Coffee C21 and protection of DNA from strand breaks: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006.

Following an application from Tchibo GmbH submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, 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 Coffee C21 and protection of DNA from strand breaks. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is Coffee C21. The Panel considers that Coffee C21, a coffee standardised by its concentration of caffeoylquinic acids (CQA), trigonelline and N-methylpyridinium (NMP), is sufficiently characterised in relation to the claimed effect. The Panel considers that the claimed effect, protection of DNA from strand breaks, is a beneficial physiological effect. Out of the two human intervention studies from which conclusion could be drawn, one study provides some evidence that daily consumption of Coffee C21 (750 mL/day) for 4 weeks decreases DNA strand breaks in habitual coffee drinkers after coffee withdrawal over the previous four weeks. However, the results of this study were not replicated in another study conducted under similar conditions in the same study centre. No studies performed in a different setting, from which conclusions could be drawn, were available. No evidence has been provided for a mechanism by which coffee (including Coffee C21) would reduce DNA damage in human cells by reducing DNA strand breaks. The Panel concludes that a cause and effect relationship has not been established between the consumption of Coffee C21 and protection of DNA from strand breaks.

Guidance for the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health: (Revision 1).

EFSA asked the Panel on Dietetic Products, Nutrition and Allergies (NDA) to update the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011. The update takes into accounts experiences gained with evaluation of additional health claim applications related to antioxidants, oxidative damage and cardiovascular health, and the information collected from a Grant launched in 2014. This guidance is intended to assist applicants in preparing applications for the authorisation of health claims related to the antioxidants, oxidative damage and cardiovascular health. The document was subject to public consultation (from 12 July to 3 September 2017). This document supersedes the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011. It is intended that the guidance will be further updated as appropriate in the light of experience gained from the evaluation of health claims.

Black tea and maintenance of normal endothelium-dependent vasodilation: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006.

Following an application from Unilever NV, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Ireland, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to black tea and maintenance of normal endothelium-dependent vasodilation. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is black tea beverages, either freshly prepared or reconstituted from water extract powders of black tea, characterised by the content of flavanols (expressed as catechins plus theaflavins) of at least 30 mg per 200 mL serving. The Panel considers that black tea characterised by the content of flavanols (expressed as catechins plus theaflavins) is sufficiently characterised. The claimed effect proposed by the applicant is 'improvement of endothelium-dependent vasodilation'. The Panel considers that maintenance of normal endothelium-dependent vasodilation is a beneficial physiological effect. Of the five human intervention studies provided on the chronic effect of black tea consumption on endothelium-dependent vasodilation, two investigated the effect after regular consumption of black tea for a sufficiently long time period (i.e. at least 4 weeks). These two studies did not allow an effect of black tea on endothelium-dependent vasodilation to be established. The Panel concludes that a cause and effect relationship has not been established between the consumption of black tea and maintenance of normal endothelium-dependent vasodilation.

Safety of Allanblackia seed oil for extended uses in vegetable oils and milk and in yellow fat and cream-based spreads up to 30% (w/w).

In 2007, the EFSA NDA Panel concluded that Allanblackia seed oil obtained from the seeds of Allanblackia trees is safe for human consumption under the proposed conditions of use. Due to its high contents of stearic-oleic-stearic and stearic-oleic-oleic triglycerides, which made the oil suitable as a 'hardstock' component, the applicant applied for its use as a novel food (NF) ingredient in yellow fat and cream-based spreads at a level of 20% (w/w). In this application, the applicant seeks (1) to increase the authorised maximum use level (i.e. 20% w/w) in yellow fat spreads and cream-based spreads to 30% (w/w) and (2) the use of this NF in mixes of vegetable oils and milk up to a maximum use level of 30% (w/w). (3) The applicant proposes also some changes in the specifications of the NF, although he noted that the oil is collected, extracted and refined using the same processes that are currently used for other edible vegetable oils and which have been evaluated in the original application assed by EFSA in 2007. According to the information provided by the applicant, the production process and the composition of the NF do not change. The Panel notes that the revised specification limits on trans-fatty acid (TFA), unsaponifiable matter, peroxide value are similar to those for other edible oils and fats. The applicant also indicated that he had performed an updated comprehensive literature search using several different databases, but no preclinical studies or human studies on Allanblackia seed oil were identified which have not been provided for the previous EFSA assessment in 2007. The Panel notes that the proposed extended uses would increase the potential intake of the NF, which is considered not to be nutritionally disadvantageous. The Panel concludes that Allanblackia seed oil is safe at the extended uses and use level.

Condensyl® and decreases sperm DNA damage which is a risk factor for male infertility: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006.

Following an application from Laboratoire Nurilia submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to 'Condensyl® and decreases sperm DNA damage. High sperm DNA damage is a risk factor for male subfertility/infertility'. Condensyl® is a fixed combination of opuntia fruit dry extract, N-acetyl cysteine, zinc, nicotinamide, vitamins B2, B6, B12 and E, and folic acid. The Panel considers that Condensyl® is sufficiently characterised. The Panel assumes that the disease that is the subject of the application is male infertility and that the target population for the claim includes males wishing to increase their fertility but excludes males with clinical infertility. The Panel considers that the reduction of DNA sperm damage is a beneficial physiological effect in the context of reducing the risk of male infertility. The applicant provided four human intervention studies conducted in males with clinical infertility, from which no conclusions could be drawn for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of Condensyl® and reduction of DNA sperm damage in the context of reducing the risk of male infertility.

Guidance on the risk assessment of substances present in food intended for infants below 16 weeks of age.

Following a request from the European Commission to EFSA, the EFSA Scientific Committee (SC) prepared a guidance for the risk assessment of substances present in food intended for infants below 16 weeks of age. In its approach to develop this guidance, the EFSA SC took into account, among others, (i) an exposure assessment based on infant formula as the only source of nutrition; (ii) knowledge of organ development in human infants, including the development of the gut, metabolic and excretory capacities, the brain and brain barriers, the immune system, the endocrine and reproductive systems; (iii) the overall toxicological profile of the substance identified through the standard toxicological tests, including critical effects; (iv) the relevance for the human infant of the neonatal experimental animal models used. The EFSA SC notes that during the period from birth up to 16 weeks, infants are expected to be exclusively fed on breast milk and/or infant formula. The EFSA SC views this period as the time where health-based guidance values for the general population do not apply without further considerations. High infant formula consumption per body weight is derived from 95th percentile consumption. The first weeks of life is the time of the highest relative consumption on a body weight basis. Therefore, when performing an exposure assessment, the EFSA SC proposes to use the high consumption value of 260 mL/kg bw per day. A decision tree approach is proposed that enables a risk assessment of substances present in food intended for infants below 16 weeks of age. The additional information needed when testing substances present in food for infants below 16 weeks of age and the approach to be taken for the risk assessment are on a case-by-case basis, depending on whether the substance is added intentionally to food and is systemically available.

Public health and budget impact of probiotics on common respiratory tract infections: a modelling study.

OBJECTIVES: Two recent meta-analyses by the York Health Economics Consortium (YHEC) and Cochrane demonstrated probiotic efficacy in reducing the duration and number of common respiratory tract infections (CRTI) and associated antibiotic prescriptions. A health-economic analysis was undertaken to estimate the public health and budget consequences of a generalized probiotic consumption in France. METHODS: A virtual age- and gender-standardized population was generated using a Markov microsimulation model. CRTI risk factors incorporated into this model were age, active/passive smoking and living in a community setting. Incidence rates and resource utilization were based on the 2011-2012 flu season and retrieved from the French GPs Sentinelles network. Results of both meta-analyses were independently applied to the French population to estimate CRTI events, assuming a generalized probiotic use compared to no probiotics during winter months: -0.77 days/CRTI episode (YHEC scenario) or odds-ratio 0.58 for ≥1 CRTI episode (Cochrane scenario) with vs. without probiotics. Economic perspectives were National Health System (NHS), society, family. Outcomes included cost savings related to the reduced numbers of CRTI episodes, days of illness, number of antibiotic courses, sick leave days, medical and indirect costs. RESULTS: For France, generalized probiotic use would save 2.4 million CRTI-days, 291,000 antibiotic courses and 581,000 sick leave days, based on YHEC data. Applying the Cochrane data, reductions were 6.6 million CRTI days, 473,000 antibiotic courses and 1.5 million sick days. From the NHS perspective, probiotics' economic impact was about €14.6 million saved according to YHEC and €37.7 million according to Cochrane. Higher savings were observed in children, active smokers and people with more frequent human contacts. CONCLUSIONS: Public health and budget impact of probiotics are substantial, whether they reduce CRTI episodes frequency or duration. Noteworthy, the 2011-12 winter CRTI incidence was low and this analysis focused on the fraction of CRTI patients consulting a practitioner.

Comparative validation of the growth hormone-releasing hormone and arginine test for the diagnosis of adult growth hormone deficiency using a growth hormone assay conforming to recent international recommendations.

CONTEXT: The GHRH plus arginine (GHRH+Arg) test is a promising alternative to the insulin tolerance test (ITT) for diagnosis of adult GH deficiency (AGHD). OBJECTIVES: The objectives of the study were to validate the GHRH+Arg test for diagnosis of AGHD, using the ITT as comparator and a GH assay calibrated according to recent international recommendations, and to study the repeatability and tolerance of both tests. DESIGN: This was a multicenter, randomized, open-label, phase III study. SETTING: The study was conducted at 10 French university hospitals. SUBJECTS: Sixty-nine subjects (38 and 15 with high and low probability of GH deficiency, respectively, and 16 healthy controls) were randomized: 35 to the GHRH+Arg-GHRH+Arg-ITT test sequence and 34 to the ITT-ITT-GHRH+Arg test sequence. INTERVENTIONS: Each subject underwent three tests of GH secretion separated by 24 h or more. MAIN OUTCOME MEASURES: The primary variable used for response assessments was serum peak GH response. Test results were compared with the final AGHD diagnosis. RESULTS: Peak GH responses in the two tests were strongly correlated. A cutoff value of 7.89 microg/liter for GHRH+Arg corresponding to 3 microg/liter for ITT was calculated. The cutoff value leading to 95% specificity with the GHRH+Arg test was measured at about 3.67 microg/liter (sensitivity 79.0%). Intermethod agreement and repeatability were high. Both tests were well tolerated. A preference for the GHRH+Arg test was expressed by 74% of subjects. CONCLUSIONS: The GHRH+Arg test demonstrated good accuracy and repeatability, was at least as sensitive as the ITT, and was associated with better subject acceptability. The GHRH+Arg test represents a good alternative to the ITT for the diagnosis of AGHD.

Phenotypic determinants of uncontrolled asthma.

BACKGROUND: Although uncontrolled asthma remains frequent, determinants of asthma control are poorly studied. OBJECTIVES: The aim was to estimate the distribution and the phenotypic characteristics of asthma control in 2 groups of subjects defined by the use of inhaled corticosteroids (ICS) in the past 12 months, in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). METHODS: Five hundred one adult current patients with asthma who participated in the follow-up of the EGEA study were included. Asthma control was assessed from survey questions reflecting asthma control, as defined in the 2006 Global Initiative for Asthma guidelines. The factors analyzed were age, sex, educational level, body mass index, active and passive smoking, sensitization to aeroallergens, total IgE, rhinitis, chronic cough/phlegm, and age at asthma onset. Analyses were stratified according to ICS use. RESULTS: Uncontrolled asthma was more frequent in ICS users (27.6%, 35.0%, and 37.4% with controlled, partly-controlled, and uncontrolled asthma respectively) compared with non-ICS users (60.0%, 23.9%, and 16.1%, respectively). In ICS users, chronic cough or phlegm and female sex were independently and significantly related to uncontrolled asthma. In non-ICS users, high total IgE and sensitization to molds were associated with uncontrolled asthma. Smoking and rhinitis were not associated with asthma control. CONCLUSION: Optimal asthma control remained unachieved in the majority of patients with asthma in this study. Factors associated with uncontrolled asthma were different in ICS users (chronic cough/phlegm, female sex) and non-ICS users (high total IgE and sensitization to molds).

Strong correlations of anti-viral capsid antigen antibody levels in first-degree relatives from families with Epstein-Barr virus-related lymphomas.

BACKGROUND: Markers of Epstein-Barr virus (EBV) infection include anti-viral capsid antigen (VCA) immunoglobulin (Ig) G. High anti-VCA titers are associated with EBV-related lymphoproliferation, such as Burkitt lymphoma (BL) and Hodgkin lymphoma (HL). METHODS: Intrafamilial correlations of anti-VCA IgG levels were studied in 3 settings: 127 families recruited through patients with HL in France (population A), 31 families recruited through patients with BL in Uganda (population B), and 74 large families from a general population in Cameroon (population C). Titers were determined by enzyme-linked immunosorbent assay (populations A and C) or by immunofluorescence analysis (population B). RESULTS: In populations A and B, the anti-VCA IgG titers of the relatives of patients with HL or BL increased significantly (P = .01 and P < .001, respectively) with those of the index case patient. In all 3 populations, anti-VCA IgG titers were significantly correlated (P < .001 for A, P = .002 for B, and P < .001 for C) between genetically related individuals (father-offspring, mother-offspring, and sibling-sibling) but not between spouses. Similar results were obtained for population A after adjustment for total IgG levels. In all cases, the pattern of correlations was consistent with a polygenic model, with heritability ranging from 0.32 to 0.48. CONCLUSION: These results provide evidence for the genetic control of anti-VCA IgG titers and pave the way for identification of the loci involved.

Molecular analyte profiling of the early events and tissue conditioning following intravesical bacillus calmette-guerin therapy in patients with superficial bladder cancer.

PURPOSE: We characterized the innate immune response to intravesical bacillus Calmette-Guerin therapy using a systems approach based on proteomic and cytometric screens. MATERIALS AND METHODS: Blood and urine were collected from patients receiving intravesical bacillus Calmette-Guerin therapy before, and 2 and 4 hours after bacillus Calmette-Guerin treatment, at the first and third instillation. Proteomic and cytometry based screens were performed. RESULTS: Molecular analyte profiling revealed a prime/boost pattern to the innate response to intravesical bacillus Calmette-Guerin. We identified 36 statistically significant changes in the proteins induced during the third instillation compared to the initial treatment. These analytes were classified into 3 categories of 1) plasma proteins that leaked into the urine, 2) cytokines/chemokines produced locally during the first hours of inflammation and 3) other innate molecules that modulate the bladder microenvironment. To characterize the marked increase in the inflammatory response after multiple treatments we evaluated the cells present in the urine and again a prime/boost response was revealed. For the locally produced analytes it was possible to define the cell source(s) and, thus, provide a first generation map of what occurs during the initial phase of bacillus Calmette-Guerin therapy. CONCLUSIONS: This study provides in vivo information concerning the ability of bacillus Calmette-Guerin to sensitize the tissue microenvironment to enhance innate responses and establishes a framework for improving vaccination strategies while decreasing adverse events.

A double-blind low dose-finding phase II study of granulocyte colony-stimulating factor combined with chemotherapy for stem cell mobilization in patients with non-Hodgkin's lymphoma.

The aim of the study was to define the minimal effective dose (MED) of granulocyte colony-stimulating factor (G-CSF) among five daily doses following chemotherapy for peripheral blood stem cell (PBSC) collection. Twenty-five patients were included in this double-blind dose-finding phase II study conducted according to a two-stage Bayesian design. The estimated probabilities of success for PBSC collection for the G-CSF doses of 50, 75, 100, 125 and 150 microg/m2/day were 84%, 87.7%, 91%, 93.9 and 96.4%, respectively. Low G-CSF doses may be used with a similar probability of success as conventional doses and could allow significant savings.

The core-specific precursor T cell response is directed to the N-terminal and central parts of the protein and positively correlates to the viral load in chronically HCV-infected patients.

The cellular immune response to hepatitis C virus (HCV) plays a critical role in determining the clearance or persistence of HCV. Moreover, in chronic HCV infection, these responses that are insufficient to eradicate virus completely may cause liver injury. In this study, the memory T cells responses specific to the core protein were measured by interferon-gamma Elispot assay after in vitro stimulation of peripheral blood mononuclear lymphocytes from chronically infected subjects. Ten out of the 22 patients studied (45%) present a core-specific response with a preferential recognition of the N-terminal and central parts. There was no relationship between T cell responses and the parameters of disease evolution as determined by ALT (serum alanine transaminase levels), and histologic hepatic damage (Metavir score A and F), but there was a positive relationship between the presence of a core-specific T cell responses and the viraemia.

Chloride transport in nasal ciliated cells of cystic fibrosis heterozygotes.

Studying subjects heterozygous for mutations of the cystic fibrosis (CF) gene may help clarify the impact on disease onset of CF transmembrane conductance regulator protein (CFTR-)-dependent chloride secretion. CFTR-mediated chloride transport was evaluated in 52 heterozygous subjects, 32 healthy control subjects, and 77 patients with CF with class I or II mutations. We measured the change in nasal potential difference in response to chloride-free isoproterenol solution for each subject and used a video-imaging fluorescent dye assay to assess the percentage of nasal ciliated cells with cAMP-dependent anion conductance. Our findings did not confirm the standard assumption that heterozygosity implies 50% of normal CFTR function. Half the heterozygous subjects had CFTR-mediated chloride transport levels below 50% of the normal range, and one-third had levels similar to those of the patients with CF. This reduced CFTR function was not associated with an elevated prevalence of CF-like symptoms in heterozygous subjects but was highly related to respiratory status in the patients with CF. These data suggest that CFTR-dependent chloride conductance does not directly modulate disease severity but may be part of a more global defect in patients with CF involving other CFTR functions or currently unknown modulatory factors.

Normal function of the cystic fibrosis conductance regulator protein can be associated with homozygous (Delta)F508 mutation.

Cystic fibrosis (CF) is caused by mutations of the gene encoding for the CFTR (CF transmembrane conductance regulator) protein. The most frequent mutation, the (Delta)F508 mutation, results in a defective cAMP-regulated chloride transport in the epithelial cells. The spectrum of clinical manifestations in patients bearing homozygous (Delta)F508 mutations can vary considerably, suggesting that, in the patients with a mild disease, CFTR could be partly functional. To test this hypothesis, we explored in nasal ciliated epithelial cells (NCC) of 9 control subjects and 23 (Delta)F508 homozygous patients the anion conductive pathway by a halide sensitive fluorescent dye assay SPQ (6-methoxy-N-3'-sulfopropylquinolinium) and the CFTR transcript levels by RT-PCR. As 50% represented the lowest fraction of the control subjects NCC demonstrating a cAMP-dependent conductance, a CF patient was considered as "cAMP responder" if at least 50% of the NCC tested displayed a cAMP-dependent conductive pathway. According to these criteria, 8 of the 23 patients were considered as cAMP responders. They had a significantly less severe disease considering the respiratory function and infectious status. The amount of CFTR mRNA did not differ between the control subjects and the patients. No statistical correlation could be found between the transcript level and the expression of a cAMP conductive pathway. This cAMP-dependent Cl(-) conductance detected in homozygous NCC could be due to a residual CFTR activity and may explain the mild phenotypes observed in some (Delta)F508 homozygous patients.