Chronic work-life stress leads to dysfunction of the hypothalamus–pituitary–adrenal axis, the autonomic nervous system, and the serotonergic system, with resultant impairment of overall well-being. Aim of the study was to improve perceived stress by a specific amino acid composition with micronutrients in the verum versus placebo group. A total of 59 participants (18–65 years) with self-reported perceived chronic stress and exhaustion conditions participated in this randomized, double-blind, placebo-controlled study. The Perceived Stress Questionnaire (PSQ₃₀), amino acid profile, anthropometric, clinical, blood, urine parameters, and dietary intake were assessed. After 12 weeks, the verum group achieved significantly greater improvements in the total PSQ₃₀ score compared with the placebo group. In the verum group, serum taurine concentration, folic acid concentration, urinary magnesium excretion, and the ratio of l-tryptophan to the sum of competing amino acids rose significantly. In the placebo group, serum concentrations of serotonin, protein, and magnesium decreased significantly, whereas the cardiometabolic risk parameters body weight, body mass index, waist circumference, and waist-to-height ratio increased significantly. Compared with placebo, the verum supplementation resulted in a higher improvement in perceived stress. Beneficial effects on the serotonergic system and preventive effects on magnesium homeostasis and some cardiometabolic risk factors were supposed. Additional effects might be caused by the optimized food intake. Full article

Milk powder and gluten are common components in Swedish infants’ diets. Whereas large intakes of gluten early in life increases the risk of celiac disease in genetically at-risk Swedish children, no study has yet evaluated if intake of milk powder by 2 years of age is associated with celiac disease. A 1-to-3 nested case-control study, comprised of 207 celiac disease children and 621 controls matched for sex, birth year, and HLA genotype, was performed on a birth cohort of HLA-DR3-DQ2 and/or DR4-DQ8-positive children. Subjects were screened annually for celiac disease using tissue transglutaminase autoantibodies (tTGA). Three-day food records estimated the mean intake of milk powder at ages 6 months, 9 months, 12 months, 18 months, and 24 months. Conditional logistic regression calculated odds ratios (OR) at last intake prior to seroconversion of tTGA positivity, and for each time-point respectively and adjusted for having a first-degree relative with celiac disease and gluten intake. Intake of milk powder prior to seroconversion of tTGA positivity was not associated with celiac disease (OR = 1.00; 95% CI = 0.99, 1.03; p = 0.763). In conclusion, intake of milk powder in early childhood is not associated with celiac disease in genetically susceptible children. Full article

Type 2 diabetes and obesity are two chronic conditions associated with the metabolic syndrome and their prevalences are increasing worldwide. The investigation of food protein-derived bioactive peptides that can improve the pathophysiology of diabetes or obesity while causing minimal side effects is desired. Egg and soy proteins generate bioactive peptides with multiple biological effects, exerting nutritional and physiological benefits. This review focuses on the anti-diabetic and anti-obesity effects of egg- and soy-derived peptides and hydrolysates in vivo and in vitro relevant to these conditions. Studies using the intact protein were considered only when comparing the results with the hydrolysate or peptides. In vivo evidence suggests that bioactive peptides from egg and soy can potentially be used to manage elements of glucose homeostasis in metabolic syndrome; however, the mechanisms of action on glucose and insulin metabolism, and the interaction between peptides and their molecular targets remain unclear. Optimizing the production of egg- and soy-derived peptides and standardizing the physiological models to study their effects on diabetes and obesity could help to clarify the effects of these bioactive peptides in metabolic syndrome-related conditions. Full article

There is an increasing amount of evidence which links the pathogenesis of irritable bowel syndrome (IBS) with food IgG hyperreactivity. Some authors have suggested that food IgG hyperreactivity could be also involved in the pathophysiology of major depressive disorder (MDD). The aim of this study was to compare levels of serum IgG against 39 selected food antigens between three groups of participants: patients with MDD (MDD group), patients with IBS (IBS group) and healthy controls (HC group). The study included 65 participants (22 in the MDD group, 22 in the IBS group and 21 in the HC group). Serum IgG levels were examined using enzyme-linked immunosorbent assay (ELISA). Medical records, clinical data and laboratory results were collected for the analysis. IgG food hyperreactivity (interpreted as an average of levels of IgG antibodies above 7.5 µg/mL) was detected in 28 (43%) participants, including 14 (64%) from the MDD group, ten (46%) from the IBS group and four (19%) from the HC group. We found differences between extreme IgG levels in MDD versus HC groups and in IBS versus HC groups. Patients with MDD had significantly higher serum levels of total IgG antibodies and IgG against celery, garlic and gluten compared with healthy controls. The MDD group also had higher serum IgG levels against gluten compared with the IBS group. Our results suggest dissimilarity in immune responses against food proteins between the examined groups, with the highest immunoreactivity in the MDD group. Further studies are needed to repeat and confirm these results in bigger cohorts and also examine clinical utility of IgG-based elimination diet in patients with MDD and IBS. Full article

Physical exercise is beneficial for general health and is an effective treatment for metabolic disorders. Vitamin E is widely used as dietary supplement and is considered to improve non-alcoholic fatty liver disease by reducing inflammation and dyslipidemia. However, increased vitamin E intake may interfere with adaptation to exercise training. Here, we explored how vitamin E alters the acute exercise response of the liver, an organ that plays an essential metabolic role during physical activity. Mice fed a control or an α-tocopherol-enriched diet were subjected to a non-exhaustive treadmill run. We assessed the acute transcriptional response of the liver as well as glucocorticoid signalling and plasma free fatty acids (FFA) and performed indirect calorimetry. Vitamin E interfered with the exercise-induced increase in FFA and upregulation of hepatic metabolic regulators, and it shifted the transcriptional profile of exercised mice towards lipid and cholesterol synthesis while reducing inflammation. Energy utilization, as well as corticosterone levels and signalling were similar, arguing against acute differences in substrate oxidation or glucocorticoid action. Our results show that high-dose vitamin E alters the metabolic and inflammatory response of the liver to physical exercise. The interference with these processes may suggest a cautious use of vitamin E as dietary supplement. Full article

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice. Full article

Childhood obesity is a significant health issue worldwide. Modifiable risk factors in early childhood relate to child healthy eating and active play, and are influenced by parents. The aim of the study was two-fold. Firstly, to determine the weight status of children aged between birth and 3.5 years in a rural and remote area of Australia. Secondly, to explore the relationship between child weight status and translation of advice on healthy eating and active play provided to parents by local, nurse-led, Maternal Child Health (MCH) services. Measured anthropometric data (n = 438) were provided by MCH services. Semi-structured interviews were conducted with two MCH nurses and 15 parents. Prevalence of overweight/obesity was calculated. Local childhood overweight/obesity prevalence was lower than the national average at age 3.5 years (11.38%; 20%). Parents identified the MCH service as a key source of healthy eating and active play advice and reported mostly following recommendations but struggling with screen time and fussy eating recommendations. We observed a relaxation in parent attitudes towards healthy child behaviours which coincided with a trend towards obesity from 12 months (p < 0.001). MCH services provide useful and effective advice to parents but ongoing support is required to prevent obesity later in childhood. Full article

A low-protein diet (LPD) can be expected to retard renal function decline in advanced stages of chronic kidney disease (CKD), including diabetic kidney disease (DKD), and is recommended in a clinical setting. Regarding the molecular mechanisms of an LPD against DKD, previous animal studies have shown that an LPD exerts reno-protection through mainly the improvement of glomerular hyperfiltration/hypertension due to the reduction of intraglomerular pressure. On the other hand, we have demonstrated that an LPD, particularly a very-LPD (VLPD), improved tubulo-interstitial damage, inflammation and fibrosis, through the restoration of autophagy via the reduction of a mammalian target of rapamycin complex 1 (mTORC1) activity in type 2 diabetes and obesity animal models. Thus, based on animal studies, a VLPD may show a more beneficial effect against advanced DKD. Previous clinical reports have also shown that a VLPD, not a moderate LPD, slows the progression of renal dysfunction in patients with chronic glomerular nephritis. However, there is insufficient clinical data regarding the beneficial effects of a VLPD against DKD. Additionally, the patients with CKD, including DKD, are a high-risk group for malnutrition, such as protein–energy wasting (PEW), sarcopenia, and frailty. Therefore, an LPD, including a VLPD, should be prescribed to patients when the benefits of an LPD outweigh the risks, upon consideration of adherence, age, and nutritional status. As the future predicts, the development of a VLPD replacement therapy without malnutrition may be expected for reno-protection against the advanced stages of DKD, through the regulation of mTORC1 activity and adequate autophagy induction. However, further studies to elucidate detailed mechanisms by which a VLPD exerts reno-protection are necessary. Full article

Pomegranate (Punica granatum L.) fruit has been demonstrated to have the inhibitory activities to various tumors. In this study, we try to uncover the molecular mechanism underlying the inhibitory capability of Taiwanese local pomegranate fruit to urinary bladder urothelial carcinoma. The results collected from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated that the ethanol extract of pomegranate peel exhibited better inhibitory activity to human urinary bladder urothelial carcinoma T24 and J82 cells than that of pulp. Furthermore, the ethylacetate layer of peel ethanol extract was observed to have the best inhibitory activity against urinary bladder urothelial carcinoma cells. One of the eight fractions (PEPE2 fraction) collected from the ethylacetate layer with Diaion HP-20 column chromatography demonstrated the highest inhibitory activity in urinary bladder urothelial carcinoma cells. The results of the flow cytometry and apoptotic pathway studies suggested that the inhibitory activity of PEPE2 fraction were attributed to the UBUC cell apoptosis. To confirm the above results, our results of xenograft-induced bladder tumor in nude mice showed that the oral consumption of the ethylacetate layer (2, 5, 10 and 100 mg/kg) could decrease the volume and weight of T24 tumors and caused the apoptosis in the xenografted tumors, which was observed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay. This study provided the likelihood that the traditionally non-edible pomegranate peel waste is re-utilized to make an affordable and promising chemopreventive product to prevent UBUC incidence or recurrence. Full article

Traditionally, healthful diets and lifestyles have been examined only in relation to single nutrients, foods, or food groups in terms of dietary exposure. An alternative approach is to conceptualize an index based on vegetarian food pyramid guidelines as a measure of overall diet and lifestyle quality. Our objectives were to: (1) develop the Vegetarian Lifestyle Index (VLI); and (2) evaluate adherence to the Vegetarian Food Guide Pyramid (VFGP) among a low-risk population of Adventists. The index was based on the operationalization of 14 dietary and lifestyle components. All components were equally weighted. Higher score reflected greater adherence to the VFGP. The analytic sample (n = 90,057) comprised 47.7% non-vegetarians, 5.6% semi-, 10.1% pesco-, and 29.0% lacto-ovo-vegetarians, and 7.7% vegans, of which 1.1% were current smokers and 9.9% were alcohol consumers. Population mean VLI score was 7.43 (SD = 1.75) ranging from 1 to 12.5. Non-vegetarians (6.14; 95% confidence interval (CI), 6.06–6.21) had a significantly lower mean compared to semi- (7.31; 95% CI, 7.22–7.40), pesco- (7.41; 95% CI, 7.32–7.49), and lacto-ovo-vegetarians (8.16; 95% CI, 8.08–8.24), as well as vegans (8.88; 95% CI, 8.78–8.96). Vegetarians scored on average 1.18 to 2.73 more points than their non-vegetarian counterparts. Results demonstrate that the index has strong discriminant ability across distinct dietary patterns. Additionally, the VLI provides a useful measure of diet and lifestyle adherence to further refine vegetarian food pyramid guidelines. Full article

Background: Over 70% of patients are prescribed antibiotics during their intensive care (ICU) admission. The gut microbiome is dramatically altered early in an ICU stay, increasing the risk for antibiotic associated diarrhea (AAD) and Clostridium difficile infections (CDI). Evidence suggests that some probiotics are effective in the primary prevention of AAD and CDI. Aim: To demonstrate safety and feasibility of a probiotic drink in ICU patients. Methods: ICU patients initiated on antibiotics were recruited, and matched with contemporary controls. Study patients received two bottles daily of a drink containing 10 billion Lactobacillus casei which was bolused via feeding tube. Tolerance to probiotics and enteral nutrition, development of adverse events, and incidence of AAD was recorded. CDI rates were followed for 30 days post antibiotic treatment. Results: Thirty-two patients participated in the trial. There were no serious adverse events in the probiotic group, compared to three in the control group. AAD was documented in 12.5% of the probiotic group and 31.3% in the control group. One patient in the probiotic group developed CDI compared to three in the control group. Discussion: A probiotic containing drink can safely be delivered via feeding tube and should be considered as a preventative measure for AAD and CDI in ICU. Full article

Background: The prevalence of depression in celiac disease (CD) is high, and patients are often burdened socially and financially by a gluten-free diet. However, the relationship between depression, somatic symptoms and dietary adherence in CD is complex and poorly understood. We used a patient powered research network (iCureCeliac^®) to explore the effect that depression has on patients’ symptomatic response to a gluten-free diet (GFD). Methods: We identified patients with biopsy-diagnosed celiac disease who answered questions pertaining to symptoms (Celiac Symptom Index (CSI)), GFD adherence (Celiac Dietary Adherence Test (CDAT)), and a 5-point, scaled question regarding depressive symptoms relating to patients’ celiac disease. We then measured the correlation between symptoms and adherence (CSI vs. CDAT) in patients with depression versus those without depression. We also tested for interaction of depression with regard to the association with symptoms using a multiple linear regression model. Results: Among 519 patients, 86% were female and the mean age was 40.9 years. 46% of patients indicated that they felt “somewhat,” “quite a bit,” or “very much” depressed because of their disorder. There was a moderate correlation between worsened celiac symptoms and poorer GFD adherence (r = 0.6, p < 0.0001). In those with a positive depression screen, there was a moderate correlation between worsening symptoms and worsening dietary adherence (r = 0.5, p < 0.0001) whereas in those without depression, the correlation was stronger (r = 0.64, p < 0.0001). We performed a linear regression analysis, which suggests that the relationship between CSI and CDAT is modified by depression. Conclusions: In patients with depressive symptoms related to their disorder, correlation between adherence and symptoms was weaker than those without depressive symptoms. This finding was confirmed with a linear regression analysis, showing that depressive symptoms may modify the effect of a GFD on celiac symptoms. Depressive symptoms may therefore mask the relationship between inadvertent gluten exposure and symptoms. Additional longitudinal and prospective studies are needed to further explore this potentially important finding. Full article

Genetic and environmental factors are thought to profoundly influence the pathophysiology of Crohn’s disease (CD). Changes in dietary and hygiene patterns affect the interactions between the immune system and environment. The gut microbiome is responsible for mediating host immune response with significant dysbiosis observed in individuals with CD. Diet therapy using exclusive enteral nutrition (EEN) has been studied as primary therapy for the management of CD. EEN may cultivate the presence of beneficial microbiota, improve bile acid metabolism, and decrease the number of dietary microparticles possibly influencing disease and immune activity. In this review, we will address the current evidence on EEN in the management of adult and pediatric CD. In adults, EEN appears to be moderately beneficial for the induction of remission of CD; however, its use is understudied and underutilized. Stronger evidence is in place to support the use of EEN in pediatric CD with the added benefit of nutrition support and steroid-sparing therapy during the growth phase. Overall, EEN is an established therapy in inducing CD remission in the pediatric population while its role as primary therapy of adult Crohn’s disease remains to be defined. Full article