis in tears is possible; further studies could define if it could be a reliable biomarker in persons exposed to high concentration of trace elements due to working or environmental reasons.

Characterization of NIES CRM No. 23 Tea Leaves II for the determination of multielements.

A candidate environmental certified reference material (CRM) for the determination of multielements in tea leaves and materials of similar matrix, NIES CRM No. 23 Tea Leaves II, has been developed and characterized by the National Institute for Environmental Studies (NIES), Japan. The origin of the material was tea leaves, which were ground, sieved through a 106-microm mesh, homogenized, and then subdivided into amber glass bottles. The results of homogeneity and stability tests indicated that the material was sufficiently homogeneous and stable for use as a reference material. The property values of the material were statistically determined based on chemical analyses by a network of laboratories using a wide range of methods. Sixteen laboratories participated in the characterization, and nine certified values and five reference values were obtained. These property values of the candidate CRM, which are expressed as mass fractions, were close to the median and/or mean values of the mass fractions of elements in various tea products. The candidate CRM is appropriate for use in analytical quality control and in the evaluation of methods used in the analysis of tea and materials of similar matrix.

A non-element-enriched, non-lyophilized candidate rat serum reference material prepared for once use in determination of inorganic elements by ICP-MS.

A practice about preparing a once-used native state candidate rat serum reference material has been described for inductively coupled plasma atomic emission spectrometry (ICP-MS) determination of inorganic elements in biological matrices, which is independently packed, easy to use, non-lyophilized, without element-spiking, and with stable quality. Various dispersing and storing factors influencing the serum quality have been investigated including container material, sampling volume, packing mode and storage time. The contents of twelve main elements in the rat serum have been not only evaluated by ICP-MS but also verified by other analytical techniques. The probation of this unconventional candidate serum reference material by different laboratories has given very similar contents of 12 main trace elements in the serum, and proven its applicability to support quality assurance of biological sample analyses.

[Comparative study on quality of Flos Lonicerae between geo-authentic and non-authentic producing areas].

OBJECTIVE: To compare the quality of Flos Lonicerae between different producing areas. METHOD: ICP-AES, UV and HPLC were used to determine the contents of trace elements, chlorogenic acid, total flavonoids, five iridoid glucosides, hederagenin, and oleanolic acid. SAS software system was used to perform data and cluster analyses. RESULT: The results showed that the geo-authentic crude drug was lower in the contents of Cr and Pb but higher in the contents of chlorogenic acid, total flavonoids, five iridoid glucosides, hederagenin, and oleanolic acid than the non-authentic crude drug. CONCLUSION: The geo-authentic crude drug of Flos Lonicerae is better in quality than the non-authentic crude drug based on the modern chemical analyses, which confirms the validity of traditional geo-based classification.

Assessment of implementation of a standardized parenteral formulation for early nutritional support of very preterm infants.

INTRODUCTION: Parenteral nutrition (PN) plays an important role in the nutritional support of very preterm newborns. It has been suggested that a high proportion of PN orders could be standardized. In 2002, we implemented in our unit the preparation of three standardized formulations for PN adapted to the nutritional requirements of premature infants<32 weeks. Following this change of practice, a retrospective observational study was conducted to evaluate the relevance of the implemented standardized PN regime. Twenty premature inborn infants<32 weeks gestation who had received standardized (STD) PN in 2003 were matched for 20 infants who had received individualized (IND) PN in 2001. Adequacy of nutrition was assessed by comparing daily intravenous nutrient intake and biochemical parameters during the first week. Amino-acid intakes on day 3 were higher in the STD group (1.5+/-0.2 g/kg/d vs. 0.9+/-0.5, p<0.001), and the calcium phosphate intakes were better balanced. The cumulated intake of amino acids for the first week was greater in the STD group (+20% ; p=0.0003). Biochemical parameters were similar in both groups. Insulin infusions were less frequent in the STD group (p<0.06). CONCLUSION: Standardized parenteral formulations provided higher early intakes of amino acid and glucose, a better calcium phosphate ratio, and a greater amount of amino-acid intakes during the first week while maintaining the same biochemical parameters. This strategy forms part of an approach concerning quality control and the respect of good professional practice for the preparation of parenteral nutrition solutions.

Between a rock and a hard place: methods for setting dietary allowances and exposure limits for essential minerals.

For each essential trace element, there are two ranges of intake associated with adverse health effects: intakes that are too low and can lead to nutritional deficits and intakes that are too high and can lead to toxicity. Between these two ranges, there is a range of safe and adequate intakes that is compatible with good health; the challenge is to define that range quantitatively. The exposure limit for toxicity traditionally has been determined by dividing a "no-observed-adverse-effect level," often from studies in experimental animals, by a series of uncertainty factors. Dietary allowances to meet nutritional requirements, on the other hand, have been based primarily on data in humans. Uncertainty, variability and limitations in the data base tend to increase estimates of nutritional requirements and decrease estimated toxic exposure limits, driving the values closer together. Chromium (III) and zinc are contrasting cases. Other factors, such as bioavailability, selection of the critical effect and interactions also can play important roles. Close coordination between the nutrition and toxicology communities, as envisioned in the NRC Food and Nutrition Board initiative on Dietary Reference Intakes, is essential in establishing acceptable ranges of intake for trace elements.

Toxicity considerations when revising the Nordic nutrition recommendations.

The Nordic countries have issued common nutrition recommendations since 1980. In connection with the 3rd revision, a joint working group of nutritionists and toxicologists assessed the toxicology of selected trace elements. Values for upper limits of intake were established for iron, zinc, iodine and selenium. The safety factors between the lowest intakes at which adverse effects had been reported and the suggested upper limits of intake were small. In the toxicological evaluation of upper safe intake levels of essential trace elements, interactions between trace elements as well as long-term exposure to moderately elevated trace element intakes have to be considered.

Background and rationale behind the SU.VI.MAX Study, a prevention trial using nutritional doses of a combination of antioxidant vitamins and minerals to reduce cardiovascular diseases and cancers. SUpplementation en VItamines et Minéraux AntioXydants Study.

The "SUpplementation en VItamines et MinérauxAntioXydants" (SU.VI.MAX) study is a randomized double-blind, placebo-controlled, primary prevention trial designed to test the efficacy of daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 micrograms; and zinc, 20 mg), at nutritional doses (one to three times the daily recommended dietary allowances), in reducing the frequency of major health problems in industrialized countries, and especially the main causes of premature death (cancers and cardiovascular diseases). The study involves 12,735 eligible subjects (women aged 35 to 60 years; men aged 45 to 60 years) included in 1994 in France. They will be followed up for 8 years. The objectives and the specific design of this intervention study are linked to its public health aim. The targeted population is the general population (not simply high-risk subjects) and the antioxidant agents tested are being administered at a level which is not pharmacologic and which may be attained by dietary intake of natural sources of these micronutrients and/or enriched foods. The amounts we are testing in the SU.VI.MAX study are those which, in observational studies have been associated with the lowest risk of diseases. This report presents the rationale and discusses the justification of the design, doses and combination of antioxidant micronutrients chosen in the SU.VI.MAX study.

Risk assessment of essential trace elements: new approaches to setting recommended dietary allowances and safety limits.

By definition, every essential trace element must have a range of intakes safe from toxicity but adequate enough to meet nutrition requirements. That range is part of the total dose-response curve and its lower and upper limits are delineated on the basis of nutrition and toxicology data, respectively. Close coordination of activities to set these limits is necessary to avoid recommendations that are either impractical (narrow zones of safe and adequate intakes) or contradictory (overlapping limits, i.e., no zones of safe and adequate intakes).