Lower carbohydrate diets for adults with type 2 diabetes.

In May 2021, the Scientific Advisory Committee on Nutrition (SACN) published a risk assessment on lower carbohydrate diets for adults with type 2 diabetes (T2D)(). The purpose of the report was to review the evidence on 'low'-carbohydrate diets compared with the current UK government advice on carbohydrate intake for adults with T2D. However, since there is no agreed and widely utilised definition of a 'low'-carbohydrate diet, comparisons in the report were between lower and higher carbohydrate diets. SACN's remit is to assess the risks and benefits of nutrients, dietary patterns, food or food components for health by evaluating scientific evidence and to make dietary recommendations for the UK based on its assessment(). SACN has a public health focus and only considers evidence in healthy populations unless specifically requested to do otherwise. Since the Committee does not usually make recommendations relating to clinical conditions, a joint working group (WG) was established in 2017 to consider this issue. The WG comprised members of SACN and members nominated by Diabetes UK, the British Dietetic Association, Royal College of Physicians and Royal College of General Practitioners. Representatives from NHS England and NHS Health Improvement, the National Institute for Health and Care Excellence and devolved health departments were also invited to observe the WG. The WG was jointly chaired by SACN and Diabetes UK.

Chapter 7. The Contributions of the ESPGHAN Committees on Nutrition to Paediatric Nutrition.

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.

Scientific opinion on the tolerable upper intake level for iron.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for iron. Systematic reviews were conducted to identify evidence regarding high iron intakes and risk of chronic diseases, adverse gastrointestinal effects and adverse effects of iron supplementation in infancy, young childhood and pregnancy. It is established that systemic iron overload leads to organ toxicity, but no UL could be established. The only indicator for which a dose-response could be established was black stools, which reflect the presence of large amounts of unabsorbed iron in the gut. This is a conservative endpoint among the chain of events that may lead to systemic iron overload but is not adverse per se. Based on interventions in which black stools did not occur at supplemental iron intakes of 20-25 mg/day (added to a background intake of 15 mg/day), a safe level of intake for iron of 40 mg/day for adults (including pregnant and lactating women) was established. Using allometric scaling (body weight0.75), this value was scaled down to children and adolescents and safe levels of intakes between 10 mg/day (1-3 years) and 35 mg/day (15-17 years) were derived. For infants 7-11 months of age who have a higher iron requirement than young children, allometric scaling was applied to the supplemental iron intakes (i.e. 25 mg/day) and resulted in a safe level of supplemental iron intake of 5 mg/day. This value was extended to 4-6 month-old infants and refers to iron intakes from fortified foods and food supplements, not from infant and follow-on formulae. The application of the safe level of intake is more limited than a UL because the intake level at which the risk of adverse effects starts to increase is not defined.

Scientific opinion on the tolerable upper intake level for selenium.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for selenium. Systematic reviews of the literature were conducted to identify evidence regarding excess selenium intake and clinical effects and potential biomarkers of effect, risk of chronic diseases and impaired neuropsychological development in humans. Alopecia, as an early observable feature and a well-established adverse effect of excess selenium exposure, is selected as the critical endpoint on which to base a UL for selenium. A lowest-observed-adverse-effect-level (LOAEL) of 330 µg/day is identified from a large randomised controlled trial in humans (the Selenium and Vitamin E Cancer Prevention Trial (SELECT)), to which an uncertainty factor of 1.3 is applied. A UL of 255 µg/day is established for adult men and women (including pregnant and lactating women). ULs for children are derived from the UL for adults using allometric scaling (body weight0.75). Based on available intake data, adult consumers are unlikely to exceed the UL, except for regular users of food supplements containing high daily doses of selenium or regular consumers of Brazil nuts. No risk has been reported with the current levels of selenium intake in European countries from food (excluding food supplements) in toddlers and children, and selenium intake arising from the natural content of foods does not raise reasons for concern. Selenium-containing supplements in toddlers and children should be used with caution, based on individual needs.

Nutrition issues in Codex: health claims, nutrient reference values and WTO agreements: a conference report.

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.

Documentation of functional and clinical effects of infant nutrition: setting the scene for COMMENT.

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.

Dose-response relationships in multifunctional food design: assembling the evidence.

Demonstrating single and multiple functions attributable to foods or specific food components is a challenge. The International Life Sciences Institute Europe co-ordinated EU concerted actions, Functional Food Science in Europe (FUFOSE) and the Process for the Assessment of Scientific Support for Claims on Food (PASSCLAIM), respectively, addressed the soundness of the evidence and its coherence with a mechanistic schema comprising valid markers of exposure, intermediate and final outcomes and the quality and integrity of the evidence overall. Demonstrating causality often relies on randomized controlled trials (RCTs). However, in public health and biomedical science there is concern about the suitability of RCTs as sole standards of evidence-based approaches. Alternative and complementary approaches using updated Hill's viewpoints for appraising the evidence can be used in conjunction with evidence-based mechanistic reasoning and the quality criteria proposed in FUFOSE and PASSCLAIM to design studies and to assemble evidence exploring single or multiple benefits from food components and foods.

The use of categorical regression in the assessment of the risks of nutrient deficiency and excess

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 out-comes 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 cat-egorical 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.

Guidance for establishing and applying tolerable upper intake levels for vitamins and essential minerals: Draft for internal testing.

Vitamins and essential minerals are micronutrients that are essential for the normal functioning of the human body. However, they may lead to adverse health effects if consumed in excess. The concept of a tolerable upper intake level (UL) is a science-based reference value, which was introduced to support policy-makers and other relevant actors in managing the risks of excess nutrient intake. EFSA's principles for establishing ULs for vitamins and minerals were originally developed by the Scientific Committee on Food in 2000. Since then, experience has been gained and the scientific field developed. This guidance from the EFSA Panel on Nutrition, Novel Foods and Food Allergens provides an updated framework to support EFSA's UL assessments. It covers aspects related to the planning of the risk assessment (problem formulation and definition of methods) and its implementation (evidence retrieval, appraisal, synthesis, integration, uncertainty analysis). As in the previous framework, the general principles developed for the risk assessment of chemicals in food are applied (hazard identification, hazard characterisation, intake assessment, risk characterisation). Peculiar to nutrients are their biochemical and physiological roles and the specific and selective mechanisms that maintain the systemic homoeostasis and body burden of the nutrient. These must be considered when conducting a risk assessment of nutrients. This document constitutes a draft guidance that will be applied in EFSA's assessments during a 1-year pilot phase and be revised and complemented as necessary. Before finalisation of the guidance, a public consultation will be launched.

Evidence to Underpin Vitamin A Requirements and Upper Limits in Children Aged 0 to 48 Months: A Scoping Review.

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.

Food & health forum meeting: evidence-based nutrition.

The present report summarises a meeting held by the Food & Health Forum at the Royal Society of Medicine, London, on 27 May 2010. The objective of the meeting was to review the problems associated with the use of evidence-based nutrition and to discuss what constitutes the efficacy for foods and food constituents and how the strength and consistency of the evidence can be assessed and adapted to circumstances in which health claims are to be used on food products. The meeting highlighted the limitations with the present evidence-based nutrition models with the prospect that this may have long-term consequences for nutrition science and ultimately the consumer who may not benefit from new science that could have an impact on health.

Statement on the derivation of Health-Based Guidance Values (HBGVs) for regulated products that are also nutrients.

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.

Guidance on safety evaluation of sources of nutrients and bioavailability of nutrient from the sources (Revision 1).

[Table: see text] This guidance describes the scientific data required to allow an evaluation of the safety of new substances that are proposed for use as sources of nutrients in food supplements, foods for the general population or foods for specific groups and an assessment of the bioavailability of the nutrient from the proposed source. This guidance describes the scientific data required to allow an evaluation of the safety of the source within the established framework for risk assessment of food additives and novel food ingredients and the bioavailability of the nutrient from this source. This document is arranged in five main sections: one on technical data aimed at characterising the proposed source and at identifying potential hazards resulting from its manufacture and stability in food; one on existing authorisations and evaluation, providing an overview of previous assessments on the proposed source and their conclusions; one on proposed uses and exposure assessment section, allowing an estimate of the dietary exposure to the source and the nutrient based on the proposed uses and use levels; one on toxicological data, describing approaches which can be used to identify (in conjunction with data on manufacture and composition) and to characterise hazards of the source and any relevant breakdown products; the final section on bioavailability focuses on determining the extent to which the nutrient from the proposed source is available for use by the body in comparison with one or more forms of the same nutrient that are already permitted for use on the positive lists. This guidance was adopted by the Panel on Food Additives and Nutrient Sources added to Food (ANS Panel) on 16 May 2018. Upon request from EFSA, the present guidance has been revised to inform applicants of new provisions set out in Regulation (EC) No 178/2002, as amended by Regulation (EU) 2019/1381 on the transparency and sustainability of the EU risk assessment in the food chain.

An exposure-response curve for copper excess and deficiency.

There is a need to define exposure-response curves for both Cu excess and deficiency to assist in determining the acceptable range of oral intake. A comprehensive database has been developed where different health outcomes from elevated and deficient Cu intakes were assigned ordinal severity scores to create common measures of response. A generalized linear model for ordinal data was used to estimate the probability of response associated with dose, duration and severity. The model can account for differences in animal species, the exposure medium (drinking water and feed), age, sex, and solubility. Using this model, an optimal intake level of 2.6 mg Cu/d was determined. This value is higher than the current U.S. recommended dietary intake (RDI; 0.9 mg/d) that protects against toxicity from Cu deficiency. It is also lower than the current tolerable upper intake level (UL; 10 mg/d) that protects against toxicity from Cu excess. Compared to traditional risk assessment approaches, categorical regression can provide risk managers with more information, including a range of intake levels associated with different levels of severity and probability of response. To weigh the relative harms of deficiency and excess, it is important that the results be interpreted along with the available information on the nature of the responses that were assigned to each severity score.

Toxicity due to excess and deficiency.

Customary approaches to setting safe upper levels for the intake of nutrients use, as critical events, adverse health that which, when adjusted using uncertainty factors (UF), produce values that, when they are applied to population risk analysis, along with dietary reference values that have been independently derived using a different approach by nutritionists, may provide narrow and unrealistic safe ranges of dietary intake. This study describes the evolving concept of the risk assessment of nutrients in which the critical events are based on homeostatic health effects that occur at the upper extreme of the physiological range of intakes. These events can be envisaged as markers of failing adaptation to high exposures and as heralds of potential later adverse events. Such markers may be associated with smaller and more easily characterized uncertainties than those applied to the more gross toxicological architectural, functional, or reproductive health effects used in standard toxicological risk assessment. The study also outlines the potential extension of this homeostatic model to the determination of safe lower limits of intake for essential nutrients and the identification, when homeostasis fails, of thresholds for inadequate intakes that can be adjusted by using uncertainty factors (UF) to derive adequate reference intakes.

Development of a copper database for exposure-response analysis.

While its precise form has not yet been defined, it is assumed that the exposure-response curve for copper (Cu) is U-shaped, as both Cu deficiency and excess can produce adverse health effects. Exposure-response relationships provide the foundation for setting recommended levels of exposure to essential and nonessential substances. A group of toxicologists, biologists, and epidemiologists formed a working group in 2002 to review the literature on Cu excess and deficiency as well as possible exposure-response modeling strategies. It was decided that in order to conduct more complex modeling exercises with studies on Cu, the information had to be organized into a database for application of emerging analytical approaches in exposure-response assessment. The database would support both current as well as proposed methods for exposure-response assessment and accommodate a variety of reporting methods found in the literature. As there are multiple studies looking at a wide range of adverse health effects attributed to excess and deficiency, data were organized into ordered categories of severity to create a common measure of response. The present study (1) outlines the approach used to identify studies for the Cu database based on their quality and usefulness for exposure-response analyses; (2) provides an overview of the process used to define a common dose metric; and (3) describes the process used to categorize a diverse number of responses from Cu excess and deficiency to an ordinal severity score. Efforts are underway to use this database to define the exposure-response curve for Cu excess and deficiency; however, the comprehensive database can be used to carry out other in-depth analyses on Cu toxicity.

The process for the assessment of scientific support for claims on food.

The concerted action "The process for the assessment of the scientific support for claims on foods", PASSCLAIM, proposed criteria that could provide an international yardstick for the harmonised transparent assessment of evidence submitted to support a claim for a food or food component. The evidence would be systematically appraised against specific criteria: namely, (1) a characterisation of the food or food component to which the claimed effect is attributed; (2) human data, primarily from intervention studies that represent the target populations for the claim; (3) a dose response relationship; (4) evidence allowing for confounders such as lifestyle, consumption patterns, background diet and food matrix etc.; (5) an appropriate duration for the study; (6) a measure of compliance; (7) adequate statistical power to test the hypothesis. Validated and quality assured markers of intermediate or final outcomes could be used when ideal endpoints are not easily accessible for measurement as long as their relationship to the development of the principal outcome relevant to the claim is well characterised and substantiated. The overall coherence and totality of published and unpublished evidence should be considered in the process. Assessments for substantiation claims need expert judgement, weighting of the strength of the claim, and intelligent use of the criteria applied on an individual basis with respect both to gaps in the knowledge and to any need for new knowledge and data.

Re-evaluation of phosphoric acid-phosphates - di-, tri- and polyphosphates (E 338-341, E 343, E 450-452) as food additives and the safety of proposed extension of use.

The Panel on Food Additives and Flavourings added to Food (FAF) provided a scientific opinion re-evaluating the safety of phosphates (E 338-341, E 343, E 450-452) as food additives. The Panel considered that adequate exposure and toxicity data were available. Phosphates are authorised food additives in the EU in accordance with Annex II and III to Regulation (EC) No 1333/2008. Exposure to phosphates from the whole diet was estimated using mainly analytical data. The values ranged from 251 mg P/person per day in infants to 1,625 mg P/person per day for adults, and the high exposure (95th percentile) from 331 mg P/person per day in infants to 2,728 mg P/person per day for adults. Phosphate is essential for all living organisms, is absorbed at 80-90% as free orthophosphate excreted via the kidney. The Panel considered phosphates to be of low acute oral toxicity and there is no concern with respect to genotoxicity and carcinogenicity. No effects were reported in developmental toxicity studies. The Panel derived a group acceptable daily intake (ADI) for phosphates expressed as phosphorus of 40 mg/kg body weight (bw) per day and concluded that this ADI is protective for the human population. The Panel noted that in the estimated exposure scenario based on analytical data exposure estimates exceeded the proposed ADI for infants, toddlers and other children at the mean level, and for infants, toddlers, children and adolescents at the 95th percentile. The Panel also noted that phosphates exposure by food supplements exceeds the proposed ADI. The Panel concluded that the available data did not give rise to safety concerns in infants below 16 weeks of age consuming formula and food for medical purposes.

Dietary reference values for chloride.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) has derived dietary reference values (DRVs) for chloride. There are no appropriate biomarkers of chloride status, no balance studies and no adequate evidence on the relationship between chloride intake and health outcomes that can be used to set DRVs for chloride. There is a close relationship between sodium and chloride balances in the body. Sodium chloride is the main source of both electrolytes in European diets and similar urinary excretion levels of sodium and chloride (on a molar basis) are typically observed in Western populations. Hence, the Panel considered that reference values for chloride can be set at values equimolar to the reference values for sodium for all population groups, and are as follows: 1.7 g/day for children aged 1-3 years, 2.0 g/day for children aged 4-6 years, 2.6 g/day for children aged 7-10 years, 3.1 g/day for children aged 11-17 years and 3.1 g/day for adults including pregnant and lactating women. Consistent with the reference values for sodium, these levels of chloride intake are considered to be safe and adequate for the general EU population, under the consideration that the main dietary source of chloride intake is sodium chloride. For infants aged 7-11 months, an adequate intake of 0.3 g/day is set.