Scientific opinion on the tolerable upper intake level for vitamin B6

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 vitamin B6. Systematic reviews of the literature were conducted by a contractor. The relationship between excess vitamin B6 intakes and the development of peripheral neuropathy is well established and is the critical effect on which the UL is based. A lowest-observed-effect-level (LOAEL) could not be established based on human data. A reference point (RP) of 50 mg/day is identified by the Panel from a case–control study, supported by data from case reports and vigilance data. An uncertainty factor (UF) of 4 is applied to the RP to account for the inverse relationship between dose and time to onset of symptoms and the limited data available. The latter covers uncertainties as to the level of intake that would represent a LOAEL. This leads to a UL of 12.5 mg/day. From a subchronic study in Beagle dogs, a LOAEL of 50 mg/kg body weight (bw) per day can be identified. Using an UF of 300, and a default bw of 70 kg, a UL of 11.7 mg/day can be calculated. From the midpoint of the range of these two ULs and rounding down, a UL of 12 mg/day is established by the Panel for vitamin B6 for adults (including pregnant and lactating women). ULs for infants and children are derived from the UL for adults using allometric scaling: 2.2–2.5 mg/day (4–11 months), 3.2–4.5 mg/day (1–6 years), 6.1–10.7 mg/day (7–17 years). Based on available intake data, EU populations are unlikely to exceed ULs, except for regular users of food supplements containing high doses of vitamin B6

Appropriate age range for introduction of complementary feeding into an infant's diet

Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) revised its 2009 Opinion on the appropriate age for introduction of complementary feeding of infants. This age has been evaluated considering the effects on health outcomes, nutritional aspects and infant development, and depends on the individual’s characteristics and development. As long as foods have an age-appropriate texture, are nutritionally appropriate and prepared following good hygiene practices, there is no convincing evidence that at any age investigated in the included studies (< 1 to < 6 months), the introduction of complementary foods (CFs) is associated with adverse health effects or benefits (except for infants at risk of iron depletion). For nutritional reasons, the majority of infants need CFs from around 6 months of age. Infants at risk of iron depletion (exclusively breastfed infants born to mothers with low iron status, or with early umbilical cord clamping (< 1 min after birth), or born preterm, or born small-for-gestational age or with high growth velocity) may benefit from earlier introduction of CFs that are a source of iron. The earliest developmental skills relevant for consuming pureed CFs can be observed between 3 and 4 months of age. Skills for consuming finger foods can be observed in some infants at 4 months, but more commonly at 5–7 months. The fact that an infant may be ready from a neurodevelopmental perspective to progress to a more diversified diet before 6 months of age does not imply that there is a need to introduce CFs. There is no reason to postpone the introduction of potentially allergenic foods (egg, cereals, fish and peanut) to a later age than that of other CFs as far as the risk of developing atopic diseases is concerned. Regarding the risk of coeliac disease, gluten can be introduced with other CFs

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

Nutritional safety and suitability of a specific protein hydrolysate derived from whey protein concentrate and used in an infant and follow-on formula manufactured from hydrolysed protein by HIPP-Werk Georg Hipp OHG (dossier submitted by meyer.science GmbH)

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from whey protein concentrate and used in infant and follow-on formula by HIPP-Werk Georg Hipp OHG. The dossier that was submitted to the European Commission aimed at requesting an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in infant and/or follow-on formula. This opinion does not cover the assessment of the safety of the food enzymes used in the manufacture of the protein hydrolysate. The&nbsp;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 1.9 g/100 kcal and consumed as the sole source of nutrition by infants for 3 months led to growth equivalent to a formula manufactured from intact cow’s milk protein with the same protein content. No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. However, given that it is consumed with complementary foods and the protein source is considered 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 1.9 g/100 kcal protein and complies with the compositional criteria of Commission Delegated Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA

Nutritional safety and suitability of a specific protein hydrolysate derived from whey protein concentrate and used in an infant and follow-on formula manufactured from hydrolysed protein by Danone Trading ELN 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 whey protein concentrate and used in an infant and follow-on formula by Danone Trading ELN 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. This opinion does not cover the assessment of the safety of the food enzymes used in the manufacture of the protein hydrolysate. 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 2.3&nbsp;g/100&nbsp;kcal and consumed as the sole source of nutrition by infants for 3.5&nbsp;months led to growth equivalent to a formula manufactured from intact cow's milk protein (2&nbsp;g protein/100&nbsp;kcal). No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. However, given that it is consumed with complementary foods and the protein source is considered nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel&nbsp;considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel&nbsp;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 2.3&nbsp;g/100&nbsp;kcal protein and complies with the compositional criteria of Commission Delegated Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA

Nutritional safety and suitability of a specific protein hydrolysate derived from whey protein concentrate and used in an infant and follow-on formula manufactured from hydrolysed protein by Danone Trading ELN 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 whey protein concentrate and used in an infant and follow-on formula by Danone Trading ELN 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. This opinion does not cover the assessment of the safety of the food enzymes used in the manufacture of the protein hydrolysate. 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 2.3 g/100 kcal and consumed as the sole source of nutrition by infants for 3.5 months led to growth equivalent to a formula manufactured from intact cow's milk protein (2 g protein/100 kcal). No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. However, given that it is consumed with complementary foods and the protein source is considered 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 2.3 g/100 kcal protein and complies with the compositional criteria of Commission Delegated Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA

The Binary Protein Interactome of Treponema pallidum – The Syphilis Spirochete

Protein interaction networks shed light on the global organization of proteomes but can also place individual proteins into a functional context. If we know the function of bacterial proteins we will be able to understand how these species have adapted to diverse environments including many extreme habitats. Here we present the protein interaction network for the syphilis spirochete Treponema pallidum which encodes 1,039 proteins, 726 (or 70%) of which interact via 3,649 interactions as revealed by systematic yeast two-hybrid screens. A high-confidence subset of 991 interactions links 576 proteins. To derive further biological insights from our data, we constructed an integrated network of proteins involved in DNA metabolism. Combining our data with additional evidences, we provide improved annotations for at least 18 proteins (including TP0004, TP0050, and TP0183 which are suggested to be involved in DNA metabolism). We estimate that this “minimal” bacterium contains on the order of 3,000 protein interactions. Profiles of functional interconnections indicate that bacterial proteins interact more promiscuously than eukaryotic proteins, reflecting the non-compartmentalized structure of the bacterial cell. Using our high-confidence interactions, we also predict 417,329 homologous interactions (“interologs”) for 372 completely sequenced genomes and provide evidence that at least one third of them can be experimentally confirmed

Scientific and technical guidance for the preparation and presentation of a dossier for evaluation of an infant and/or follow-on formula manufactured from protein hydrolysates (Revision 1)

Following a request from the European Commission, EFSA was asked to provide scientific and technical guidance for the preparation and presentation of a dossierfor evaluation of an infant and/or follow-on formula manufactured from protein hydrolysates. This guidance document addresses the information and data to be submitted to EFSA on infant and follow-on formulae manufactured from protein hydrolysates with respect to the nutritional safety and suitability of the specific formula and/or the formula's efficacy in reducing the risk of developing allergy to milk proteins. The guidance will be further reviewed and updated with the experience gained from the evaluation of specificdossiers, and in the light of applicable Unionguidelines and legislation. The guidance was adopted by the Panel on Dietetic Products, Nutrition and Allergies on 5 April 2017.Upon request from the European Commission in 2020, it has been revised to inform food business operators of the new provisions in the pre-submission phase and in the procedure set out in the General Food Law, as amended by the Transparency Regulation. This revised guidance applies to all dossiers submitted as of 27 March 2021 and shall be consulted for the preparation of dossiers intended to be submitted from that date onwards. For dossiers submitted prior to 27 March 2021, the previous guidance, published in May 2017 remains applicable

KsgA, a 16S rRNA adenine methyltransferase, has a novel DNA glycosylase/AP lyase activity to prevent mutations in Escherichia coli

The 5-formyluracil (5-foU), a major mutagenic oxidative damage of thymine, is removed from DNA by Nth, Nei and MutM in Escherichia coli. However, DNA polymerases can also replicate past the 5-foU by incorporating C and G opposite the lesion, although the mechanism of correction of the incorporated bases is still unknown. In this study, using a borohydride-trapping assay, we identified a protein trapped by a 5-foU/C-containing oligonucleotide in an extract from E. coli mutM nth nei mutant. The protein was subsequently purified from the E. coli mutM nth nei mutant and was identified as KsgA, a 16S rRNA adenine methyltransferase. Recombinant KsgA also formed the trapped complex with 5-foU/C- and thymine glycol (Tg)/C-containing oligonucleotides. Furthermore, KsgA excised C opposite 5-foU, Tg and 5-hydroxymethyluracil (5-hmU) from duplex oligonucleotides via a β-elimination reaction, whereas it could not remove the damaged base. In contrast, KsgA did not remove C opposite normal bases, 7,8-dihydro-8-oxoguanine and 2-hydroxyadenine. Finally, the introduction of the ksgA mutation increased spontaneous mutations in E. coli mutM mutY and nth nei mutants. These results demonstrate that KsgA has a novel DNA glycosylase/AP lyase activity for C mispaired with oxidized T that prevents the formation of mutations, which is in addition to its known rRNA adenine methyltransferase activity essential for ribosome biogenesis