Emerging Role of Corticosteroid-Binding Globulin in Glucocorticoid-Driven Metabolic Disorders

Glucocorticoid hormones (GCs) are critical for survival since they ensure the energy supply necessary to the body in an ever challenging environment. GCs are known to act on appetite, glucose metabolism, fatty acid metabolism, and storage. However, to be beneficial to the body, GC levels should be maintained in an optimal window of concentrations. Not surprisingly, conditions of GC excess or deficiency, e.g., Cushing's syndrome or Addison's disease, are associated with severe alterations of energy metabolism. Corticosteroid-binding globulin (CBG), through its high specific affinity for GCs, plays a critical role in regulating plasma GC levels and their access to target cells. Genetic studies in various species including humans have revealed that CBG is the major factor influencing interindividual genetic variability of plasma GC levels, both in basal and stress conditions. Some, but not all, of these genetic studies have also provided data linking CBG levels to body composition and insulin levels. The examination of CBG-deficient mice submitted to hyperlipidic diets unveiled specific roles for CBG in lipid storage and metabolism. An influence of CBG on appetite has not been reported but remains to be more finely analyzed. Finally, only male mice have been examined under high-fat diet, while obesity is affecting women even more than men. Overall, a role of CBG in GC-driven metabolic disorders is emerging in recent studies. Although subtle, the influence of CBG in these diseases could open the way to new therapeutic interventions since CBG is easily accessible in the blood

Safety evaluation of steviol glycoside preparations, including rebaudioside AM, obtained by enzymatic bioconversion of highly purified stevioside and/or rebaudioside A stevia leaf extracts

[EN] The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of steviol glycoside preparations, including rebaudioside AM, obtained by enzymatic bioconversion of highly purified stevioside and/or rebaudioside A stevia leaf extracts. These steviol glycoside preparations are produced via enzymatic bioconversion of highly purified stevioside and/or rebaudioside A extracts obtained from stevia plant using two UDP-glucosyltransferases and one sucrose synthase enzymes produced by the genetically modified strains of E. coli K-12 that facilitate the transfer of glucose to purified stevia leaf extracts via glycosidic bonds. The Panel considered that the parental strain is a derivative of E. coli K-12 which is well characterised and its safety has been documented; therefore, it is considered to be safe for production purposes. The Panel concluded that there is no safety concern for steviol glycoside preparations, including rebaudioside AM, obtained by enzymatic bioconversion of highly purified stevioside and/or rebaudioside A stevia leaf extracts using UDP-glucosyltransferases and sucrose synthase enzymes produced by the genetically modified strains of E. coli K-12, to be used as a food additive. The Panel recommends the European Commission to consider the proposal of establishing separate specifications for steviol glycoside preparations, including rebaudioside AM, obtained by enzymatic bioconversion of highly purified stevioside and/or rebaudioside A stevia leaf extracts in Commission Regulation (EU) No 231/2012. (C) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.Younes, M.; Aquilina, G.; Castle, L.; Engel, K.; Fowler, P.; Frutos Fernandez, MJ.; Furst, P.... (2021). Safety evaluation of steviol glycoside preparations, including rebaudioside AM, obtained by enzymatic bioconversion of highly purified stevioside and/or rebaudioside A stevia leaf extracts. EFSA Journal. 19(8):1-22. https://doi.org/10.2903/j.efsa.2021.669112219

Safety evaluation of crosslinked polyacrylic acid polymers (carbomer) as a new food additive

[EN] The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of crosslinked polyacrylic acid polymers (carbomer) proposed for use as food additive in solid and liquid food supplements. Carbomer is formed from the monomer, acrylic acid, which is polymerised and crosslinked with allyl pentaerythritol (APE). The polymers are synthesised in ethyl acetate using as free-radical polymerisation initiator. In vivo data showed no evidence for systemic availability or biotransformation of carbomer. Carbomer does not raise a concern regarding genotoxicity. Considering the available data set, the Panel derived an acceptable daily intake (ADI) of 190 mg/kg body weight (bw) per day based on a no observed adverse effect level (NOAEL) of 1,500 mg/kg bw per day from a sub-chronic 13-week study in rat, applying a compound specific uncertainty factor (UF) of 8. At the proposed maximum use levels, the exposure estimates ranged at the mean from 1.1 to 90.2 mg/kg bw per day and at the p95 from 12.5 to 237.4 mg/kg bw per day. At the proposed typical use level, the exposure estimates ranged at the mean from 0.7 to 60.2 mg/kg bw per day and at the p95 from 10.3 to 159.5 mg/kg bw per day. The Panel noted that the maximum proposed use levels would result in exposure estimates close to or above the ADI. The Panel also noted that level of exposure to carbomer from its proposed use is likely to be an overestimation. Taking a conservative approach, the Panel considered that exposure to carbomer would not give rise to a safety concern if the proposed maximum use level for solid food supplements is lowered to the typical use level reported by the applicant. (C) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.Younes, M.; Aquilina, G.; Engel, K.; Fowler, P.; Frutos Fernandez, MJ.; Furst, P.; Gürtler, R.... (2021). Safety evaluation of crosslinked polyacrylic acid polymers (carbomer) as a new food additive. EFSA Journal. 19(8):1-26. https://doi.org/10.2903/j.efsa.2021.669312619

Safety of the proposed amendment of the specifications for enzymatically produced steviol glycosides (E 960c): Rebaudioside D produced via enzymatic bioconversion of purified stevia leaf extract

[EN] The EFSA Panel on Food Additives and Flavourings (FAF Panel) provides a scientific opinion on the safety of a proposed amendment of the specifications of enzymatically produced steviol glycosides (E 960c) with respect to the inclusion of rebaudioside D produced via enzyme-catalysed bioconversion of purified stevia leaf extract. Rebaudioside D (95% on dry basis) is produced via enzymatic bioconversion of purified stevia leaf extract using uridine diphosphate (UDP)-glucosyltransferase (UGT) and sucrose synthase enzymes produced by the genetically modified yeast K. phaffii UGT-A, that facilitates the transfer of glucose to purified stevia leaf extract via glycosidic bonds. The same enzymes from K. phaffii UGT-A may be used in the manufacturing process of the food additive, rebaudioside M produced via enzyme modification of steviol glycosides from stevia (E 960c(i)). The Panel considered that separate specifications would be needed for this food additive produced via the manufacturing process described in the current application, aligned with those already established for E 960c(i). The Panel concluded that there is no toxicological concern for Rebaudioside D produced via enzymatic bioconversion of purified stevia leaf extract using UDP-glucosyltransferase and sucrose synthase produced by a genetically modified strain of the yeast K. phaffii. However, based on the available data, the Panel could not exclude the possibility that some residual amount of DNA coding for the kanamycin resistance gene could remain in the final product. Should this gene propagate in microbiota due to the presence of recombinant DNA in the final product, this would be of concern. Therefore, the Panel concluded that the safety of Rebaudioside D produced via this enzymatic bioconversion was not sufficiently demonstrated with the available data given that the absence of recombinant DNA was not shown.Younes, M.; Aquilina, G.; Engel, K.; Fowler, P.; Frutos Fernandez, MJ.; Fürst, P.; Gürtler, R.... (2022). Safety of the proposed amendment of the specifications for enzymatically produced steviol glycosides (E 960c): Rebaudioside D produced via enzymatic bioconversion of purified stevia leaf extract. EFSA Journal. 20(5):1-23. https://doi.org/10.2903/j.efsa.2022.729112320

Safety evaluation of buffered vinegar as a food additive

[EN] The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of buffered vinegar as a new food additive. Buffered vinegar is a liquid or dried product prepared by adding sodium/potassium hydroxides (E 524 to E 525) and sodium/potassium carbonates (E 500 to E 501) to vinegar, compliant with European Standard EN 13188:2000 and exclusively obtained from an agricultural source origin (except wood/cellulose). The primary constituents of buffered vinegar are acetic acid and its salts. No biological or toxicological data obtained with the proposed food additive were submitted by the applicant as part of the dossier as, following oral ingestion, buffered vinegar dissociates into the acetic anion and acetate a natural constituent of the diet, and of the human body for which extensive data on their biological effects exist and for which EFSA in 2013 has previously concluded that the establishment of an acceptable daily intake (ADI) is not considered necessary. At the proposed maximum/typical use levels, the mean exposure to buffered vinegar from its use as a food additive expressed as acetic acid equivalents ranged from 8.9 mg/kg body weight (bw) per day in infants to 280.3 mg/kg bw per day in children. The 95th percentile of exposure to buffered vinegar ranged from 27.9 mg/kg bw per day in infants to 1,078 mg/kg bw per day in toddlers. The Panel concluded that there is no safety concern for the use of buffered vinegar as a food additive at the proposed maximum/typical use levels. The Panel could not conclude on the safety for the proposed uses at quantum satis as Group I food additive since the resulting exposure could not be estimated.The Panel wishes to thank the following for the support provided to this scientific output: Alkiviadis Stagkos-Georgiadis.Younes, M.; Aquilina, G.; Degen, G.; Engel, K.; Fowler, P.; Frutos Fernandez, MJ.; Fürst, P.... (2022). Safety evaluation of buffered vinegar as a food additive. EFSA Journal. 20(7):1-21. https://doi.org/10.2903/j.efsa.2022.735112120

Safety evaluation of long-chain glycolipids from Dacryopinax spathularia

[EN] The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of long-chain glycolipids from Dacryopinax spathularia (also called AM-1) as a food additive. AM-1 is a purified mixture of long-chain glycolipid congeners obtained by fermentation of the edible non-genetically modified fungus Dacryopinax spathularia. AM-1 glycolipids have very low oral bioavailability and overall available toxicology data do not demonstrate any adverse effects of the proposed food additive. Considering the available data set the Panel established an ADI of 10 mg/kg bw per day based on a range of NOAELs between 1,000 and 1,423 mg/kg bw per day (the highest doses tested), from the reproductive and a prenatal developmental toxicity studies in rats and 90-day studies in rat and dog. At the proposed maximum use levels, the exposure estimates ranged at the mean from 0.01 to 1.07 mg/kg bw per day and at the p95 from 0 to 3.1 mg/kg mg/kg bw per day. At the proposed typical use levels, the exposure estimates ranged at the mean from < 0.01 mg/kg bw per day to 0.23 mg/kg bw per day and at the p95 from 0 to 0.64 mg/kg bw per day. The Panel noted that the highest estimate of exposure of 3.1 mg/kg bw per day (in toddlers) is within the established ADI of 10 mg/kg bw per day and concluded that the exposure to long-chain glycolipids from Dacryopinax spathularia does not raise a safety concern at the uses and use levels proposed by the applicant.Younes, M.; Aquilina, G.; Engel, K.; Fowler, P.; Frutos Fernandez, MJ.; Furst, P.; Gurtler, R.... (2021). Safety evaluation of long-chain glycolipids from Dacryopinax spathularia. EFSA Journal. 19(6):1-28. https://doi.org/10.2903/j.efsa.2021.660912819

Low-Temperature drying of salted cod (Gadus morhua) assisted by high power ultrasound: Kinetics and physical properties

[EN] Low-temperature convective drying could be considered an affordable alternative to conventional freeze-drying for foodstuffs. The process intensification should be based on non-thermal technologies, such as power ultrasound. Thereby, the aim of this work was to evaluate the air-borne application of power ultrasound on the low-temperature drying of salted cod. For that purpose, drying experiments were carried out at &#8722;10, 0, 10 and 20 °C on salted cod slices at 2 m/s with (AIR + US, 20.5 kW/m3) and without ultrasonic application (AIR). In the dried-salted cod, its rehydration capacity was analyzed, as were the microstructural, textural and color changes. At every temperature tested, ultrasound application increased the drying rate; thus, an average increase of 74%was observed in the effective diffusivity. AIR+US dried samples were softer and exhibited a higher rehydration capacity than AIR ones, which was linked to the microstructural changes produced by ultrasound. In addition, color changes were induced by ultrasound application. Industrial relevance: Nowadays, low-temperature convective drying represents a promising alternative for the production of high-quality dried products. However, this technology is mostly limited by the low drying rate, which retards the dehydration process and directly increases the processing costs. Power ultrasound, a nonthermal technology, represents an interesting alternative means of improving low-temperature convective drying due to the fact that acoustic (mechanical)waves may affectwater removal during dryingwith a low heating capacity. Thereby, the ultrasonically enhanced low-temperature convective drying could constitute an affordable alternative to lyophilization (or freeze-drying), which is mainly restricted to high-quality food commodities.The authors acknowledge the financial support both from the Ministerio de Economia y Competitividad (Ref. DPI2012-37466-C03-03) and Carmen Cambra S.L. for their technical support with the selection of the raw material. Cesar Ozuna was the recipient of a fellowship from the Universitat Politecnica de Valencia for his research stay in Aalesund University College.Ozuna López, C.; Cárcel Carrión, JA.; Walde, PM.; García Pérez, JV. (2014). Low-Temperature drying of salted cod (Gadus morhua) assisted by high power ultrasound: Kinetics and physical properties. Innovative Food Science and Emerging Technologies. 23:146-155. https://doi.org/10.1016/j.ifset.2014.03.008S1461552

Safety of the proposed amendment of the specifications for enzymatically produced steviol glycosides (E 960c): Rebaudioside D produced via enzymatic bioconversion of purified stevia leaf extract

The EFSA Panel on Food Additives and Flavourings (FAF Panel) provides a scientific opinion on the safety of a proposed amendment of the specifications of enzymatically produced steviol glycosides (E 960c) with respect to the inclusion of rebaudioside D produced via enzyme-catalysed bioconversion of purified stevia leaf extract. Rebaudioside D (95% on dry basis) is produced via enzymatic bioconversion of purified stevia leaf extract using uridine diphosphate (UDP)-glucosyltransferase (UGT) and sucrose synthase enzymes produced by the genetically modified yeast K. phaffii UGT-A, that facilitates the transfer of glucose to purified stevia leaf extract via glycosidic bonds. The same enzymes from K. phaffii UGT-A may be used in the manufacturing process of the food additive, rebaudioside M produced via enzyme modification of steviol glycosides from stevia (E 960c(i)). The Panel considered that separate specifications would be needed for this food additive produced via the manufacturing process described in the current application, aligned with those already established for E 960c(i). The Panel concluded that there is no toxicological concern for Rebaudioside D produced via enzymatic bioconversion of purified stevia leaf extract using UDP-glucosyltransferase and sucrose synthase produced by a genetically modified strain of the yeast K. phaffii. However, based on the available data, the Panel could not exclude the possibility that some residual amount of DNA coding for the kanamycin resistance gene could remain in the final product. Should this gene propagate in microbiota due to the presence of recombinant DNA in the final product, this would be of concern. Therefore, the Panel concluded that the safety of Rebaudioside D produced via this enzymatic bioconversion was not sufficiently demonstrated with the available data given that the absence of recombinant DNA was not shown

Safety evaluation of buffered vinegar as a food additive

The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of buffered vinegar as a new food additive. Buffered vinegar is a liquid or dried product prepared by adding sodium/potassium hydroxides (E 524 to E 525) and sodium/potassium carbonates (E 500 to E 501) to vinegar, compliant with European Standard EN 13188:2000 and exclusively obtained from an agricultural source origin (except wood/cellulose). The primary constituents of buffered vinegar are acetic acid and its salts. No biological or toxicological data obtained with the proposed food additive were submitted by the applicant as part of the dossier as, following oral ingestion, buffered vinegar dissociates into the acetic anion and acetate a natural constituent of the diet, and of the human body for which extensive data on their biological effects exist and for which EFSA in 2013 has previously concluded that the establishment of an acceptable daily intake (ADI) is not considered necessary. At the proposed maximum/typical use levels, the mean exposure to buffered vinegar from its use as a food additive expressed as acetic acid equivalents ranged from 8.9 mg/kg body weight (bw) per day in infants to 280.3 mg/kg bw per day in children. The 95th percentile of exposure to buffered vinegar ranged from 27.9 mg/kg bw per day in infants to 1,078 mg/kg bw per day in toddlers. The Panel concluded that there is no safety concern for the use of buffered vinegar as a food additive at the proposed maximum/typical use levels. The Panel could not conclude on the safety for the proposed uses at quantum satis as Group I food additive since the resulting exposure could not be estimated

Safety evaluation of synthesised DNA oligonucleotides as a food additive

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of synthesised DNA oligonucleotides as a new food additive, in accordance with Regulation (EC) No 1331/2008. Considering that the additional information requested by the Panel during the risk assessment was not provided by the applicant, the assessment was concluded on the basis of the sole information available in the application. The proposed food additive consists of purified synthetic DNA sequences intended to be used for traceability purposes, alone or combined with carriers. Information provided by the applicant on the identity, characterisation and production process of the proposed food additive was considered insufficient. The Panel considered that the product specifications as proposed by the applicant do not adequately define and characterise the proposed food additive. The applicant proposed for the food additive the maximum use levels of 0.001 mg/kg for a variety of food categories. The food additive was also proposed as a Group I additive at a specific maximum level of quantum satis. The applicant did not provide exposure estimates according to the EFSA ANS Panel guidance (2012). No biological or toxicological data were provided by the applicant for the proposed food additive. Considering the inadequate information available and the uncertainty introduced by the proposal at quantum satis, along with the insufficient specifications, the Panel could not conclude on the safety of the food additive as proposed and described by the applicant