Claimed Effects, Outcome Variables and Methods of Measurement for Health Claims on Foods Related to Vision Proposed Under Regulation (EC) 1924/2006.

Adequate visual function has a strong impact on the quality of life of people. Several foods and food components have been hypothesized to play a role in the maintenance of normal visual function and in the prevention of eye diseases. Some of these foods/food components have been the object of a request of authorization for use of health claims under Articles 13(5) or 14 of the Regulation (EC) 1924/2006. Most of these requests have received a negative opinion from the European Food Safety Authority (EFSA) due to the choice of inappropriate outcome variables (OVs) and/or methods of measurement (MMs) applied in the studies used to substantiate the claims. This manuscript refers to the collection, collation and critical analysis of OVs and MMs related to vision. Guidance document and requests for authorization of health claims were used to collect OVs and MMs related to vision. A literature review was performed to critically analyse OVs and MMs, with the aim of defining their appropriateness in the context of a specific claimed effect related to vision. The results highlight the importance of adequate choices of OVs and MMs for an effective substantiation of claims related to visual function.

Claimed effects, outcome variables and methods of measurement for health claims on foods related to the gastrointestinal tract proposed under regulation (EC) 1924/2006.

Most of the requests of authorisation to the use of health claims pursuant to Regulation EC 1924/2006 related to the gastrointestinal (GI) tract have received a negative opinion by the European Food Safety Authority (EFSA), mainly because of an insufficient substantiation of the claimed effect (CE). The present manuscript refers to the collection, collation and critical analysis of outcome variables (OVs) and methods of measurement (MMs) related to the GI tract compliant with Regulation 1924/2006. The critical evaluation of OVs and MMs was based on the literature review, with the final aim of defining their appropriateness in the context of a specific CE. The results obtained are relevant for the choice of the best OVs and MMs to be used in randomised controlled trials aimed to substantiate the claims on the GI tract. Moreover, the results can be used by EFSA for updating the guidance for the scientific requirements of such health claims.

Alpha-Lipoic Acid Shows Promise to Improve Migraine in Patients with Insulin Resistance: A 6-Month Exploratory Study.

Alpha-lipoic acid (ALA) is known to lower insulin resistance (IR), which is common among migraineurs. To assess the effect of ALA on headache in migraineurs with IR, we performed an exploratory study on a cohort of patients with migraine, followed at our Headache Center. The 32 patients took ALA 400 mg b.i.d. for 6 months in addition to their on-going treatment. The percentage of patients with a reduction of at least 50% of the attacks was 0.53 (confidence interval [95% CI] 0.36-0.70) at 2 months, 0.56 (0.39-0.73) at 4 months, and 0.69 (0.53-0.85) at 6 months. The incidence rate ratio of attacks at 6 months versus baseline was 0.48 (0.43-0.53, P < .001), corresponding to a mean (95% CI) number of attacks of 5 (4-6) versus 11 (10-12). The number of days of treatment in the previous month was 7.7 (6.8-8.7) at baseline, 5.4 (4.6-6.2) at 2 months, 5.3 (4.5-6.1) at 4 months, and 4.3 (3.6-5.0) at 6 months. Baseline and 120-min glucose and insulin and quantitative insulin sensitivity check index (QUICKI) and the Stumvoll index did not change at 6 months versus baseline. This exploratory study shows that the administration of ALA may be associated with a reduction in the number of attacks and the days of treatment in migraineurs with IR. A randomized controlled trial is needed to test this possibility.

Diagnostic Performance Analysis of the Point-of-Care Bilistick System in Identifying Severe Neonatal Hyperbilirubinemia by a Multi-Country Approach.

IMPORTANCE: The real prevalence and clinical burden of severe neonatal jaundice are undefined due to difficulties in measuring total serum bilirubin (TSB) outside secondary and tertiary clinical centers. OBJECTIVE: To assess the diagnostic performance of the point-of care Bilistick System (BS) in identifying neonatal jaundice patients requiring treatment. DESIGN: Between April 2015 and November 2016, 1911 neonates, were recruited to participate in the study. Blood samples were simultaneously collected for the TSB determination by BS and by hospital laboratory (Lab). Data were collected and sent to the Bilimetrix headquarter in Trieste where statistical analysis was performed. Newborns with neonatal jaundice were treated with phototherapy according to each center's guidelines. SETTING: 17 hospitals from Nigeria, Egypt, Indonesia, and Viet Nam. PARTICIPANTS: 1911 newborns were included, of which 1458 (76·3%) fulfilled the inclusion criteria. RESULTS: TSB level measured by BS agreed (p < .0001) with the lab result in all four countries. The diagnostic performance of BS showed a positive predictive value (PPV) of 92·5% and a negative predictive value (NPV) of 92·8%. CONCLUSIONS AND RELEVANCE: BS is a reliable system to detect neonatal jaundice over a wide range of bilirubin levels. Since Bilistick is a point-of-care test, its use may provide appropriate and timely identification of jaundiced newborns requiring treatment.

Claimed Effects, Outcome Variables and Methods of Measurement for Health Claims Proposed Under European Community Regulation 1924/2006 in the Framework of Maintenance of Skin Function.

Evidence suggests a protective role for several nutrients and foods in the maintenance of skin function. Nevertheless, all the requests for authorization to use health claims under Article 13(5) in the framework of maintenance of skin function presented to the European Food Safety Authority (EFSA) have received a negative opinion. Reasons for such failures are mainly due to an insufficient substantiation of the claimed effects, including the choice of inappropriate outcome variables (OVs) and methods of measurement (MMs). The present paper reports the results of an investigation aimed at collecting, collating and critically analyzing the information with relation to claimed effects (CEs), OVs and MMs related to skin health compliance with Regulation 1924/2006. CEs, OVs and MMs were collected from both the EFSA Guidance document and from the authorization requests of health claims under Article 13(5). The critical analysis of OVs and MMs was based on a literature review, and was aimed at defining their appropriateness (alone or in combination with others) in the context of a specific CE. The results highlight the importance of an adequate choice of OVs and MMs for an effective substantiation of the claims.

Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial.

BACKGROUND: Children with cow's milk allergy (CMA) have an increased risk of other allergic manifestations (AMs). OBJECTIVE: We performed a parallel-arm randomized controlled trial to test whether administration of an extensively hydrolyzed casein formula (EHCF) containing the probiotic Lactobacillus rhamnosus GG (LGG) can reduce the occurrence of other AMs in children with CMA. METHODS: Children with IgE-mediated CMA were randomly allocated to the EHCF or EHCF+LGG groups and followed for 36 months. The main outcome was occurrence of at least 1 AM (eczema, urticaria, asthma, and rhinoconjunctivitis). The secondary outcome was tolerance acquisition, which was defined as the negativization of a double-blind food challenge results at 12, 24, and 36 months. AMs were diagnosed according to standardized criteria. Tolerance acquisition was evaluated every 12 months. RESULTS: A total of 220 children (147 boys [67%]) with a median age of 5.0 months (interquartile range, 3.0-8.0 months) were randomized; 110 children were placed in the EHCF group, and 110 children were placed in the EHCF+LGG group. In the complete case analysis the absolute risk difference for the occurrence of at least 1 AM over 36 months was -0.23 (95% CI, -0.36 to -0.10; P < .001), and the absolute risk difference for the acquisition of cow's milk tolerance was 0.20 (95% CI, 0.05-0.35; P < .01) at 12 months, 0.24 (95% CI, 0.08-0.41; P < .01) at 24 months, and 0.27 (95% CI, 0.11-0.43; P < .001) at 36 months. In the sensitivity analysis the effect size of the main outcome was virtually unchanged when the occurrence of AMs was assigned to all 27 missing children. CONCLUSIONS: EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE-mediated CMA.

Nutrition in Pediatric Inflammatory Bowel Disease: From Etiology to Treatment. A Systematic Review.

Nutrition is involved in several aspects of pediatric inflammatory bowel disease (IBD), ranging from disease etiology to induction and maintenance of disease. With regards to etiology, there are pediatric data, mainly from case-control studies, which suggest that some dietary habits (for example consumption of animal protein, fatty foods, high sugar intake) may predispose patients to IBD onset. As for disease treatment, exclusive enteral nutrition (EEN) is an extensively studied, well established, and valid approach to the remission of pediatric Crohn's disease (CD). Apart from EEN, several new nutritional approaches are emerging and have proved to be successful (specific carbohydrate diet and CD exclusion diet) but the available evidence is not strong enough to recommend this kind of intervention in clinical practice and new large experimental controlled studies are needed, especially in the pediatric population. Moreover, efforts are being made to identify foods with anti-inflammatory properties such as curcumin and long-chain polyunsaturated fatty acids n-3, which can possibly be effective in maintenance of disease. The present systematic review aims at reviewing the scientific literature on all aspects of nutrition in pediatric IBD, including the most recent advances on nutritional therapy.

Pidotimod for the prevention of acute respiratory infections in healthy children entering into daycare: A double blind randomized placebo-controlled study.

Acute respiratory tract infections (ARTIs) are very common in pediatric age and reach a peak in the first 4 years of life, especially in children attending daycare. Pidotimod, a synthetic immunostimulant, may reduce the incidence of ARTIs in children with predisposing risk factors. Nevertheless studies on healthy children are presently lacking. We performed a double-blinded randomized placebo-controlled trial study to assess the efficacy of Pidotimod in a population of 3-year-old healthy children who just entered kindergarten. The main outcome was the incidence of respiratory infections in this population and the secondary outcome was the prescription of antibiotics. The study group consisted of healthy 3-year-old children who had not yet attended day-care centers. Patients were enrolled by a convenience sample of 17 family pediatricians (FP). Children were randomized to receive either Pidotimod 400 mg per os or placebo twice daily for the last 10 days of each month from October 2013 to April 2014. Any time a child presented to his/her FP with fever and ARTI was diagnosed, clinical and therapeutic data were collected. A total of 800 children were pre-screened, 733 did not meet the inclusion criteria and 10 refused to participate. Of the 67 eligible subjects, 57 were successfully enrolled within the study recruitment period and randomized to receive Pidotimod (n = 29) or placebo (n = 28). Eight children were lost to follow-up. In the final analysis were thus included 24 children who received Pidotimod and 25 who received placebo. The incidence rate ratio for respiratory infections was 0.78 (95%CI 0.53 to 1.15, p = 0.211) for Pidotimod vs. placebo. The corresponding risk ratio for antibiotic usage was 0.56 (95%CI 0.27 to 1.16, p = 0.120). In our trial, Pidotimod did not prove to be statistically superior to placebo for the prevention of ARTI in a population of healthy children who entered kindergarten. However, Pidotimod showed some potential as a means for reducing antibiotic usage in these children.

Nutrient intake in Italian infants and toddlers from North and South Italy: the Nutrintake 636 study.

We performed a cross-sectional study to compare the intake of energy, macronutrients, fiber, sodium and iron and the anthropometric status of infants and toddlers living in North (Milano) and South Italy (Catania). Nutrient intake was evaluated using a 7-day weighed food record. Out of 400 planned children aged 6 to 36 months, 390 (98%) were recruited, 189 in Milano and 201 in Catania. The mean (standard deviation) age was 17 (9) months in Milano and 17 (10) months in Catania. Anthropometry, energy intake and macronutrient intake were similar in Milano and Catania. However, iron intake was 27% lower and fiber intake 16% higher in Milano than in Catania. Despite normal anthropometry and energy intake, in the pooled sample there was a high intake of proteins, simple carbohydrates, saturated fats and sodium, and a low intake of iron and fiber compared to Italian reference values. This is the first study to report the macro- and micro-nutrient intake of children aged <12 months using the 7-day weighed food record and one of the very few studies that have employed such reference method in children from the general population.

The I148M variant of PNPLA3 reduces the response to docosahexaenoic acid in children with non-alcoholic fatty liver disease.

The aim of this secondary analysis of a randomized controlled trial was to test whether the I148M variant of Patatin-like phospholipase domain-containing protein-3 (PNPLA3) is associated with the response to docosahexaenoic acid (DHA) in children with non-alcoholic fatty liver disease (NAFLD). Sixty children with NAFLD were randomized in equal numbers to DHA 250 mg/day, DHA 500 mg/day or placebo. Coherently with the primary analysis, the probability of more severe steatosis after 24 months of DHA supplementation was 50% lower [95% confidence interval (CI) -59% to -42%)] in the combined DHA 250 and 500 mg/day groups versus placebo. The present secondary analysis revealed an independent effect of PNPLA3 status on the response to DHA. In fact, the probability of more severe steatosis was higher (37%, 95% CI 26-48%) for the PNPLA3 M/M versus I/M genotype and lower (-12%, 95% CI -21% to -3%) for the I/I versus I/M genotype (Somers' D for repeated measures). We conclude that the 148M allele of PNPLA3 is associated with lower response, and the 148I allele with greater response, to DHA supplementation in children with NAFLD.

Cholecalciferol supplementation in HIV-infected youth with vitamin D insufficiency: effects on vitamin D status and T-cell phenotype: a randomized controlled trial.

OBJECTIVES: In addition to its known effects on bone metabolism, vitamin D may regulate immune function. DESIGN: We performed a randomized controlled trial (RCT) to test whether cholecalciferol supplementation can improve vitamin D status and affect the T-cell phenotype in HIV-infected youth with vitamin D insufficiency. METHODS: Fifty-two HIV-infected patients aged 8 to 26 years and with serum 25(OH) D <30 ng/mL were randomized to receive orally vitamin D3 100,000 IU or placebo every 3 months for 4 doses. Serum 25(OH)D, 1,25(OH)2D, PTH, and CD4+ T cells were assessed 3 months before baseline and at 0, 3, 6, 9, and 12 months, while Th1-, Th2-, Th17-, and Treg-subsets and T-lymphocyte vitamin D receptor were assessed at 0, 3, and 12 months. RESULTS: Forty-eight subjects (25 receiving vitamin D and 23 receiving placebo) completed the RCT. Cholecalciferol supplementation produced an early (3 months) decrease in PTH, a concomitant increase in 25(OH)D, and a later (6 months) increase in 1,25(OH)2D levels, all persisting at 12 months. The frequency of vitamin D insufficiency at 12 months was 20% versus 60% in the intervention versus placebo group (P = .007). Cholecalciferol supplementation had no effect on CD4+ T-cell counts but was associated with a decreased Th17:Treg ratio at 3 months. CONCLUSIONS: In our cohort of HIV-infected youth, a 12-month cholecalciferol supplementation increased 25(OH)D and 1-25(OH)2D and decreased PTH levels but had no effect on CD4+ T-cells. However, it was associated with changes in CD4+ T-cell phenotype, warranting further investigation.

Epigenetic mechanisms elicited by nutrition in early life.

A growing number of studies focusing on the developmental origin of health and disease hypothesis have identified links among early nutrition, epigenetic processes and diseases also in later life. Different epigenetic mechanisms are elicited by dietary factors in early critical developmental ages that are able to affect the susceptibility to several diseases in adulthood. The studies here reviewed suggest that maternal and neonatal diet may have long-lasting effects in the development of non-communicable chronic adulthood diseases, in particular the components of the so-called metabolic syndrome, such as insulin resistance, type 2 diabetes, obesity, dyslipidaemia, hypertension, and CVD. Both maternal under- and over-nutrition may regulate the expression of genes involved in lipid and carbohydrate metabolism. Early postnatal nutrition may also represent a vital determinant of adult health by making an impact on the development and function of gut microbiota. An inadequate gut microbiota composition and function in early life seems to account for the deviant programming of later immunity and overall health status. In this regard probiotics, which have the potential to restore the intestinal microbiota balance, may be effective in preventing the development of chronic immune-mediated diseases. More recently, the epigenetic mechanisms elicited by probiotics through the production of SCFA are hypothesised to be the key to understand how they mediate their numerous health-promoting effects from the gut to the peripheral tissues.

Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial.

OBJECTIVE: To investigate whether dietary supplementation with docosahexaenoic acid (DHA) decreases liver fat content in children with non-alcoholic fatty liver disease (NAFLD). DESIGN, SETTING AND PATIENTS: We performed a randomised controlled trial of DHA supplementation (250 and 500 mg/day) versus placebo in 60 children with biopsy-proven NAFLD (20 children per group). MAIN OUTCOME MEASURES: The main outcome was the change in liver fat content as detected by ultrasonography after 6 months of treatment. Secondary outcomes were the changes in insulin sensitivity index, alanine transaminase, triglycerides and body mass index after 6 months of treatment. RESULTS: Blood DHA increased in children supplemented with DHA (0.65%, 95% CI 0.30% to 1.10% for the DHA 250 mg group and 1.15%, 0.87% to 1.43% for the DHA 500 mg group). The odds of more severe versus less severe liver steatosis after treatment was lower in children treated with DHA 250 mg/day (OR = 0.01, 0.002 to 0.11, p <0.001) and DHA 500 mg/day (OR = 0.04, 0.002 to 0.46, p = 0.01) as compared to placebo but there was no difference between the DHA groups (p = 0.4). Insulin sensitivity index increased and triglycerides decreased to a similar degree in both DHA groups as compared to placebo but there was no effect on alanine transaminase and body mass index. CONCLUSION: DHA supplementation improves liver steatosis and insulin sensitivity in children with NAFLD.