Does fluoride exposure affect thyroid function? A systematic review and dose-response meta-analysis.

INTRODUCTION: Fluoride exposure may have various adverse health effects, including affecting thyroid function and disease risk, but the pattern of such relation is still uncertain. METHODS: We systematically searched human studies assessing the relation between fluoride exposure and thyroid function and disease. We compared the highest versus the lowest fluoride category across these studies, and we performed a one-stage dose-response meta-analysis for aggregated data to explore the shape of the association. RESULTS: Most retrieved studies (27 of which with a cross-sectional design) were conducted in Asia and in children, assessing fluoride exposure through its concentrations in drinking water, urine, serum, or dietary intake. Twenty-four studies reported data on thyroid function by measuring thyroid-related hormones in blood (mainly thyroid-stimulating-hormone - TSH), 9 reported data on thyroid disease, and 4 on thyroid volume. By comparing the highest versus the lowest fluoride categories, overall mean TSH difference was 1.05 µIU/mL. Dose-response curve showed no change in TSH concentrations in the lowest water fluoride exposure range, while the hormone levels started to linearly increase around 2.5 mg/L, also dependending on the risk of bias of the included studies. The association between biomarkers of fluoride exposure and TSH was also positive, with little evidence of a threshold. Evidence for an association between fluoride exposure and blood concentrations of thyroid hormones was less evident, though there was an indication of inverse association with triiodothyronine. For thyroid disease, the few available studies suggested a positive association with goiter and with hypothyroidism in both children and adults. CONCLUSIONS: Overall, exposure to high-fluoride drinking water appears to non-linearly affect thyroid function and increase TSH release in children, starting above a threshold of exposure, and to increase the risk of some thyroid diseases.

Dietary intake of protein and fat of 12- to 36-month-old children in a Dutch Total Diet Study.

PURPOSE: This study attempted gaining insight into the intake of protein and fat of 12- to 36-month-old children in the Netherlands. METHODS: In 2017, a Total Diet Study (TDS) was carried out in the Netherlands including following three age groups: 12-17-, 18-23- and 24- to 36-month-old children. Protein and fat concentrations of 164 composite samples were analysed and combined with the consumption data from the Dutch National Food Consumption Survey 2012-2016 (DNFCS). RESULTS: Median protein intake of the 12- to 35-month-old Dutch children based on the TDS was 35 g/day with main contributions from the food subgroups "milk and milk-based beverages", "beef" and "yoghurts and desserts". Median fat intake was 34 g/day with main contributions from the food subgroups "margarines", "cheeses" and "milk and milk-based beverages". For the youngest age group (12- to 18-month-old children), (ready to drink) follow-on formula was one of the main contributors to the fat intake. CONCLUSION: Compared to the EFSA reference values, protein intake of the Dutch 12- to 36-month-old children is high, whereas fat intake follows the reference intake. A TDS is a suitable instrument to estimate macronutrient intakes.

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System.

Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (<100 nm) of TiO2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2.

Potential cofactors in accidental food allergic reactions are frequently present but may not influence severity and occurrence.

BACKGROUND: Cofactors, such as physical exercise and alcohol intake, might be associated with the severity or occurrence of food allergic reactions. OBJECTIVE: To gain insight into the frequency of presence of potential cofactors in accidental food allergic reactions in adults and to what extent these factors influence the severity and occurrence of allergic reactions. METHODS: A prospective cohort study was conducted, with a 1-year follow-up in adult patients with a physician-diagnosed food allergy. Patients were required to fill in a questionnaire after every accidental allergic reactions to food over a 1-year period. The primary outcome measure was the frequency that potential cofactors were present in these allergic reactions. RESULTS: A total of 157 patients were included, of which 46% reported a total of 153 reactions during a 1-year follow-up period. In 74% of the reactions, ≥1 potential cofactor was reported to be present: tiredness (38%), alcohol intake (16%), stress (14%), symptoms of pollinosis (16%), symptoms of asthma (9%), sickness/flu (3%), physical exercise (3%) and use of analgesics (2%). More than one potential cofactor was reported in almost half of all reactions (47%). There was no significant difference in the presence of these factors between mild, moderate and severe reactions (P = 0.522). In the total study population, 9% of the patients used medication that might act as cofactor (antacids, angiotensin receptor blockers [ARBs], beta blockers and angiotensin-converting enzyme inhibitors [ACEIs]) on a daily basis, which however did not influence the occurrence of reactions. Furthermore, 38% daily used allergy-suppressing medication. CONCLUSIONS: Although factors suggested to be cofactors were frequently present during accidental food allergic reactions, we found no evidence for an association between the potential cofactors examined and reaction severity, in a population where most reactions were of mild to moderate severity.

Accidental food allergy reactions: Products and undeclared ingredients.

BACKGROUND: Accidental allergic reactions to food are frequent and can be severe and even fatal. OBJECTIVE: We sought to analyze the culprit food products and levels of unexpected allergens in accidental reactions. METHODS: A prospective cohort study was conducted in adults (n = 157) with a physician-confirmed diagnosis of food allergy. During a 1-year follow-up, 73 patients reported accidental allergic reactions and the culprit food products. Food samples received (n = 51) were analyzed for a wide range of suspected noningredient allergens, and risk was quantified. RESULTS: A very diverse range of food products was responsible for the unexpected allergic reactions. Thirty-seven percent (19/51) of products analyzed had 1 to 4 culprit allergens identified that were not supposed to be present according to the ingredient declaration. Concentrations varied from 1 to 5000 mg of protein of the allergenic food per kilogram of food product and were greatest for peanut, milk, and sesame. Milk proteins posed the highest estimated risk for objective allergic reactions. The intake of culprit allergens by patients varied considerably. For those cases in which culprit allergens were detected, the intake of at least 1 allergen exceeded the reference dose or a culprit allergen with a yet unknown reference dose was present. Both patient neglect of precautionary allergen labeling statements and omission of using a precautionary allergen labeling statement by food manufacturers seem to contribute to accidental reactions. CONCLUSION: A wide range of food products are causing accidental reactions in patients with food allergy. Eight different allergens not declared on the ingredient lists were detected in the culprit food products, all of which were representative of allergens regulated in the European Union.

Prediction of fruit and vegetable intake from biomarkers using individual participant data of diet-controlled intervention studies.

Fruit and vegetable consumption produces changes in several biomarkers in blood. The present study aimed to examine the dose-response curve between fruit and vegetable consumption and carotenoid (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C concentrations. Furthermore, a prediction model of fruit and vegetable intake based on these biomarkers and subject characteristics (i.e. age, sex, BMI and smoking status) was established. Data from twelve diet-controlled intervention studies were obtained to develop a prediction model for fruit and vegetable intake (including and excluding fruit and vegetable juices). The study population in the present individual participant data meta-analysis consisted of 526 men and women. Carotenoid, folate and vitamin C concentrations showed a positive relationship with fruit and vegetable intake. Measures of performance for the prediction model were calculated using cross-validation. For the prediction model of fruit, vegetable and juice intake, the root mean squared error (RMSE) was 258.0 g, the correlation between observed and predicted intake was 0.78 and the mean difference between observed and predicted intake was - 1.7 g (limits of agreement: - 466.3, 462.8 g). For the prediction of fruit and vegetable intake (excluding juices), the RMSE was 201.1 g, the correlation was 0.65 and the mean bias was 2.4 g (limits of agreement: -368.2, 373.0 g). The prediction models which include the biomarkers and subject characteristics may be used to estimate average intake at the group level and to investigate the ranking of individuals with regard to their intake of fruit and vegetables when validating questionnaires that measure intake.

Joselito® and lowering of LDL-cholesterol concentration, blood pressure, and reduction of coronary heart disease risk: Evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006.

Following an application from Cárnicas Joselito S.A. pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Spain, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to 'Joselito ham increases antioxidant substances in the body, reduces blood pressure and plasma triglycerides, decreases oxidative stress and prevents effect in diseases related to the cardiovascular and intestinal systems'. The scope of the application was proposed to fall under a health claim referring to disease risk reduction. The food constituent that is the subject of the health claim is Joselito, an Iberian ham characterised by a high content of oleic acid. The Panel considers that the food is sufficiently characterised. The Panel considers that lowering of LDL-cholesterol concentration and blood pressure is a beneficial effect by decreasing the risk of coronary heart disease. Upon a request from EFSA, the applicant identified one human intervention study as being pertinent to the claim. However, due to methodological limitations, the Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim. The Panel notes that no human intervention studies from which conclusions could be drawn for the scientific substantiation of the claim were provided by the applicant. The Panel concludes that a cause and effect relationship has not been established between the intake of Joselito® ham and the reduction of LDL-cholesterol concentration or blood pressure.

'Citicoline' and support of the memory function: Evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006.

Following an application from Egde Pharma Sp. z o.o, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Poland, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to citicoline and memory. The Panel considers that the food, citicoline (cytidine 5-diphosphocholine, CDP-Choline) inner salt, is sufficiently characterised. Improvement, maintenance or reduced loss of memory is a beneficial physiological effect for middle-aged or elderly adults encountering age-associated subjective memory impairment. The applicant identified three pertinent human intervention studies in healthy individuals that investigated the effect of citicoline on memory. In weighing the evidence, the Panel took into account that only one randomised controlled trial in healthy participants showed a beneficial effect of citicoline on episodic memory when consumed at doses of 500 mg/day for 12 weeks, whereas this effect has not been observed in another study using citicoline at doses of 1 g/day for 3 months or supported by data obtained in patients with dementia using doses of 1 g/day for 12 weeks and 12 months. No convincing evidence of a plausible mechanism by which citicoline or any of its components (in addition to their endogenous synthesis) could exert an effect on memory in humans has been provided. The Panel concludes that a cause-and-effect relationship has not been established between the consumption of citicoline (CDP-Choline) inner salt and improvement, maintenance or reduced loss of memory in middle-aged or elderly adults encountering age-associated subjective memory impairment.

Scientific opinion on the tolerable upper intake level for preformed vitamin A and ß-carotene.

Following two requests from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and ß-carotene. Systematic reviews of the literature were conducted for priority adverse health effects of excess vitamin A intake, namely teratogenicity, hepatotoxicity and endpoints related to bone health. Available data did not allow to address whether ß-carotene could potentiate preformed vitamin A toxicity. Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 µg RE/day for adults. This UL applies to men and women, including women of child-bearing age, pregnant and lactating women and post-menopausal women. This value was scaled down to other population groups using allometric scaling (body weight0.75), leading to ULs between 600 µg RE/day (infants 4-11 months) and 2600 µg RE/day (adolescents 15-17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental ß-carotene. The available data were not sufficient and suitable to characterise a dose-response relationship and identify a reference point; therefore, no UL could be established. There is no indication that ß-carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing ß-carotene. The use of supplemental ß-carotene by the general population should be limited to the purpose of meeting vitamin A requirements.

Scientific Opinion on additional scientific data related to the safety of preparations of Rheum palmatum L., Rheum officinale Baill. and their hybrids, Rhamnus purshiana DC., Rhamnus frangula L. and Cassia senna L., submitted pursuant to Article 8(4) of Regulation (EC) No 1925/2006.

The Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the safety of plant preparations from the root or rhizome of Rheum palmatum L., Rheum officinale Baill. and their hybrids, from the bark of Rhamnus frangula L. and Rhamnus purshiana DC. and from the leaf or fruit of Cassia senna L., which have been placed under Union scrutiny in Part C of Annex III in accordance with Article 8(4) of Regulation (EC) No 1925/2006. The NDA Panel reviewed the additional scientific data submitted during the period of scrutiny and the public consultation by interested parties. The pertinent scientific data were in vitro and in vivo genotoxicity studies on the plant preparations under consideration. All the results of the genotoxicity studies on plant preparations were negative. However, the plant preparations that were tested in the submitted studies were not sufficiently characterised with respect to the content of total and individual hydroxyanthracene derivatives (HADs) and components other than HADs. The studies confirmed the presence of ■■■■■, known to be genotoxic in vivo, and ■■■■■, shown to be genotoxic in vitro. In line with the EFSA Scientific Committee statement on genotoxicity assessment of chemical mixtures, considering the presence of an in vivo genotoxic compound, the plant preparations used in these studies have to be considered of concern for genotoxicity. Thus, the safety of preparations containing HADs from the root or rhizome of Rheum palmatum L., Rheum officinale Baill. and their hybrids, from the leaf or fruit of Cassia senna L. and from the bark of Rhamnus frangula L. and Rhamnus purshiana DC. cannot be established based on the submitted studies.

Safety of isomaltulose syrup (dried) as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on isomaltulose syrup (dried) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of a mixture of mono- and disaccharides in powder form, mainly composed of isomaltulose (≥ 75%) and trehalulose (< 13%). The applicant intends to use the NF as a replacement for sucrose already on the market. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. No absorption, distribution, metabolism and excretion (ADME) or toxicological data were provided for the NF. Instead, the safety of the NF was assessed based on literature data available on isomaltulose and mixtures of isomaltulose and trehalulose. In addition, considering the nature, compositional characterisation and production process of the NF, the Panel considered that such data were sufficient to conclude that the NF is as safe as sucrose.

Safety of vitamin D2 mushroom powder as a Novel food pursuant to Regulation (EU) 2015/2283 (NF 2020/2226).

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on vitamin D2 mushroom powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is produced from Agaricus bisporus mushroom powder that has been exposed to ultraviolet (UV) irradiation to induce the conversion of provitamin D2 (ergosterol) to vitamin D2 (ergocalciferol). The NF contains concentrations of vitamin D in the form of vitamin D2 in the range of 245-460 µg/g. The information provided on the production process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF as an ingredient in a variety of foods and beverages in amounts that result in either 1.2 or 2.4 µg vitamin D2 per 100 g or 100 mL of the food as consumed. The applicant also intends to add the NF in food supplements at a maximum of 15 µg vitamin D2/day for individuals above 1 year of age, as well as in foods for special medical purposes (FSMPs). The estimates for combined intake of vitamin D from the NF, the background diet and fortified foods, were below the ULs for vitamin D as established previously by the NDA Panel for children, adolescents and adults, i.e. 50 and 100 µg/day. The estimated combined vitamin D intake in infants (6-12 months) is also below the UL for vitamin D of 35 µg/day. The Panel considers that taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous for the proposed target population. The Panel concludes that the NF is safe under the proposed conditions of use.

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.

Safety of ashitaba sap as a Novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on ashitaba sap as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Ashitaba sap is collected from harvested stems of Angelica keiskei plants. The principal constituents of the sap with regard to the safety assessment are chalcones (1%-2.25%) and furanocoumarins (< 0.01%). The applicant proposed to use the NF in food supplements at a maximum dose of 780 mg per day. The target population is adults excluding pregnant and lactating women. Taking into consideration the composition of the NF and the proposed uses, the composition of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study performed with the product as intended to be placed on the market (30% ashitaba sap powder and 70% cyclodextrins), the Panel establishes a safe dose of 0.5 mg/kg body weight (bw) per day for the product as it is intended to be placed on the market. For the target population, i.e. adults, this safe dose corresponds to 35 mg per day of the product as it is intended to be placed on the market and 137 mg per day of the NF, which is lower than the use level proposed by the applicant. The Panel concludes that the NF is safe for the target population at intake levels up to 137 mg per day.

Extension of use of isomalto-oligosaccharide as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the extension of use of isomalto-oligosaccharide (IMO) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of glucose oligomers with degrees of polymerisation of 3-9, along with various amounts of mono- and disaccharides. The NF comes in both syrup and powder form. The applicant intends to extend the current uses of the NF as an ingredient in several foods, and use the NF in food supplements aimed at the general population older than 10 years of age. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. Along with literature data, the applicant carried out a tolerability study in adult volunteers with the NF at doses up to 120 g/day. The Panel concludes that this study provides reassurance that the NF is tolerable at doses of 120 g/day. Conservative intake estimates resulting from the use of the NF as an ingredient according to the currently authorised uses and new proposed uses result in a highest intake estimate in adolescents of 112 g/day at the 95th percentile, and reach 142 g/day in adolescents when the use as a food supplement is included. The Panel notes this amount is higher than the dose of 120 g/day for which tolerability has been demonstrated. However, considering the source, compositional characterisation, production process and nature of the NF, as well as the available nutritional and toxicological data on the NF, the Panel considers that the NF does not present safety concerns under the proposed conditions of use.

Safety of magnesium l-threonate as a novel food pursuant to regulation (EU) 2015/2283 and bioavailability of magnesium from this source in the context of Directive 2002/46/EC.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of magnesium l-threonate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of magnesium from this source in the context of Directive 2002/46/EC. The NF, produced by chemical synthesis, is intended to be used as new source for magnesium in food supplements at a maximum intake level of 3000 mg per day by adults, except for pregnant and lactating women. This dose corresponds to ~ 2730 mg l-threonate and 250 mg magnesium, which also corresponds to the UL for supplemental magnesium from readily dissociable magnesium salts. Based on results obtained from a dissociation study, two rat studies and one human trial, the Panel considers that magnesium is bioavailable from the NF. The NF may contain up to 1% oxalic acid. The Panel considers that an additional exposure to oxalic acid, that is up to 30 mg daily from the NF, is not to be of safety concern. The Panel concludes that the NF is not nutritionally disadvantageous. In 2008, the EFSA ANS Panel concluded that a human intake of l-threonate of 2700 mg per day is safe. This intake is similar to the maximum intake of l-threonate from the NF under the maximum proposed uses, and the NDA Panel concurs with the ANS Panel that this intake is safe. The Panel considers that there are no concerns regarding the genotoxicity of the NF. The Panel concludes that the NF, Mg l-threonate, is safe under the proposed conditions of use. The Panel concludes that the NF is a source from which magnesium is bioavailable.

Safety of HelixComplex snail mucus (HSM) as a novel food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on HelixComplex Snail Mucus (HSM) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of snail mucus collected from Helix aspersa maxima and is proposed to be used by adults as a food supplement. The data provided by the applicant about the composition and stability of the NF together with the report of the subchronic toxicity study were overall considered unsatisfactory. The Panel noted inconsistencies in the reporting of the certificates of analysis and of the data on the subchronic toxicity provided by the applicant. Owing to these deficiencies, the Panel cannot establish a safe intake level of the NF. The Panel concludes that the safety of the NF has not been established.

Nutritional safety and suitability of a specific protein hydrolysate derived from a whey protein concentrate and used in an infant formula and follow-on formula manufactured from hydrolysed protein by FrieslandCampina Nederland B.V.

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from a whey protein concentrate and used in an infant and follow-on formula manufactured by FrieslandCampina Nederland B.V., which submitted a dossier to the European Commission to request an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in the manufacture of infant and/or follow-on formula. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 2.4 g/100 kcal and consumed as the sole source of nutrition by infants for 3 months led to a growth equivalent to a formula manufactured from intact cow's milk protein with a protein content of 2.1 g/100 kcal. Data on gastrointestinal tolerance of the formula did not raise any concerns. No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. Given that it is consumed with complementary foods and the protein source is nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow-on formula, as long as the formula in which it is used contains a minimum of 2.4 g/100 kcal protein and complies with the compositional criteria of Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

Choline and contribution to normal liver function of the foetus and exclusively breastfed infants: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006.

Following an application from Procter & Gamble BV pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to choline and contribution to normal liver function of the foetus and exclusively breastfed infant. The scope of the application was proposed to fall under a health claim referring to children's development and health. The Panel considers that choline is sufficiently characterised. The claimed effect proposed by the applicant is contribution 'to normal foetal and infant development, especially liver'. The proposed target population is 'unborn fetuses and breastfed infants'. Choline is involved in the structure of cell membranes, cell signalling, metabolism and transport of lipids and cholesterol and neurotransmitter synthesis. Although choline can be synthesised de novo by the human body, depletion-repletion studies in humans show that low choline intake leads to liver dysfunction and muscle damage, which are reverted by the administration of dietary choline. For these functions, de novo synthesis of choline by the human body is insufficient and choline must be obtained from dietary sources. No human studies have addressed the effect of low maternal dietary choline intake on liver function in the fetus or exclusively breastfed infants. However, the Panel considers that the biological role of choline in normal liver function and dietary choline being essential for the function applies to all ages, including fetus and infants. The Panel concludes that a cause and effect relationship has been established between the intake of choline by pregnant and lactating women and contribution to normal liver function of the fetus and exclusively breastfed infants.