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Vitamin A deficiency is a major health risk for infants and children in low- and middle-income countries. This scoping review identified, quantified, and mapped research for use in updating nutrient requirements and upper limits for vitamin A in children aged 0 to 48 months, using health-based or modelling-based approaches. Structured searches were run on Medline, EMBASE, and Cochrane Central, from inception to 19 March 2021. Titles and abstracts were assessed independently in duplicate, as were 20% of full texts. Included studies were tabulated by question, methodology and date, with the most relevant data extracted and assessed for risk of bias. We found that the most recent health-based systematic reviews and trials assessed the effects of supplementation, though some addressed the effects of staple food fortification, complementary foods, biofortified maize or cassava, and fortified drinks, on health outcomes. Recent isotopic tracer studies and modelling approaches may help quantify the effects of bio-fortification, fortification, and food-based approaches for increasing vitamin A depots. A systematic review and several trials identified adverse events associated with higher vitamin A intakes, which should be useful for setting upper limits. We have generated and provide a database of relevant research. Full systematic reviews, based on this scoping review, are needed to answer specific questions to set vitamin A requirements and upper limits.

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies - thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes, and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these outcomes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of categorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity.

Vitamin A deficiency is a major health risk for infants and children in low- and middle-income countries. This scoping review identified, quantified, and mapped research for use in updating nutrient requirements and upper limits for vitamin A in children aged 0 to 48 months, using health-based or modelling-based approaches. Structured searches were run on Medline, EMBASE, and Cochrane Central, from inception to 19 March 2021. Titles and abstracts were assessed independently in duplicate, as were 20% of full texts. Included studies were tabulated by question, methodology and date, with the most relevant data extracted and assessed for risk of bias. We found that the most recent health-based systematic reviews and trials assessed the effects of supplementation, though some addressed the effects of staple food fortification, complementary foods, biofortified maize or cassava, and fortified drinks, on health outcomes. Recent isotopic tracer studies and modelling approaches may help quantify the effects of bio-fortification, fortification, and food-based approaches for increasing vitamin A depots. A systematic review and several trials identified adverse events associated with higher vitamin A intakes, which should be useful for setting upper limits. We have generated and provide a database of relevant research. Full systematic reviews, based on this scoping review, are needed to answer specific questions to set vitamin A requirements and upper limits.

Vitamin A deficiency is a major health risk for infants and children in low- and middle-income countries. This scoping review identified, quantified, and mapped research for use in updating nutrient requirements and upper limits for vitamin A in children aged 0 to 48 months, using health-based or modelling-based approaches. Structured searches were run on Medline, EMBASE, and Cochrane Central, from inception to 19 March 2021. Titles and abstracts were assessed independently in duplicate, as were 20% of full texts. Included studies were tabulated by question, methodology and date, with the most relevant data extracted and assessed for risk of bias. We found that the most recent health-based systematic reviews and trials assessed the effects of supplementation, though some addressed the effects of staple food fortification, complementary foods, biofortified maize or cassava, and fortified drinks, on health outcomes. Recent isotopic tracer studies and modelling approaches may help quantify the effects of bio-fortification, fortification, and food-based approaches for increasing vitamin A depots. A systematic review and several trials identified adverse events associated with higher vitamin A intakes, which should be useful for setting upper limits. We have generated and provide a database of relevant research. Full systematic reviews, based on this scoping review, are needed to answer specific questions to set vitamin A requirements and upper limits.

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies - thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes, and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these outcomes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of categorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity.

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies - thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes, and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these outcomes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of categorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity.

Recommendations aimed at protecting the public from toxicity of essential elements including essential metals have usually been developed separately from those recommendations aimed at protection from deficiency. Because of the uncertainties involved in the evaluations, these recommendations have sometimes been in conflict, emphasizing the need for a new approach, including a balanced consideration of nutritional and toxicological data. In developing these new principles of evaluation, some basic concepts based on interindividual variability in sensitivity to deficiency and toxicity must be considered. Such variation translates into one interval of (low) daily intakes, at which there is a risk of developing deficiency, and another interval of (high) dietary intakes at which toxicity may occur. In most instances, there is a third set of intakes in between, which represents the acceptable range of oral intake (AROI), in which no adverse effects occur. This range determined from a homeostatic or biologically based (BBM) approach, which is discussed here, would be expected to apply to the general population. It must be noted, however, that this range would not protect all persons from adverse effects: this applies to those with genetically determined sensitivity, who may require higher intakes to avoid deficiency or lower intakes to avoid toxicity than those defined by the AROI. Nonetheless, AROI could be derived to protect 95% of the general human population from minimal adverse effects of deficiency or toxicity arising from inadequate and excessive intakes. As such the correspondence of these values to current Health-Based Guidance Values (HBGVs) and reference intakes of essential metals (EMs), and the roles of the BBM/Homeostatic Approach in Risk Assessment of EMs are of important public health interest.

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies - thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes, and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these outcomes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of categorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity.

Vitamin A deficiency is a major health risk for infants and children in low- and middle-income countries. This scoping review identified, quantified, and mapped research for use in updating nutrient requirements and upper limits for vitamin A in children aged 0 to 48 months, using health-based or modelling-based approaches. Structured searches were run on Medline, EMBASE, and Cochrane Central, from inception to 19 March 2021. Titles and abstracts were assessed independently in duplicate, as were 20% of full texts. Included studies were tabulated by question, methodology and date, with the most relevant data extracted and assessed for risk of bias. We found that the most recent health-based systematic reviews and trials assessed the effects of supplementation, though some addressed the effects of staple food fortification, complementary foods, biofortified maize or cassava, and fortified drinks, on health outcomes. Recent isotopic tracer studies and modelling approaches may help quantify the effects of bio-fortification, fortification, and food-based approaches for increasing vitamin A depots. A systematic review and several trials identified adverse events associated with higher vitamin A intakes, which should be useful for setting upper limits. We have generated and provide a database of relevant research. Full systematic reviews, based on this scoping review, are needed to answer specific questions to set vitamin A requirements and upper limits.

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies - thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes, and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these outcomes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of categorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity.

Vitamin A deficiency is a major health risk for infants and children in low- and middle-income countries. This scoping review identified, quantified, and mapped research for use in updating nutrient requirements and upper limits for vitamin A in children aged 0 to 48 months, using health-based or modelling-based approaches. Structured searches were run on Medline, EMBASE, and Cochrane Central, from inception to 19 March 2021. Titles and abstracts were assessed independently in duplicate, as were 20% of full texts. Included studies were tabulated by question, methodology and date, with the most relevant data extracted and assessed for risk of bias. We found that the most recent health-based systematic reviews and trials assessed the effects of supplementation, though some addressed the effects of staple food fortification, complementary foods, biofortified maize or cassava, and fortified drinks, on health outcomes. Recent isotopic tracer studies and modelling approaches may help quantify the effects of bio-fortification, fortification, and food-based approaches for increasing vitamin A depots. A systematic review and several trials identified adverse events associated with higher vitamin A intakes, which should be useful for setting upper limits. We have generated and provide a database of relevant research. Full systematic reviews, based on this scoping review, are needed to answer specific questions to set vitamin A requirements and upper limits.

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies - thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes, and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these outcomes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of categorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity.

Vitamin A deficiency is a major health risk for infants and children in low- and middle-income countries. This scoping review identified, quantified, and mapped research for use in updating nutrient requirements and upper limits for vitamin A in children aged 0 to 48 months, using health-based or modelling-based approaches. Structured searches were run on Medline, EMBASE, and Cochrane Central, from inception to 19 March 2021. Titles and abstracts were assessed independently in duplicate, as were 20% of full texts. Included studies were tabulated by question, methodology and date, with the most relevant data extracted and assessed for risk of bias. We found that the most recent health-based systematic reviews and trials assessed the effects of supplementation, though some addressed the effects of staple food fortification, complementary foods, biofortified maize or cassava, and fortified drinks, on health outcomes. Recent isotopic tracer studies and modelling approaches may help quantify the effects of bio-fortification, fortification, and food-based approaches for increasing vitamin A depots. A systematic review and several trials identified adverse events associated with higher vitamin A intakes, which should be useful for setting upper limits. We have generated and provide a database of relevant research. Full systematic reviews, based on this scoping review, are needed to answer specific questions to set vitamin A requirements and upper limits.

This Statement presents a proposal for harmonising the establishment of Health-Based Guidance Values (HBGVs) for regulated products that are also nutrients. This is a recurrent issue for food additives and pesticides, and may occasionally occur for other regulated products. The Statement describes the specific considerations that should be followed for establishing the HBGVs during the assessment of a regulated product that is also a nutrient. It also addresses the elements to be considered in the intake assessment; and proposes a decision tree for ensuring a harmonised process for the risk characterisation of regulated products that are also nutrients. The Scientific Committee recommends the involvement of the relevant EFSA Panels and units, in order to ensure an integrated and harmonised approach for the hazard and risk characterisation of regulated products that are also nutrients, considering the intake from all relevant sources.

This Statement presents a proposal for harmonising the establishment of Health-Based Guidance Values (HBGVs) for regulated products that are also nutrients. This is a recurrent issue for food additives and pesticides, and may occasionally occur for other regulated products. The Statement describes the specific considerations that should be followed for establishing the HBGVs during the assessment of a regulated product that is also a nutrient. It also addresses the elements to be considered in the intake assessment; and proposes a decision tree for ensuring a harmonised process for the risk characterisation of regulated products that are also nutrients. The Scientific Committee recommends the involvement of the relevant EFSA Panels and units, in order to ensure an integrated and harmonised approach for the hazard and risk characterisation of regulated products that are also nutrients, considering the intake from all relevant sources.

This Statement presents a proposal for harmonising the establishment of Health-Based Guidance Values (HBGVs) for regulated products that are also nutrients. This is a recurrent issue for food additives and pesticides, and may occasionally occur for other regulated products. The Statement describes the specific considerations that should be followed for establishing the HBGVs during the assessment of a regulated product that is also a nutrient. It also addresses the elements to be considered in the intake assessment; and proposes a decision tree for ensuring a harmonised process for the risk characterisation of regulated products that are also nutrients. The Scientific Committee recommends the involvement of the relevant EFSA Panels and units, in order to ensure an integrated and harmonised approach for the hazard and risk characterisation of regulated products that are also nutrients, considering the intake from all relevant sources.

When extrapolating data from animal toxicological studies a default factor (dUF) of 100 is applied to derive a heath based guidance value. The UF takes into account the interspecies differences (ID) and the intraspecies variability (IV). When re-evaluating the safety of phosphates used as food additives nephrocalcinosis was identified as the critical endpoint. The underlying mechanism for nephrocalcinosis was attributed to the precipitation of calcium phosphate in the kidney, depending on its solubility, irrespective of the species and the population. Based on the mechanism, the volume of primary urine, for which the glomerular filtration rate (GFR) was used as a proxy, was considered to be the only parameter relevant for ID and IV. Median value of GFR in rats was 4.0 ml/min/kg bw. In humans it was 1.6 ml/min/kg bw in healthy adults and 0.9 in elderly. These values were calculated from the distribution of the GFR data from 8 studies in rats (n = 191), 16 studies in adults (n = 1540) and 5 studies in elderly (n = 2608). Multiplying the distribution of the ratio rat/healthy humans (ID) with the distribution of the ratio healthy humans/elderly human (IV) resulted in a phosphate specific factor of 4.5 (3.3-6.7) (median; 25th - 75th percentile). [Abstract copyright: Copyright © 2020. Published by Elsevier Inc.]

When extrapolating data from animal toxicological studies a default factor (dUF) of 100 is applied to derive a heath based guidance value. The UF takes into account the interspecies differences (ID) and the intraspecies variability (IV). When re-evaluating the safety of phosphates used as food additives nephrocalcinosis was identified as the critical endpoint. The underlying mechanism for nephrocalcinosis was attributed to the precipitation of calcium phosphate in the kidney, depending on its solubility, irrespective of the species and the population. Based on the mechanism, the volume of primary urine, for which the glomerular filtration rate (GFR) was used as a proxy, was considered to be the only parameter relevant for ID and IV. Median value of GFR in rats was 4.0 ml/min/kg bw. In humans it was 1.6 ml/min/kg bw in healthy adults and 0.9 in elderly. These values were calculated from the distribution of the GFR data from 8 studies in rats (n = 191), 16 studies in adults (n = 1540) and 5 studies in elderly (n = 2608). Multiplying the distribution of the ratio rat/healthy humans (ID) with the distribution of the ratio healthy humans/elderly human (IV) resulted in a phosphate specific factor of 4.5 (3.3-6.7) (median; 25th - 75th percentile). [Abstract copyright: Copyright © 2020. Published by Elsevier Inc.]

When extrapolating data from animal toxicological studies a default factor (dUF) of 100 is applied to derive a heath based guidance value. The UF takes into account the interspecies differences (ID) and the intraspecies variability (IV). When re-evaluating the safety of phosphates used as food additives nephrocalcinosis was identified as the critical endpoint. The underlying mechanism for nephrocalcinosis was attributed to the precipitation of calcium phosphate in the kidney, depending on its solubility, irrespective of the species and the population. Based on the mechanism, the volume of primary urine, for which the glomerular filtration rate (GFR) was used as a proxy, was considered to be the only parameter relevant for ID and IV. Median value of GFR in rats was 4.0 ml/min/kg bw. In humans it was 1.6 ml/min/kg bw in healthy adults and 0.9 in elderly. These values were calculated from the distribution of the GFR data from 8 studies in rats (n = 191), 16 studies in adults (n = 1540) and 5 studies in elderly (n = 2608). Multiplying the distribution of the ratio rat/healthy humans (ID) with the distribution of the ratio healthy humans/elderly human (IV) resulted in a phosphate specific factor of 4.5 (3.3-6.7) (median; 25th - 75th percentile). [Abstract copyright: Copyright © 2020. Published by Elsevier Inc.]

When extrapolating data from animal toxicological studies a default factor (dUF) of 100 is applied to derive a heath based guidance value. The UF takes into account the interspecies differences (ID) and the intraspecies variability (IV). When re-evaluating the safety of phosphates used as food additives nephrocalcinosis was identified as the critical endpoint. The underlying mechanism for nephrocalcinosis was attributed to the precipitation of calcium phosphate in the kidney, depending on its solubility, irrespective of the species and the population. Based on the mechanism, the volume of primary urine, for which the glomerular filtration rate (GFR) was used as a proxy, was considered to be the only parameter relevant for ID and IV. Median value of GFR in rats was 4.0 ml/min/kg bw. In humans it was 1.6 ml/min/kg bw in healthy adults and 0.9 in elderly. These values were calculated from the distribution of the GFR data from 8 studies in rats (n = 191), 16 studies in adults (n = 1540) and 5 studies in elderly (n = 2608). Multiplying the distribution of the ratio rat/healthy humans (ID) with the distribution of the ratio healthy humans/elderly human (IV) resulted in a phosphate specific factor of 4.5 (3.3-6.7) (median; 25th - 75th percentile). [Abstract copyright: Copyright © 2020. Published by Elsevier Inc.]

The first Committee on Nutrition (CoN) was founded in 1974. Two years later nutrition (N) was added to the society's name, which then became ESPGAN. The Committee systematised compositional and quality criteria for breast milk substitutes and food for special medical purposes, the first of many examples on how recommendations and comments published by the Committees on Nutrition (CsoN) were adopted by the European Economic Community, later the European Union and also influenced the World Health Organization/Food and Agriculture Organization of the United Nations Codex standards. A second CoN focusing on preterm infants was established in 1979 and its recommendations on nutrition of these infants were widely implemented. The third and standing CoN, established 1986, started to organise high-quality symposia at the annual meetings appreciating the need to enhance the expertise in nutritional research. From 1991 the CoN has organised Summer Schools in paediatric nutrition for young colleagues further emphasising its educational interest and more recently an annual, more specialised Nutrition Masterclass. Successively the interest of the CoN has expanded to other areas, such as highlighting dilemmas and uncertainties in the field of nutrition including the design, choice of outcomes and statistical analysis of trials in infant nutrition. The work of the CsoN have had great impact on paediatric nutrition and the committee will continue its important role by writing commentaries and systematic reviews and revising guidelines when required to inform and stimulate discussion among colleagues as well as stimulate training in paediatric nutrition by organising workshops and scientific meetings, training courses, and other approaches, and by interaction with other expert groups., Supplement: 1

Characterizing the U-shaped exposure response relationship for manganese (Mn) is necessary for estimating the risk of adverse health from Mn toxicity due to excess or deficiency. Categorical regression has emerged as a powerful tool for exposure-response analysis because of its ability to synthesize relevant information across multiple studies and species into a single integrated analysis of all relevant data. This paper documents the development of a database on Mn toxicity designed to support the application of categorical regression techniques. Specifically, we describe (i) the conduct of a systematic search of the literature on Mn toxicity to gather data appropriate for dose-response assessment; (ii) the establishment of inclusion/exclusion criteria for data to be included in the categorical regression modeling database; (iii) the development of a categorical severity scoring matrix for Mn health effects to permit the inclusion of diverse health outcomes in a single categorical regression analysis using the severity score as the outcome variable; and (iv) the convening of an international expert panel to both review the severity scoring matrix and assign severity scores to health outcomes observed in studies (including case reports, epidemiological investigations, and in vivo experimental studies) selected for inclusion in the categorical regression database. Exposure information including route, concentration, duration, health endpoint(s), and characteristics of the exposed population was abstracted from included studies and stored in a computerized manganese database (MnDB), providing a comprehensive repository of exposure-response information with the ability to support categorical regression modeling of oral exposure data.

Characterizing the U-shaped exposure response relationship for manganese (Mn) is necessary for estimating the risk of adverse health from Mn toxicity due to excess or deficiency. Categorical regression has emerged as a powerful tool for exposure-response analysis because of its ability to synthesize relevant information across multiple studies and species into a single integrated analysis of all relevant data. This paper documents the development of a database on Mn toxicity designed to support the application of categorical regression techniques. Specifically, we describe (i) the conduct of a systematic search of the literature on Mn toxicity to gather data appropriate for dose-response assessment; (ii) the establishment of inclusion/exclusion criteria for data to be included in the categorical regression modeling database; (iii) the development of a categorical severity scoring matrix for Mn health effects to permit the inclusion of diverse health outcomes in a single categorical regression analysis using the severity score as the outcome variable; and (iv) the convening of an international expert panel to both review the severity scoring matrix and assign severity scores to health outcomes observed in studies (including case reports, epidemiological investigations, and in vivo experimental studies) selected for inclusion in the categorical regression database. Exposure information including route, concentration, duration, health endpoint(s), and characteristics of the exposed population was abstracted from included studies and stored in a computerized manganese database (MnDB), providing a comprehensive repository of exposure-response information with the ability to support categorical regression modeling of oral exposure data.

Characterizing the U-shaped exposure response relationship for manganese (Mn) is necessary for estimating the risk of adverse health from Mn toxicity due to excess or deficiency. Categorical regression has emerged as a powerful tool for exposure-response analysis because of its ability to synthesize relevant information across multiple studies and species into a single integrated analysis of all relevant data. This paper documents the development of a database on Mn toxicity designed to support the application of categorical regression techniques. Specifically, we describe (i) the conduct of a systematic search of the literature on Mn toxicity to gather data appropriate for dose-response assessment; (ii) the establishment of inclusion/exclusion criteria for data to be included in the categorical regression modeling database; (iii) the development of a categorical severity scoring matrix for Mn health effects to permit the inclusion of diverse health outcomes in a single categorical regression analysis using the severity score as the outcome variable; and (iv) the convening of an international expert panel to both review the severity scoring matrix and assign severity scores to health outcomes observed in studies (including case reports, epidemiological investigations, and in vivo experimental studies) selected for inclusion in the categorical regression database. Exposure information including route, concentration, duration, health endpoint(s), and characteristics of the exposed population was abstracted from included studies and stored in a computerized manganese database (MnDB), providing a comprehensive repository of exposure-response information with the ability to support categorical regression modeling of oral exposure data.

Recommendations aimed at protecting the public from toxicity of essential elements including essential metals have usually been developed separately from those recommendations aimed at protection from deficiency. Because of the uncertainties involved in the evaluations, these recommendations have sometimes been in conflict, emphasizing the need for a new approach, including a balanced consideration of nutritional and toxicological data. In developing these new principles of evaluation, some basic concepts based on interindividual variability in sensitivity to deficiency and toxicity must be considered. Such variation translates into one interval of (low) daily intakes, at which there is a risk of developing deficiency, and another interval of (high) dietary intakes at which toxicity may occur. In most instances, there is a third set of intakes in between, which represents the acceptable range of oral intake (AROI), in which no adverse effects occur. It must be noted, however, that a range cannot be found that protects all persons from adverse effects. Those persons with genetically determined sensitivity may require higher intakes to avoid deficiency or lower intakes to avoid toxicity than those defined by the AROI. The AROI is defined as protecting 95% of an unselected human population from minimal adverse effects of deficiency or toxicity.

The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged <3 years; (2) agree on a range of outcome measures relevant to nutrition trials in this age group for which agreed criteria are needed; (3) agree on an updated 'core data set' that should generally be recorded in nutrition trials in infants and young children, and (4) provide guidance on the use of surrogate markers in paediatric nutrition research. The participants discussed these objectives and agreed to set up six first working groups under the auspices of the Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT). Five groups will aim to identify and define criteria for assessing key outcomes, i.e. growth, acute diarrhoea, atopic dermatitis and cows' milk protein allergy, infections and 'gut comfort'. The sixth group will review and update the 'core data set'. The COMMENT Steering Committee will discuss and decide upon a method for reaching consensus which will be used by all working groups and plan to meet again within 2 years and to report and publish their conclusions.

The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged

The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged <3 years; (2) agree on a range of outcome measures relevant to nutrition trials in this age group for which agreed criteria are needed; (3) agree on an updated 'core data set' that should generally be recorded in nutrition trials in infants and young children, and (4) provide guidance on the use of surrogate markers in paediatric nutrition research. The participants discussed these objectives and agreed to set up six first working groups under the auspices of the Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT). Five groups will aim to identify and define criteria for assessing key outcomes, i.e. growth, acute diarrhoea, atopic dermatitis and cows' milk protein allergy, infections and 'gut comfort'. The sixth group will review and update the 'core data set'. The COMMENT Steering Committee will discuss and decide upon a method for reaching consensus which will be used by all working groups and plan to meet again within 2 years and to report and publish their conclusions.

BACKGROUND: Codex documents may be used as educational and consensus materials for member governments. Also, the WTO SPS Agreement recognizes Codex as the presumptive international authority on food issues. Nutrient bioavailability is a critical factor in determining the ability of nutrients to provide beneficial effects. Bioavailability also influences the quantitative dietary requirements that are the basis of nutrient intake recommendations and NRVs. HEALTH CLAIMS: Codex, EFSA and some national regulatory authorities have established guidelines or regulations that will permit several types of health claims. The scientific basis for claims has been established by the US FDA and EFSA, but not yet by Codex. Evidence-based nutrition differs from evidence-based medicine, but the differences are only recently gaining recognition. Health claims on foods may provide useful information to consumers, but many will interpret the information to mean that they can rely upon the food or nutrient to eliminate a disease risk. NUTRIENT REFERENCE VALUES: NRVs are designed to provide a quantitative basis for comparing the nutritive values of foods, helping to illustrate how specific foods fit into the overall diet. The INL-98 and the mean of adult male and female values provide NRVs that are sufficient when used as targets for individual intakes by most adults. WORLD TRADE ORGANIZATION AGREEMENTS: WTO recognizes Codex as the primary international authority on food issues. Current regulatory schemes based on recommended dietary allowances are trade restrictive. A substantial number of decisions by the EFSA could lead to violation of WTO agreements.

The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged

Objective: The objective was to define the term evidence based nutrition on the basis of expert discussions and scientific evidence. Methods and procedures: The method used is the established Hohenheim Consensus Conference. The term “Hohenheim Consensus Conference” defines conferences dealing with nutrition-related topics. The major aim of the conference is to review the state of the art of a given topic with experts from different areas (basic science, clinicians, epidemiologists, etc.). Based on eight to 12 questions, the experts discuss short answers and try to come to a consensus. A scientifically based text is formulated that justifies the consensus answer. To discuss the requirements for the scientific substantiation of claims, the 26th Hohenheim Consensus Conference gathered the views of many academic experts in the field of nutritional research and asked these experts to address the various aspects of a claims substantiation process and the possibilities and limitations of the different approaches. Results: The experts spent a day presenting and discussing their views and arrived at several consensus statements that can serve as guidance for bodies performing claims assessments in the framework of regulatory systems. Conclusion: The 26th Hohenheim Consensus Conference addresses some general aspects and describes the current scientific status from the point of view of six case studies to illustrate specific areas of scientific interest: carotenoids and vitaminA in relation to age-related macular degeneration, the quality of carbohydrates (as expressed by the glycemic index) in relation to health and well-being, probiotics in relation to intestinal and immune functions, micronutrient intake and maintenance of normal body functions, and food components with antioxidative properties and health benefits.

The IMPACT questionnaire was developed in Canada to measure quality of life in children with inflammatory bowel disease (IBD). In the present study, 20 children with IBD completed 2 versions of the IMPACT questionnaire with a Likert scale or visual analog scale (VAS), 5 of whom expressed problems with language or phrasing. Difficult words included "restrictions," "moderate," "diarrhea," "school break," and the abbreviation "IBD." Fifteen children preferred the Likert scale to the VAS (chi = 20, P < 0.01). Rewording the difficult words and using a Likert scale should facilitate completion of the IMPACT questionnaire in the United Kingdom. Further validation is needed to ensure that the instrument is reliable and valid.

The IMPACT questionnaire was developed in Canada to measure quality of life in children with inflammatory bowel disease (IBD). In the present study, 20 children with IBD completed 2 versions of the IMPACT questionnaire with a Likert scale or visual analog scale (VAS), 5 of whom expressed problems with language or phrasing. Difficult words included "restrictions," "moderate," "diarrhea," "school break," and the abbreviation "IBD." Fifteen children preferred the Likert scale to the VAS (chi = 20, P < 0.01). Rewording the difficult words and using a Likert scale should facilitate completion of the IMPACT questionnaire in the United Kingdom. Further validation is needed to ensure that the instrument is reliable and valid.

The IMPACT questionnaire was developed in Canada to measure quality of life in children with inflammatory bowel disease (IBD). In the present study, 20 children with IBD completed 2 versions of the IMPACT questionnaire with a Likert scale or visual analog scale (VAS), 5 of whom expressed problems with language or phrasing. Difficult words included "restrictions," "moderate," "diarrhea," "school break," and the abbreviation "IBD." Fifteen children preferred the Likert scale to the VAS (chi = 20, P < 0.01). Rewording the difficult words and using a Likert scale should facilitate completion of the IMPACT questionnaire in the United Kingdom. Further validation is needed to ensure that the instrument is reliable and valid.

The IMPACT questionnaire was developed in Canada to measure quality of life in children with inflammatory bowel disease (IBD). In the present study, 20 children with IBD completed 2 versions of the IMPACT questionnaire with a Likert scale or visual analog scale (VAS), 5 of whom expressed problems with language or phrasing. Difficult words included "restrictions," "moderate," "diarrhea," "school break," and the abbreviation "IBD." Fifteen children preferred the Likert scale to the VAS (chi = 20, P < 0.01). Rewording the difficult words and using a Likert scale should facilitate completion of the IMPACT questionnaire in the United Kingdom. Further validation is needed to ensure that the instrument is reliable and valid.

Aim. This paper is a report of a study to compare the perceptions of adult patients, family carers, nurses and dietitians regarding home percutaneous endoscopic gastrostomy feeding. Background. Healthcare professionals have a major role in patient selection for gastrostomy placement and the provision of aftercare but it is not clear if patients, their carers and healthcare professionals have similar perceptions of the initiation and delivery of feeding and of the care in general. Method. A cross-sectional mixed-method study using purposive sampling, semi-structured interviews and questionnaires was performed. Interviews were undertaken during 2005 with adult patients and carers of adults receiving home feeding. A questionnaire containing comparable questions was distributed to the lead district nurse and dietitian providing the individual patient's care. Binomial regression was used to analyse any differences in perceptions across the groups of respondents. Results. Nurses and dietitians had similar perceptions of gastrostomy feeding in adults. Family carers’ perceptions matched those of professionals more closely than did those of patients. The greatest difference in perceptions was between patients and their family carers. Respondents’ views about success of feeding and the appropriateness of the feeding regimen were similar, but greater differences existed regarding quality of life, withdrawal of feeding and choice in decision-making about tube placement. Conclusion. There is a need for increased patient and carer involvement in decision-making and for sufficient, appropriate information to facilitate informed decision-making. Practitioners who involve carers in decision-making, where patients lack capacity, need to be aware that carers may not represent the views of patients.

Aim. This paper is a report of a study to compare the perceptions of adult patients, family carers, nurses and dietitians regarding home percutaneous endoscopic gastrostomy feeding. Background. Healthcare professionals have a major role in patient selection for gastrostomy placement and the provision of aftercare but it is not clear if patients, their carers and healthcare professionals have similar perceptions of the initiation and delivery of feeding and of the care in general. Method. A cross-sectional mixed-method study using purposive sampling, semi-structured interviews and questionnaires was performed. Interviews were undertaken during 2005 with adult patients and carers of adults receiving home feeding. A questionnaire containing comparable questions was distributed to the lead district nurse and dietitian providing the individual patient's care. Binomial regression was used to analyse any differences in perceptions across the groups of respondents. Results. Nurses and dietitians had similar perceptions of gastrostomy feeding in adults. Family carers’ perceptions matched those of professionals more closely than did those of patients. The greatest difference in perceptions was between patients and their family carers. Respondents’ views about success of feeding and the appropriateness of the feeding regimen were similar, but greater differences existed regarding quality of life, withdrawal of feeding and choice in decision-making about tube placement. Conclusion. There is a need for increased patient and carer involvement in decision-making and for sufficient, appropriate information to facilitate informed decision-making. Practitioners who involve carers in decision-making, where patients lack capacity, need to be aware that carers may not represent the views of patients.

Aim. This paper is a report of a study to compare the perceptions of adult patients, family carers, nurses and dietitians regarding home percutaneous endoscopic gastrostomy feeding. Background. Healthcare professionals have a major role in patient selection for gastrostomy placement and the provision of aftercare but it is not clear if patients, their carers and healthcare professionals have similar perceptions of the initiation and delivery of feeding and of the care in general. Method. A cross-sectional mixed-method study using purposive sampling, semi-structured interviews and questionnaires was performed. Interviews were undertaken during 2005 with adult patients and carers of adults receiving home feeding. A questionnaire containing comparable questions was distributed to the lead district nurse and dietitian providing the individual patient's care. Binomial regression was used to analyse any differences in perceptions across the groups of respondents. Results. Nurses and dietitians had similar perceptions of gastrostomy feeding in adults. Family carers’ perceptions matched those of professionals more closely than did those of patients. The greatest difference in perceptions was between patients and their family carers. Respondents’ views about success of feeding and the appropriateness of the feeding regimen were similar, but greater differences existed regarding quality of life, withdrawal of feeding and choice in decision-making about tube placement. Conclusion. There is a need for increased patient and carer involvement in decision-making and for sufficient, appropriate information to facilitate informed decision-making. Practitioners who involve carers in decision-making, where patients lack capacity, need to be aware that carers may not represent the views of patients.

Aim. This paper is a report of a study to compare the perceptions of adult patients, family carers, nurses and dietitians regarding home percutaneous endoscopic gastrostomy feeding. Background. Healthcare professionals have a major role in patient selection for gastrostomy placement and the provision of aftercare but it is not clear if patients, their carers and healthcare professionals have similar perceptions of the initiation and delivery of feeding and of the care in general. Method. A cross-sectional mixed-method study using purposive sampling, semi-structured interviews and questionnaires was performed. Interviews were undertaken during 2005 with adult patients and carers of adults receiving home feeding. A questionnaire containing comparable questions was distributed to the lead district nurse and dietitian providing the individual patient's care. Binomial regression was used to analyse any differences in perceptions across the groups of respondents. Results. Nurses and dietitians had similar perceptions of gastrostomy feeding in adults. Family carers’ perceptions matched those of professionals more closely than did those of patients. The greatest difference in perceptions was between patients and their family carers. Respondents’ views about success of feeding and the appropriateness of the feeding regimen were similar, but greater differences existed regarding quality of life, withdrawal of feeding and choice in decision-making about tube placement. Conclusion. There is a need for increased patient and carer involvement in decision-making and for sufficient, appropriate information to facilitate informed decision-making. Practitioners who involve carers in decision-making, where patients lack capacity, need to be aware that carers may not represent the views of patients.

Survival of small premature infants has markedly improved during the last few decades. These infants are discharged from hospital care with body weight below the usual birth weight of healthy term infants. Early nutrition support of preterm infants influences long-term health outcomes. Therefore, the ESPGHAN Committee on Nutrition has reviewed available evidence on feeding preterm infants after hospital discharge. Close monitoring of growth during hospital stay and after discharge is recommended to enable the provision of adequate nutrition support. Measurements of length and head circumference, in addition to weight, must be used to identify those preterm infants with poor growth that may need additional nutrition support. Infants with an appropriate weight for postconceptional age at discharge should be breast-fed when possible. When formula-fed, such infants should be fed regular infant formula with provision of long-chain polyunsaturated fatty acids. Infants discharged with a subnormal weight for postconceptional age are at increased risk of long-term growth failure, and the human milk they consume should be supplemented, for example, with a human milk fortifier to provide an adequate nutrient supply. If formula-fed, such infants should receive special postdischarge formula with high contents of protein, minerals and trace elements as well as an long-chain polyunsaturated fatty acid supply, at least until a postconceptional age of 40 weeks, but possibly until about 52 weeks postconceptional age. Continued growth monitoring is required to adapt feeding choices to the needs of individual infants and to avoid underfeeding or overfeeding

BACKGROUND: Insulin sensitivity is a key function in human metabolism because it has a crucial role in the development of disease that are increasingly common in modern society. Impaired insulin sensitivity is an important determinant of type 2 diabetes; moreover, it has been proposed as an independent risk factor for cardiovascular disease. Thus, reduced insulin sensitivity is strongly associated with the metabolic syndrome, which represents a cluster of metabolic abnormalities and cardiovascular risk factor. Insulin sensitivity can be modulated by different environmental factors, including dietary habits. Obesity, especially if associated with abdominal adiposity, impairs insulin-sensitivity while physical activity can improve it; however, the composition of the habitual diet is clearly an important regulator of this function. AIM: To evaluate methodologies and markers that can be used to substantiate existing and potential claims of beneficial effects of foods on relevant functions connected with body fat deposition, insulin sensitivity and blood glucose regulation. RESULTS: We have reviewed the scientific basis for existing and potential claims, based not only on modifications of the target functions (body fat deposition, insulin sensitivity and blood glucose regulation) but also on modifications of other relevant associated functions (energy intake, energy expenditure, fat storage and oxidation, lipotoxicity, body fat composition, inflammation, oxidative stress, vascular function, glucose production and utilization). In this context we have identified a number of markers and evaluated appropriate method to measure and validate them. CONCLUSIONS: Relevant functions contributing to overweight, the metabolic syndrome and diabetes have been identified. The evidence reviewed indicates that in this field the link between nutrition, biological responses and diseases is clearly established. Therefore, there is a strong potential to develop functional food science. The

Fractional apparent absorption of Zn and Ca from a wheat-milk-based infant cereal was studied in six healthy infants (18-30 weeks old). Mineral absorption was measured by a stable-isotope technique based on faecal excretion of the isotopes. Each test meal (40 g cereal) was extrinsically labelled with 70Zn and 42Ca before intake. All faecal material passed during the 21 d following intake of the labelled test meal was collected on trace-element-free nappies. Individual stool samples were analysed for their content of ‘OZn and 42Ca by thermal ionization mass spectrometry. Apparent absorption was calculated as intake minus total faecal excretion of the isotopes over 68-92 h after administration. The fractional apparent absorption values for Zn and Ca were 33.9 (SD 164) % (range 19.2-639 %) and 53.5 (SD 12.6) %) (range 36.7-71.7 %) respectively. Re-excretion of absorbed 70Zn (> 68-92 h to 21 d after intake of the labelled meal) was 044 (SD 038) %] of administered dose while only one infant re-excreted detectable amounts of 42Ca (1.74%) of administered dose). The analysis of individual stool samples confirmed that 72 h is a sufficient time period for complete collections of non-absorbed isotopes in faecal material from infants during the weaning period and that re-excretion of initially absorbed 70Zn and 42Ca (> 68-92 h to 21 d after intake of the labelled meal) is negligible